Atlas Hematologie crop

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INTRODUCTION 3

The book contains a short descriptive text of the development of the blood cells followed by a table of normal haematological values and thereafter the illustrations are placed in seven main sections . The first section covers the red cell series which includes both normoblastic and megaloblastic erythropoiesis; the next section covers illustrations of all white cell series in the order of granular lcucocytcs, which arc sub-divided into neutrophil, eosinophil, and basophil polymorphonuclear lcucocytcs, followed by lymphocytes, monocytcs and plasma cells . This is followed by a section on the megakaryocyte series and platelet formation. Following this there is a section on phase contrast microscopy. A short section of illustrations of parasitic conditions of the blood follows. The following section, tumours of the lymphoid tissue and other neoplasms, includes a table of compara tive terminology with particular reference to tumours of the lymphoid tissue . Finally a section on artefacts and other abnormali ties follows. For ease of comparison a separate section has not been devoted to the leukaemias, the several types being included under the appropriate white cell sub-division.

An attempt has been made to maintain the same sequence for each cell series, i.e. normal marrow, normal blood, non-neoplastic conditions of marrow and blood, neoplastic conditions and then cell abnormalities and anomalies, as these are common to both non-neoplastic and neoplastic cells. This has not always been possible however, and on occasion the marrow and/or blood pictures have been placed immediately preceding the illust rations of tissue changes in the same condition.

At first glance it might appear that some illustrations of a cell series have been duplicated but, if the captions are read carefully , it will be seen that various cell types, e.g. early megaloblasts and promyclocytcs, may figure in one illustration, thereby allowing the reader to compare cell types within the one field. It would be as impossible to give an accurate diagnosis from one high-power photomicrograph as it would be to do so from one microscopic field; this is the reason for showing more than one illustration in several of the more common conditions. Wherever great variation in size and nuclear configuration of any cell type is a common feature, many small illustrations have been built up to a composite thus giving the trainee in haematology a ready means of comparison.

Throughout the book low- and high-power illustrations of the principal and common histological appearances of the visceral tissues in the various blood conditions have been included in their proper context and illustrations of normal tissues have been included in close proximity for comparison of overall pattern and cell type. No attempt has been made to demonstrate a comprehensive series of the lesions in such conditions as lupus erythematosus and no attempt has been made to cover the enormous range of mixed patterns seen in tumours of the lymphoid tissue .

A separate maturation scheme is provided for easy comparison when studying the illustrations.

INTRODUCTION 3

The book contains a short descriptive text of the development of the blood cells followed by a table of normal haematological values and thereafter the illustrations are placed in seven main sections. The first section covers the red cell series which includes both normoblastic and megaloblastic erythropoiesis; the next section covers illustrations of all white cell series in the order of granular leucocytes, which are sub-divided into neutrophil, eosinophil, and basophil polymorphonuclear leucocytes, followed by lymphocytes, monocytes and plasma cells. This is followed by a section on the megakaryocyte series and platelet formation. Following this there is a section on phase contrast microscopy. A short section of illustrations of parasitic conditions of the blood follows. The following section, tumours of the lymphoid tissue and other neoplasms, includes a table of comparative terminology with particular reference to tumours of the lymphoid tissue. Finally a section on artefacts and other abnormalities follows. For ease of comparison a separate section has not been devoted to the leukaemias, the several types being included under the appropriate white cell sub-division.

An attempt has been made to maintain the same sequence for each cell series, i.e. normal marrow, normal blood, non-neoplastic conditions of marrow and blood, neoplastic conditions and then cell abnormalities and anomalies, as these are common to both non-neoplastic and neoplastic cells. This has not always been possible however, and on occasion the marrow and/or blood pictures have been placed immediately preceding the illustrations of tissue changes in the same condition.

At first glance it might appear that some illust rations of a cell series have been duplicated but, if the captions are read carefully, it will be seen that various cell types, e .g. early megaloblasts and promyelocytes, may figure in one illustration, thereby allowing the reader to compare cell types within the one field. It would be as impossible to give an accurate diagnosis from one high-power photomicrograph as it would be to do so from one microscopic field; this is the reason for showing more than one illustration in several of the more common conditions. Wherever great variation in size and nuclear configuration of any cell type is a common feature, many small illustrations have been built up to a composite thus giving the trainee in haematology a ready means of comparison.

T hroughout the book low- and high-power illustrations of the principal and common histological appearances of the visceral tissues in the various blood conditions have been included in their proper context and illustrations of normal tissues have been included in close proximity for comparison of overall pattern and cell type. No attempt has been made to demonstrate a comprehensive series of the lesions in such conditions as lupus erythematosus and no attempt has been made to cover the enormous range of m ixed patterns seen in tumours of the lymphoid tissue .

A separate maturation scheme is provided for easy comparison when studying the illustrations .

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DEVELOPMENT OF THE BLOOD CELLS 7

All blood cells are derived from the undifferentiated mesenchymal cell of the reticuloendothelial system (haemohistioblast). Normally these primitive blood cells are present in small numbers and are difficult to identify in marrow smears but in pathological states with marrow hyperplasia they may be more numerous.

In haemopoietic tissue the haemohistioblast gives rise to the haemocytoblast which has a potentiality of progression to the erythroid, myeloid or megakaryocyte series . Thus, the haemocytoblast may develop to a pronormoblast, a myeloblast or a megakaryoblast. The cells of the monocytic, lymphocytic and plasmocytic series also develop from the haemocytoblast but their main source of origin is the lymphoid tissue outwith the bone marrow.

Stem cell ( haemohistioblast). This cell varies in size from 20 to 40 !J.m, its cytoplasm is abundant and spreading with indefinite limits in many instances; it is commonly ruptured during the 'preparation of the fi lm. The cytoplasm is faintly basophilic and on occasion contains a few azurophilic granules. Usually the nucleus is oval, small in comparison to the volume of the cytoplasm and invariably found to be lying in relation to the long axis of the cell. The nucleus shows a finely reticular chromatin pattern and generally stains a pale rose colour. One or more nucleoli are usually discernible.

Haemocytoblast. In this cell, which is approximately 2~ !J.m in diameter, the volume of the cytoplasm is small in comparison to the size of the nucleus. The cell is usually irregular in outline, moderately basophilic and non-granular. The nucleus, which is large, round or oval shows a fine reticular chromatin network , the staining·react ion being heavier than that seen in the haemohistioblast. It contains several definite blue stained nucleoli which may show considerable variation in shape.

It should be borne in mind thin the process of maturations is progressive and continuous and that transitional forms between the various stages will be seen.

H istioblast. This cell , which is the precursor of the monocyte, the plasma cell , the mast cell and possibly the lymphocyte, develops directly from the haemohistioblast. It is usually oval in shape and approximately 20 1-l-m in diameter, with a high nucleo-cytoplasmic ratio. The nucleus, which is usually positioned to the long axis of the cell , stains a rose colour and contains one or two pa.Je bl~e nucleoli which are bounded by a well-marked rim of deeply stained chromatin. The cytoplasm shows a blue-grey staining reaction similar, but deeper in shade, to that of the monocyte.

ERYTHROPOIESIS

NORMOBLASTIC ERYTHROPOIESIS

Pronormoblast. This is the first cell which is recognisable as definitely belonging to the erythroid series. It is approximately 12 to 20 IJ.m in diameter and is distinguishable from the myeloblast by its deep blue cytoplasm, which is usually only a narrow rim around the relatively large nucleus; it often stains unevenly and may show a perinuclear halo. The nucleus consists of a network of uniformly distributed chromatin strands giving a fine reticular appearance. It stains a reddish purple colour and contains several darker staining nucleoli.

Early normoblast. There is a very close resemblance between this cell and the pronormoblast; it varies from 10 to 16 !J.m in diameter. The nucleus is relatively large, stains deeply and the chromatin strands are thicker than in the pronormoblast, giving a coarser appearance; generally no nucleoli are to be seen.

Intermediate normoblast. In this cell , which is from 8 to 14 1-l-m in d iameter, the cytoplasm shows a polychromatic staining reaction, i.e. a tendency to take both the basic and acid stains,

8 ATLAS OF HAEMATOLOGY

thus giving a purple tint which becomes more acidophilic as the cell matures, due to haemoglobin appearing. The nucleus occupies a relatively smaller part of the total and decreases in size as the cell ages; it now stains deeply and the chromatin is arranged in clumps.

Late normoblast. The cytoplasm of this cell , although acidophilic, may show a faint polychromatic tint. The cell varies from 8 to 10 fJ.m in diameter. The nucleus is small and may still show very coarse clumped chromatin which disappears as the nucleus shrinks and is eventually seen as a homogenous blue-black structureless mass . As the cell matures the nucleus is commonly eccentric, occasionally lobulated and is eventually lost by extrusion, fragmentation or dissolution.

R eticulocyte . This is a young erythrocyte which still has a content of fine basophilic reticulum which can be demonstrated with a supravital stain such as brilliant cresyl blue. When stained by any of the Romanowsky methods these cells exhibit a diffuse pale basophilia. In normal blood the reticulocyte content is from 0.02 to 2% . This cell is flat and disc-shaped and as it loses its basophilic reticulum it develops into a mature red cell or erythrocyte.

Erythrocyte. This is a biconcave cell which shows a moderate variation in size, from 6.7 to 7.7 fJ.m with a mean of 7.2 fJ.m, is readily distorted because of its flexibility; hence the variations in shape seen in stained blood fi lms. It exhibits an eosinophilic reaction when stained by the Romanowsky methods, the staining being deep at the periphery and gradually lessening towards the centre because of the biconcavity of the cell. This pale central area is commonly known as the area of central pallor and occupies less than one-third of the diameter of the normal erythrocyte, but this may vary according to the staining technique. Cells with a normal haemoglobin content are described as being normochromic.

MEGALOBLASTIC ERYTHROPOIESIS

Megaloblasts are not present in normal marrow. Their occurrence is due to disturbance of cell growth and maturation caused by deficiency of vitamin B12 and/or folic acid. The maturation of the megaloblastic series is similar to that of the normoblastic series but there are morphological differences at each stage. Megaloblastic erythropoiesis is frequently accompanied by abnormalities in development of the myeloid and megakaryocyte series. A moderate increase in the number of haemohistioblasts and haemocytoblasts also occurs.

T he earliest cell in this series, in transition from the haemocytoblast is the promegaloblast and maturation develops through early, intennediate and late megaloblast to the macrocyte. The morphological differences from the normoblastic series affect the cell size and the appearance of the nucleus.

The cell size is larger and the cytoplasm more abundant in comparison to normoblasts at equivalent stages of maturation:

I. Promegaloblast 2. Early megaloblast 3. !ntelmediate megaloblast 4. Late megaloblast 5. Macrocyte

20 to 30 fJ.m 18 to 25 fJ.m 16 to 20 f).m 12 to 15 fJ.m 9 to 12 fJ.m

The nucleus is larger in comparison to the normoblast at all stages of development. The chromatin has a more open pattern, being arranged in a fine reticular fashion giving the nucleus a stippled appearance . This is often quite well marked in the intermediate stage and may still be present in the late megaloblast. As the cell matures the clumping of the chromatin is much less obvious than in normoblasts at the corresponding stages. Nuclear maturation lags behind


cytoplasmic haemoglobinisation with the result that megaloblasts with eosinophilic cytoplasm may still show nuclei with fine reticular chromatin. One of more Howell-Jolly bodies may be present in the late stages.

Promegaloblasts and early megaloblasts may constitute over SO% of the erythroid series in the marrow in a severe megaloblastic anaemia.

LEUCOPOIESIS

THE MYELOID (GRANULOCYTIC) SERIES

Mature granular leucocytes are cells with cytoplasmic granules which give either a neutrophilic, eosinophilic or basophilic reaction to the Romanowsky stains. Because of their lobula ted (segmented) polymorphic nuclei these cells are referred to as polymorphonuclear leucocytes (polymorphs) . When used without qualification, the term 'polymorph ' refers to a mature neutrophil leucocyte.

The myeloblast is the first recognisable cell of the granulocytic series from which the promyelocyte, and then by progression, the myelocyte, the metamyelocyte, the non-segemented (stab) forms and finally the mawre (segmented) granular leucocytes develop. Specific granules which determine the nature of the mature cell , i.e. neutrophil, eosinophil or basophil begin to appear at the promyelocyte stage and are fully differentiated in the myelocyte. Mitotic divisions occurs up to the myelocyte stage, the normal metamyelocyte being incapable of mitosis.

The neutrophil (polymorphonuclear) series

Maturation of this cell type is characterised by the development of specific cytoplasmic granules and changing of the staining reaction of the cytoplasm from basophilic to eosinophilic at which stage the granules take an admixture of both staining elements. As the nucleus ripens it becomes lobulated. There is also the development of motility and phagocytosis.

Myeloblast. Variation in the size of this cell is between 15 to 20 JJ.m. The cytoplasm may be non-granular or may exhibit a few azurophil granules depending on the stage of development. It is moderately deep blue in staining reaction which may be uneven, often being somewhat lighter in the perinuclear region. The nucleus is round or oval and occupies about four-fifths of the total cell area. The nuclear chromatin is arranged in fine strands which stain a reddishpurple colour and give an even, reticular appearance. There may be up to six nucleoli but two to five are usual; they are of medium size and are generally sharply defined with a well-marked chromatin border.

Promyelocyte. This cell , which is from 22 to 25 JJ.m in diameter, resembles the myeloblast except that the cytoplasm contains granules (azurophil granules) which stain from blue to reddish purple. The nuclear chromatin is somewhat coarser than in the myeloblast and although nucleoli are still present they are less well defined.

Myelocyte. The differences between this cell and the promyelocyte are that the cytoplasmic granules have now assumed their neutrophilic character and no nucleoli are discernible. The cell is from 18 to 20 JJ.m in diameter, although at the very early stage it may be as large as 25 JJ.m. At this earlier stage the cytoplasm stains light blue and the cytoplasmic nuclear ratio is increased. The cytoplasm progressively acquires a pinkish hue and in the mature form is predominantly or completely pink. The nucleus is round or oval and the nuclear chromatin is in the form of thick strands which stain deeper than in the promyelocyte.

Metamyelocyte. At this stage of development the cytoplasm is pink and contains fine

10 ATLAS OF J-IAEMATOLOGY

neutrophil granules resembling the myelocyte. The nucleus is smaller and slightly indented (kidney-shaped); there can be considerable variation in the size of this cell , from 14 to 20 j.lm.

Juvenile (non-segmemed) neutrophil leucocyte. Usually smaller than the metamyelocyte, this cell has a deeply staining u-shaped nucleus in which the chromatin is coarse and clumped. They are often described as 'stab' (rod-like) forms.

Mature (segmented) neutrophil leucocy te. The diameter of this cell is from 12 to 14 j.lm, the pink cytoplasm containing numerous fine neutrophil granules which are evenly distributed. Its nucleus is lobulated, the number of lobes, which may overlap, varying from two or five ; they also show variation in size and shape and are connected by thin chromatin strands, the nuclear chromatin being arranged in larger clumps. Some neutrophi ls of the female have a nuclear appendage with a well-defined head shaped like a drumstick attached to one nuclear lobe by a thin chromatin strand . Such appendages do not occur in the neutrophils of the male.

The eosinophil (polymorphonuclear) series

This cell series develops through the same stages as the polymorphonuclear neutrophil series. Apart from the large eosinophilic cytoplasmic granules which common ly have a reddish-orange colour and which are apparent at the myelocyte stage, the cells have the same structural characteristics as their neutrophil counterparts

The mature eosinophil leucocyte averages 16 j.lm in diameter. Its nucleus is usually bi-lobed and the large cytoplasmic granules do not overlap it as a general rule. These cells are very fragile and are often damaged during the spreading of blood films, leaving the nucleus surrounded by free granules.

T he basophil (polymorphonuclear) series

In this series the cells are characterised by the presence of large, round , deeply basophilic staining grunules. Otherwise this cell type progresses through the same stage as the neutrophil and eosinophil series.

The mature basophil leucocyte varies from 14 to 16 j.lm in diameter; its cytoplasm stains pink and contains numerous large granules which tend to overlie the nucleus and obscure detai l but do not pack the cytoplasm as do the granules of the eosinophil leucocyte. The nucleus of the mature cell is usually bi-lobed.

Mast cell (tissue basophil)

These cells which develop from the histioblast are not found in human peripheral blood. They are present in bone marrow in which tissue they may be numerous in cases of aplastic anaemia, chronic blood loss, anaphylaxis and tumours of the lymphoid tissue involving the bone marrow. This cell type differs from the true basophil in that its granules are insoluble whereas the granules of the basophil leucocyte are soluble to a large degree in methyl alcohol. The granules are much more numerous, coarser and stain deeply basophi lic; they exhibit a metachromatic staining reaction to toluidine blue . The nucleus of this cell is usually round, not bi-lobed as in the basophil leucocyte. It is a large cell, usually from 20 to 25 j.lm in diameter and may be elongated. 1


THE LYMPHOCYTIC SERIES

Lymphocytes develop mainly in the lymphoid tissues of the body, e.g. lymph nodes, lymphoid follicles of the spleen and gastrointestinal tract, tonsils and other sites. Throughout the marrow there are a number of small , primary lymphoid follicles.

Lymphoblasl. The primitive cell of this series is the lymphoblast from which large and small lymphocytes develop. This cell , which resembles the myeloblast in general structure is approximately IS to 20 1-'-m in diameter. It has non-granu lar cytoplasm which stains deep blue at the periphery and a lighter colour centrally. The nucleus is large, usually occupying four-fifths of the cell area and the nuclear chromatin is arranged in a reticular fashion and tends to be stippled . As a general rule only one or two nucleoli arc present.

Prolymphocyte. This cell is smaller than its precursor and usually has a broad band of blue staining cytoplasm, the nuclear chromatin tends to be clumped and no definite nucleolus can be seen. As the transition from the lymphoblast to the lymphocyte is brief the term 'prolymphocyte' is of no great significance.

Large lymphocyte. Variation in the size of this cell is commonly from 12 to 16 1-'-m in diameter. Its cytoplasm is fairly abundant and stains a sky-blue colour and there may be a few small, sharply-defined azurophil cytoplasmic granules present. The densely staining nucleus is round or may be slightly indented and the chromatin tends to be clumped .

Small lymphocyte. This cell varies from 9 to 12 1-'-m in diameter and except for the difference in size and the scanty cytoplasm which is generally little more than a narrow rim around the large nucleus it is identical to the large lymphocyte.

THE MONOCYTIC SERIES

This cell type is formed mainly in the spleen and lymphoid tissues and to a much lesser extent in the bone marrow.

Monoblast. This primitive cell which is from 18 to 22 1-'-m in diameter is very similar in appearance to the myeloblast except that the cytoplasm is usually lighter in colour and the nuclear chromatin less definite . Several nucleoli may be visible.

Promonocyte. The size of this cell is variable, usually approximately 20 IJ..m in diameter. Its cytoplasm which stains grey-blue may contain fine azurophil granules. The nucleus is large and generally convoluted giving a folded appearance; the chromatin is usually loose, resembling a network and no definite nucleoli arc visible.

Monocyte. The diameter of this large cell is generally from IS to 18 1-'-m with cytoplasm which stains a grey-blue colour and often described as having a ground glass appearance. Fine azurophil granules and vacuoles may be present in the cytoplasm. The nucleus is generally round or kidney-shaped, but may be lobulated with two or more lobes, the chromatin being arranged in skein-like strands.

THE PLASMA CELL SERIES

The plasma cell is thought to be a derivative of the stem cell (haemohistioblast) although o ther cell types have been named as its precursor.

Plasmablast. The primitive cell of this series, closely resembling the lylJ)phoblast in size, shape and staining reactio~ , has an average size of 18 IJ..m. No cytoplasmic granulation is visible and it is difficult to resolve the nucleoli although up to six may be present.

Pro plasma cell. Exhibiting considerable variation in size, from 1 S to 25 IJ..m the cytoplasm has


a deep blue colour, is non-granular and usually shows a pale perinuclear halo. The nucleus is generally eccentric but may be situated centrally within the cytoplasm. The nuclear chromatin appears to be in the form of a loose mesh; several nucleoli may be discernible and are usually more obvious than in the plasmablast.

Plasma cell. This mature cell varies in size, generally between 14 and 20 f-lm and has a deep blue staining non-granular cytoplasm which may contain one or more vacuoles even in the normal state. The nucleus is eccentric and small in relation to the size of the cytoplasm and generally a clear perinuclear halo can be seen. In paraffin embedded sections from wellpreserved material, the chromatin is often clumped towards the margin of the nucleus in a so-called cartwheel fashion. This appearance is not found in blood or marrow smears. Plasma cells with two or more nuclei are a common finding in the marrow in chronic inflammatory conditions and plasma cell myeloma. This is probably due to mitotic division of the nucleus without corresponding division of the cytoplasm; the chromatin structure is usually denser in these multiple nuclei.

THE MEGAKARYOCYTE SERIES AND PLATELET FORMATION

Megakatyoblasts. The primitive cell of this series varies from 25 to 30 J-lm in diameter ; its cytoplasm, which stains intensely blue, is generally just an irregular rim to the large nucleus which is usually oval or kidney-shaped. The nuclear chromatin is poorly defined and contains several deep blue staining nucleoli which are usually indefinite. In normal marrow, this cell comprises less than 1 per cent of all the megakaryocyte series and is therefore difficult to find. Megakaryoblasts with two, three or four nuclei may be seen, due to mitotic division of the nucleus without corresponding division of the cytoplasm; this is a perfectly normal finding.

Promegakatyocyte (basophilic megakatyocyte). This cell is much larger than the megakaryoblast; the cytoplasm which may exhibit a finely granular appearance, has a basophilic staining reaction to the Romanowsky methods. The nucleus is large and usually indented, its chromatin appearing as coarse, intertwining, deeply staining strands against a lighter stained background.

Megakatyocyte (granular megakaryocyte). This is the largest cell found in marrow and can be up to 100 f-lm in diameter. The cytoplasm is bulky and contains many azurophil granules which are well marked against a pale stained background. The cell margin is irregular and in the late stages of maturation (budding megakaryocyte) will show differentiation of granular platelets in pseudopodia-like structures. The nucleus of this cell is small in comparison to the volume of cytoplasm; it is usually multilobed or indented, with chromatin which is arranged in coarse, deeply staining strands.

Platelets. These are small fragments of cytoplasm which have become detached from the periphery of the megakaryocyte. They are usually from 2 to 3 f-lm in diameter but may range from 1 to 4 f-lm. The cytoplasm stains light blue and contains a central area of azurophil staining material.

3. Normal haematological values


Terms commonly used to describe anomalies and artefacts seen in red blood cells in stained preparations

Acanthocytes. These are red cells with fine projections from the surface. They occur as an inherited abnormality associated with abnormal phospholipid metabolism.

Anisocywsis. This term is used to denote variation in cell size. Anulocytes. Due to a lowered haemoglobin conrent these erythrocytes exhibit a large area of

central pallor. Basophilic stippling. These small blue granules arc formed by condensation of basophilic

substance within the cytoplasm giving it a stippled appearance . In condit ions such as severe anaem ia these granules may be quite coarse .

Burr cells. T hese cells have several poinred projections resembling the burrs of certa in plants. T hey are poikilocytes and are readily confused with crenated forms.

Cabot ,-ings. In some forms of severe anaemia these appear as purplish rings in the centre or near the periphery of erythrocytes. Like Howell-Jolly bodies they are nuclear remnants.

Crenated red blood cells. This artefact is usually due to faulty drying of a blood fi lm. Echinocytes. These cells have spicules evenly distributed over the surface of the red cell as the

result of alteration of intra- and extracellular environment. The term is synonymous with Burr cell .

Elliptocywsis. This is a form of poikilocytosis and is a heredi tary anomaly where a large number of ell iptical erythrocytes are present.

Heinz bodies. Polymerisation and precipitation of denatured haemoglobin molecules result in Heinz bodies which are best demonstrated when supravitally stained by methyl violet.

Howell-Jolly bodies. These are nuclear remnants and appear as dense blue inclusions. They may be single or multiple, as a rule are commonly near the periphery of the cell and may be up to 1 f.Lm in diameter. Both Howell-Jolly bodies and Cabot rings are found in blood films following splenectomy and occasionally in dyshaemopoietic states such as megaloblastic anaemia and the leukaemias, but Cabot rings are found less frequentl y than Howell-Jolly bodies.

Hypochromia. This denotes a decrease in the intensity of staining which may vary from only a slight increase in size of the area of central pallor to a very large area surrounded by a small rim of haemoglobinised cytoplasm.

Lepwcyte. This is a thin hypochromic cell of normal d iameter and decreased MCV. Commonly found in thalassaemia.

Microcytes. These are smaller and paler than normal erythrocytes. Microspherocytes. Erythrocytes of spherical form, these cells are smaller than normal

erythrocytes and because of their spherical shape do not exhibit an area of central pallor. They are present in haemolyt ic diseases.

Pincered cells. These are erthrocytes which appear as if part of their substance had been indented by pincers . This appearance probably represents the process of fragmentation.

Poikilocywsis. T hese are irregularly shaped erythrocytes . T his term includes such alterations in shape as burr cells, ell iptocytes, pear- and tear-shaped cells and sickle cells.

Polychromasia. This denotes that the cell is taking both the basic and the acid dyes due to alteration in the haemoglobin content of the erythrocyte, the cell exhibit ing much the same colouration as seen in the intermediate stage of erythropoiesis. In this instance the cytoplasm has lagged behind the nucleus in maturation and has not completely lost its ribonucleic acid .

Pyknocyte. Distorted and contracted red cells similar to the echinocyte. Schiswcytes. These are the products of red cell fragmentation and many take a triangular or

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THE RED CELL SERIES 19

small elliptical form with indentation, or may appear as irregularly crenated cells. They are common in haemolytic anaemia.

Sickle cells. In cases of haemolytic anaemia (sickle-cell anaemia) this anomaly occurs, many of the erythrocytes exhibiting a definite sickle-shape and taking the stain much more heavily than the surrounding erythrocytes.

Siderocytes. These are erythrocytes which contain one or more unevenly distributed ironcontaining granules, demonstrated by a positive Prussian Blue reaction. They are sometimes discernible as basophilic dots in films stained by the Romanowsky methods and may then be referred to as Pappenheimer bodies. These cells are found in peripheral blood in disorders associated with impaired haemoglobin synthesis, e.g. thalassaemia and lead poisoning. They are also present in blood following splenectomy where this has been undertaken for the treatment of certain haemolytic conditions.

Spherocytes. Spheroidal cells occuring in many types of haemolytic anaemia including hereditary spherocytosis, immune haemolytic anaemia and in burns.

Stomatocytes. These are red cells in which the central biconcave area appears as a slit rather than a circular concavity. Large numbers of this type of red cell have been noted in an uncommon type of hereditary haemolytic anaemia.

Target cells. In these cells there is a rounded central area of normally stained cytoplasm surrounded by a clear lightly stained area which in turn is surrounded by a normochromic peripheral ring.


Fig. 1 Marrow film Normoblastic erythropoiesis Left: The cell types seen are: ( I) Transitional stage between pronormoblast and early normoblast. (2, 3) Early normoblasts. (4, 5, 6) Transitional forms between early and intermediate normoblasts. (7; 8, 9) Intermediate normoblasts, of which (9) is the metaphase stage of mitosis. (10) Late normoblast. Leishma11 stailz x 1200 Right: This field shows intermediate and late normoblasts and one lymphocyte (L). Leishma11 stai11 x 1200

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Fig. 2 Marrow film Normoblastic hyperplasia pNb- pronormoblast; INb- intermediate normoblast; ENb - early normoblast; L - lymphocyte; Stab- nonsegmented polymorphonuclear leucocyte. In this illustration the majority of the cells are normoblasts in varying stages of development. The lymphocytes are useful for comparison of nuclear structure and intensity of staining. In this condition the myeloid-erythroid ratio is markedly decreased . May-Griit~wald-Giemsa stai11 x 1200


Fig. 3 Marrow film Macronormoblastic hyperplasia In this condition the normoblasts are larger than their normal counterparts of similar age, but in all other respects, including nuclear structure, they are normal in appearance. Leislrma11 stain x I 200

Fig. 4 Marrow film Iron deficiency anaemia There is marked erythroid hyperplasia present in this specimen , the increase being mainly in the more mature forms of normoblasts, which are smaller than normal. This is often described as rnicronormoblastic hyperplasia. The cytoplasm of the normoblasts is decreased, the cell borders are ragged·and their staining reaction irregular. May-Gronwald-Giemsa stai11 x 1200


Fig. 5 Marrow film Iron deficiency The Prussian Blue reaction stains haemosidcrin blue. In this preparation there is absence of stainable haemosiderin. Absent stainable ha~mosiderin is a sensitive indication of iron deficiency. ?russian Blue reaction, cozmterstained Methyl R ed x 800

Fig. 6 M arrow film Left: Howell-Jolly bodies. Small, densely staining dark blue particles are seen in the polychromatic cytoplasm of the late megaloblasts. These bodies are most often seen following splenectomy but are also present in blood from the leukaemias and dyshaemopoietic conditions such as megaloblastic anaemia, as in this example . Leishman stai1z x 1200 Right: Basophilic stippling. Basophilic stippling is demonstrated as very fine pin-point cytoplasmic granules and is often associated with toxic conditions, e.g. lead poisoning and dyshaemopoietic states such as megaloblastic anaemia and thalassaemia. Polychromasia is also present and is seen as a diffuse light blue staining in several erythrocytes. These are normally present in small numbers in the peripheral blood where they stain as reticulocytes (Fig. 21) . Leishman stain x 1200


Fig. 7 Blood film Normal erythrocytes Cells are of uniform size and shape with a normal haemoglobin concentration. One cell, centre of field, reveals a small area of central pallor which is less than one-third of the total cell volume. Wright's stain x 1200


Fig. 8 Blood film Abnormal erythrocytes These fields from a case of pernicious anaemia, show anisocytosis, macrocytosis (Mac), poikilocytosis (Poik), an intermediate normoblast (INb) and a late normoblast (LNb) with a Howell-Jolly body (HJ). This composite illustration along with Figure 9 serves to show how a number of red cell anomalies may occur in an individual patient. Leishma11 stai11 X 1200


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Fig. 9 Blood film Abnormal erythrocytes This demonstrates some of the red cell anomalies found in the blood in pernicious anaemia, such as anisocytosis, macrocytosis (Mac), poikilocytosis (Poik), and polychromasia (Pol). Also present is an intermediate megaloblast (1Mb) and a late normoblast (LNb) with polychromatic cytoplasm. In the right-hand illustration is a late normoblast in which the nucleus is pyknotic and gives the impression that it is beginning to break up. Leishman stain x 1200


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~ Fig. 10 Blood film Pernicious anaemia (under treatment) This illustration shows poikilocytosis, anisocytosis, polychromasia (Pol), basophilic stippling (BS), a normoblast with polychromatic cytoplasm and a Howell-Jolly body (HJ). Also seen are several schistocytes (Sc) and a normoblast in mitosis, a piece of the nucleus of which has broken away; this would have been seen eventually as a Howell-Jolly body. Note the hypochromia of the red blood cells due to deficient hacmoglobinisation. Leishman stain x 1200


Fig. 11 Blood film Left: Hereditary spherocytosis. The spherocytes are small, round, deeply staining erythrocytes. In the lower portion of the illustration a late normoblast can be seen. Leishma11 stai11 x 1200 Right: Elliptocytosis. Over 50% of the erythrocytes present have a moderate or pronounced elliptical form. Leishma11 stai11 x 1200


Fig. 12 Blood film Spherocytosis This illustration is from a film of blood from a patient who had been severely burned. The extremely small spherical cells are erythrocytes which have been affected by heat. This condition is sometimes referred to as thermal haemolytic anaemia. May-Griinwald-Giemsa stain x 1200

30 ATLAS OF H AEMATOLOGY

Q ~ ~ GBG () riZ ~~ k

k

~

0 9 ~ODa 8 8~u

Po;k \)

Fig. 13 Blood film Lefc: Poikilocytosis and schistocytosis. The erythrocytes show marked poikilocytosis (Poik) and schistocytosis (Sc) also anisocytosis, polychromasia (Pol) and hypochromia. From a case of thalassaemia minor. May-Griinwald-Giemsa scain x 1200 Righc: Poikilocytosis and macrocytosis . Pear-shaped, tear-shaped and small irregular poikilocytes (Poik) are seen, and also numerous rnacrocytes (Mac). From a case of pernicious anaemia. May-Griinwald-Giemsa scain x 1200


/

Fig. 14 Blood film Left: Poikilocytosis and macrocytosis. This illustrates the alteration in shape of the erythrocytes. Poikilocyte (Poik), sickle cell (S) and macrocyte (Mac). Leishman stain x 1200 Right: Hypochromia and target cells. In this extreme example of hypochromia (Hyp) a large area of central pallor is seen in many of the erythrocytes . Four target cells (T ) are present; these have a normochromic centre separated from the normochromic peripheral ring by a broad unstained band. Leishman stain x 1200


Fig. 15 Blood film Target cells These cells exhibit a rounded central area of normal staining surrounded by a clear lightly stained area, which is surrounded by a normochromic peripheral ring . Target cells are commonly associated with chronic liver disease. Wright's stain x 1200

Fig. 16 Blood film Left: Anisocytosis. This illustration demonstrates the marked inequality in size of the erythrocytes. Leishman stain x 1200 Right: H ypochromia. In this condition there is a marked decrease in the intensity of staining of the erythrocytes. Many of the cells show a large area of central pallor surrounded by a darker rim at the periphery of the cell. This is referred to as ring staining. A target cell is present at uppel' right of the field. Leishman stain x 1200


F ig. 17 Blood film Pincered cells This illustration shows a curious type of erythrocyte which is occasionally seen in cases of hereditary haemolytic anaemia and also in cases of haemolytic anaemia resembling hereditary spherocytosis. Several of the erythrocytes have an indented appearance as if they had been gripped by pincers. May-Griinwald-Giemsa stain x 1200

Fig. 18 Blood film Dimorphism In this condition both macrocytic and hypochromic microcytic anaemia exist at the same time. In this example the macrocytosis is not as pronounced as in pernicious anaemia and does not overshadow the associated iron deficiency. Wright's stai1z x 1200

I


Fig. 19 Blood film Stomatocytes In these red cells the central biconcave area appears as a slit rather than a circular concavity. This may be a congenital abnormality but may also be present in severe liver disease. May-Griinwald-Giemsa stain x 1200

Fig. 20 Blood film M acrocytic anaemia of pregnancy Left: The blood picture is similar to that seen in pernicious anaemia; marked oval macrocytosis, anisocytosis and poikilocytosis are all present. May-Grii11wald-Giemsa stain x 1200 Right: This illustration , from the same patient, shows the appearance after treatment with folic acid. Many of the erythrocytes exhibit varying degrees of polychromatic staining which indicates a satisfactory response to therapy. Note also the late normoblast in this field. May-Griinwald-Giemsa stain x 1200


Fig. 21 Blood film Haemolytic anaemia Preparation from a patient suffering from idiopathic acquired haemolytic anaemia. Polychromatic cells and microcytic cells are prominent. Note the intermediate and late normoblasts. May-Grii11wald-Giemsa staill x 1200

Fig. 22 Blood film Sickle-cell anaemia The bizarre-shaped red blood corpuscles include elongated narrow types with rounded and pointed ends; they are sickle or oat-shaped and tend to take the stain to a heavier degree than the other erythrocytes. May-Grii11wa/d-Giemsa stai11 X / 200


Fig. 23 Blood film Acanthocytosis In this film, practically all of the red cells have fine projections from the surface. This appearance differs from burr cells (Fig. 34) in that the projections are more filamentous. May-Griir~wald-Giemsa stam x 1200

Fig. 24 Blood film Polychromasia, nucleated red blood cells This illustrations show large polychromatic cells staining blue grey and nucleated red blood cells. May-GriilzwaldGiemsa stain X 1200


Fig. 25 Blood film Haemolytic disease of the newborn The prominent feature in this preparation is that of polychromatic cells and nucleated red blood cells. May-GriillwaldGiemsa stai11 x 1200

Fig. 26 Blood film H aemolytic uraemic syndrome In this illustration there are many polychromatic cells, nucleated red blood cells, and prominent burr cells. MayGriillwald-Giemsa stai11 x 1200


•

Fig. 27 Blood film Microangiopathic haemolytic anaemia In this condition, contracted and distorted cells, some of which are irregular and angular in shape are illustrated. These are known as triangular or helmet cells. Red cell fragments, some with spinous processes and polychromatic cells (bottom left), are also present. Wright's stain x 1200

I I

; y

1

THE RED CELL SERI ES 39

..

Fig. 28 Blood film Howell-Jolly bodies Howell-Jolly bodies are nuclear remnants appearing as small round, densely staining, dark purple particles, commonly near the periphery of the cell. They are seen most often following splenectomy, but are occasionally present in dyshaemopoietic states such as megaloblastic anaemia and leukaemia. May-Griinwald-Giemsa stain x 1200

..

., • It ·•• .. • •. - --••• e • e

a e . -- ~~ Fig. 29 Blood film Reticulocytes from a case of hereditary spherocytosis (acholuric jaundice) Left: The basophilic granules and filaments are clearly defined in this preparation stained with Brilliallt Cresyl Blue X 1200 Right: This film has been stained with Brilliant Cresyl Blue and counterstained with Leishman and clearly demonstrates the microspherocytes. The filaments and granules are not so well differentiated as in the fi lm which has not been counterstained . x 1200


•

•

F ig. 30 Blood film Heinz bodies Deep purple bodies are seen, some lying close to the periphery of the red cells and others attached to the outer surface. Several bodies may be present in the same cell, but when large they are usually found singly. T he large bodies can be up to 1 JJ.m in diameter. Heinz bodies are the result of polymerization and precipitation of denatured haemoglobin molecules. Methyl Violet. x 1200

F ig. 31 Blood film Siderocytes (Pappenheimer bodies) Many of the erythrocytes show varying numbers of iron-containing granules which are deep blue in colour; the individual granules can be up to 2 JJ.m in diameter. Prussian Blue reaction, May-Griirzwald-Giemsa stairz X 1200

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••

i


Fig. 32 Blood film H owell-Jolly bodies Howell-Jolly bodies can be seen near the periphery of the cell. This preparation is from a post-splenectomy patient who developed megaloblast ic anaemia. Macrocytes containing Howell-Jolly bodies are illust rated. May-Grii11wa/d-Giemsa srai1z x 1200

Fig. 33 Blood film Roulea ux formation T his illustration demonstrates the phenomenon of running together of the red blood cells to form aggregates resembling piles of coins which is known as rouleaux formation. It is sometimes difficult to distinguish between t rue agglut ination and rouleaux formation when the latter appears in a marked degree , forming compact masses very similar to the appcaran~e gzven by true agglutination (Fig. 40). Rou leaux formation is seen in conditions where the albumi n: globulin serum protein balance is disturbed, as occurs in multiple myeloma o r when too concentrated a cell suspension is used. Le1shma11 stai11 x 1200


Fig. 34 Blood film Burr cells This illustration shows the contracted red blood cells with spiny surface projections which are often referred to as 'burr' cells because of their resemblance to the burrs from certain plants. T hese cells are deformed poikilocytes and are commonly seen in blood films from patients with chronic renal failu re. Leishman stai11 x 1200


J

Fig. 35 Blood film Thalassaemia major T he red cells vary greatly in size, are distorted in shape and contain little pigment. The haemoglobin outlines the periphery of the cell. Target cells are present, as are distorted nucleated red blood cells. Bizarre poikilocytes and distorted red cell remnants are also present. Leishman stain x 1200

1

' 44 ATLAS OF HAEMATOLOGY

-

Fig. 36 Blood film T halassaemia minor The red cells exhibit hypochromia , anisocytosis, moderate poikilocytosis and microcytosis. Target cells are also present, as are basophilic stippled cells in lower part of the field, left centre. Leishman stain x 1200

Fig. 37 Blood film Basophilic stippling This shows fine basophilic stippling in three of the red cells present in this illustration. The blood film was prepared from a patient suffering from lead poisoning. May-Griinwald-Giemsa stain x 1200

THE RED CELL SERI ES 4·5

. •

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Fig. 38 Blood film Haemoglobin 'H' inclusions The small fine inclusions in the red cells appear after incubation with Brilliant Cresyl Blue and contrast with the more coarse basophilic granules of the reticulocytes. Brilliam Cresy/ Blue x 1200

Fig . 39 Blood film Haemoglobin 'C' The red cells exhibit anisocytosis and poikilocytosis as well as targeting with some hypochromia. These morphological changes are usually associated in this condition with minimal anaemia. May-Griinwald-Giemsa stain X 1200


Fig. 40 Blood film Autoagglutination The red cells have formed clumps or aggregates, the shape of the agglutinated masses being quite distinguishable from the intertwining columns seen in rouleaux formation (Fig. 33). This specimen is from a patient suffe ring from cold agglutinin disease. Leishma11 stai11 x 1200


F ig. 41 Blood film Autoagglutination In this illustration there is agglutination of both erythrocytes and neutrophil leucocytes. The leucocytes appear to be much smaller than in Figure 40; this is due to the pressure on these cells by the surrou nding masses of erythrocytes. Leishma11 stail1 x 1200


Fig. 42 Necrobiotic changes and inclusion bodies- Red cell series This series of illustrations shows necrobiotic changes and inclusion bodies in the red cell series, as follows: A, Band C, necrobiotic change in late normoblasts; in C the nucleus has been in the prophase stage of mitosis but has become necrotic. D is a late stage of mitosis in a normoblast which is necrotic.

E and F depict single and multiple Howell-Jolly bodies in a late normoblast and a normocyte, whereas G, Hand I show Howell-Jolly bodies in macrocytes. Note also the polychromasia of many of these cells. J , K , L , M and N are examples of Cabot rings which , like Howell-Jolly bodies, are nuclear remnants. N is an example where the ring is at the periphery of the cell , whereas the others show an outer band of cytoplasm. K and M have double rings. All of these cells show fine basophilic stippling and K, M and N also contain Howell-Jolly bodies. Cabot rings are seen following splenectomy and in dyshaemopoietic states such as megaloblastic anaemia and leukaemia.

0 , P , Q and R show basophilic stippling in varying degrees of coarseness, this phenomenon being associated with toxic states such as lead poisoning and dyshaemopoietic states, e.g. megaloblastic anaemia and thalassaemia. Polychromasia is also present in several of the cells. Leishmau scaiu x 1200

I

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Fig. 43 Blood fi lm Hypcrscgmentcd neutrophil leucocytcs Normally the nucleus of the segmented neutrophils have less than five lobes. Increased segmentation as illustrated is usually the first morphological abnormality to appear in a developing megaloblastic state. May-Griilzwald-Giemsa stai1z X /200

--


Fig. 44 Marrow film Megaloblast series Left: Shows an early megaloblast (EMb) with indistinct nucleoli and an intermediate megaloblast (1Mb) and late megaloblasts (LMb). May-Griinwald-Giemsa stain X 1200 Right: This field illustrates an early megaloblastic (EMb) and an early megaloblast in the anaphase stage of mitosis, also intermediate (1Mb) and late (LMb) megaloblasts. May-Griinwald-Giemsa stain X 1200

l \


Fig. 45 Marrow film Megaloblastic erythropoiesis This illustrates early and intermediate megaloblasts and also an early myeloblast in the anaphase stage of mitosis. Note the typical spongy stippled appearance of the nuclei , and in the early megaloblasts, some definite nucleoli and shadow necleoli . May-Griirzwald-Giemsa stairz x 1200

Fig. 46 M arrow film Megaloblast series A is an example of an early megaloblast, the nucleus of which is large and spongy and the cytoplasm basophilic. B is an intermediate form and should be compared with A, when it will be seen that the nucleus is smaller and that the cytoplasm is becoming polychromatophilic. C, D and E are all late megaloblasts; note the acidophilic cytoplasm and that the nucleus is becoming smaller and denser in its staining properties. In E the nucleus is being expelled . D shows several Howell-Jolly bodies. F is a typical macrocyte. Leishmarz stairz x 1200

52 ATLAS OF HAEM A TO LOGY

Fig. 47 Marrow film Megaloblast series Left : A megaloblast in the anaphase stage of mitosis; also a promeylocyte (pMy). M ay-Griinwald-Giemsa stain X 1200 Right : This composite field shows two intermediate megaloblasts and two late megaloblasts, one of which shows a Howell-Jolly body and the other twinning of the nucleus. May-Griinwald-Giemsa Stain x 1200

I THE RED CELL SERIES 53

Fig. 48 Marrow film Stages of mitosis Immature haemopoietic cells in early prophase (A) (the nuclear membrane (NE) is still apparent), early metaphase (B), metaphase-anaphase (C), anaphase (D ), anaphase-telophase (E), telophase (F). Also illustrated is a pair of daughter cells (G). Leishman stain x 1200

54 ATLAS OF HAEMA TO LOGY

Fig. 49 Early megaloblast The nucleus is of premature appearance with pronounced nucleoli and no chromatin condensation. The cytoplasm contains large mitochondria, lysosomal granules and numerous free ribosomes. The cell exhibits marked nuclear crythroplasmic asynchrony. Glutaraldehyde, urauy lacetate, lead cirate x 18 200


®

Fig. 50 Marrow film Megaloblastic anaemia Left: Several early megaloblasts (EMb), which vary in size, are present along with a typical promyelocyte (pMy). Right: Shows a large early megaloblast (EMb) in which shadow nucleoli can be resolved; also present are two late megaloblasts (LMb). Note also the variation in size of the red blood corpuscles. May-Grii11wa/d-Giemsa Szai11 x 1200


A

B

c

• THE RED CELL SERIES 57

Fig. 51 Megaloblastic anaemia A. Marrow film. This field shows numerous megaloblasts at various stages of development, from the promegaloblast to the late megaloblast. Note that in the more primitive cells, to the top and left of the field, shadows of nucleoli are still apparent. May-Griinwald-Giemsa szain x 1200 B. Marrow aspirate section. This section of marrow is from the same aspirated specimen as field A and shows the marked shrinkage and distortion which takes place during fixation and processing of the tissue. While it would still be possible to give an opinion on the type of cells present it could not be stated definitely that the large cells are megaloblasts. Haemalum & Eosin x 800 C. Marrow trephine needle biopsy. This is a section from a trephined specimen from the same case of megaloblastic anaemia. The gross distortion and disruption of the cells, due to fixation and decalcification, make a definitive diagnosis impossible. The large pleomorphic cells with large nuclei mimic the appearance of malignant epithelial cells. This pseudo-carcinomatous appearance is a well known artefact in histological rather than cytological specimens in megaloblastic erythropoiesis. For this reason the diagnosis of megaloblastic erythropoiesis should be based on cytological rather than histological preparations. Haemalum & Eosin x 800


Fig. 52 Marrow film Megaloblastic erythropoiesis This illustrates frank megaloblastic erythropoiesis. An early megaloblast, intermediate and late megaloblasts are illustrated, as well as one megaloblast in mitosis. The early and intermediate forms exhibit a stippled appearance of the nucleus which becomes more coarse at the late megaloblast stage. May -Gnl11wald-Giemsa stai11 x 1200


F ig. 53 Marrow Erythrophagocytosis Erythrophagocytosis seems to be common to primitive marrow cells of all types as shown in this series of illustrations. A shows a giant erythroblast with a bi-lobed nucleus. B is a p rimitive monoblast. C the cell shown here is a lymphoblast the nucleus of which has been compressed by an ingested erythrocyte. D is a myeloblast which shows toxic granulation in addition to the ingested erythrocyte. E shows two mast cells, the lower of which contains two ingested erythrocytes. May-Griinwald-Giemsa stain x 1200

Fig. 54 Marrow film Erythroleukaemia (Di Guglielmo's disease) Left: There is a complete absence of cells of the myeloid series, all the cells p resent being of erythroblastic origin. Note the early and late erythroblasts with multiple nuclei, and also the mitotic forms. May -Griinwald- Giemsa x 500 Right: At the top of this illustration a late normoblast with twin nuclei can be seen and lying in close proximity is an atypical late normoblast with a four lobed nucleus which shows 'megaloblastoid' changes. Lower in the field are several primitive cells of erythroblastic potentiality, one of which has a twin lobed nucleus. May -GninwaldGiemsa stain x 1200


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Fig. 55 Marrow film Erythroleukaemia (Di Guglielmo's disease) All the cells in this composite illustration belong to the erythroblastic series and several in varying stages of development exhibit multiple nuclei . At bottom left, a cell which is either a proerythroblast or an early normoblast has twin nuclei and also peculiar vacuolation of the cytoplasm, while at bottom right there is an atypical late normoblast with four distinct nuclei showing megaloblastoid change. M ay-Griinwald-Giemsa stain X 1200

Fig. 56 Marrow film Erythroleukaemia (Di Guglielmo's disease) The Periodic Acid-Schiff Reaction commonly shows strong diffuse and granular positivity in the abnormal erythroblasts depicted here from a case of erythrolcukacmia. Periodic A cid-Schiff (PAS) x 1200


F ig. 57 Spleen Norm al A non-reactive lymphoid follicle is shown with its arteriole. Compare the amount of lymphoid tissue with that in Figures 78 and 256. Haemalwn & Eosin x 50

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F ig. 58 Sternal m a rrow aspira te section Norma l Left : In this biopsy specimen, no bone trabeculae or fat spaces are present. Compare th is with Figure 59. H aema/um & Eosin x 150 R ight : In this mass of haemopoietic tissue, only a few cells are readily distinguishable. Near the bottom margin there is a large megakaryocyte and slightly to the right of it, two mitotic figures can be seen. Several late normoblasts are easily distinguished by their dark-blue nuclei and red cytoplasm. Haemalum & Eosin x 450


Fig. 59 Vertebral marrow section Normal T his shows bone trabeculae, fat spaces and haemopoietic tissue in normal proportions. Haema/wn & Eosin x 40

,

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Fig. 60 Ma rrow Trephine needle biopsy specimen Aplastic anaemia This shows a marked increase in the proportion of fat cells along with a corresponding marked decrease in the proportion of haemopoietic cells; only a very occasional blood cell is present between the fat spaces. Compare this illustration with Figure 58. Haemalum & Eosin x 90


Fig. 61 Spleen Polycythaemia rubra vera This shows sinusoidal congestion, with some swelling of the sinusoidal lining cells seen in the h igh power (right). Red cells and leucocytes are prominent in the 'red pulp'. Extra-medullary haemopoiesis is not a feature. H aemalum & Eosin x 55, x 120

Fig. 62 Bone biopsy Polycythaemia rubra vera This specimen exhibits a markedly hyperplastic marrow. The marrow spaces are completely filled with haemopoietic, leucopoietic tissue as well as megakaryocytes. Haemalum & Eosiu x 100, x 350

1

I' IN , 6.1 Mur row film S ideroblastic anaemia 1,1'/t : This illustration, at low magnification, shows numerous erythroblasts (sideroblasts) containing large qunntitics of siderotic granules. Prussian Blue reaction, cowuerstained Neutral Red x 120 Ri~:lu : I Iigh magnification reveals sideroblasts showing the cytoplasmic Perls positive granules, and also the perinuclear arrangement of the iron deposits in 'ringed sideroblasts'. Prussian Blue reaction, coumerstained Neutral Red x 1200

l


Fig. 64 Ringed sidero blast The perinuclear mitochond ria contain large quantities of non-crystalline iron-containing material termed 'ferruginous micelles'. To the right of the nucleus the centrosome and well resolved golgi complex are visible. Osmium tetroxide, lead citrate x 8500 l llSet: At higher magnification a typical mitochondrion is seen con taining the 'ferruginous micelles'. Osmium tetroxide, lead citrate x 22000

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Fig. 65 Spleen Erythroleukaemia (Di Guglielmo's disease) Upper field : The red pulp contains many abnormally large cells which show a tendency to occur in groups within sinusoids. Haemalum & Eosin x 120 Lower field: The cells vary considerably in size, they have basophilic cytoplasm and large vesicular nuclei with fine chromatin strands. The cell to the right of the centre containing two nuclei is probably an atypical · normoblast showing megaloblastoid change. Haemalwn & Eosin x 600


F ig. 66 Bone marrow Congential dyserythropoiesis This disorder is characterised by bizarre nuclear abnormalities of erythrocyte precursors as illustrated. A E & F illustrate the pronounced multinuclearity commonly found in type III. B illustrates b inuclearity and intranuclear chromatin bridging with megaloblastOid features, commonly found in type I. C & D illustrate the binuclearity usually associated with type II. There is frequently an overlap of morphological features in types I and II. M ayGriinwald-Giemsa stain x 1200

~~~--~'----------------~--------~~~-----------------------------------


Fig. 67 S pleen Acquired haemolyt ic anaemia The lymphoid follicles have prominent germinal centres. The red pulp is engorged with b lood. Compare with Figure 57. Haema/um & Eosin x 60

Fig. 68 Spleen Acquired haem olytic anaemia This composite illustration is of high-power fields from the same spleen as Figure 67, showing the congested sinusoids and the presence of haemosiderin pigments in histocytes. Left : Haemalum & Eosin x 450 Right: ?russian Blue reaction, coumerstained Newral R ed x 450

r THE RED CELL SERIES 69

Fig. 69 Liver Haemolytic anaemia Kupffer cells contain large quantities of stainable iron whereas hepatocytes do not. Prussian Blue x 500

Fig. 70 Liver Haemochromatosis Left : Yellow-brown granules of varying size are seen .in the cytoplasm of many of the parenchymal cells with the Eosin stain. Haemalum & Eosin x 400 Right : Prussian Blue reaction emphasizes the enormous amount of haemosiderin which has been deposited. Prussian Blue x 400


Fig. 71 Liver Sickle-cell anaemia Veins and sinusoids are packed with red cells, the distorted shape of which is clearly seen in the high power field (right). Note also the cloudy swelling and fatty change in the liver cells, resulting from anoxia . Haemalum & Eosin X }20, X 800

Fig. 72 Liver Transfusion siderosis Note the contrast between the coarse granules in the parenchymal cells and the fine diffuse distribution in Kupffer cells lining the greatly d istended sinusoids. ?russian Blue reaction, cormterstained Newral Red x 350

l


Fig. 73 Gastric mucosa Normal (left) and in pernicious anaemia (right). Compare the thickness of the mucous membrane, and the number and length of the glands. In each instance the muscularis mucosae can be seen at the lower margins. H aema/um & Eosin x 35

Fig. 74 Gastric mucosa The central illustration is of normal mucous membrane whereas those to the left and right are from a case of pernicious anaemia. The normal glands contain numerous parietal cells (arrow) but no Paneth cells, which may be numerous in pernicious anaemia (right, arrow). Note also the presence of goblet cells in surface epithelium and glands in pernicious anaemia, i.e. metaplasia to intestinal epithelium has occurred. Inflammatory foci are also present and include plasma cells with Russell bodies (left, arrow). H aema/um & Eosin x 120

1

5. The white cell series

70 ATLAS OF HAEMA TOLOGY

Fig. 71 Liver Sickle-cell anaemia Veins and sinusoids are packed with red cells, the distorted shape of which is clearly seen in the high power field (right). Note also the cloudy swelling and fatty change in the liver cells, resulting from anoxia. Haemalwn & Eosin X /20, X 800

Fig. 72 Liver Transfusion siderosis Note the contrast between the coarse granules in the parenchymal cells and the fine diffuse distribution in Kupffer cells lining the greatly d istended sinusoid s. ?russian Blue reaction, cormterstained Neutral Red x 350


Fig . 73 Gas tric mucosa Normal (left) and in pernicious anaemia (right). Compare the thickness of the mucous membrane, and the number and length of the glands. In each instance the muscularis mucosae can be seen at the lower margins. Haemalum & Eosin x 35

Fig. 74 Ga stric mucosa T he central illustration is of normal mucous membrane whereas those to the left and right arc from a case of pernicious anaemia. The normal glands contain numerous parietal cells (arrow) but no Paneth cells, which may be numerous in pernicious anaemia (right, arrow). Note also the presence of goblet cells in surface epithelium and glands in pernicious anaemia, i.e. metaplasia to intestinal epithelium has occurred. Inflammatory foci are also present and include plasma cells with Russell bodies (left, arrow). Haemalum & Eosin x 120


Fig. 75 Maturation of the neutrophil polymorphonuclear leucocyte A. Myeloblast. This shows the typical, uneven staining, basophilic cytoplasm which contains a few azurophil

granules; the staining reaction is lighter in the perinuclear region. The nucleus, which occupies four-fifths of the total cell area, shows fine chromatin strands which are stained reddish-purple. Three pale blue nucleoli, with sharply defined chromatin borders, are discernible.

B . Promyelocyte. At this stage of development the cell can be either larger, as in this example, or smaller than its precursor; azurophil cytoplasmic granules are now evident and the nucleo-cytoplasmic ratio is diminished. The nuclear chromatin appears to be coarser, and nucleoli, although still present, are not well defined.

C. Myelocyte. This example is intermediate between the promyelocyte and the fully developed myelocyte in that the cytoplasm still contains azurophil granules, although in a large area they have now assumed their neutrophilic character and the cytoplasm is beginning to show a pinkish (acidophil) hue.

D. Myelocyte. The granules are now typical in neutrophil character and the cytoplasm is more acidophilic in staining reaction. The nucleus is smaller than that of the promyelocyte, contains masses of chromatin and is indented (kidney-bean shaped) which indicates progression to the metamyelocyte stage.

E. Metamyelocyte. This cell is smaller than the myelocyte and the nucleus is now reniform in shape. The cytoplasm is pink and contains numerous neutrophil granules.

F. Juvenile (non-segmented) neutrophil.leucocyte. The nucleus has attained the typical U-shape of this stage of development and contains coarse clumps of chromatin. The cytoplasm is typical in colour and granularity.

G. Transitional stage between F and H . The nucleus is beginning to attain its lobulated appearance while all other features of this cell are similar to those of the mature form.

H. Mature (segmented) neutrophil leucocyte. This is a typical example of the final stage of development. The cytoplasm displays the neutrophil granules and pink staining reaction. The nucleus has three definite lobes and coarse clumping of chromatin is obvious.

Note. From the promyelocyte stage to the final stage in the normal development of cells in this series there is a gradual diminution in size. It should, however, be borne in mind that the developmental process is continuous and therefore cells will be found which are intermediate to the stages depicted. Leishman stain x 1200

THE WHITE CELL SERIES 75

Fig. 76 Marrow film Neutrophil leucocyte series In the centre of the field there is a promyelocyte (pMy). The upper two cells are neutrophil metamyelocytes (mMy). Above and below the promyelocyte are myelocytes (My) and bottom left neutrophil polymorphs. May Griinwald-Giemsa szain x 1200


Fig. 77 Marrow film Neutrophil leucocyte series A promyelocyte, myelocyte and several non-segmented neutrophil leucocytes. May -Griinwald-Giemsa stain X 1200

Fig. 78 Marrow film Giant m etamyelocytes This illustrates an abnormality in the developing granulocytes seen in megaloblastic erythropoiesis . The illustrations show giant metamyelocytes with large U -shaped nuclei, some of which are irregular in outline. These giant forms result from asynchronism between the development of the nucleus and the cytoplasm. I t is possible that the large hypersegmented neutrophil leucocytes seen in peripheral blood, in some cases of megaloblastic anaemia, are derived from these giant metamyelocytes, several of which are nearing the juvenile stage of development. May-Griinwald-Giemsa stain x 1200


Fig. 79 Blood film Normal This is a typical field of a blood fi lm from a normal person; two neutrophil polymorphonuclear leucocytes and one lymphocyte can be seen. M ay-Griiuwald-Giemsa staiu x 1200

A

Fig. 80 Blood film P olymorphonuclear neutrophilleucocytes to show the female sex chromatin The characteristic 'drumsticks' found in the female neutrophil leucocytes are shown in A, B and C . A thin strand of chromatin joining the head to a nuclear lobe can be clearly seen. In D , E and F 'small clubs' are present such as may be seen in neutrophil leucocytes from the male. These should not be confused with d rumsticks. Leishman stain x 1200


Fig. 81 Blood film Polymorphonuclear leucocytosis This demonstrates the multilobular appearance of the nuclei of these mature neutrophil leucocytes. MayGriinwald-Giemsa stain x 1200

Fig. 82 Blood film Autoagglutination of polymorphonuclear leucocytes and erythrocytes This illustrates sheets of leucocytes which have coalesced by the pressure from surrounding masses of agglutinated erythrocytes; the leucocytes appear to be smaller than normal due to this pressure. This appearance is occasionally seen as an artefact at the margins of blood films due to faulty spreading. Leishman stain x 1200

. .a, ·trPc:· .. ~ :· .


Fig . 83 Blood film Polymorphonuclear leucocytosis with toxic granulation There is an increase in the number of polymorphonuclear leucocytes, some of which are not fully developed. Note also that the granules are much coarser and that Ll-teir staining reaction is more acidophilic than in normal neutrophil leucocytes. May-Griinwald-Giemsa stain x 1200

Fig . 84 Blood film Chediak-S teinbrink-Higashi anoma ly or gia n t gr a nulation of leucocytes At top left a lymphocyte containing a large coarse and small granule; bottom left, a mature basophil with giant granules and several smaller granules. Centre, a mature eosinophil containing granules of varying size; top right and bottom right, mature neutrophil polymorphs containing sparse and coarse granules . May-Gnlnwald-Giemsa stain x 1200


Fig. 85 Blood film Leucocyte alkaline phosphatase This blood film has been subjected to the modified azo-dye cytochemical technique. Numerous coarse granules giving a heavy dark brown precipitate are seen in the cytoplasm of the neutrophil polymorphs. This indicates intense alkaline phosphatase activity. This specimen was prepared from a case of polycythaemia rubra vera. M odified azo-dye cycochemicalteclmique x 1200

Fig. 86 Blood film Pelger-Huet's anomaly Stab forms and bisegmented Pelger neutrophil leucocytes are shown. The cytoplasm of these cells is less granular than that of the cells depicted in Figure 87, but the coarse chromatin and pouch-like appearance of the bisegmented nucleus of the mature cells are similar. M ay-Griinwald-Giemsa stain x 1200

'


Fig. 87 Blood film P elger -Huet 's anomaly Left: Two bisegmented Pelger neutrophil leucocytes are shown. Leishman stain x 1200 Right: One bisegmented Pelger neutrophil leucocyte and two stab forms are seen. The nuclei of the Pclger cells are small and thick with lumpy coarse chromatin. The cytoplasm shows coarse granulation which is a common feature in the Pelger cell. Leishman stain x 1200

Fig.88 Blood film (defibrinated specimen ) Systemic lupus erythema tosus T he LE cells are neutrophil polymorphonuclear lcucocytes with large opaque structureless basophil ic cytoplasmic inclusions which have displaced the nuclei, these now appearing to be wrapped round the inclusions. The rosette form shown at bottom left precedes the mature LE cell and consists of several polymorphs around free lysed nuclear material. M ay-Griinwald-Giemsa stain x 1200


Fig. 89 Neutrophil polymorph T his cell exhibits the typical features of the mature neutrophil polymorph: marked chromatin condensation, segmented nucleus, cytoplasmic granulation, glycogen particles and pinocytosis. Glwaraldehyde, urany l acetate, lead citrate x 18 200

!o

l I


Fig. 90 Blood film Myeloid leukaemoid reaction In this illustration a marked increase in the total white cell count is obvious (total count, !03 x 109 / 1). Myelocytes and immature myeloid cells are apparent. This is the usual type of myeloid leukaemoid reaction, the patient suffering from a non- leukaemic disorder. The peripheral blood picture resembles that of leukaemia (marked elevation of total white cells or the presence of immature cells or both). May -Griinwald-Giemsa stain X J200

-


Fig. 91 B lood film Acute undifferentiated leukaem ia- MO In this preparation practically all of the cells present are atypical 'blast' cells, the nuclei of which have a fine structure, their nucleoli being pale with no thickening of the chromatin at the circumference. The majority of the cells have a narrow border of basophilic cytoplasm. From this preparation it is not possible to state whether these very primitive cells are of lymphoblastic, myeloblastic or monoblastic origin. Leishman stain x 1200

I~


CLASSIFICATION OF ACUTE LEUKAEMIAS

The variability in the morphological features of acute leukaemias has resulted in the development of several systems of classification.

The generally accepted scheme is the French-American-British (FAB) classification. Two groups of acute leukaemia, lymphoblastic and myeloid, are sub-divided into three and six groups.

Lymphoblastic leukaemia. Lymphoblastic leukaemia is divided into three types, Ll, L2, and L3, according to the occurrence of individual cytological features and the degree of heterogeneity in the leukaemia cell population.

Classification

Ll

L2

L3

Cell type( s)

Microlymphoblasts

Large undifferentiated lymphoblasts Burkitt type

Characteristics

Small microlymphoblasts, nucleoli often not present or small and inconspicuous. Large more undifferentiated cell. Nucleoli are nearly always present and vary in size and number. Large cell with an oval to round regular nucleus with one or more prominent vesicular nucleoli. Prominent cytoplasmic vacuolation in the majority of cells, identical to that described in Burkitt lymphoma cells.

Myeloid leukaemia. Myeloid leukaemia is divided into six main types, according to the direction of differentiation along one or more cell lines and the degree of maturation. Ml, M2, and M3 show predominantly granulocytic differentiation. M4 shows both granulocytic and monocytic differentiation, MS predominantly monocytic differentiation and M6 predominantly erythroblastic differentiation.

Classification Cell type(s)

Ml Myeloblasts

M2 Myeloblasts, promyelocytes Myelocytes

M3 H ypergranular promyelocytes

M4 Promyelocytes,

MS (a)

MS (b)

M6

myelocytes, promonocytes, monocytes

Monoblasts Monoblasts, promonocytes, monocytes Erythroblasts

Megakaryoblast leukaemia

Classification Cell type(s)

M 7 Megakaryocytes

Characteristics

Non-granular myeloblasts usually containing one or more distinct nucleoli. Maturation beyond the promyelocyte stage. Cells containing Auer rods are common.

The majority of the cells are promyelocytes with a characteristic pattern of heavy granulation. Both granulocytic and monocytic differentiation are present in varying proportions.

Poorly differentiated monoblastic. Differentiated monoblasts, promonocytes and monocytes.

Bizarre erythropoiesis. Erythroblasts with multiple lobation of the nucleus, multiple nuclei, nuclear fragments, giant forms and megaloblastic features.

Ch a racteristics

Acute megakaryoblast leukaemia in which immature megakaryocytes with abnormal platelets are prominent.

r ~ ~~L--------------------~----------------------~--------~----------------------------------~


Fig. 92 Marrow film Acute myeloid leukaemia - Ml Non-granular myeloblasts with lack of granulocytic different iation. May-Gnlnwald-Giemsa stain x 1200

THE WH ITE CELL SERIES 87

Fig. 93 Marrow film Acute myeloid leukaemia - M2 There is some degree of maturation beyond the promyelocyte stage with dysplastic forms. May -Gnlnwald-Giemsa scain x 1200

Fig. 94 Marrow film Acute m yeloid leukaemia - M3 The cells are predominantly promyclocytcs with prominent coarse granulations. May-Gnlnwald-Giemsa scain x 1200

,


Fig. 95 Blood film Acute myelomonocytic leukaemia - M4 The cells in this illustration are primitive cells of the monocyte series, monoblast and promonocyte (left centre), and primitive cells of the myeloid series promyelocyte and myeloblasts (lower right). May-Gnl11wald-Giemsa stai11 X 1200

Fig. 96 Marrow film Acute m yelomonocytic leukaemia - M4 The cells in this illustration are primitive cells of the myeloid and monocyte series. Monoblasts top left and myeloblasts bottom righ t. May -Grii11wald-Giemsa scain x 1200

j


• Fig. 97 Ma rrow film Acute monobla stic leukaemia- MS (b ) This illustrates proliferat ion of cells of the monocytic series at various stages of development, monoblasts and promonocytes with variation in size and nuclear configuration. May -Grii11wald-Giemsa stai11 x 1200

Fig. 98 M a rrow film Erythroleukaemia - M6 At low magnification (left) and high magnification (right) the bizarre nature of erythropoiesis is evident. There is complete absence of cells of the myeloid series. Erythroblasts with multiple lobation of the nucleus and multiple nuclei are present. May-Grii11wald-Giemsa staill x 1200


Fig. 99 Blood film Myelodysplastic syndrome The blood film exhibits macrocytosis and anisopoikilocytosis. Large platelets are present on the right of the field. May-Gninwald-Giemsa scai11 x 1200

Fig. 100 Marrow film Myclodysplastic syndrome Left : Erythroid hyperplasia with dyserythropoiesis and megaloblastoid features. M ay-Griinwald-Giemsa stain X 1200 Right: Promyelocytes with sparse granules and hypogranularity of myelocytes. May-Gninwald-Giemsa stain X 1200

THE W HITE CELL SERIES 91

Fig. 101 Marrow film Acute myeloid leukaemia- M2 In this illustration the chief cells are myeloblasts with variable nucleo-cytoplasmic ratios. Their nuclei are large, with smooth finely stranded chromatin, and contain nucleoli. Promyelocytes, some of which possess azurophil granules, but with otherwise similar characteristics to the myeloblasts are also present. May -Gninwa/d-Giemsa stain x 1200


Fig. 102 Blood film Acute myeloid leukaemia- M2 In the low power illustration (top left) the cells are seen to be all of the same cell type. Higher magnification illustrates many myeloblasts with moderately deeply basophilic cytoplasm. Some of the myeloblasts exhibit fine cytoplasmic vacuolation and a spongy reticular appearance. Both the myeloblasts and promyelocytes show irregular indentation and folding of the nucleus and these cells are sometimes referred to as paramyeloblascs and parapromyelocyces. May -Grii11wa/d-Giemsa stain x 600, x 1200


..

Fig. 103 Blood film Acute myeloid leukaemia- M2 Numerous myeloblasts (Myb) which vary considerably in size are present in this composite illustration. Also present are promyelocytes (pMy), myelocytes (My) and a metamyelocyte (mMy). The main featu res of this illustration are the complete lack of mature granular cells, and the many cells with giant nucleoli, which are common in this condition. M ay-Grtlnwald-Giemsa stain x 1200


Fig. 104 B lood film Acute m yeloid leukaemia Auer rods - M2 Several of the myeloblasts, in this composite illustration, contain single or multiple rod-shaped structures in their cytoplasm; these are known as Auer bodies. These bodies are probably fo rmed by the coalescence of cytoplasmic granules in leukaemic myeloblasts. May-Gnlnwald-Giemsa stain x 1200


Fig. 105 Blood film Acute myeloid leukaemia With the staining method depicted here the nucleoli of the myeloblasts give a positive (blue) staining reaction, against the rose pink stained nucleus, and are more clearly delineated. Chromozrope-Giemsa scaiu x 1200

Fig. 106 Blood film Rieder cells in leukaemia All the primitive leucocytes illustrated exhibit lobular division of their nuclei; most are bi- or trifoliate. The lobes are separated by deep clefts. Cells with such a nuclear configuration are known as Rieder cells and are frequently seen in blood films in acute leukaemia. M ay-Grrluwald-Giemsa scaiu x 1200


-----------------------------------------------------------------------

Fig. 107 B lood film Acute myeloid leukaemia - M 1 The cells in this illustration are of the same type, myeloblasts of varying size with basophilic cytoplasm; irregular shaped nucleus with nucleoli. May -Griinwald-Giemsa stain x 1200

Fig. 108 Marr ow film Acute myeloid leukaemia- M 1 Marrow film from the patient whose blood film is illustrated in Figure 107. The marrow is heavily infiltrated with myeloblasts similar in morphology to that of the blood film. The myeloblasts are larger with a spongy appearance of the nucleus compared with the myeloblasts in the peripheral blood film. May -Griinwald-Giemsa stain x 1200


Fig. 109 Marrow film Acute myeloid leukaemia- Ml This illustration demonstrates the Sudan Black positivity of the myeloblasts from the same marrow sample as Figure 108. The stain detects lipids. Sudan Black, and coumerstained L eishman stain x 1200

Fig. 110 Marrow film Promyelocytic leukaemia- M3 In this illustration the majority of the immature cells exhibit cytoplasmic granulation ranging from fine to coarse. T he nucleus of the promyelocytes appear more immature than in the normal promyelocyte. May -GrtlnwaldGiemsa stain x 1200


Fig. 111 Blood film Blast cell transformed chronic myeloid leukaemia This preparation is from a patient in whom chronic myeloid leukaemia has undergone b last cell transformation, the blood picture now resembling .that of acute myeloblastic leukaemia. Many primitive myeloid cells are present but more mature cells are also noted in the illustration (left). It is of interest that in spite of the acute transformation the total platelet count remained elevated as evidenced by the many platelets seen in this illustration; note the several giant forms. May -Griinwald-Giemsa stain x 500

Fig. 112 Marrow film Acute myeloid leukaemia in remission The marrow is active and exhibits hyperplastic-macro-normoblastic erythropoiesis. The previous myelobhistic infiltration has been cleared and myelopoiesis is normal, no increase in blast cells being noted. May -GriinwaldGiemsa stain x 1200


Fig. 113 Blast cell This cell shows no features of differentiation but it was taken from a patient with acute myeloblastic leukaemia. Glutaraldehyde, ura11yl acete, lead citrate x 18 200

'


Fig. 114 Marrow film Chronic m yeloid leukaemia There is a marked increase in the cells of the myeloid series; many myelocytes (My), metamyelocytes (mMy), non-segmented (Stab) and segmented (Neut) neutrophil leucocytes are present. A haemohistioblast (R), an eosinophil (Eos), and a basophil (Bas) leucocyte are also shown. Leishma11 s1ai 11 x 1200

t

THE WHITE CEL L SERIES 101

Stab

9 mM,

Stab'(Y 0 g ~ 0e

~ 0 (iycl

rnMy

Stab

S tab Neut

F ig. ll 5 Blood film C hronic m yeloid leukaemia ' Marked proliferation of the cells in the myeloid series is demonstrated . Myelocytes (My) and metamyelocytes

(mMy) are seen in addition to numerous non-segmented and segmented neutrophil leucocytes. M ay-GninwaldGiemsa stain x 1200


Fig. 116 Marrow film Myeloid leukaemia The cytoplasmic granules of the neutrophil myelocytes show a blue positive peroxidase reaction. Peroxidase reaction, coumerstained Leishman stain x 1200

Fig. 11 7 Marrow film Myeloid leukaemia In this preparation the peroxidase method was modified and the granules of the eosinophil myelocytes give a positive reaction of a translucent yellow-green colour with a blue margin, whereas the granules of the neutrophil myelocytes give a blue positive reaction. Peroxidase reaction, counterstained Leishman stain x 1200


Fig. 118 Blood film Chronic myeloid leukaemia This illustration demonstrates the Sudan Black positivity of the granules of the myeloid series. The more mature cells show a heavier reaction than the more primitive cells. Many free granules are scattered throughout the film, due to rupture of cells during spreading. Sudan Black and M ethyl R ed x 200, x 800


Fig. 119 Blood film Tra nsforming o r accelerated phase, chronic m yeloid leukaemia This illustrates increasing cellular immaturity of the myeloid ser ies with an increase in atypical promyelocytes, myelocytcs and basophi ls. May-Gn111wald-Giemsa scai11 x 1200

THE WHITE CELL SERIES I 05

Fig. 120 Marrow film Myelomonocytic leukaemia- M4 The majority of the cells in this composite illustration are primitive cells of the myeloid and monocyte series. The azurophilic granulation in many of the cells indicate their myeloid potential whereas the agranular primitive cells, best seen in fie ld C , exhibit a more grey-blue cytoplasmic staining reaction and their nuclei show the more open arrangement of chromatin pattern; both these feature~ arc typ ical of the primitive cells of the monocyte series. Note the large nucleoli in several of the cells, especially in the h istioblast in the upper left margin of field A. The myelocyte (left of centre, fie ld C ) contains nu merous small Auer bodies . (See also I." ig . I 2 1.) Jllay-Uriinn•aldGiemsa srai11 x 1200

-- -


Fig. 121 Marrow film Myelomonocytic leukaemia- M4 These illustrations from the same marrow as depicted in Figure 120 and illustrating similar features also show pronounced erythroid hyperplasia. This is sometimes called Di Guglielmo's syndrome when referring to cases of leukaemia in which erythroid hyperplasia and abnormal erythroblasts are a feature. In field A several abnormal erythroblasts are present; one in the centre of the field shows erythrophagocytosis. At the upper left margin there is a monoblast with azurophilic granulation of the cytoplasm and at the upper right margin a large promyelocyte. Field B contains a monoblast, a promyelocyte and an abnormal erythroblast. Field C consists mainly of cells of the erythroid series, although a giant polymorphonuclear leucocyte is present in the upper part of the field. At the lower right quadrant a large polyploid erythroblast can be seen and to the left margin there is an erythroblast with a reniform nucleus resembling that of a metamyelocyte. All the cells in field D, including the cell in mitosis, are of the erythroid series. (See also Figs. 54, 55 and 56.) May -Griinwald-Giemsa slain x 1200

THE WHITE CEL L SERIES 107

Fig. 122 Marrow film . Eosinophilia The majority of the cells in this preparation are of the eosinophil granulocyte series at all stages of maturation. This marrow specimen was aspirated from a patient with mycosis fungoides. The b lood picture from the same case is shown in Figure 314. May-Griinwald-Giemsa stain x 1200

Fig. 123 Blood film Eosinophilia These illustrations show numerous segmented eosinophil leucocytes, several of which contain two pouch-shaped nuclear Jobes. May -Griinwald-Giemsa stain x 1200


c

Fig. 124 Basophil le ucocyte development Compare this series with mast cells ( tissue basophils) as shown in f-igurL· I '3H. A is an example of a basophil promyelocyte. B shows a basophil myelocyte (right) and to the left a transit ional stage between A and B . C shows a basophil metamyelocyte, and D a mature basophil leucocyte. Note that the cytoplasm of the basophil leucocyte is pink and that the large granules overlie and mask the nucleus, frequently making it difficult to decide which stage of maturation .a cell has reached. Leishma11 stai11 x 1200

Fig. 125 Marrow film Chronic myeloid leukaemia This illustration shows a marked increase in the number of basophil leucocytes. In addition to the mature basophils several immature forms with large coarse granules and multiple nucleoli arc present. Leishma11 srai11 x 1200

THE WHITE CELL SERIES 1 09

Fig. 126 Fe moral m arrow Chronic m yeloid le ukaemia This illustration shows almost complete replacement of hacmopoietic tissue by tumour. Huemalum & Eosi11 x 120

Fig. 127 Femoral marrow Myeloid leukaemia Lej1: This is a typical example of the acute form of this disease. Only primitive cells can be seen, several of which are in varying stages of mitosis (arrow). Haemalum & Eosi11 x 450 Righi: In the chronic disease, both immature and segmented cells arc seen, most of the cells with small dark nuclei are normoblasts. Haemalum & Eosi11 x 450

-_


Fig. 128 Marrow section Chronic myeloid leukaemia The prominent features of this preparation are eosinophilia and the presence of Charcot Leyden crystals. H aemalum & Eosin x I 200

Fig. 129 Spleen Normal A non-reactive lymphoid follicle has a b ilobed appearance with the arteriole between the two halves. Haemalum & Eosin x 50

THE WHITE CELL SERI ES 11 1

Fig. 130 Spleen Acute m yeloid leuka emia The margin of a lymphoid follicle (bottom right) abuts on red pulp which contains many p rimitive cells and very few mature granulocytes. Haemalum & Eosin x 450

Fig. 131 Heart Acute myeloid leukaemia Left: This shows a massive infiltration of the heart muscle and epicardial fat by immature myeloid cells. Haemalum & Eosin x 120 Right: T his high magnification confirms that a ll the infiltrating cells are primitive myeloid cells. Haemalum & Eosin x 450

11 0 A'IIA~IIl y

t,.. I ll l ,y m p h node M yeloid metaplasia ti ,IIIIIIIJHtkl it tclb arc seen in the distended sinusoid and in an adjacent medullary cord. A megakaryocyte, ""'""'hht~l' uno cosinophils, a t different stages of maturation, arc readily visib le. Other immature myeloid cells 1111 JIH'\Cill. 1/acmalron & Eosin x 400

Fig. 133 Liver Norma l A single portal tract can be seen in the right half of the field; in it the portal vein containing erythrocytes lies adjacent to a small bile duct. Two central hepatic veins are present to the left of the field. Haemalwn & Eosin X /20

THE WHITE CELL SERIES 11 3

Fig. 134 Liver Chronic m yeloid leukaemia The sinusoids show the characteristic diffuse infiltration common in th is disease. Note that there is pressure atrophy of the parenchymal cells. Haemalum & Eosin x 120

Fig. 135 Liver Acute m yeloid leukaemia This is a typical example of the liver in acute myeloid leukaemia; the sinusoids contain great numbers of primitive cells, many of which a re large; no mature granulocytes a re seen. Haemalum & Eosin x 450


Fig. 136 Skin Acute m yeloid leukaemia The upper illustration shows densely packed foci of cells in the dermis. At high power it is seen that there is little variation in the size and staining reaction of the cells. The diagnosis was confirmed by haematological examination. Haemalum & Eosin x 100, x 475

.. v

-


Fig. 137 Lym p h nod e C hronic g ra nulocytic leukaemia Most of the cells are pr imitive members of the myeloid series and cannot really be identified further . However a megakaryocyte and several cosinophils are clearly visible. H aema/um & Eosin x 500

-

116 ATLAS O F HAEMATOLOGY

Fig. 138 Marrow fi lm Mast cells .\1\ast cells or tissue basophils arc not normally found in bone marrow but may be seen in cases of aplastic anaemia, chronic blood loss, anaphylaxis, and tumours of the lymp hoid tissue involving bone marrow. These cells arc larger and do not have the rounded appearance of mature basophil lcucocytcs; the granules arc also larger and can be seen best in cells which have been slightly flauened during the spreading of the film. T he nucleus of a mast cell is always pale in colour and although the granules are deeply basophilic when stained by the routine blood stains they show marked metachromasia when sta ined with toluidine blue. Leishman stall/ x 8UU

Fig. 139 M a rrow fi lm s Tissue m ast cell leukaemia A. It is ob,·ious that there is a marked increase in the number of mast cells in this preparation. The granules of

the cells arc deeply basophilic and there is difficu lty in resolving individual granules. M ay-Gn11twald-Giemsa stain x 800

B. The metachromatic granules arc easi ly resolved when stained by toluidine blue, this identifying the cells. Toluidine LJ/ue srain x 800 '

'

T HE WHITE CELL SERIES 11 7

LYMPHOBLAST

t MONOBLAST

t PLASMABLAST

t

PROLYMPHO CYTE

t PROMO NOCYTE

t PR OPLASMA C EL L

LARGE SMAll

LYMPH OCYTES MONOCYTE PLASMA CE LL S

F ig. 140 M aturation of lymphocytes, m onocytes and plasma cells This composit.: illustration of developing lymphocytes, monocytcs and plasma cells demonstrates the differences in size, staining reaction, nuclear configll ration and chromatin structure at various stages of maturation . For fu rther details of development in each cell series see Figures 141 , 180 and 20 1. l .ei .<hma>l .<t a i11 x 121111

(

-·--

118 ATLAS OF HAEMATO LOGY

Fig. 141 Maturation of the lymphocyte Fr<;>m the left, the cells present are as follows. A lymphoblast containing a large nucleus surrounded by a narrow rim of basophilic cytoplasm; even at this stage of development the resemblance to the mature lymphocyte is obvious. Next in sequence is a prolymphocyte which is smaller than its precursor and shows a shadow nucleolus within the large nucleus. The other illustration shows mature lymphocy tes in peripheral blood. Lcishmau staiu X 1200

Fig. 142 Blood film Infectious mononucleosis Preparation from a patient with severe infectious mononucleosis and associated grossly elevated heterophil antibody titre. T he atypical lymphocytes vary considerably in size with irregular outlines flowing around the adjacent red cells. The abundant basophilic cytoplasm in some cells contain fine eosinophilic granules (lower cell, middle illustration) others exhibit marked vacuolation (right lower cell). Leishmau staiu x 1200


Fig. 143 Blood film Infectious mononucleosis This composite illustrates the atypical features which lymphocytes may exhibit in this condition. T he nuclei are lobulated or kidney shaped. The chromatin , which is in coarse strands, is irreg ular ly dis tribu ted , giving a mottled appearance. ote the variation in size of these abnormal lymphocytes, and that the cytoplasm tends to be more basophilic than normal. May-Grii11wa/d-Giemsa srai11 x 1200

A

Fig. 144 Blood film Lymphocytes in viral pneumonia A exhibits a lymphocytosis, the field being devoid of granular cells. x 600. B & C shows marked variation in size and shape. D-H exhibit abnormal cytoplasmic and nuclear features- in particular, nuclear indentation and c~·toplasmic vacuolation. May-Griimvald-Giemsa stain x 1200

,--- - -- -- ---

•.

120 AT LAS OF H AEMATOLOGY

Fig. 145 Blood film Neonata l cytomegalovirus infection This illustrates bizarre lymphoid cells of varying maturity (centre and upper left field ), normoblastosis and thrombocytopenia . The stressed neonate frequently exhibits normoblastosis and thrombocytopenia, not indicating marrow pathology. May-Grrlnwald-Giemsa stain x 1200

Fig . 146 Blood film Alder - Reilly a nomaly Red cytoplasmic inclusions shaped like a dot or comma surrounded by vacuoles a re present in both the lymphocytes illustrated. These inclusions in blood lymphocytes arc sometimes refe r red to as Ciasser's cells. This preparation was from a t:hild ~11ffering from mucopolysaccharidosis. May-Grrlnwald-Gicmsa .(taiu x 1200


Fig . 147 Blood and m a rrow fi lms Waldcnstro m 's macroglobulina emia Left: This blood film shows large lymphocytes with lobulated, indented and irregularly shaped nuclei. No granular cells are p resent. J\lfay-Gnluwald-Gicmsa staiu x 800 Right : T hi s fi lm of marrow exhibits a marked increase in lymphocytes, many of which have scanty or absent cytoplasm. There is also a decrease in erythroid and myeloid cells. Several plasma cells arc present. M ayGriimuald-Giemsa staiu x 800


Lymphoblastic leukaemia

Classification

L1 L2

L3

Cell type( s)

Microlymphoblasts Large undi fferentiated lymphoblasts Burkitt T ype

Fig. 148 Marrow film Acute lymphoblas tic leukaemia - Ll The cells in this illustration are small lymphoblasts with a h igh nuclear-cytoplasmic ratio and indistinct nucleoli. These are often described as microlymphoblasts. May -Gnlnwald-Giemsa sea in x I 200


Fig. 149 Marrow film Acute lymphoblastic leukaemia- L2 The lymphoblasts are large with more cytoplasm compared to the cells illustrated in Figure 148. Prominent nucleoli varying in size and number are also present in these cells. May-Gnlnwald-Giemsa srain x 1200

Fig. ISO Marrow film Acute lymphoblastic leukaemia - L3 The prominent features in this illustration are the heavily vacuolated large lymphoblasts. These cells are morphologically similar to those found in Burkitt's lymphoma. May-Griinwald-Giemsa stain x I 200


Fig. 151 Marrow film Acute lymphoblastic leukae mia- L 2 The predominant cells in th is illustration arc lymphoblasts. These cells arc very similar in size and general appearance to myeloblasts, but have coarser, more deeply staining nuclear chromatin , and nucleoli arc less obvious. (See Figs. 276- 278.) May -Griinwald-Giemsa srain x 1200

THE WHITE CE LL SERIES 125

Fig. 152 Blood film Acute lymphoblastic leukaemia- L2 The cells are predominantl y large lymphoblasts with nucleoli of var ying size. M ay-G riimuald-Giemsa stai11 x 1200

(

..


Fig. 153 Blood fi lm Acute lym phoblastic leukaemia- L2 The predominating cells in this illustration are lymphoblasts; these cells possess round, oval or indented nuclei containing coarse granular or stippled chromatin and also one or two poorly defined nucleoli. The agranular cytoplasm is moderately basophilic and, in several of the cells, is seen to contain fine vacuoles. May-GninwaldGiemsa stain x 1200

Fig. 154 Blood fi lm Acute lymphoblastic leukaemia The lymphoblasts show strong and coarse PAS positivity, with moderately large discrete cytoplasmic granules, arranged in a perinuclear manner. Two neutrophil polymorphonuclear leucocytes containing very large amounts of PAS positive material are also present (lower left) Periodic Acid-Schiff r PAS) x 1200

T H E WHITE CELL SERIES 127

... •

' ~ • ~

OJ u ttl ~

1)1, 3 ~t . ~

··' t.:l

t\ c. i (I. OJ

Ce .:>o· c.• o 0

€?

F ig. ISS E-rosetting T - ceil acute lymphoblastic leukaemia T he lymphoblasts arc surrounded by sheep red cells forming rosettes, thus confirming the T-cell phenotype. Leishman stain x 500, x I 200

Fig. 156 M arrow film Subacute lymphocytic leukaemia These ill ustrations show a marked increase in the num ber of small lymphocytes, and also several lym phoblast and prolymphocytes. L eishman stain x I 200


Fig. 157 Blood film Subacute ly mphocytic leukaemia This composite illustration shows a predominance of the cells of the lym phocytic ser ies. Lym phocytes at all stages of development a rc presen t, ranging from the lymphoblast to the matu re small lymphocyte. M ay-Griimuald-Giemsa srain x 600, x 1200 ·


Fig. 158 Blood film Prolymphocytic leukaemia A well marked increase in the total white cell count is obvious, the cells being mainly prolymphocytes and a small percentage of lymphoblasts. May-Gnlmuald- Giemsa stai11 x 500

Fig. 159 Blood film Prolymphocytic leukaemia This higher magnification of a field taken from Fig. 158 illustrates the prolymphocytes with indented nuclei and shadow nucleoli; lymphoblaHs with large distinct nucleoli. \1ay - Gnl11wald-Giemsa srai11 x I 200


Fig. 160 Blood film Prolym phocy tic leukae mia Coarse PAS positivity is shown in some of the cells with discrete small cytoplasmic granules. The three neutrophil polymorphs contain large amounts of PAS positive material. This preparation was taken from the same patient as shown in Figs. 158 and 159. Periodic Acid-Schiff f PAS) x 900

Fig. 16 1 Marrow film Chronic lymphocytic leukaemia '-In this preparation, there is a marked predominance of mature small lymphocytes, in addition to which, several immature and mature neutrophil and eosinophil leucocytes are present. Leishman srailz x 1200


Fig. 162 Marrow section C hronic lymphocytic leukaemia Apart from the megakaryocyte in the centre of the fie ld all the cells are mature small lymphocytes. H aema/um & £osi11 x 500

Fig. 163 Blood film Chronic lymphocytic leukaemia Note the marked uniformity of the cell type. Medium-sized lymphocytes with light-blue cytoplasm and smaller lymphocytes with a very narrow rim of dark-blue cytoplasm are seen. Several of the larger cells show indentation of the nucleus, which is a common find ing in this condition. M ay-Grtl11wald-Giemsa stai11 x 1200


Fig. 164 Blood film Chronic lymphocytic leukaemia The majority of the cells are medium sized lymphocytes with inden tation of the nucleus and light blue cytoplasm. M ay-Gnl11wa/d-Giemsa srai11 x 1200

Fig. 165 Blood film Large granular lymphocytic leukaemia The lymphocytes are much larger in size than the lymphocytes illustrated in Figs . 163 and 164. The striking fea tures arc the large red cytoplasmic granules, abundant, cytoplasm and variation in size and shape of the nucleus. May Gnillwald-Giemsa srai11 x 1200


Fig. 166 Lymphocyte Thb cell appears quite active, the cytoplasm contains numerous free ribosomes, some mitochondria and some \ trands of rough endoplasmic reticulum. There is a relatively large nucleus with only moderate chromatin condensation around the nuclear membrane. Several nuclear pores arc seen in tangential section. A Golgi uppnratus is present at the bottom of the illustration. A prominent centriole is seen below the nucleus. Ul111araldehyde, uranyl acetate, lead citrate x 26 000


Fig. 167 Lymph node Infectious mononucleosis The architecture of the cortex is obscured so that only an ill defined follicle can be seen (left). Vascularity is increased by pro liferation of post-capillary venules (centre). The polymorphic nature of the inter-follicular infiltrate with lymphocytes, plasma cells and immature lymphoid cells is seen at h igh magnification ( right). Haemalum & Eosi11 x 25, x 250, x 450

Fig. 168 Femoral marrow Lymphocytic leukaemia This illustration shows almost complete replacement of the marrow tissue by a mass of tumour cells; only a few fat cells which are seen as clear spaces remain. Haemalum & Eosi11 x I 20

..... ._.


Fig. 169 Femora l m a rrow Ly mphocytic leukaemia A high-power view of par.t of the fie ld seen in Fig. 168, showing the almost completely lymphocytic nature of the infiltrate. ote that many similar cells are present in the venule shown in the upper part of the illustration. Haema/um & Eosin x 450

Fig. 170 Lymph node (left)' and spleen ( right) Lymphocytic leukaemia Both tissues show obliteration of the normal architecture by masses of cells of the lymphocyte series. Haema/wn & Eosin x 40, x 120

136 ATLAS OF H AEMAT OLOGY

Fig. 171 Testicular biopsy T -cell acu te lymph oblastic leukaemia The interstitial tissue between atrophic seminiferous tubules is heavily infilt rated with small lymphocytes. Many of the nuclei have an irregular configuration. Haemalwn & Eosin x 300

Fig. 172 Liver Acute lymphoblastic leukaemia The distribution of the infiltrating cells is predominantly periportal although several small groups can be seen lying in the sinusoids . Haemalum & Eosin x 120

THE W H ITE CELL SERIES 137

Fig. 173 Blood film Leukaemic reticuloendotheliosis ('hair y' cell leuka emia) This illustrates the characteristic hairy lymphocytes, found in this condition. T he grey-blue cytoplasm exhibits irregular villi resulting in an irregular serrated 'ha iry' edge and also pseudopodia! extensions. May-Griinwa/dGiemsa srain x 1200

Fig. 174 Blood film Leuka emic reticuloendotheliosis ('hairy' cell leukaemia) The irregular cy toplasm ic villi of the lymphocytes, similar to Fi~. 171 is illustrated in this preparation. May Griinwald-Giemsa .<rain x 1200


Fig. 175 Blood film Leukaemic reticulocndotheliosis ('hairy' cell leukaemia) Tartrate-resistant positive acid phosphatase reaction in hairy lymphocytes. Acid phosphatase reaction and M ethyl Green x 1200

I

Fig. 176 Imprint from spleen Leukaemic reticuloendotheliosis ('hairy' cell leukaemia) In this imprint from the spleen some of the cells exhibit weak to moderate tartrate resistant positive acid phosphatase reaction and one cell, strong activity. Acid phosphatase reacrion and Merhyl Green x 900


Fig. 177 Blood film Leukaemic reticuloendotheliosis There are pseudopodia projecting from the cell surfaces, corresponding with the hairs seen on light microscopy. Glutaraldehyde, ura11yl acetate, lead citrate x 10 350


Fig . 178 Spleen Leukaemic r e ticulocndotheliosis Left: This section reveals absence of germinal centres and a diffuse infiltration of the red pulp by lymphoid cells. Haema/um & Eosin x 125 Right: T he appearance suggests a well-di fferentiated lymphocytic lymphoma, the main problem being that the typical 'hairy' cells are impossible to identify in histological sections. Haema/um & Eosin x 600

Fig. 179 Liver Leukaemic reticuloendotheliosis Left: This section shows sinusoidal infiltration with lymphoid cells. Haemalum & /:"Min x 125 Right: The lymphoid nature of the cells is seen; but typical 'hairy' cells can not be identified. Haema/wn & Eosin X 600


Fig. 180 Maturation of the m onocyte From the left, this shows a primitive cell which provides a link between the haemohistioblast (stem cell) and the monoblast. A monoblast, the cytoplasm of which exhibits the typical non-granular pale grey-blue staini ng reaction common to this cell type; nucleoli arc present but are only resolved with d ifficu lty. The other two cells are a promonocyte which has a typical large con\'Oiuted nucleus, and a mature monocyte with an indented (kidneyshaped) nucleus. Leishma11 srailt x 1200

F ig. 181 M a rrow film Monocytcs Top left: The monocyte present is larger than normal, the nucleus is deeply indented and the cytoplasm contains man~· very large azurophilic granules. Granulation of this type is often present in monocytic leukaemia . I.eishma11 S/CI/11 X 1200 Bottom hft: Two monoblasts arc seen , both of which show distinct nucleoli and a deep-blue cytoplasm. T he other cells present arc mature monocvtcs. l.ershma/1 srai11 x 1200 RiKht: This illustration is typical of the variation in size and shape of mature monocytes which are found in the marrow or blood in monocytic leukaemia. Note that several of the cells show fine granulation. Leishma11 srailt X / 200


Fig . 182 M arrow film M onocytes L eft : A large promonocyte (pMon) which is coarsely granular and appears to be necrobiotic is shown. The other cells present are monocytes of normal size. Inset shows a monocyte in prophase stage of mitosis, the cytoplasm of which is markedly granular. The size of the cells in this illustration can be compared with the normal large lymphocyte (L ). L eishman stain x 1200 Right: Shows a monoblast (Mon. b) and several monocytes (Mon) which vary considerably in size, the largest of which has a deeply indented nucleus. Leishman srai11 x 1200


Fig. 183 Marrow film Monocytes Top left: A typical promonocyte. The cell is large and the cytoplasm appears to have both azurophilic and basophilic granulation which is probably due to either break-up of or damage to, the cytoplasm. Leishma11 stai11 X 1200 Top right : This monocyte has three nuclear lobes which do not appear to be joined; the cytoplasm is filled with coarse azurophilic granules. Leishma11 staill x 1200 Cemre left: Shows a monocyte in the prophase stage of mitosis, and also a monocyte of normal size with a segmented nucleus. Leishma11 s1ai11 x 1200 Cemre right: T he anaphase stage of mitosis is clearly seen in this monocyte. Leislmtall s1ai11 x I 200 The two large cells in the lower part of the illustration are monocytes which are normal in all appearances except size. Leishma11 s1ai11 x 1200


Fig. 184 Blood film Monocytes The monocytes present are typical of the wide variation in size and nuclear configuration wh ich is to be found in monocytic leukaemia. The cell at centre righ t migh t at first glance be mistaken fo r a plasma cell if it were not for the fact that many cells showing this appearance are found in the blood in cases of monocytic leukaemia. Leishman stai11 X I 200

Fig. 185 Blood film Monocytes This composite illustration shows two extremely large monocytes, the one on the left having a nucleus which takes up practically the whole of the cell area. The cell on the r ight is in early prophase mitosis. The other cells present are three monocytes and one promonocyte. r:ine granules can be seen in several of the cells. Leishman stain x I 200


Fig. 186 Ma rrow film- Monocytic leukaemia- M S (b) Marked proliferation of cells of the monocyte series is the main fea ture of this illustration. Monocytes at all stages of development are present; several show multi lobulation of their nucleus including one cell with a quinquefoliate nucleus at the lower right part of the illustration. These features are reminiscent of the nuclear changes seen in Rieder cells. (See Fig. 106.) May-Gnlnwald-Giemsa stain x 1200


Fig. 187 Blood film Monocytic leukaemia- MS (b) This illustration shows massive proliferation of monocytes in varying stages of maturity. Several of these cells show fine cytoplasmic granules which are normally found only in immature cells of this type. Leishman srain X /200


Fig. 188 Marrow film Acute monocytic leukaemia - MS (a) Left: The marrow is heavily infiltrated by immature cells of the monocytic series, May-Grunwald-Giemsa stai1z X 900 Right: The non-specific esterase stain is positive in all cells illustrated, indicating the monocytic origin of the cells. Combined chloroacetate esterase/non-specific esterase, coumersrained Methyl Green x 900

Fig. 189 Blood film Chronic monocytic leukaemia This illustrates a marked increase in the number of mature monocytes, exhibiting variation in size and nuclear configuration. Leishman stain x 1200


Fig. 190 M on ocyte

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This large cell has an irregular nucleus with a single cleft containing cytoplasmic organelles. There is a moderate amount of chromatin condensation around the nuclear membrane. The cytoplasm appears active, with mitochondria, several short strands of rough endoplasmic reticulum and a variety of secretory granules, small in size and with varying electron-density. In addition, there are free ribosomal granules. Glwaraldehyde, uranyl acetate, lead citrate x 14 000

THE W H ITE CELL SER IES' 149

Fig. 191 Femoral marrow Monocytic leukaemia There is almost complete replacement of the normal haemopoietic tissue by tumour. The majority of the cells in the blood vessel, seen at the lower right of the field, are monocytes . Haemalum & Eosin x 120

Fig. 192 Femoral m a rrow Monocytic leukaemia This is a high-power magnification of the field shown in Fig. 191. The cells present are almost entirely monocytes and normob1asts. Haemalum & Eosin x 450


Fig. 193 Liver Monocytic leukaemia The distribution of the infiltrating cells may be either periportal (left), as in lymphocytic leukaemia, or diffuse (right), as in myeloid leukaemia; mixtures of these two patterns m::y be seen . Haemalum & Eosin x 120

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THE W H ITE CELL SER IES 151

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Fig. 194 Lung Monocytic leukaemia A sma ll vein ( top left) and a cap illary of an interalveolar septum (bottom left) are p lugged with masses of tumour cells which are identifiable at h igh magnificat ion ( righ t) as either m onoblasts o r monocytes. Haemalum & Eosin X /20, X 400, X 800


Fig. 195 Skin Monocytic leukaemia The dermis is densely infiltrated by tumour cells with resulting pressure atrophy of a hair shaft. T he monocytic nature of the cells is clearly seen in the high-power field. T his mater ial is from the same case as Fig. I Y·l. Haema/um & Eosin X 200, X 800

Fig. 196 Marrow film Sea blue histiocytosis The characteristic cell infilt rating the marrow is ill ustrated . T his is a large ret iculoendothelial cc.:ll with a single eccentric nucleus. The cytoplasm contains a large n umber of sea blue granules. Leishman stain x 600

THE WHITE CELL SERIES l)j

Fig . 197 Marrow film Niemann-Pick's disease Foam cells These cells (monocytes), which are commonly round or ovoid, are filled with small hyaline droplets which give a foamy or honeycomb appearance. Compare this appearance with the wrinkled cytoplasm of the Gaucher cell ( Fij(. I <lR). {,,•t .<IIIIW/1 .<l cJ/11 X '}()()

Fig. 198 M arrow film Gaucher's disea se The Gaucher cells (monocytes) have a distinctive large oval or round shape with one or more small eccentrically placed nuclei. The ·cytOplasm has a laminated appearance with numerous blue fibri llae and open spaces from which the lipid kerasin has been removed by the alcohol in the staining reagent. The Gaucher cell may also exh ibit a foamy appearance, in which case the lipid material is contained as droplets, and in this form the cells have a much greater resemblance to the foam cells found in Niemann-Pick's disease t Fig. I 117). / ,,·,,/ullc/11 .•I aut X /200


Fig. 199 Spleen Gaucher's disease The capsule (top) and a trabecula (bottom) arc separated by a mass of pale cells in pseudo-follicular arrangement. Note the widely distended sinusoids. Haemalwn & Eosin x 40

Fig. 200 Spleen Gaucher's disease The characteristic Gaucher cells are large histiocytes with abundant pale pink foamy cytoplasm, the foamy appearance being due to the lipid kerasin having been dissolved from the cells during the processing of the tissue. Haemalum & Eosin x 450

THE WH ITE CELL SERIES ! 55

•

Fig. 20 1 M a t u r a t ion of the p lasm a cell From left to right, the upper row sho ws two plasmablasts, the firs t being the more primitive and the second commenci ng to take on the characteristics of the proplasma cell although it still shows shadow nucleoli. The next cell is a proplasma cell; the nucleus has now taken up an eccen tric position and no nucleoli are obvious. Note that in all these cells a perinuclear halo can be seen. The lower illustrations arc all of mature plasma cells, o ne o f which is binucleate. note that in the other two cells the nuclei have assumed an eccentric position . Leishman stain X / 200

F ig. 202 M arrow film D yspr ote inaemia T his composite illustration shows the typical 'flaming' appearance which is to be seen in many of the p lasma cells in this disorder. M ay-Griinwa/d-Giemsa stain x 1200

1


Fig. 203 Blood film P lasm a cell myeloma This illustrates rouleau formation of the red .cells which is a characteristic finding in the blood film in plasma cell myeloma and associated dysproteinaemias. May -Gnlnwald-Giemsa stain x 1200

•

Fig. 204 Mar row film (>lasma cell myeloma

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The marrow is grossly infiltrated with plasma cells at all stages of maturation but in particular many large plasmablasts are present. M ay-Gninwald-Giemsa stain x 300

THE W H ITE CELL SERIES 157

Fig. 205 Marrow film Plasma cell m yeloma High power magnificat ion of a field taken from Fig. 2<H confi rming the presence of plasmablasts. Nucleoli a re clearly seen in the nucleus of the plasmablasts. May-Gnlnwald-Giemsa srain x 1200

Fig. 206 Marrow film Plasma cell m yeloma T he marrow is heavily infiltrated with plasmablasts indicating the acute proliferative nature of this type of the disease. May-Gnlnwald-Gicmsa stain x I 200


Fig. 207 M arrow film Plasm a cell m yeloma This illustrates a proplasma cell (top) and mature plasma cells (lower part of the field). The background staining is due to the high level of circulating immunoglobulin. May-Gnlnwald-Giemsa stain x 1200

Fig. 208 M arrow film Plasm a cell m yelom a There is a complete absence of any white cell type other than plasma cells. The eccentric position of the nucleus is well seen in these myeloma (plasma) cells which show considerable variation in size. Note the binucleate forms. Leishman stain x 600


Fig. 209 Marrow film Plasma cell m yeloma l .efl: A binucleate plasma cell is present, also a plasma cell in metaphase stage of mitosis. Leis/mum sraut x 600 Right: This shows a giant plasma cell with five nuclei; compare this cell for size with the normal sized plasma cell in contact with it at bottom right. Leishma11 stai11 x 1200


Fig. 210 Marrow film Plasma cell myeloma This illustration shows several immature plasma cells in which nucleoli can be seen; they have coarse cytoplasmic granules which are commonly seen in this condition. The mature plasma cells, which predominate, show clumping of the nuclear chromatin and several of these cells also exhibit granules. Two binucleate fo rms are present. Leishma11 stai11 x 1200

l


Fig. 211 Bone marrow Plasma cell myeloma In this touch preparation plasma cells vary considerably in size and shape, but are readily recognisable by the nuclear structure, its eccentric position and pale staining paranuclear region. Occasional b inucleated cells are seen. Thionine stain x 1200

Fig. 212 Femoral marrow Plasma cell m yeloma T his marrow consists almost entirely of cells of one type, identifiable in the high-power field as p lasma cells. Haemalum & Eosin x 200, x 600


Fig. 213 Bone marrow Plasma cell myeloma Three views of the same field in which amyloid has been fo rmed within a deposit of the tumour. T his is confirmed in the Congo Red preparation (centre) when this is examined under polarised light the amyloid displays green birifringence (r ight). Haemalum & Eosin, Congo Red, Congo Red polarised, x 250

I


•

Fig. 214 Blood film Plasma cell leukaemia The majority of cells in this blood film are plasma cells. This occurs in the end stage of plasma cell myeloma, plasma cells appearing in the peripheral blood. May-Griinwald-Giemsa stain x 1200

Fig. 215 Blood film Plasma cell leukaemia This composite illustration shows several plasma cells, and also intense rouleaux formation and agglutination of the red blood cells. The patient exhibited signs and symptoms suggestive of leukaemia, and plasma cells were repeatedly seen in blood films, as was also a moderate leucocytosis and signs of anaemia. Leishman stain x 1200


F ig. 216 M a r row film Plasm a cell m yeloma This illustration shows marked variation in the size of the plasma cells. The nuclei exhibit indentation and lobulation similar to that seen in Rieder cells in acute leukaemia ( Fig. 106). May-Gnlnwald-Giemsa stain x 1200

Fig. 21 7 Marrow film Plasm a cell myeloma These cells illustrate two of the malformations which are found in plasma cells in myeloma. The cytOplasm exhibits some vacuolisation and many fus iform bodies similar to Auer bodies. May -Grllnwald-Giemsa stain X /200

..


F ig. 218 Marrow Plasm a cell abnorm alities The illustration at top left shows a large binucleate plasma cell, and also part of a smalle r cell wi th a single nucleus. Both of these cells contain many large azurophilic granules which are frequently referred to as SnapperSchneid inclusion bodies. This and the subsequent three illustrations which show b inucleate plasma cells with peculiar mottling of the cytoplasm and what appears to be basophilic granulation are all from a case of plasma cell myeloma. Leishma11 stai11 x 1200

F ig. 219 Ma r row Plasm a cell abnorma lities rrom left to righ t: a cell in the metaphase stage of mi tosis wh ich exhibits azurophil granulation of the cytoplasm; a necrobiotic plasma cell; a binucleate cell in which cytoplasmic vacuoles are beginning to appear; a typical Mott cell and a cell with marked reticulation of the cytoplasm, in both of which the nuclei are pyknotic. (Mott cells are plasma cells which exhibit large clear globules within the cytoplasm .) Leishma11 staill x 1200


Fig. 220 Marrow film Plasm a cell m yelom a At this low power magnification extremely large plasma cells a re noted. These cells are extraordinari ly large when compared with the megakaryocyte (lower right). May-Griinwald-Giemsa stain x 300

Fig. 221 Bone m ar row P ost cytotoxic ther apy Lej1.· At low magnification -a very striking gelatinous change in the marrow is noted with an increase in the proportion of fat cells. Haemalum & Eosin x 30 Right: At higher magnification this change Is even more striking, with small islets of hacmopoietic cells between the fat spaces. This specimen was taken from a patient who had received long- term chemotherapy for multiple myeloma. Haema/um & Eosin x 120


Fig. 222 P lasm a cell Note the eccentric nucleus with peripheral chromatin clumping. There are some mitochondria present, but the main cytoplasmic feature is the tight layering of rough endoplasmic reticulum in a concentric fashion. Some small vacuoles are present. The two rod- like structures to the left of the nucleus are azurophil crystals. Glutaraldehyde, uranyl acetate, lead citrate x 14 000


Fig. 223 Blood film Lcuco-erythroblastic reaction The erythrocytes exhibit anisocytosis and poikilocytosis. Nucleated red cells are also present. The total white cell count is elevated with a shift to the left, myelocytcs, metamyclocytes and a myeloblast arc seen. M ay-GnlllwaldGiemsa stain x 600, x 1200

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1


Fig. 224 Blood film Leuco-erythroblastic anaemia This composite illustration depicts the immature myeloid cells found in the peripheral blood in leucoerythroblastic anaemia. The term leuco-ery throblastic a11aemia describes the abnormality seen in the blood resulting from infiltration of the bone marrow by foreign or abnormal tissue. This anaem ia is characterised by the occurrence of immature myeloid cells, and also nucleated red cells as shown in G . This example is from a case of myelofibrosis. May-Gnlmvald-Giemsa stain x 1200

Fig. 225 Rib Myelosclerosis T he bone trabeculae are markedly increased in size and number. The haemopoietic tissue, though reduced in amount, is of normal appearance. Haemalum & l!osi11 x 40

170 ATLAS OF HAEMAT OLOGY

Fig. 226 Trephine needle biopsy Bone Acute m yelofibrosis The amount of haemopoietic tissues is reduced (upper), shows increased stainable reticulin fib res (centre), and an increase in atypical megakaryocytes (lower). Haemalum & Eosin x 40, x 450, Gordon & Sweec, cow11erscained Neucra/ Red x 40


Fig. 227 Trephine Needle Biops y Bone M yelofibrosis At an intermittent stage in the disease reticulin stained fibres are much increased with atrophy of haemopoietic tissue. Haemalum & Eosin x 40, Gordon & S weet, coumerscained Neutral Red x 40

Fig. 228 Vertebra l m a rrow Myelofibrosis In this advanced example, the bone trabeculae are atrophic and the haemopoietic tissue has been completely replaced by rather loose fibrous tissue. Haemalrtm & Eosin x 40

..,


Fig. 229 Spleen Myelofibrosis Sinusoids are distended; the only identifiable haemopoietic cells are megakaryocytes. Haemahm1 & Eosin x 50, X 250

Fig. 230 Liver Myelofibrosis There is diffuse infiltration of the sinusoids by cells of many types, including a giant cell (left). Haemalwn & Eosin x 120


Fig. 231 Liver Myelofibrosis High-power illustration of pan of the field in Fig. 210, showing the haemopoietic nature of the cells. The giant cell is a megakaryocyte and many normoblasts can be recognised ; it is difficult to determine the precise nature of the other cell types. Haemalum & Eosin x 450

6. The megakaryocyte series


Fig. 232 Megakaryoblasts Left: The upper example is a typical megakaryoblast. Note the large nucleus with scanty indefinite chromatin, and also that as in many cells of this type nucleoli cannot be resolved. T he cytoplasm is scanty and deeply basophilic. The lower cell is developing to the promegak'aryocyte stage, its nucleus is small in comparison to the cytoplasm, the chromatin structure shows a more definite pattern and remnants of several nucleol i can be seen. The cytoplasm is less basophil ic than in the previous cell. Leishma11 stai11 x 1200 Right: Both cells are at the same stages of development as those at the left; each have three nuclei due to division by mitosis without corresponding division of the cytoplasm. This is a common finding and cells with two, three or four nuclei are seen more often than megakaryoblasts with a single nucleus. Leishma11 stai11 x 1200

THE MEGAKARYOCYTE SER I ES 177

Fig. 233 Marrow fi lm Megakaryoblasts The megakaryoblast may have several nuclei. Examples are shown here with two, three and four nuclei, a·ll of which exhibit numerous definite nucleoli. T hese arc especially well seen in the binucleate cell at bottom left. Leishman stain x 1200


Fig. 234 M arrow fi lm Megakaryobla sts Left: Note the coarse chromatin network of the nucleus and the basophi lic cytoplasm. While it is not possible to state definitely that nucleoli can be seen, several pale blue areas of irregular size are present and these may be nucleoli. This cell is in the early prophase stage of mitosis. May-Griinwald-Giemsa stain x 1200 Right: This cell is in the metaphase stage of mitosis; the cytoplasm is losing its basophilic properities. MayGriillwald-Giemsa stain x 1200

THE MEGAKARYOCYTE SERIES 179

Fig. 235 Marrow film Megakaryocytes Both of the cells shown arc much smaller than normal granular megakaryocytcs. This is often the case in conditions where there is a marked increase in the number of cells of this type. For size, compare with Figures 237 and 238. Leishman stain x I 200

Fig. 236 Marrow film Atypical Megakaryocytes L eft: Promegakaryocyte (basoph ilic megakaryocyte). Note the numerous tiny vacuoles in the cytoplasm of this ce ll. Leishman stain x I 200 Right: Promegakaryocyte. T h is cell is developing towards the granular megakaryocyte b ut the cytoplasm has not completely lost its basophi lic p roperties . The cytoplasm contains rosette-shaped vacuoles. The changes present in these two illustrations are usually seen in cases of ch ronic leukaemia and aplastic anaemia. L eishman swilt x I 200


Fig. 237 Marrow film Megakaryocyte This granular megakaryocyte gives the impression that it might be on the point of ingesting a neutrophil leucocyte, the elongated tag of cytoplasm being a pseudopodium. Leishman stain x 1200

Fig. 238 Marrow film Megakaryocytcs Left: This illustration shows a basophilic megakaryocyte which has ingested·a neutrophil polymorphonuclear leucocyte. Leishman stain x 1200 Right: A granular megakaryocyte has ingested a neutrophil leucocyte. Leishman stain x 1200 (Note that the ingested leucocyte in both illustrations is in the same plane of focus as the cytoplasm of the megakaryocyte. Had these cells been ly ing under or over the cytoplasm, they would not have been in the same focal plane at this high magnification. )

T HE MEGAKARYOCYTE SERieS 181

Fig. 239 Marrow film Megakaryocyte This illustration shows a granular megakaryocyte with nuclear h ypersegmentation . From a case of pernicious anaemia. M ay-Gnlnwald-Giemsa stain x 1200

Fig. 240 Marrow film Idiopathic thrombocythaemia Left : In this low-power illustration, megakaryocytcs, clumps of platelets and fragments of megakaryocyte cytoplasm can be seen. May-Griinwald-Giemsa stain x 400 Right: This shows well-marked clumping of platelets. M ay-Griinwald-Giemsa stain x 1200


Fig. 241 Marrow film Thrombocythae mia L ej1: A gross increase in the number of megakaryocytes. May-Griinwa/d-Giemsa sea in x 200 Right: At high-power magnification large sheets of platelets are apparen t. M ay-Gnlnwald-Giemsa s1ai11 x 1200

Fig. 242 Bone biopsy Thrombocythacmia Lej1: The marrow is h yperplastic with a gross increase in the number of mcgakaryocytes, the majority of which appear normal. H aemalum & Eosin x 200 Righ1: The gross increase in the number of mcgakaryocytcs is confirmed by the positive PAS reaction which demonstrates the well marked megakaryocytic hyperplasia. Periodic Acid-Sclziff rPASJ x 200


Fig. 243 M a rrow film Atypica l m egakaryocytes Thrombocytha emia Left: Promcgakaryocyte. Note the large spongy nucleus with a suggestion of several nucleoli. May-GnlnwaldGiemsa stain x 1200 Right: Megakaryocyte con taining numerous nuclei which d o not appear to be attached to one another . Compare th i~ wuh Figure 239, which shows hypcrscgmentation of the nucleus. M ay-Gnlnwald-Giemsa stain x 1200

Fig. 244 Blood film H aemorrhagic thrombocythaemia N umerous platelets are easily identifiable in this illustration , many of them show abnormalities of morphology; pltuclcts with irregular outlines and giant forms arc pr.:sent. The erythrocytes show hypochromia and uni~ocytosis. There is also an increase in polymorphonuclear leucocytes. May-Gnlnwald-Giemsa stain x 1200


Fig. 245 Blood film Thrornbocythaernia . Numerous platelets varying in size and shape are apparent in this illustration . May -Griinwald-Giemsa stain X /200

Fig. 246 Blood film Giant platelets This composite illustration shows platelet anisocytosis; a marked increase in the average platelet diameter is obvious. T he field to the right shows a platelet which is almost equal in size to the accompanying neutrophil leucocyte. May-Grzlnwald-Giemsa stain x 1200


Fig. 247 Blood film Giant platelets Platelet anisocytosis is present in this illustration, as are giant platelets, top left and bottom right-the marked increase in platelet diameter is obvious when compared with the diameter of the red cells and neutrophil polymorphs. May-Gnlnwald-Giemsa stain x 1200

Fig. 248 Blood film Megakaryocyte fragments In this illustration the lightly stained megakaryocyte fragments are obvious. An atypical myeloblast, neutrophil polymorph, and nucleated red b lood cell are present in this field. This blood sample was from a patient with t~:rminal myelofibrosis. May -Gnlnwald-Giemsa stain x 1200

186 ATLAS OF HAEMAT OLOGY

F ig. 249 Blood film Thrombocythaemia This illustration is from a specimen of b lood from a patient with th rombocythaemia associated with splenic hypofunction . An isocytosis, ta rget cells and schistocytes are all present. Note also the numerous pla te lets wh ich show co nsiderable variation in size. M ay-Gnlnwald-Giemsa stain x 1200

Fig. 250 Blood film Pla t e let sa te llitis m in thro mbocythaemia T his composite ill ustration ind icates the polymorphonuclear leucocytosis wh ich is often associated with thrombocythaem ia. The apparent satcll itism of platelets to the neutrophil lcucocytes is seen in blood preparations made from a specimen which has stood for some time prior to the fi lm being spread. This phenomenon is also seen in thicker pan s of the preparation, especiall y at the margins of the film. May -Gnlnwald-Gw nsa stain x 1200

ems

1200

--.. __ ,...

T HE MEGAKARYOCYTE SERIES 187

Fig. 251 Blood film Platelet aggregates Two areas of platelet aggregates a re evident. Note the variation in size of the platelets. Platelets clump readily and may be seen in blood films as aggregates. May -Grrlnwald-Giemsa stain x 1200

Fig. 252 Marrow film Idiopathic thrombocytopenia In this condition there is a marked increase in the number of mcgakaryocytes which are non-platelet producing. Many young forms of these cells arc usually present. The illustration is a typical example of the low-power microscopic appearance in this condition. Leishman stain x 120


Fig. 253 Marrow film Idiopathic thrombocytopenia In this condition megakaryocytes appear in increased numbers. No platelet budding and a tendency towards immaturity with some lack of granularity of the megakaryocytes is evident. May -Griinwald-Giemsa stain x 400

Fig. 254 Marrow film Idiopathic thrombocytopenia No platelet budding is evident. The megakaryocyte lower righ t exhibits nuclear hypersegmentation and the megakaryocyte top left exhibits fine vacuolation of the cytoplasm. May-Gnlnwald-Giemsa stain x 500

• T l·-IE MEGAKARYOCYTE SERIES 189

F ig. 255 B one biopsy Megakaryocyt ic hyperplasia Left : At low magnification, it is evident that there is a well marked increase in the number of megakaryocytes. Haemalum & Eosin x 100 Right: High magnification confi rms the megakaryocytic hyperplasia. Most of these cells do not exhibit any abnormal features. Haemalum & Eosin x 350

Fig. 256 Spleen Idiopa thic thrombocytopenia Left: This field shows the characteristic development of germinal centres in lymphoid follicles which, although of normal size, are increased in number. H aemalwn & Eosin x 40 Right: This is a high-power view showing increased numbers of neutrophil and eosinophilleucocytes in the splenic pulp. A megakaryocyte can be seen in a sinusoid at upper left. Haemalwn & Eosin x 450


Fig. 257 Sternal marrow section Megakaryoblast leukaemia-M7 There is a great increase in the number of immature megakaryocytcs which, even at this low magnification, show much variation in morphology. H aemalum & Eosin x 120

Fig. 258 Sternal marrow section Megakaryoblast leukaemia - M 7 This is a high-power illustration from the same section as Figure 2'57 . Note the high nucleo-c~ .~>plasmic ratio in several of the megakaryocytes, and also the abnormal lobulation of their nuclei. Haemalum & l.:'osin x 450


F ig. 259 Budding megaka r yocyt e This megakaryocyte, surrounded by erthrocytes, is in the process of producing platelets. Glutaraldehyde, ura11yl acetate, lead citrate x 6720

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190 ATLAS OF HAEMATOI.OGY _.; rrt

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Fig. 260 Platelet This platelet has been sectioned in its largest diameter. The marginal bundle of microtubules is seen almost in its entirety. The open canalicular system is seen clearly and secretory granules are present. Close to the marginal bundles there are small collections of cytoplasmic granules; these may be either glycogen granules or granules containing platelet phospholipid. In the centre of the platelet there is a vacuole containing several membranous structures. Glutaraldehyde, ura11y l acetate, lead citrate x 31 200

7. Phase contrast microscopy

This system enables the observer to study Jiving cells and reveals detail in objects of little contrast. Such intra-cellular components as nuclear chromatin, chromosomes, nucleoli, mitochondria, the centrosome and specific cytoplasmic granulation are clearly revealed free from the artefacts which may be produced during fixation and staining. Cell motility can also be studied with ease.

Although the phase contrast microscope has wide application in the study of normal and leukaemic leucocytes in the Jive state, it has not, as yet, revealed any characteristic abnormality or distinctive features in leukaemic cells. There is no doubt, however, that this system is the greatest advance in microscopy since the electron microscope.

Figures 261 to 280 are examples of leucocytes photographed under phase contrast conditions, and show detail which would not have been discernible under bright field conditions or in stained preparations. Good examples of this can be seen by comparing Figures 276 to 278 with Figure 153, all of which were prepared from the same specimen of blood from a case of acute lymphoblastic leukaemia. Compare also Figures 271 to 273 with Figure 102, all of which are from specimens of blood in the same case of acute myeloid leukaemia.

I

PHASE CONTRAST MICROSCOPY 195

Jill(. 261 Blood: fresh wet preparation Neutrophil (polymorphonuclear) leucocyte The extreme motility of this cell is obvious. Note the cytoplasmic processes into which the granules are flowing, the best examples being G, H , I and J. Interval time between exposures, 5 minutes. Phase comrast x 1200


Fig. 262 Blood: fresh wet prepara tion Eosinophil and neutrophil (polymorphonuclear) leucocytes T he difference in size of the two types of cytoplasmic granule is well demonstrated. Note also the greater motility of the neutrophil leucocyte and the elongated cytoplasmic p rocesses of this cell. Interval time between exposures, 3 minutes. Phase com rast x 1200


tllg. 263 Blood: fres h wet preparation Eosinophil {polymorphonuclear) leucocyte This preparation demonstrates the motility of the eosinophil which is shown thrusting its way between the nci!(hbouring red blood corpuscles. Note how the granules, which are well defined, flow into the cytoplasmic tags (pseudopodia) . In F, G , H, I and J a platelet, showing alteration in shape, can be seen. It should also be noted thor defini te nucleoli are present in the nuclear lobes of the eosinophil leucocyte. These illustrations were taken at ') minute intervals and should be compared with F igure 264, which is of the same type of cell taken at 30-second lr1rcrvnl s, in which the movement appears to be more limited. Phase comrast x 1200


F ig. 264 Blood: fresh wet preparation Eosinophil (polymorphonuclear) leucocyte Interval time between exposures, 30 seconds. Compare this series with Figure 263 when it will be noted that even at this much shorter time lapse the motility of the cell and movement of the granules is obvious. The change in shape of the cell is seen as it thrusts its way between the red b lood corpuscles. Phase comras1 x 1200

:n

PI lASE CONTRAST MICROSCOPY 199

11hf. 265 Blood: fresh wet preparation Phagocytosis of platelet by neutrophil polymorphonuclear hmcocytc Haemorrhagic thrombocythaemia I hl·~c illustrations were taken at two-minute intervals, while the temperature of the preparation was maintained at 17 C . A, a neutrophil leucocyte which appears, by the projection of its cytoplasm, to be moving towards a platelet

(11rrmu) which is lying in contact with a crenated erythrocyte. B , the leucocyte has moved closer to the platelet lltlll it b obvious, by the position of the cytoplasmic pseudopodia, that it is traversing in the direction of the pltott•lct. C, the platelet is now attached to the margin of the leucocyte. D , the platelet is lying within the cytoplasm 111 tlw leucocyte and the neutrophil granules are flowing around it. E , phagocytosis is now completed and the lrllwtyl c is moving out of the field; note the elongated cytoplasm filled with granules. Phase comrast x 2500

\A TO LOGY

Fig. 266 Blood: fresh wet preparation Phagocytosis of p latelet by neutrophil polymorphonuclear leucocytye Haemorrhagic thrombocythaemia The temperature of the preparation was maintained at 42•c while this series of illustrations was made at twominute intervals. Compare with Figure 265. A, shows two platelets (arrowed) with elongated protrusions, one of which is indicated by a white arrow, and also an elongated neutrophil leucocyte. B , shows that the p latelet (with arrow) has been engulfed and now lies within the cytoplasm of the leucocyte. C, the leucocyte is now moving towards the upper margin of the field and the engulfed platelet can be clearly seen. Note that the platelet indicated by the black arrow remains in a constant position in all three illustrations. Phase contrast x 1200

Fig. 267 Blood: fresh wet preparation P hagocytosis of platelet by neutrophil polymorphonuclear leucocyte Haemor r hagic thrombocythaem ia These illustrations should be compared with Figure 265 as in this instance the temperature was raised to 42•c, at which temperature the leucocyte has become much more rapidly motile and exhibits a more elongated appearance. A, shows a leucocyte almost in contact with a platelet, while B, taken two minutes later, shows the p latelet lying within the cytoplasm. Phase contrast x 1200

l

PHASE CONT RAST M ICROSCOPY 201

Fig. 268 Blood: fresh wet preparation Polymorphonuclear leucocytosis The increased motility of these cells with much pseudopodia formation is demonstrated. Note also the aggregation of the cells at B and C, after which they start to separate again . Interval time between exposures, 5 minutes. Phase comrasc x 1200


Fig. 269 Blood: fresh wet preparation Eosinophilia in m ycosis fungoides Four eosinophil leucocytes are seen lying in close proximity to one another. It is obvious, by the alteration in shape of these cells, that they are highly motile. Interval time between exposures, 2 minutes. Phase comrast x 1200

Fig. 270 Blood: fresh wet preparation Basophilleucocytes The basophil leucocyte seen in fields A and B has a single lobed nucleus, whereas the cell in fie ld C has a bilobed nucleus. The cell illustrated in A and B was kept under observation for 15 minutes, during which time the only apparent movement was in the disposition of the granules. Numerous small vacuoles are seen in the cytoplasm; these are probably the result of granules having been expelled. The archoplasm is obvious in the cell in fie ld C; it lies at the cleft of the bilobed nucleus. Phase comrast x 1200


Fig. 271 B lood: fresh wet preparation Acute myeloid leukaemia All the cells in this pair of sequence illustrations are leukaemic myelocytes; the cell at the upper right of the field is progressing to the metamyelocyte stage and appears to be more motile than the others. T he lower cell of the group shows, in addition to the granules, clumping of mitochondria. Note the well-resolved nucleoli and nuclear membranes in all these cells. Exposure interval between fields A and B was 5 minutes. Phase comrast x 1200


Fig. 272 Blood: fresh wet preparation Acute myeloid leukaemia The cell depicted in this series of illustrations is a myelocyte which, at 5-minute intervals between exposures, shows limited amoeboid movement. A cytoplasmic protrusion can be seen at the right of the cell, into which the granules are flowing. Phase comrast x 1200

Fig. 273 Blood: fresh wet preparation Acute myeloid leukaemia Fields A, B and C all show leukaemic myelocytes in which there is clumping of the mitochondria. The cell in field B also shows a relatively clear archoplasm. Fields D , E and F are examples of metamyelocytes from the same preparation of blood. Phase contrast x 1200

-

me


Fig . 274 Blood: fresh wet preparation Neutrophil (polymorphonuclear), leucocyte and lymphocyte T he marked contrast in motility of these two cell types is well seen, the lymphocyte exhibiting only slow amoeboid movement against the very vigorous movement of the polymorph. Interval time between exposures, 2 minutes. Phase comrasc x 1200 ·

l


Fig. 275 B lood: fresh wet preparation Lymphocyte The slow amoeboid movement of the lymphocyte is well demonstrated. Note the rather thick cytoplasmic processes producing pseudopodia formation. As these processes extend, the nucleus appears to move in the same direction. The lighter area at the indentation of the cytoplasm into the nucleus is the centrosome and the dark material below it is the mitochondria. The two platelets present also appear to exhibit extending cytoplasmic p rocesses. Interval time between exposures, I minute. Phase comrast x I 200


Fig. 276 Blood: fresh wet prepar ation Acute lymphoblastic leukaemia This illustrated sequence shows the limited amoeboid movement of several leukaemic lymphoblasts. Note the large nucleoli, the well marked nuclear membranes and the high nucleo-cytoplasmic ratios of these primitive cells. The cell in the upper right part of the fie ld shows only a faint shadow of the cytoplasmic outline, due to pressure. The mitochondria are well resolved in this cell and appear to be lying in relationship to the archoplasm; this feature is most obvious in field C . Interval time between exposures, 10 minutes. Phase comrasr x 1200

"" •• • :!< • ~ .., "'~ ? ,. ~ r ' • ' • - •


Fig. 277 Blood: fresh wet preparation Acute lymphoblastic leukaemia The cells shown in this illustrated sequence are all lymphoblasts . The cell at the upper part of the field shows active movement and when each frame is compared it will be noted that there is quite a marked alteration in the configuration of the nucleus between A and D . All the cells show well resolved nucleoli also the high nucleocytoplasmic ratio typical of this cell type. Interval time between exposures, 10 minutes. Phase co111rasr x 1200

Fig. 278 B lood: fresh wet preparation Acute lymphoblast ic leukaemia This composite illustration shows numerous leukaemic lymphoblasts which vary considerally in size; the larger, more primitive, cells have a broader rim of cytoplasm than the smaller, more mature cells. The nuclei of all these cells contain either one or two large nucleoli. Several of the cells show cytoplasmic protrusions, indicating that the cells were motile. Phase contrast x 1200

----


fig. 279 Blood: fresh wet preparation Monocyte Compare this series with Figures 261 to 264, when the diminished motility of this cell type will be obvious. The kidney-shaped nucleus shows definite nucleoli which would not be apparent in a similar cell in a stained preparation. Above the nuclear indentation is a dark granular mass which is the mitochondria. Interval time between exposures, I minute. Phase contrast x 1200

~..... - ~ ~ ~ ~- • _, • 4 • • • • • • •• ·-


Fig . 280 Blood: fresh wet preparation H a emorrhagic thrombocythaemia Three polymorphonuclear leucocytes arc seen converging on a platelet mass; one of the cells is vacuolated as if containing some foreign matter. Phase comrast x 1200

Fig. 281 Blood: fresh wet preparation Fibrin formation Long slender fibrin strands arc seen adjaccm the red cells during the process of blood coagu lation. Phase comrast x 1200

•

8. The blood parasites

I

l


0 Hepatic cycle (Exo-erythrocytic)

Fig. 282 Asexual cycle (schizogony) of th e malarial parasite Erythrocytic and hepatic (exo-erythrocytic) cycles.

- THE BLOOD PARASITES 213

ra>· . . .

2 3

10 8

·-

11 12

4

7

!'; :N ·; · ~ · · ~- . :: .. ~: . .. .

Fllo(. 283 Malaria The asexual cycle (schizogony) of Plasmodium v ivax 'f'hb is the pa rasite which causes benign tertian malaria. I . i\s n rule merozoi tes are not seen adhering to red blood corpuscles . .! . Trophozoite- early. I. T rophozoitc-'signet ring' stage.

5

·I 7. The trophozoites show increase in size, alteration in shape, protrusion of pseudopodia and depositton of ~(olden-yellow pigment. H. Schiwnt stage. !l , Segmentation of schizont, forming rosette of sixteen merozoites; note the golden-yellow pigment in the centre nl the rosette, and also the enlargement of the red blood corpuscle . The presence of Schi.iffner's dots in 3- 9 should also be noted. (Schi.iffner's dots are bright red staining particles which arc a diagnostic feature of some value. They lie within the red b lood corpuscles, but separate from the pnrn~itcs and should not be confused with pigment granules which lie within the parasite. ) I 0. Merozoites are liberated after ruptu re of the red blood corpuscle. I I . Macrogametocyte (female), see sporogony Figure 287. 12. Microgarnetocyte (male), see sporogony Figure 287. / ,,•t</11/UI// .<tail/ X / 200

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Q 4

2 3

7 , 10 9 8

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Fig. 284 Malaria The asexual cycle (schizogony) of Plasmodium malariae T his is the parasite which causes benign quartan malaria. I. As a rule merozoites are not seen adhering to red b lood corpuscles. 2, 3. Early stage of trophozoites-rings. 4-7. Developing stages of trophozoites showing amoeboid appearance, pseudopodia and abundant golden-brown pigment. T he characteristc 'band' form of trophozoite is seen in 6. 8. Schizont stage. 9. Segmentation of schizon t, forming rosette of eight merozoites; note that the red blood corpuscle is not enlarged as in the cycle of Plasmodium vivax (Fig. 283). I 0. Merozoites are liberated after rupture of the red blood corpuscle. II. MacrogametOcyte (female), see sporogony, Figure 287. 12. Microgametocyte (male), see sporogony, Figure 287. It should be noted that no Schiiffner's dots are present in this form. Leishman stain x 1200

-

n

~ed

tin

THE BLOOD PARASITES 215

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( 2 3 4

~0 Q Ot)o 10- 9 8 oo. ~ 7

~ 0 0 • • 0 "" ~. "

11 12

Jllg. 285 Malaria The asexual cycle (schizogony) of Plasmodium falciparum This is the parasite which causes estivo-autumnal malaria (malignant tertian malaria). I. Merozoite adhering to red blood corpuscle. 2. Trophozoite-early, more than one parasite may be seen in a red cell.

~ 5

6

~

}, Trophozoite and Maurer's dots in red cell. (Maurer's dots are characteristic grey-b lue staining particles, and nrc n useful diagnostic feature. These dots are not p igment granules, with which they should not be confused.) '' · Trophozoite-'signet ring' stage. 'J, 6, 7. Trophozoite increasing in size; the parasites now contain golden-brown p igment. R. Schizont stage. 9. The schizont becomes segmented and a large number of merozoites are formed. I 0. The red cell ruptures and the merozoites are liberated. · I I . Macrogametocyte (female crescent). 12. M icrogametocyte (male crescent). S1ngcs II and 12 are characteristic of Plasmodium falciparum. Note that in this type of malaria, stages I, 2, 3, 4, I I nnd 12 occur in the circulating blood, whereas stages 5-l 0 occur in the red blood corpuscles in the internal

1> rguns. l.t'ishma11 stai11 x 1200

'

2 16 ATLAS OF HAEMATOLOGY

Ookinete

Exflagellation

Oocyst development

Oocyst ruptured

Fig. 286 Sexual cy,cle (sporogony) of th e m a laria l par asite in the body and stomach of the mosquito See Figure 287.

-

nosquito

THE BLOOD PARASITES 21 7

4

8

7

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9 I I_ _____ J

rig. 287 Mala ria Sexual cycle (sporogony) of malarial parasites in stom ach a nd body of t he mosquito I . M icrogametocyte showing exflagellation, i.e. extrusion of microgametes which penetrate and fertilise the macrogametocyte 2. 3. Ookinete or zygote (ferti lised macrogametocyte). I, 2, and 3 occur in the stomach of the mosquito. 4. Ookinete as it penetrates the stomach wall. 5. Sporocyst (oocyst) as in stomach wall of mosquito. 6. Sporoblasts inside sporocyst. 7. Transformation of sporoblasts into sporozoites. 8. Oocyst rupturing and sporozoites being liberated, many will enter the salivary gland of the mosquito and be injected intO human blood when the insect bites. 9. Sporozoite attached to surface of human red blood corpuscle. l .eishma11 s1ai11 x 1200

2 18 ATLAS OF HAEMATOLOGY

Fig. 288 Blood film Benign tertia n malaria In this composite illustration three roselle forms are present, the rosette at top left being the most typical and sixteen merozoites can be counted . All other parasites present are variations of the trophozoite stage. Note that all the red blood corpuscles containing parasites of the Plasmodium vivax sho\\' well defined SchlifTner's dots. Muy Griinwald-Giemsa s1ai11 X 1200

Fig. 289 B lood film Benign tertian and m aligna nt tertian m alaria mixed infection In this illustration the thick ring form of P. vivax (centre upper right) and the thin ring form of P. falciparum (bottom left) are present. The patient had previously undergone splenectomy and H owell-Jolly bodies are present in the red cells left centre and upper right of field. The double chromatin dots of the ring forms of P. falciparum arc present in the cell, bottom cent re of field. May-Gnlnwald-Giemsa stain x 1200

-

II

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•

·-Fig. 290 Blood film Malignant tertian malar ia Left: To the left of the centre a merozoite of Plasmodium falciparum is seen attached to a red blood corpuscle. All other parasites present are trophozoites of the 'signet ring' fo rm. May-Grzinwald-Giemsa stain x 1200 Right: In this thick blood preparation from the same case, several macrogametocytes are present. May-GriinwaldGiemsa stain x 1200

Fig. 291 Liver M a laria This illustration shows two foci of exo-erythrocytic malarial parasite (Plasmodium vivax ) sporozoites developing in parenchymal cells of the liver. See Figure 282. Haemalum & Eosi11 x 1000


Fig. 292 Liver Malaria The sinusoids are distended by swollen Kupffer cells, the cytoplasm of which contain characteristic granules of malarial pigment. Haemalum & Eosin x 450

Fig. 293 Spleen Malaria The red pulp contains reticulo-endothelial ·cells with prominent nuclei. Black or dark brown granules of malarial pigment are seen in histiocytes and in erythrocytes. Haema/um & Eosin x 450


Fig. 294 Left: Marrow film Leishmaniasis The cytoplasm of the monocytes contains numerous Leishmania donovani. Right: (Leishmania) Culture preparation NNN (Nicolle, Novy and MacNeal) media This illust rates the promastigote forms with a dark staining trophonucleus and si ngl.: free fiagellum arising from the anterior end of the kinetoplast. In culture these forms tend to agglomerate in clusters or rosettes with the flagella centrally directed. Morphologically L. tropica, L. braziliensis and L. donovani are indistinguishable from each other. M ay-Griinwald-Giemsa stain x 1200

Fig. 295 Skin Leishmaniasis Left: Large clumps of histiocytes, surrounded by a dense in fi ltrate of lymphocytes and plasma cells, occupies the dermis. Haemalwn & Eosin x 130 Right : At high magnification, numerous parasites, Leishmania donovani, are seen in the cytoplasm of the enlarged histiocytes. Haemalum & J:'osi11 x 1100


l

Fig. 296 Blood film T rypa nosomiasis The parasites are between the red cells in which the flagellum and darkly staining kinetoplast are seen. The average size of the parasite is 25 ~11n long and 2 ~11n thick. The parasite Try panosoma rhodesiene is the causative agent of acute sleeping sickness and is transmitted to man by the Glossina morsitmzs (tsetse fl y) . Leishman stain x 1200

Fig. 297 Lymph node smea r Histoplasm a capsula tum Left : Free fungi. L eishman stain x 1000 R ight: A large monocyte with numerous phagocytised fungi. The nuclei and capsules of the parasites are visible. Leishman stain x I 000

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THE BLOOD PARASITES

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• Fig. 298 Blood film (thick drop preparation) Filariasis Wuchereria bancrofti The microfilaria, which is found in the blood, is covered by an outer sheath and the body cells, which do not reach to the end of the graduall y tapering tail, have darkl y staining nuclei. (The filariae, which a rc the adult parasites, are threadworms and belong to the class Nematoda. They cause elephantiasis and lymphangitis and are found in the lymphatic vessels in these conditions. The larvae, known as microfilariae, are about 300 ~tm long, 7~tm th ick and arc transmiued by the Culex and other mosyuiwcs. ) A/ay-Griimvalci-Giemsa stall/ X 300, X 900

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Fig. 299 Blood film (thick drop preparation) Filariasis Acanthocheilonema Dipetalonema

223

This type of microfiaria is shorter than Wuchereria bancroft!, has no sheath and the nuclei extend as far as the tip of the tail. May-Grzlnwald-Giemsa stain x 300

•

9. Tumours of lymphoid tissue and other neoplasms

The Rappaport classification of non-Hodgkin lymphomas used in the last edition has been superceded in the literature and in practice by the Kiel classification in Europe and by the Lukes-Collins classification in North America. It is relatively early to place a lesion in ei ther of these classifications because the major differences between them are terminological. This is shown in T able 1.

The Working Formulation produced on behalf of the US National Cancer Inst itute for 'clinical usage' is based on morphological appearances but it is difficult to compare the Formulation with ei ther the Kiel or Lukes-Collins classifications. The practical value of the Formulation has yet to be assessed: it is being used in some cancer clinics as an alternative to the Rappaport classification. The two are compared in T able 2.

The nomenclature for the various forms of H odgkin 's disease continues to be the Rye modification of the L ukes-Butler classification: lymphocytic predominant, nodular sclerosis, mixed cellularity and lymphocytic depleted. The name used in this text for the characteristic cell of the disease reflects the name of the disease itself rather than other eponyms.


T a ble 1 Pathological classifica tions of non-Hodgkin's lym p h om as.

KIEL

Low grade

Lymphocytic: CLL, B or T cell

Hairy cell leukemia Mycosis fungoides & Sezary syndrome T-zone lymphoma

Lymphoplasmacytoid

Plasmacytic

Centrocytic

*Centroblastic-centrocytic

Unclassified

High grade

Centroblastic

Lymphoblastic: 8 -lymphoblastic, Burkitt type

T -lymphoblastic, convoluted cell type Unclassified

Immunoblastic: With or without plasmablastic or plasmacytic differentiation, B or T cell type

Unclassifiable

*May be diffuse and/or follicular

LUKES & COLLINS

B or T cell, small lymphocyte (CLL)

T cell, mycosis fungoides & Sezary syndrome

T cell, immunoblastic sarcoma

B cell, plasmacytoid lymphocyte

B cell, plasmacytoma

*B cell, small or large cleaved follicle centre cell

B cell, large non-cleaved follicle centre cell

B cell, small non-cleaved Burkitt or non-Burkitt

T cell, convoluted lymphocyte

U cell

B or T cell, immunoblastic sarcoma

Many T cell tumours arc not classifiable

RAPPAPORT

L ymphocytic, well differentiated

Histiocytic

Plasmacytoma

Lymphocytic, poorly differentiated

Mixed cell

Histiocytic

Lymphocytic, poorly differentiated

Undifferentiated

T UMOURS OF LYMPHOID T ISSUE & OTHER NEOPLASMS 227

Table 2 Classification of non-Hodgkin lymphomas in clinical use.

NCl WORKING FORMULATION

Low grade

A. Small lymphocytic CLL Plasmacytoid

B. Follicular, small cleaved cell

C. Follicular, small cleaved and large cell

lmermediace grade

D. Follicular, predominamly large cell

E. Diffuse, small cleaved cell

F. Diffuse, small and large cell

G. Diffuse, small aud large cell

H igh grade

H. Large cell, immunoblastic plasmacytoid clear cell polymorphous

I. Lymphoblastic, convoluted non-convoluted

J. Small non-cleaved cell Burkitt

RAPPAPORT

Well-differentiated lymphocytic, diffuse

Poorly differentiated lymphocytic, nodular

Mixed lymphocytic/histiocytic, nodular

Histiocytic, uodular

Poorly differemiated lymphocytic, diffuse

M ixed lymphocytic/histiocytic, diffuse

H istiocytic, diffuse

Histiocytic, diffuse or undifferentiated, diffuse

Poorly differentiated lymphocytic, d iffuse

Poorly differentiated lymphocytic, diffuse


Fig. 300 Lymph node Normal Note the size of the lymphoid follicles in cortex (left) and the p resence of lighter-staining germinal centres in many of them. Reticular fibres are most numerous between the follicles (right). Note that no lymphoid tissue occurs outside the capsule. H aema/um & Eosin x 60, Gordon & Sweet coumerstained Neutral Red x 40

Fig. 301 Lymph node Normal This shows a high power illustration of a germinal centre (left) and the mantle of small lymphocytes to the right. The lightly stained areas within the germinal centre represent histiocytes which are always prominent in normal germinal centres. Haema/wn & Eosin x 250

-

l t . II

T UMOU RS OF LYMPHO ID TISSUE & OTHER NEOPLASMS 229

F ig. 302 Lymph node Follicular hyperplasia At low magnification , the increase in the size of the lymphoid follicles is seen, each of them having a mantle of mature lymphocytes. Even at this magnifica tion , histiocytes can be ident ified as the relatively clear spaces in the centres of the follicles. Haemalum & Eosin x 30

Fig. 303 Lymph node Follicular H yperplasia T he details of individual cells can be seen in this touch preparation from the same node as in Figure 302. The difference in nuclear morphology of mature lymphocytes and follicle centre cells is readily seen; both centrocytes and centroblasts can be distinguished and the occasional ce.ntroblast is in mitosis (arrow). The ovoid outline of the nucleus of the histiocyte contrasts with the much more rounded outline of the centroblasts. Many fragments of nuclear debr is are seen in the cytoplasm. M ay-Gnlnwald-Giemsa x 1200


Fig. 304 Lymph node Toxoplasmosis Left: The cytoplasm of the histiocyte contains nuclear debris and distorted ring forms, probably organisms. Haemalum & Eosi11 x 1200 Right: Clusters of eosinophilic structures, probably organisms and apparently intracellular. Haemalw11 & Eosi11 x 1200

- TUMOURS OF LYMPHOID TISSUE & OTHER NEOPLASMS 231

Fig. 305 Lymph node Malignant lymphoma, diffuse This illustration shows the pattern which occurs in any lymphomatOus process when the follicular structure has been completely obliterated by the proliferating tumour cells. I t is not possible tO make any statement about the cell type at this magnification. H aemalum & Eosin x 35

Fig. 306 Lymph node Follicular lymphoma This shows the pattern in any lymphomatous process of follicu lar type: follicles are both larger and less clearly defined than normal: a mantle layer may or may not be present. The reticular content of the follicles is not increased. Haemalum & Eosin x 40, Gordon & Sweet x 40


Fig. 307 Lymph node Malignant lymphoma, diffuse This is a lesion of lymphocytic type. The monomorphic nature of the lesion and the frequency of nuclei with ang.ular outline is well seen. Occasional centroblastic nuclei (arrow) have prominent nucleoli, and two histiocytes with plentiful cytoplasm are also seen (top right). Haemalum & Eosin x 450

Fig. 308 Skin Malignant lymphoma The deep dermis and subcutaneous fat are diffusely infiltrated with small lymphocytes, many of which have the angular nuclei of cleaved cells. H aemahmr & Eosin x 50, x 500

• TUMOURS OF LYMPHOID TISSUE & OTHER NEOPLASMS 233

Fig. 309 Iliac crest marrow Trephine specimen Malignant lymphoma, lymphocytic The haemopoietic tissue has been replaced by a mass of tumour cells. The marrow picture in this condition is indistinguishable from that of lymphocytic leukaemia (see Figs. 168 and 169) Haemalum & Eosin x 120, x 800


Fig. 310 Blood film Follicular lymphoma These cells are larger than the mature lymphocyte. The nuclear structure is coarse and in several cells there is marked clumping of chromatin; the nuclear outline is kidney-shaped or, in some cases, deeply indented . Nucleoli are not well demonstrated by this staining method (see Figs. 323 and 324). L eishman stain x 150, x 1200

Fig. 311 Lymph node Lymphoplasmaeytoid lymphoma This is a diffuse lesion in which mature lymphocytes and mature plasma cells are seen in more or less equal numbers. Haema/um & Eosin x 400

-

·li

TUMOURS OF LYMPHOID T ISSUE & OTHER NEOPLASMS 235

Fig. 312 Lymph node Malignant lymphoma, T-zone At low magnification the contrast between the compressed non-neoplastic tissue (top) and the paler staining neoplastic tissue is seen. There is also a suggestion of increased vascularity. The reticulin stain confirms this. Haemalum & Eosin x 25, Gordon & Sweet x 64

Fig. 313 Lymph node Touch preparation Maligna nt lymphoma, T -zone The convoluted T -cell nuclei produce the apparent clefts in this preparation. May-Griimvald-Giemsa stain x 1200


Fig. 314 Skin Mycosis fungoides There is diffuse involvement of superficial and mid-dermis with a polymorphic infiltrate including small lymphocytes and large cells. Haema/um & Eosin x 120

Fig. 315 Skin Mycosis fungoides Details of the cellular infiltrate: note that some of the large cells appear to have bilobed nuclei . Haemalum & Eosin x 675

TUMOURS OF LYMPHOID TISSUE & OTHER NEOPLASMS 237

Fig. 316 S kin Mycosis fungoides This thionin-stained section shows the close association between the tumour cells and epidermal epithelium, a characteristic feature of this disease. Methacrylate-embedded x 1200

Fig. 317 Skin M ycosis fungoides The true nature of the large atypical lymphoid cell is revealed-a T -cell with a characteristic convoluted nucleus. Electron micrograph x 20 000

Fig. 318 Lymph node Malignant lymphoma, follicular A narrow band of mature lymphocytes runs vertically in the centre of the field. On either side of it, there is tumour tissue showing marked pleomorphism with centrocytes and centroblasts (small and large cells of follicle centre type). Haemalum & Eosin x 400

Fig. 319 Lymph node Malignant lymphoma, centrocytic This is a touch preparation in which the great majority of tumour cells are small, often with cleaved nuclei. The presence of an occasional centroblast or large cell (arrow) is quite usual in this condition. M ay-Cnlnwald-Giemsa stain x 1200


Fig. 320 Lymph node Malignant lymphom a, centroblastic/centrocytic Most of the cells are centroblasts or centrocytes: only a few small lymphocytic nuclei can be seen. Haemalum & Eosin x 450

Fig. 321 Lymph node Centrocytic lym phoma This is a touch preparation from a similar case to Figure 320. The relative sizes of the nuclei of mature small lymphocytes (arrow) and of the tumour cells are seen. Note also the outline of the nuclei and the much looser arrangement of the chromatin in the centrocytes, a few of which are cleaved. May -Griinwald-Giemsa x 1200


Fig. 322 Bone biopsy Malignant lymphoma, lymphoblastic Left: This illustrates intensive lymphoid infiltration of the bone marrow. Haemalum & Eosin x 125 Right: At higher magnification the predominant lymphoid cells are all of the small cleaved type. Haemalum & Eosin x 600

Fig. 323 Blood film Malignant Lymphoma, lympho blastic This illustrates large abnormal lymphoid cells, some of which have a cleaved nucleus. Giant single nucleoli are also present in some of the nuclei. May-Gnlnwald-Giemsa stain x 1200


Fig. 324 Blood film Malignant lymphoma, lymphoblas tic The majority of the cells in this illustration are lymphoid cells. These show a large single nucleolus eccentrically placed and obvious as a blue coloured area around which is a dense rim of chromatin. Brilliam Cresy/ Blue, coumerstained May-Griinwald-Giemsa stain x I 200


Fig. 325 Lymph node Burkitt's lymphoma The normal architecture of the node has been completely replaced, most of the cells present are tumour cells; clear spaces, giving the 'starry sky' appearance, are occupied by histiocytes. Haemalum & Eosin x 40

Fig. 326 Lymph node Burkitt's lymphoma A: Section. High-power view of part of the lesion shown in F igure 325. The tumour cells resemble lymphoblasts. Several mitotic figures can be seen. The histiocytes contain intracytoplasmic nuclear debris. Haema/um & Eosin x 400 B: Touch preparation . The characteristic cytoplasmic vacuolation of the tumour cells is well seen. Two or three nucleoli can be seen in some of the cells. Giemsa x 1200


Fig. 327 Blood film Burkitt's lymphoma This ill ustration from the leukaemic form of the disease shows typical Burkitt's lymphoma cells . Leishmmz stai11 X /200


Fig. 328 Lymph node Immunoblastic sarcoma The node is diffusely replaced by masses of large cells. Haemalum & Eosin x 50

Fig. 329 Lymph node Immunoblastic sarcoma The tumour cells have amphophilic cytoplasm which is pyroninophilic. T he large nuclei have prominent nucleoli and are occasionally seen in mitosis. Haemalum & Eosin x 400, M ethyl-Green-Pyronin x 400


Fig. 330 Lymph node Signet r ing cell lymphoma This diffuse lesion consists of large cells with markedly vacuolated cytoplasm. The resemblance to a poorly

. differentiated mucus-secreting carcinoma is obvious but all stains for proteoglycans are negative. Haemalum & Eosin x 35, x 450

Fig. 331 Liver Malignant histiocytosis T his material shows distention of the sinusoidal spaces by large cells with fairly clear cytoplasm. The liver cells contain hemosiderin granules. Erythrophagocytosis is seen in many of the histiocytes. The nuclei of these cells vary considerably in appearance, some being very large, and occasional cells are binucleated. Haemalum & Eosin X /00, X 400


Fig. 332 Lymph node Hodgkin's disease, lymphocytic predominant The normal architecture has been lost, by masses of lymphocytes with small numbers of Hodgkin cells, one of which contains four nuclei. Also present are eosinophils and lymphocytes. Haemalum &· Eosin x 450

Fig. 333 Lymph node Hodgkin's disease, mixed cellularity Lefc: The normal architecture is lacking, due to diffuse infiltration, but no fib rosis is present in this early lesion. Haema/um & Eosin x 40 Right: Even at this low magnification, multinucleate cells arc recognisable. A focus of recent necrosis is seen in the upper part of the field. Haemalr1111 & Eosin x 120


Fig. 334 Lymph node Hodgkin's disease, mixed cellular ity This is a high-power view of Figure 333; the polymorphic nature of the cells is illustrated by the presence of Hodgkin cells, one of which contains four nuclei . Also present are eosinophils and lymphocytes. Haemalum & Eosin x 450

Fig. 335 Lymph node Hodgkin's disease, mixed cellularity In this touch preparation a Hodgkin cell with multilobulated nucleus is seen in the centre of the fie ld. There is a considerable amount of very pale staining cytoplasm. May-Griinwald-Giemsa stain x 1200


Fig. 336 Bone biop sy Hodgkin's disease A: At low-power magnification it is obvious that the haemopoietic tissue has been replaced by tumour in which several different types of cell are present. Haemalum & Eosin x 120 B: In this high-power field Hodgkin cells predominate. Haemalum & Eosin x 400 C: Three reticulum cells are surrounded by numerous eosinophils. Haemalum & Eosin x 400


Fig. 337 Lymph node Hodgkin's disease, nodular sclerosing Well-defined bands of collagenous tissue separate nodules of the lesion. Both the capsule and the interior of the node are affected. The high power view shows the mixed cellular makeup of the lesion, lymphocytes, eosinophils and large (Hodgkin) cells being present. Many of the latter are of the lacunar variety with very little cytoplasm visible; in this particular example, multinucleated Hodgkin cells were very uncommon. Haema/um & Eosin x 25, X 400

Fig. 338 Lymph node Hodgkin's disease, nodular sclerosing This is a touch preparation from the node illustrated in Figure 337. A very large, multinucleated Hodgkin cell is seen in the centre surrounded by a variety of mononuclear cells. Distorted mature lymphocytes are recognizable by their deeply staining relatively structureless nuclei. Note the very large amount of very pale staining cytoplasm in the Hodgkin cell. When compared with Figure 339, the very close relationship between the giant cells in the two varieties of the disease is obvious. May-Grii11wa/d-Giemsa stain x 1200


Fig. 339 Lymph node Hodgkin's disease, lymphocytic depleted As in Hodgkin's disease, lymphocytic predominant (Fig. 332) the normal architecture has been lost. Hodgkin cells are much more numerous than in Figure 334, but lymphocytes and eosinophils are still seen. Haemo/um & Eosin x 120, x 450

TUMOURS Of' LYMPHOID TISSUE & OTHER NEOPLASMS 25 1

Fig. 340 Lymph node Malignant Lymphoma, undifferentiated This field is representative of the microscopic appearance of the entire node. The normal tissue is completely replaced by a mass of undifferentiated lymphoid cells, with numerous mitotic figures (arrows). Haemalum & Eosin X 450

Fig. 341 Lymph node M a lignant lymphoma, undifferentiated This shows a great excess of reticular fibres, many of which surround single or small groups of cells. Gordon & Sweet, counter stained Neutral Red x I 20


Fig. 342 Marrow films Metastatic tumour cells Left: This shows large foamy cells which are probably mucus-secreting carcinoma cells from the stomach. They exhibit the clumped arrangement often seen in metastatic tumours invading the marrow. Leishman stain X 900 Right: These discrete. metastatic cells arc derived from a bronchial carcinoma. Note the multiple and giant nucleoli also the pale staining marrow. Leishman stain x 900 In both cases the haematologists' findings were confirmed at autopsy.


Fig. 343 Marrow film and section Metastatic carcinoma Left: The upper field consists entirely of tumour cells of unknown origin. At higher magnification (lower field) the cells have similar morphological appearances to those seen in Figure 346. May-Grunwald-Giemsa stain x 200, x 800 Right: Section, the upper fie ld illustrates the well marked infiltration of the marrow with tumour, cells. These are shown in great detail in the lower right field. Haemalum & Eosin x 200, x 600

252 /> H AEM A TOLOGY

-, ~

Fig. 344 Marrow film M etas t a t ic cells from a ca se o f ad enocarcinoma of prostate Left: A group of large cells with hyperchromatic nuclei and scanty cytoplasm is present in this fie ld. Right: High-power magnification reveals the high nucleo-cytoplasmic ratio of these malignant cells. The large nuclei show an obvious chromatin pattern and several contain pale blue nucleoli. A trephine specimen (Fig. 345) from this case shows the adenocarcinomatous nature of the tumour. May -Griinwald-Giemsa stain x 200, x 800


A

Fig. 345 Iliac crest marrow Trephine specim en Secondary carcinoma A: This shows the extent of the specimen obtained by this technique. The excessive number of small trabeculae towards the centre of the specimen represent newly-formed bone. Haemalum & Eosi11 x 6 B: Most of the tumour in this field shows an adenocarcinomatous pattern. Osteoblastic activity can be seen along the margins of trabeculae of bone (bottom right). Haema/um & Eosi11 x 80 C: In this field the tumour is less well differentiated. Such a portion as this is illustrated in Figure 344. Subsequent investigation disclosed that the primary tumour was in the prostate. Haemalw11 & Eosi11 x 400

. ,


Fig. 346 Marrow film Metastatic cells from a case of bronchial ca rcinoma Left: It is obvious that the cells of this large group are not of haemopoietic origin, although in some respects they resemble primitive cells of either the lymphocyte or monocyte series. May -Griinwa/d-Giemsa stain x 200 Right: At high-power magnification it becomes more obvious that these invading undifferentiated cells resemble lymphoblasts. A few of the cells at the per iphery of the group show a narrow, uneven rim of cytoplasm. May Gnlnwa/d-Giemsa Stain x 800 Autopsy examination confirmed that the primary tumour was an anaplastic bronchial carcinoma of the small cell type.

Fig. 347 M arrow aspirate section Secondary carcinoma This material, taken from the same patient as that in Figure 346, illustrates the appearances, in a section, of a small cell anaplastic bronchial carcinoma. Haema/um & Eosin x 200, x 800

T UMOURS OF LYMPHOID T ISSUE & OTHER NEOPLASMS 257

Fig. 348 Iliac crest marrow Trephine specimen Metastatic anaplastic carcinoma of unknown origin The undifferentiated nature of the tumour is apparent (left). Groups of tumour cells are seen to be surrounded by a reticulum framework (right). H aemf! lum & Eosin x 350, Gordon & Sweet, coumerstained Neutral Red x 350

Fig. 349 Iliac crest marrow T r ephine needle biopsy Metastatic tumou r cells This illustrates the ill-defi ned metastatic tumour cells in contrast to small lymphocytes and an eosinophil. Wright's stain x 1000

II

.

10. Non-haemopoietic cells, artefacts and other abnormalities

Artefacts may be encountered in any blood film or marrow smear and unless these are recognised they may lead to hazards in diagnosis. T hey can be due to improper manipulation during the spreading of the preparation and/or faulty fixation.

The large primitive cells, eosinophils, basophils and mast cells are those most likely to exhibit artefactual changes in smears of marrow because of their size or fragile nature .


Fig. 350 Osteoblasts in marrow film This illustration shows several osteoblasts surrounded by haemopoietic cells. This is due to the dislodgement of the osteoblasts during the puncturing of the bone by the needle in the collection of the marrow specimen. The basophilic cytoplasm appears to be granular due to the many ribosomes which take the stain and to the mitochondria which remain unstained. Note the eccentric position of the nuclei. Leishman stai11 x 1200

tain

1 I

NON-HAEMOPOIETIC CELLS, ARTEFACTS & OTHER ABNORMALITIES 261

Fig. 351 Blood fi lm This preparation shows a group of epithelial cells surrounded by a ring of pink staining material which has been formed by lysed red cells. The epithelial cells have prominent nuclei and their cytoplasm appears to be wrinkled and folded. Note the bacteria lying over and adjacent to these cells, which in all probability are from the mouth, having been introduced to the slide during the making of the blood film. May-Griinwald-Giemsa stain x 600


Fig. 352 Blood film Left: Crenated red blood corpuscles. These forms are artefacts produced by allowing the blood film to dry slowly. Fluid passes from the red cells into the surrounding plasma which becomes increasingly hypertonic as drying proceeds, thus allowing the red cells to shrink irregularly. Leishman stain x I 200 Right: Distorted red blood corpuscles. This artefact is due to faulty spreading of the film. Leishman stain x 1200

ON-HAEMOPO IETIC CELLS, ARTEFACTS & OTHER ABNORMALITIES 263

Fig. 353 Necrobiosis, vacuolation and nuclear hypersegmentation of the granular series A shows a myeloblast with irregular staining of both cytoplasm and nucleus which contains a giant nucleolus. B is a necrotic myeloblast, but in this instance it is not possible to differentiate between the nucleus and cytoplasm although the granules can still be resolved. C is a promyelocyte which exhibits a peculiar clumping of the nuclear chromatin, also dissolution of the cytoplasmic granules. D and E are examples of leucocytes with mitotic nuclei which are undergoing necrotic change. F shows a peculiar lumpiness of the nuclear segments which appear to be auached by fine bridges: compare this with J, where the nuclear segments are completely separated. G shows hypersegmentation; two separated nuclei can be seen and the cell is much larger than usual. H to L (necrobiosis): all show irregular staining, clumping of the nuclear chromatin and vacuolation of the cytoplasm. M ay-GnluwaldGiemsa sriau x I 200


.·

Fig. 354 Marrow film Myeloid leukaemia Many of the p rimitive cells of the myeloid series, in this illustration, reveal evidence of heavy azurophilic granulation similar to that described in Alder 's constitutional granulation anomaly. It will be noted that there is a 'haziness' in all these fields, as if the illustrations were slightly out of focus, and also that the cells have stained lighter than usual; this phenomenon is due to the specimen having been retained for some time prior to fixation and staining. The cells are, therefore, in the process of degeneration. M ay - Gru11wald-G iemsa stai11 x 1200


Fig. 355 Blood film Morphological changes in leucocytes in hyposplenism These cells of the myeloid, lymphocyte and monocyte series were all encountered in a blood film from a patient with thrombocythaemia and hyposplenism. A is a promyelocyte, the nucleus of which contains a definite nucleolus. The cytoplasm is stippled with coarse azurophil granules. B and C are both myelocytes, the cytoplasm of C being much more granu lar than that of B. D to H are all monocytes, the nuclei of which show marked lobulation. The cytoplasm of several of these cells shows fine or coarse vacuolation. I to L are all immature lymphocytes which show multilobulation of their nuclei and the example at I shows three peculiar projections at the left margin of its nucleus. May-Grunwald-Giemsa stain x 1200

OF HAEMATOLOGY

Fig. 356 Artefacts A. Fixation artefact in marrow smear: there is a loss of definition and also disruption of cytoplasm. These changes are most often encountered when the smear has been subjected to heat prior to, or during, fixation . B and C. 'Basket cells' are commonly seen in smears or films, especially where there is a high mononuclear count. I n B, the nucleus remains intact whereas in C, both the cytoplasm and the nucleus have been damaged in spreading the film. D . In this primitive cell the cytoplasm has been fragmented and at first glance the fragments simulate Leishmania donO'Uarzi. E and F. 'Smear cells': this artefact is most likely to be encountered where there is a high mononuclear count and is caused by a still greater pulling out of the cytoplasm as already seen in B. G . Denuded nuclei: in this illustration the cells are large lymphocytes. This artefact is frequently seen in blood films in lymphocytic leukaemia. May-Grrlrzwald-Giemsa stain x 1200

NON-HAEMOPO!ET!C CELLS, ARTEFACTS & OTHER ABNORMALITIES 267

Fig. 357 Artefacts A. Agglutination, rouleaux formation and air bubbles due to faulty spreading of blood film. The bubbles of air lie under the erythrocytes and give the appearance of crystals; there is a complete loss of cell borders except in one or two instances. B. In this illustration strands of cytoplasm of disrupted white cell entangle several e rythrocytes. C. There is a total loss of definition in both red and white cells in this preparation, probably due to excessive heat prior to fixation. D . Crushing of cells: this appearance is most likely to be encountered at the margins of the preparations and such areas should be avoided when screening films. E, F, G and H. Elongation and disruption of the cytoplasm of primitive cells due to undue pressure being employed in spreading smears. I. This primitive granular cell, most likely a promyelocyte, has been distorted during spreading. The cytoplasm has been compressed around the nucleus and pulled out at the lower margin giving it a vacuolated appearance. J, K and L. These are examples of disrupted eosinophils at various stages of maturation. M. This is a distorted basophil leucocyte which has been crushed and spread out, thus releasing the basophil granules and now resembling a mast cell. May -Gninwald-Giemsa scai11 x 1200


...

Fig. 358 Blood film Stain deposit as artefact The appearance of stain deposit can simulate Howell-Jolly bodies and other red cell inclusions. Careful manipulation of the fine focusing mechanism will confirm tliat the deposit is on a different focal plane from the cells. M ay-Griinwald-Giemsa stain x I 200


Fig. 359 Blood film Fibres as artefact Fibres are most often introduced by inefficient cleansing of the glass slide or cover glass. May-Gnlnwald-Giemsa stain x 800

Index

Acanthochielonema dipetalonema, 223 Acanthocytes, 18, 36 Acholuric j~undice, 39 Acute leukaemias see Leukaemia , acute Agglutination, 46, 47, 78 , 163, 267 Alder-Reilly anomaly, 120, 264 Alkaline phosphatase, leucocyte, 80 Amyloid, plasma cell myeloma, 162 Anaemia

aplastic, 10, 62, 179 haemolytic, 29, 33, 35, 68, 69

acquired, 29, 35, 68 hypochromic microcytic, 33 iron deficiency, 22, 23, 33 leucoerythroblastic, 168, 169 macrocytic, 25, 26, 30, 32, 33

pregnancy, 34 megaloblastic, 9, 18, 23, 39, 41, 48, 55-57 microangiopathic, 38 pernicious, 25, 26, 27, 30, 71 sickle cell, 19, 35, 70 sideroblastic, 64

Anaphase stage, mitosis, 50- 53, 143 Anaphylaxis, 10 Anaplastic carcinoma, 257 Anisocytosis, 18, 25, 26, 27, 30, 32, 34, 44, 45, 168 Anisopoikilocytosis, 90 Anomalies

Alder-Reilly, 120, 264 Chediak-Steinbrinck-Higashi, 79 Pelger-Huet, 80, 81 red cell, 18, 19, 25 et seq., 48, 266-289

Anulocytes (ring staining), 18, 32 Aplastic anaemia, 10, 62, 179 Archoplasm, 202, 207 Artefacts, 18, 19, 48, 266-269 Auer bodies, 94, 105, 164 Autoagglutination, 46, 47, 78 Azurophil granules, 7, 9, 11, 12, 74 et seq.

Basket cells, 266 Basophilia 8, 108 Basophilic megakaryocytes, 12, 179, 180 Basophilic reticulum (reticulocytes), 8, 39 Basophilic stippling, 18, 23, 27, 44, 48 Basophils

count, IS granules, 9, 10, 45, 79, 108, 116, 267

leucocyte, 1 0, 108 development , 10, 108 phase contrast, 202

metamyelocyte, 108 myelocyte, 15, 108 polymorphonuclear series, 10, 108 promyelocyte, 108 tissue, 10, 116

Benign quartan malaria, 214 Benign tertian malaria, 213, 218 Blast cells, 84

see also various types Blood

acanthocytosis, 18, 36 acute lymphoblastic leukaemia, 125, 126, 127

phase contrast, 207, 208 acute myeloid leukaemia , 92-96

phase contrast, 203, 204 acute myelomonocytic leukaemia , 88 acute undifferentiated leukaemia , 84 anisocytosis, 18, 25-27, 30, 32, 34, 44, 45, 168 autoagglutination, 46, 47, 78 cell development, 7, 20, 74 et seq. chronic lymphocytic leukaemia , 131, 132

large granular, 132 chronic monocytic leukaemia, 147 chronic myeloid leukaemia, 98, 101, 103, 104

terminating in acute phase, 98 cytomegalovirus infection, neonatal, 120 E-rosetting, 127 elliptocytosis, 18, 28 eosinophilia, I 07

phase contrast, 202 fibrin formation, phase contrast, 210 filariasis, 223 follicular lymphoma, 234 giant platelets, 184, 185 haemorrhagic thrombocythaemia , 183

phase contrast, 199, 200, 210 hereditary spherocytosis, 28, 39 hypochromia, 18, 27 , 30-33, 40, 45 infectious mononucleosis, 118, 119 leucocytosis, 78, 79, 186

phase contrast, 201 leucoerythroblastic reaction, 168 leukaemic reticuloendotheliosis, 137, 138, 139 lymphoma, malignant lymphoblastic, 240, 241 lymphosarcoma cells, 234 macrocytosis, 25, 26, 30, 31, 33, 34,90 malaria, 212-219

271

272 INDEX

Blood (contd) monocytes, 144-154

phase contrast, 209 monocytic leukaentia, 146 myelodysplastic syndrome, 90 myeloid leukaemoid reaction, 83 normal, 7, 10, 11, 12, 14, 15 , 24, 77 parasites, 212-223 pernicious anaentia, 25-27, 30 plasma cellleukaentia, 163 plasma cell myeloma, 156 platelet satellism, 182, 186 poikilocytosis, 18, 25-27, 30, 31 , 34, 43, 44, 45, 168 polychromasia, 26, 27, 30, 34-38, 48 polymorphonuclear leucocytosis, 78, 79, 186, 201 prolymphocytic leukaentia, 129, 130 schistocytosis, 30 spherocytosis, 28 , 29, 39 stomatocytes, 19, 34 subacute lymphocytic leukaentia, 128 systentic lupus erythematosus, 81 target cells, 19, 31, 32, 43,44 thalassaemia, 30, 43, 44 thrombocythaentia, 184, 186 trypanosontiasis, 222 viral pneumonia, lymphocytes, 119

Brilliant cresyl blue stain, 8, 39 Budding megakaryocyte, 12 Burkitt's lymphoma, 242, 243 Burkitt-type lymphoblastic leukaentia, 122, 123 Burr cells (echinocytes), 18, 36, 37, 42

Cabot rings 18, 48 Carcinoma

anaplastic, 257 secondary, bone marrow, 252-257

Cell motility, 9, 193, 195-210 Central pallor, 8, 9, 24, 31 , 32 Centrosome, 193, 195, 206 Charcot Leyden crystals, 110 Chediak-Steinbrinck-Higashi anomaly, 79 Chromatin, 7, 74, 80, 81, 193

female sex, 14, 71 Chromosomes, 193 Chronic leukaentia see Leukaemia, chronic Congo red staining, 162 Crenated red cells, 18, 262 Crystals, Charcot Leyden, 110 Cytomegalovirus infection, neonatal, 120 Cytoplasntic granules, 7, 9, 10, 23, 64, 74 et seq., 132

phase contrast, 193, 195-204

Daughter cells, 53 DiGuglielmo's disease, 59, 60, 66, 89 Differential counts

leucocyte 16 marrow, 16

Dimorphism, 33 Dissolution of nucleus, 8

Distorted red blood cells, 262, 267 Drumstick chromatin, 10, 77 Dyserythropoiesis, congenital, 67 Dyshaemopoietic states, 18

see also individual disorders Dysproteinaemia, ISS

E-rosetting, T-cell leukaemia, 127 Early cells

megaloblasts, 8-9, 50-51, 54-58 normoblasts, 7, 16, 20-22

Echinocytes (burr cells) 18, 36, 37, 42 Electron microscopy

blast cell, 99 leukaemic reticuloendotheliosis, 139 lymphocyte, 133 megakaryocyte, budding, 191 megaloblast, early, 54 monocyte, 148 neutrophil polymorph, 82 plasma cell, 167 platelets, 192 sideroblast, 65

Elliptocytosis, 18, 28 Eosinophilia, 107

phase contrast, 202 Eosinophils

count, IS granules, 9, 10, 79, 102, 107, 118

phase contrast, 196- 198, 202 leukocyte, 10, 102, 107

phase contrast, 196-198, 202 myelocyte, 10, 15, 75, 102 polymorphonuclear series, 10 promyelocyte, 22

Epithelial cells, as artefact, 261 Erythroblasts, 8, 18, 59, 60, 106 Erythrocytes, 8, 24

abnormal, 8, 18, 23, 25-48 agglutinated, 78 see also Red cells

Erythroleukaentia, 59, 60, 66 Erythrophagocytosis, 59, 106 Erythropoiesis, 7-9, 20

megaloblastic, 8-9,51 , 57,58 normoblastic, 7-8, 20

Estivo-autumnal malaria, 215, 218, 219 Extrusion, nucleus, 8, S I

Ferruginous micelles, 64, 65 Fibres, as artefact, 269 Fibrin formation, phase contrast, 210 Filariasis, 223 Flanting plasma cells, ISS Foam cells, Niemann-Pick disease, 153, !54 Follicular lymphoma, 231 , 234, 238

blast cell phase, 240, 241 malignant, 238

Fragmentation , nucleus, 8, 48 •

l

Gasser's cells, 120 Gastric mucosa

normal, 71 pernicious anaemia, 71

Gaucher cell, !53, !54 Gaucher disease, !53, !54 Germinal centres, lymphoid follicle , 189, 228 Giant cells

metamyelocytes, 76 platelets, 98, 184, 185

Giant granulation, leucocytes, 79 Glandular fever, 118, 119, 134 Golgi complex, 65 Granular leucocytes, 9, 74 ec seq. Granularmegakaryocytes, 12, 179-181 Granulation. toxic, 79 Granules

azurophil, 7, 9, 11 , 12, 74 ec seq. basophil, 9, 10, 45, 79, 108, 116, 267 cytoplasmic, 9, 10, 23, 64, 74 ec seq., 132 eosinophil, 9, 10, 79, !02, 107, 118, 196- 198,202 iron-containing, 19, 40, 64, 65, 68, 69 metachromatic, 116 neutrophil, 9, 74 ec seq., 195, 196, 199-201 Perls, 64

Granulocytic series, 9, 74 ec seq.

Haemachromatosis, 69 Haematological values, normal, 14-15 Haemocytoblasts, 7, IS Haemoglobin, 14, 24, 40

c, 45 H,45

Haemoglobinisation, 8 Haemohistioblasts, 7, 11, 15, 22 Haemolytic anaemia, 29, 33, 35, 68, 69

acquired, 29, 35, 68 thermal, 29

Haemolytic disease, newborn, 37 Haemolytic uraemic syndrome, 37 Haemorrhagic thrombocythaemia, 183, 199, 200, 210 Haemosiderin, 23, 64, 68-70 Hairy cell leukaemia, 137-140 Halo, perinuclear, 7, 12, 155 Heart , myeloid leukaemia, 111 Heinz bodies, 18, 40 Hepatocytes, 69 Hereditary spherocytosis, 28, 39 Histioblasts, 7, 10, 11, 105 Ilistiocytosis

malignant, 245 sea blue, !52

1/iscop/asma capsu/acum, 222 Hodgkin's disease, 246-250

lymphocytic depleted, 250 lymphocytic predominant, 246 mixed cellularity, 246, 247 nodular sclerosing, 249

Howell-Jolly bodies, 9, 18, 23, 25, 27, 39, 41, 48, 51, 52, 218, 268

Hyperplasia erythroid, 22, 90

follicular, 229 macronormoblastic, 22 micronormoblastic, 22 normoblastic, 21

Hypersegmentation neutrophil leucocyte, 49, 66 nucleus, 181, 263

H ypochromia, 18, 27, 30-33,40,45 Hypochromic microcytic anaemia, 33 Hypoplasia, marrow, 62 H yposplenism, 265

thrombocythaemia, 186

INDEX 273

Idiopathic thrombocythaemia, 181 Idiopathic thrombocytopenia, 187, 188, 189 Immunoblastic sarcoma, 244 Immunoglobulin, 158 Intermediate cells

megaloblast, 8, 26, S0-52, 56-58 normoblast, 7-8, 16, 20- 22

Iron deficiency 22, 23, 33

Juvenile neutrophil leucocytes, 10, 21, 74 ec seq.

Kupffer cells, 69, 70, 220

Large lymphocytes, 11, 117, 118, 132 Late cells

megaloblasts, 8, 50, 51, 52, SS-57 normoblasts, 8, 16, 20, 22, 28

LE cells, 81 Lead poisoning, basophilic stippling, 23 , 44, 48 Leishmania donovani, 221 Leishmaniasis, 221 Leptocytes, 18 Leucocytes

alkaline phosphatase, 80 basophil, 10, 16, 108 count, 14-15 eosinophil, 10, 102, 107, 196-198,202 granular , 9, 74 ec seq. morphological changes, 265 neutrophil, 9, 10, 47, 49, 74 ec seq., 195, 196, 199-

201 Leucocytosis, 78, 79, 186

phase contrast, 20 I with toxic granulation, 79

Leucoerythroblastic anaemia, 168, 169 Leucoerythroblastic reaction, 168 Leucopoiesis, 9 Leukaemia

hairy cell, 137-140 mast cell, 116 megakaryoblastic, 85, !90 monocytic, 145-152

.~ .I I

I

II

~ I

I

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i I

I

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274 INDEX

Leukaemia (coned) myeloid, 85- 106, 203, 204, 264 myelomonocytic, 88, 105, 106 plasma cell, 163 prolymphocytic, 129, 130 promyelocytic, 97 Rieder cells, 95, 145

Leukaemia, acute classification, 85 lymphoblastic, 85, 122- 127, 136

classification, 85, 122 phase contrast 207, 208

monoblastic, 89 monocytic, 147 myeloid , 85, 87-89, 91-97, 98, Ill, 113, 114

phase contrast;203, 204 myelomonocytic, 88, 105, 106 undifferentiated, 84

Leukaemia, chronic granulocytic, II 5 lymphocytic, 130-135, 266 myeloid , 100, 101, 103, 108-1 10, 113

blast cell transformed, 98 transforming (accelerated), 104

Leukaemic reticulendotheliosis, 137- 140 Leukaemoid reaction, 83 Liver

acute lymphoblastic leukaemia, 136 chronic myeloid leukaemia , 11 3 haemochromatosis, 69 haemolytic anaemia, 69 leukaemic reticuloendotheliosis, 140 malaria, 219, 220 malignant histiocytosis, 245 monocytic leukaemia, ISO myelofibrosis, 172, 173 normal, 112 sickle cell anaemia , 70 transfusion siderosis, 70

Lung, monocytic leukaemia, lSI Lupus erythematosus, systemic, 81 Lymph nodes

Burkitt's lymphoma, 242 chronic granulocytic leukaemia, II 5 follicular hyperplasia, 229 follicular lymphoma, 231 glandular fever, 134 histoplasmosis, 222 Hodgkin's disease, 246, 247, 249, 250

lymphocyte depleted, 250 lymphocyte predominant , 246 mixed cellularity, 246, 247 nodular sclerosing, 249

immunoblastic sarcoma, 244 lymphocytic leukaemia, 170 lymphoplastoid lymphoma, 234 malignant lymphoma, 231,232,235,238,239,240,

251 myeloid metaplasia, 112 normal, 228 signet ring cell lymphoma, 245 toxoplasmosis, 230

Lymphoblastic leukaemia , acute, 122-7, 136, 207, 208 classification, 85, 122

Lymphoblasts, II , 59,1 17,1 18, 122-129 phase contrast, 207, 208

Lymphocytes, 7, I I , IS, 20, 21 , 117 et seq. count, IS development, 117, 118 large, I I, 11 7, 118, 132 maturation, 117, 118 phase contrast, 205, 206 small , I I, 117, 118 T-cell , 127, 136 viral pneumonia, 119

Lymphocytic leukaemia chronic, 130, 131 , 132 large granular, 132 lymph node, 135 marrow, 130, 131, 134, 135 spleen, 135

. subacute, 127, 128 Lymphocytosis, viral pneumonia, 119 Lymphoid follicles, II, 61, 68, 110, Ill , 189, 228

hyperplasia, 229 see also Follicular lymphoma

Lymphoid tissue, I I neoplasms, 225-250

Lymphoma Burkitt 's, 242, 243 follicular, 23 1, 234, 238 lymphocytic, 140 lymphoplastoid , 234 non-Hodgkin, classification, 225-227 signet ring cell , 245 see also Hodgkin's disease; Malignant lymphoma

Macrocytes, 8, 25, 26,30-32,34, 41 ,5 1 Macrocytic anaemia, 25, 26, 30, 32, 33

pregnancy, 34 Macrocytosis, 25, 26, 30, 31, 33, 34, 90 Macroglobulinaemia, Waldenstriim's, 121 Macronormoblastic hyperplasia, 22 Malaria, 212-220

asexual cycle, 212-215 benign quartan , 214 benign tertian, 213, 218 estivo-autumnal, 215, 218, 219 malignant tertian, 215,218,219 pigment, 213- 220 sexual cycle, 216-217

Malignant histiocytosis, liver , 245 Malignant lymphoma, 232

centroblastidcentrocytic, 239 centrocytic, 238, 239 diffuse, 23 1, 232 follicular , 238 lymphoblastic, 240-24 1 lymphocytic, 140, 232, 233 T-zone , 235 undifferentiated, 25 I

Malignant tertian malaria, 215, 218, 219 Marrow

acute lymphoblastic leukaemia, 122- 124

,~,w~~~-=----~------------------------------~~

acute monocytic leukaemia, 147 acute myeloid leukaemia , 86, 87, 91, 96- 98

in remission, 98 aplastic anaemia, 62 basophils, I 08 chronic lymphocytic leukaemia, 130, 131, 134, 135 chronic myeloid leukaemia, 100, 108-110 counts, differential, IS DiGuglielmo's disease, 58, 59 dysproteinaemia, ISS eosinophilic, 107 erythroleukaemia, 58, 59 erythrophagocytosis, 59 Gaucher's disease, 153 Hodgkin'~ disease, 248 hyperplasia, 21 , 22,62 idiopathic thrombocythaemia, 181 idiopathic thrombocytopenic purpura, 187, 188 iron deficiency anaemia, 22 leishmaniasis, 221 lymphocytic leukaemia, 134, 135 macronormoblastic hyperplasia, 22 malignant lymphoma, lymphocytic , 233 mast cell leukaemia, 11 6 megakaryoblastic leukaemia, 190 megakaryoblasts, 177, 178, 187, 190 megakaryocytes, 179-183, 187- 190

hyperplasia, 189 megaloblastic anaemia, 55, 57 metastatic tumour cells, 252-257 micronormoblastic hyperplasia, 22 monocytes, 141-143, 145, 147, 149 monocytic leukaemia, 147, 149 myelofibrosis, 170, 171 myeloid leukaemia, 102, 109, 264 myelomonocytic leukaemia, 88, lOS, 106 myelosclerosis, 169 neutrophil leucocyte series, 74-76 Niemann-Pick disease, 153 normal, 61, 62 normoblastic erythropoiesis, 20 normoblastic hyperplasia, 21 osteoblasts, 260 plasma cell myeloma, 156-162 polycythaemia rubra vera, 63 post-cytoxic therapy, 166 promyelocytic leukaemia, 97 sea blue histiocytosis, 152 secondary tumours, 252-257 sideroblastic anaemia, 64 thrombocythaemia, 182, 183

Mast cell, 7, 10,116 leukaemia, 116

Maturation lymphocyte, 117, 118 monocyte, 117, 118etseq., 141 neutrophil polymorponuclear leucocyte, 9, 74 plasma cell, 11 , 117, 15 5

Mature neutrophil leucocytes, 9, 10, 74 et seq. Maurer's dots, 215 Mean corpuscular haemoglobin concentration, 14 Mean corpuscular volume, 14 Megakaryoblastic leukaemia, 85, 190 Megakaryoblasts, 8, 12 , 176, 178, 187

INDEX 275

Megakaryocytes, 12 , 15, 61, 170, 172, 173, 179-183, 187- 191

atypical , 170, 179, 181 - 183, 185 basophilic, 12 , 179, 180 budding, 12, 191 count, 15 fragments, 185 granular, 12 , 179-181 nuclear hypersegmentation, 181 series, 12

Megakaryocytic hyperplasia , 182, 189 Megaloblastic anaemia, 9, 18, 23, 39, 41 , 48, 55-57 Megaloblastic erythropoiesis, 8- 9, 51 Megaloblasts

early,8,9,50,51,54-58 intermediate, 8, 26, S0-52, 56- 58 late, 8, 50, 51, 52, 55-57 series , 8, 50- 57

Membrane, nuclear, 50, 53, 203 Metachromatic granules, 10, 116 Metachromatic staining, 10, 116 Metamyelocytes, 9-10, 15 , 22, 74, 76, 93, 101, 203,

204 basophil, 108 early form, 15 giant, 76 neutrophil , 10, 74

Metaphase, mitosis, 20, 53 Metastatic tumour cells, marrow, 252-257 Methyl violet, 18, 40 Microangiopathic haemolytic anaemia, 38 Microcytes, 18, 35 Microcytic anaemia, hypochromic, 33 Microcytosis, 44 Microfilaria, 223 Microlymphoblasts, 122 Micronormoblastic hyperplasia, 22 Microspherocytes, 18, 39 Mitochondria, 62, 193, 203, 204, 207 Mitosis, 9, 48 et seq.

anaphase, 50-53, 143 daughter cells, 53 metaphase, 20, 53 in monocytes, 142- 144 prophase, 48, 53 , 142, 143, 144 telophase, 53

Monoblasts, 11, 59, lOS, 106, 117 et seq. Monocytes, 7, 11, 15, 117, 118 ec seq., 148

abnormal, 141 - 147 count, 15 development, 117, 118 et seq., 141 maturation, 117, 11 8 et seq., 141 mitosis, 141- 144 phase contrast, 209

Monocytic leukaemia, 144, 145-147, 149- 152 Mononucleosis, infectious, 118, 119, 134 Morphological changes, leucocytes, 265 Motility, cell , 9, 193, 195-210 Mott cell, 165 Mucopolysaccharidosis, 120 Mycosis fungoides, 107 , 202, 236, 237 Myeloblasts, 7, 9, 59, 74 et seq.

count, 15 Myelocytes, 9- 10, 15,74 et seq.

·--· ,

276 INDEX

Myelocytes (comd) basophil, 10, IS, 108

count, 15 eosinophil , 10, 15, 75, 102

count, 15 neutrophil , 9, 10, 15, 74 et seq.

count, 15 phase contrast, 203, 204

Myelodysplastic syndrome, 90 Myelofibrosis, 170, 173 Myeloid-erythroid ratio, 15, 21 Myeloid leukaemia, 85, 86, 98, 100-106, 108-111, 113,

114 acute, 85, 86, 87, 91 .:97, 98, 111, 113, 114

phase contrast, 203, 204 chronic, 98, 100, 101, 103, 104, 108- 110, 113

Myeloid Jeukaemoid reaction , 83 Myeloid metaplasia, lymph node, 112 Myeloma

multiple, 41 plasma cell, 12, 156-162, 164

Myelomonocytic leukaemia, 88, 105, 106 Myelosclerosis, 169

Necrobiosis granular series, 263 red cell, 48

Neutrophils count, 15 granules, 9, 74 et seq. leucocyte, 9, 10, 47, 74 et seq.

hypersegmented, 49 non-segmented, 9, 10, 21 , 74 et seq. phase contrast, 195, 196, 199-201 series, 9, 10, 74 et seq.

myelocyte, 9, 10, 15, 74 et seq. polymorph, 15, 74 el seq., 82

maturation, 9, 74 phase contrast, 195, 196, 199-201

segmented, 9, 10, 49, 74 et seq. Niemann-Pick disease, 153 Non-segmented neutrophilleucocytes, 9, 10, 21 , 74 et

seq. Normoblastic erythropoiesis, 7-8, 20 Normoblastic hyperplasia, 21 Normoblastosis, 120 Normoblasts, 7, 20-22, 173

count, 15 early, 7, 15, 20-22 intermediate, 7, 8, 15, 20-22, 25 late, 8, 15, 22, 25, 26, 28, 48, 59, 60, 61

Nucleoli, 7, 9, 50, 51, 74 et seq. giant, 240, 241, 252 phase contrast, 203, 204, 207, 208

Nucleus chromatin, 193 envelope, SO, 53, 203 extrusion, 51 hypersegmentation, 181, 263 membrane, 50, 53, 203

remnants, 18, 48 see also Howell-Jolly bodies

Osteoblasts, 260

Packed cell volume, 14 Pallor, central, 8, 19, 24, 31, 32 Paneth cells, 71 Pappenheimer bodies, 19,40 Paramyeloblasts, 92 Parapromyelocytes, 92 Parasites

filarial, 223 histoplasma, 222 ieishmania, 221 plasmodia, 212-220 trypanosoma, 222

Pelger-Huet's anomaly, 80, 81 Perinuclear halo, 7, 12, ISS Periodic acid-Schiff, 126, 130, 182 Perls granules, 64 Pernicious anaemia, 25-27, 30, 71 Peroxidase reaction, I 02 Phagocytosis, 9, 59, 199, 200 Phase contrast microscopy, 193, 195-210 Phosphatase, alkaline, 80 Pincered cells, 18, 33 Plasma cells, 7, 11, 12, 15,117,121,155-167

abnormalities, 164, 165 count, IS development, 11, 117, ISS flaming, 155 leukaemia, 163 maturation, 11 , 117, 155 myeloma, 9, 156- 162, 164 series, 11, 12, 117, 155-167

Plasmablasts, 11 , 117, 155-157 Plasmodiumfalciparum, 215, 218 Plasmodium malariae, 214 Plasmodium vivax, 213, 218, 219 Platelets, 12, 15, 98, 181-187, 192, 199,200,206,2 10

aggregates, 187 count, 15 formation, 12 giant, 98, 184, 185 satellitism, 182, 186

Poikilocytosis, 18, 25-27, 30, 31, 34, 43-45, 168 Poisoning, lead, basophilic stippling, 23, 44, 48 Polychromasia, 18, 23 , 26, 27, 30, 34-38, 48 Polycythaemia rubra vera, 63, 80 Polymorphic nuclei, 9, 74 et seq. Polymorphonuclear leucocytes, 9, 15, 74 et seq.

agglutination, 78 Polymorphonuclear leucocytosis, 78, 79, 186, 201

thrombocythaemia, 186 toxic granulation, 79

Polymorphs, 9, 15, 71 eosinophil, I 5

I

neutrophil, 15, 75, 82 non-segmented, 9, 10, 21, 74 el seq. segmented, 9, 10, 49, 74 ez seq.

Pregnancy, macrocytic anaemia, 34 Prolymphocytes, 11, 15, 52, 57, 117, 118, 127 Prolymphocytic leukaemia, 129, 130 Promegakaryocytes, 12, 176, 179, 180, 183 Promegaloblasts, 8, 9, 57 Promonocytes, 11, 117, 141-147 Promyelocytes, 9, 15, 22, 74 ez seq., 90, 93

basophil, 108 count, IS eosinophil, 22

Promyelocytic leukaemia, 97 Pronormoblasts, 7, 15, 20, 21 Prophase stage, mitosis, 48, 53, 143, 144 Proplasma cell, 11 - 12, 117, !55, 158 Prussian blue reaction, 19,68-69 Pseudopodia, !95-197, 199,200,206 Purpura, idiopathic thrombocytopenic, 187, 188, 189 Pyknocytes, 18

Red cells agglutination, 46, 47, 78, 163, 267 anomalies/artefacts, 18, 19, 25 ez seq ., 48, 266-289 distortion , 262, 267 values, 14 see also various r.ypes

Remnants, nuclear, 18, 48 Reticulocytes, 8, 14, 39, 45 Reticuloendothelial system, 7 Reticulum

basophilic (reticulocytes), 8, 14, 39, 45 cells, 248, 249

Ribonucleic acid , 5 Rieder cells, 95, 145, 164 Ring staining, 18, 32 Ringed sideroblasts, 64, 65 Romanowsky methods, 8 Rouleaux formation, 41, 163, 210, 251, 267 Russell bodies, 71

Sarcoma, immunoblastic, 245 Satellitism, platelet, 182, 186 Schistocytes, 18, 19, 27, 30,186 Schistocytosis, 30 Schiiffner's dots, 213, 218 Sea blue histiocytosis, !52 Secondary carcinoma, marrow, 252- 257 Segmented neutrophilleucocytes, 9, 10, 49, 74 el seq. Sex chromatin, female, 14, 77 Sickle cell anaemia, 19, 35, 70 Sickle cells, 19, 35, 70 Sideroblastic anaemia, 64 Sideroblasts, 64, 65 Siderocytes, 19, 40 Siderosis, transfusion, 70

INDEX 277

Skin leishmaniasis, 221 malignant lymphocytic lymphoma, 232 monocytic leukaemia, !52 mycosis fungoides, 236, 237 myeloid leukaemia, 114

Small lymphocytes, 11, 117, 118 Smear cells, 266 Snapper-Schneid inclusion bodies, 165 Spherocytosis, 19, 29

hereditary, 28, 39 Spleen

acquired haemolytic anaemia, 68 acute myeloid leukaemia, Ill erythroleukaemia, 66 Gaucher's disease, 154 idiopathic thrombocytopenic purpura, 189 leukaemic reticuloendotheliosis, 138, 140 lymphocytic leukaemia, 135 malaria, 260 myelofibrosis, 172 myeloid leukaemia, I l l normal, 61, 110 polycythaemia rubra vera, 63

Splenectomy, 18, 39, 41, 218 Stab (non-segmented) granular leucocytes, 10, 15, 21,

74 ec seq. Stain deposit, as artefact, 268 Stem cells, 7, II, IS, 22 Stippling, basophilic, 18, 23, 27, 44,48 Stomatocytes, 19, 34 Subacute lymphocytic leukaemia, 127, 128 Sudan black stain, 103 Supravital staining, 8, 18 Systemic lupus erythematosus, 81

T-cells, 237 lymphoblastic leukaemia, 136

E-rosetting, 127 Target cells, 19, 31, 32, 43, 44 Telophase stage, mitosis, 53 Testes, T-celllymphoblastic leukaemia, 136 Thalassaemia, 19, 48

major, 43 minor, 30, 44

Thermal haemolytic anaemia, 29 Threadworms, 223 Thrombocythaemia, 182- 184

haemorrhagic, 183, 199, 200, 210 hyposplenism, 186 idiopathic, 181 polymorphonuclear leucocytosis, 186

Thrombocytopenia, 120 Thrombocytopenic purpura, idiopathic, 187, 188, 189 Toluidine blue stain, 10, 116 Toxic granulation, leucocytosis, 79 Toxoplasmosis, 230 Transfusion siderosis, 70 Trypanosoma rhodesimse, 222 Trypanosomiasis, 222

278 INDEX

Undifferentiated neoplasms acute leukaemia, 84 malignant lymphoma, 251

Uraemia, haemolytic syndrome, 37

Vacuolation granular series, 263 plasma cells, 165

Viral pneumonia, lymphocytes, 119

Waldenstrom's macroglobulinaemia, 121 Wuchereria bancrofti, 223

Contents

1. Introduction

2. Development of the blood cells 5

3. N ormal haematological values 13

4. The red cell series 17

5. The white cell series 73

6. The megakaryocyte series 175

7. Phase contrast microscopy 193

8. The blood parasites 211

9. Tumours of lymphoid tissue and other neoplasms 225

10. Non-haemopoietic cells, artefacts and other abnormalities 259

Index 271

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Atlas Hematologie crop