Cell Identificationwebapps.cap.org/apps/docs/committees/hematology/... · lymphocytes with occasional large granular lymphocytes. Persistent polyclonal B cell lymphocytosis has distinctive

3

Cell Identification

Case History This peripheral blood smear is from a 1-month-old male infant with a three-week history of cough and difficulty breathing. Laboratory data include: Bordetella pertussis antigen smear = positive; Bordetella pertussis culture = positive; WBC = 37.4 x 109/L; HGB = 13.6 g/dL; HCT = 39.9%; MCV = 96 fL; RDW = 16.7; Platelet = 416 x 109/L; Absolute lymphocyte count = 29.5 x 109/L. (PERIPHERAL BLOOD, WRIGHT-GIEMSA)

VP

BS

-02

Participants Identification No. % Evaluation

Teardrop cell (dacrocyte) 999 95.3 Educational

The image is of a teardrop shaped red blood cell (dacrocyte) and was correctly identified by 95.3% of participants. A teardrop shaped erythrocyte is typically normocytic in size but may be microcytic. Teardrop cells contain a single, short or long, blunted or rounded end. Unlike red blood cells with a short sharp pointed end which are artifacts of slide preparation, a true teardrop cell should taper into a blunt tip. Teardrop cells are typically associated with an abnormality of the spleen or bone marrow which causes the erythrocyte to stretch in order to continue circulating through the splenic cords or bone marrow sinuses.

4

Case History

This peripheral blood smear is from a 1-month-old male infant with a three-week history of cough and difficulty breathing. Laboratory data include: Bordetella pertussis antigen smear = positive; Bordetella pertussis culture = positive; WBC = 37.4 x 109/L; HGB = 13.6 g/dL; HCT = 39.9%; MCV = 96 fL; RDW = 16.7; Platelet = 416 x 109/L; Absolute lymphocyte count = 29.5 x 109/L. (PERIPHERAL BLOOD, WRIGHT-GIEMSA)

VP

BS

-03


Lymphocyte 1038 99.0 Educational

The image is of a lymphocyte and was correctly identified by 99.0% of participants. A lymphocyte may range in size from 7 to 15 µm and typically has a high N:C ratio. Most lymphocytes are small with round to oval nuclei; however occasional normal lymphocytes may be medium in size due to increased cytoplasm. The nuclear chromatin is diffusely dense or coarse and clumped. Nucleoli, if present, are small and inconspicuous.

5


VP

BS

-04


Basophil, any stage 1044 99.6 Educational

The image is of a basophil that was correctly identified by 99.6% of the participants. Basophils are round to oval and are 10 to 15 µm in size. Basophils characteristically contain a number of coarse, densely stained granules that vary in color from blue-black to red-purple. These granules are present throughout the cell and vary in size and shape and can obscure visualization of the nucleus.

6


VP

BS

-05


Eosinophil, any stage 1047 99.9 Educational

The image is of an eosinophil and was correctly identified by 99.9% of participants. Mature eosinophils are round to oval and are 10 to 15 µm in size. Eosinophils contain characteristic coarse, orange-red granules of uniform size which typically do not overlie the cell nucleus. The nucleus is usually segmented into two to three lobes separated by a thin filament of chromatin. The chromatin is typically dense and compact. The nuclear lobes are equal in size and exhibit the same nuclear characteristics as neutrophils.

7


VP

BS

-06


Lymphocyte, reactive (to include plasmacytoid and immunoblastic forms)

566 54.1 Educational

Lymphocyte 246 23.5 Educational Monocyte 106 10.1 Educational Lymphoma cell (malignant), includes

Hairy cell and Sezary cell 63 6.0 Educational

The image is of a lymphocyte or reactive lymphocyte and was correctly identified by 77.6% of participants. A lymphocyte may range in size from 7 to 15 µm with variable, typically high N:C ratio. The nucleus in the current cell shows an unusual deeply cleaved nucleus; however maintains the dense clumped chromatin. Normal lymphocytes may occasionally contain an indented nucleus which are more frequently seen in infants and children. This cell contains the characteristic findings of Bordetella pertussis lymphocytosis including the deeply clefted nucleus, coarse chromatin, small size and high to moderate N:C ratio.

Kathryn Rizzo, DO, PhD

Hematology and Clinical Microscopy Resource Committee

8

Discussion

Bordetella pertussis is a highly contagious bacteria which causes acute upper respiratory tract infection and the well-known epidemic disease, whooping cough (pertussis). Pertussis occurs worldwide, numbering over 48 million cases a year. Although vaccinations in the United States have decreased the incidence, pertussis infections can occur in previously vaccinated adolescents and adults and then can be transmitted to unvaccinated or partially immunized infants and children. Infection is transmitted from person-to-person by airborne transmission and typical pertussis infection is divided into three symptomatic stages. The first stage is the catarrhal stage which may last for several weeks. During this stage the person may have symptoms similar to a mild cold. The second stage is the paroxysmal stage where the patient experiences the characteristic severe coughs and “whooping” of air with the rapid inspiration of breath into the lungs. During this time, the patient develops a lymphocytosis. The last stage is the convalescent stage. Pertussis infection may be detected via culture, direct fluorescent antibody testing, serologic testing, and molecular testing by PCR methods. The lymphocytosis seen in pertussis infection usually occurs in infected infants and children and is typically in the range of 10.0 x 109/L but may reach levels of 30.0 x 109/L or higher. The lymphocytes are predominantly T cells with a normal CD4 to CD8 ratio. Additionally, there may be an increase in monocytes, neutrophils and other lymphocytes such as B cells and NK (natural killer) cells. The lymphocytosis and overall increased white blood cell count is thought to be due to a decrease in the cell membrane protein known as L-selectin. L-selectin allows for migration of leukocytes out of the blood and into peripheral tissue and is integral in lymphocyte migration to lymph nodes. The decreased amount of this protein thus causes an accumulation of lymphocytes in the blood stream. Benign Causes of Lymphocytosis

Benign causes of an absolute lymphocytosis can be subclassified into two main categories based on the morphology of the lymphocytes. The first category includes benign lymphocytosis with activated/reactive morphology (i.e. pleomorphic lymphocytosis). These lymphocytes are activated lymphocytes with varying morphology and size. The lymphocytes are typically large and have more abundant cytoplasm with radiating basophilia often seen at the periphery of the cell cytoplasm. The chromatin is typically somewhat more dispersed than a small lymphocyte. The nucleus may be round, oval, or irregular, and inconspicuous to distinct nucleoli may be seen in large immunoblasts. The main cause for this type of lymphocytosis is viral infections, many of which are due to Epstein-Barr virus (EBV) infection. (Figure 1) However other viruses may cause an infectious mononucleosis-like syndrome including cytomegalovirus (CMV), adenovirus and acute human immunodeficiency virus (HIV) infection. Additional causes of an activated/reactive appearing lymphocytosis include drug reaction, post-vaccination, chronic inflammatory disorders (e.g. autoimmune disorders), and other infectious agents. The second category includes benign lymphocytosis with a mature or non-activated/non-reactive morphology. This type of lymphocytosis is typically composed of normal sized lymphocytes with high nuclear to cytoplasmic (N/C) ratios and mature coarse chromatin. A common cause for this type of lymphocytosis is Bordetella pertussis infection in children, as seen in our current case. (Figure 2) In pertussis infection the mature appearing lymphocytes may contain the characteristic deeply cleaved nuclei.

9

Figure 1. Activated lymphocyte in EBV infection Figure 2. Bordetella pertussis lymphocyte

Additional benign causes for a non-activated lymphocytosis include transient stress lymphocytosis and less commonly, persistent polyclonal B cell lymphocytosis and acute infectious lymphocytosis. Transient (acute) stress lymphocytosis may be seen in patients with acute medical conditions including myocardial infarction (heart attacks) and trauma. Typically the lymphocytosis is mild to moderate and composed mostly of small mature lymphocytes with occasional large granular lymphocytes. Persistent polyclonal B cell lymphocytosis has distinctive clinical findings, typically occurring in asymptomatic young to middle aged women who are smokers. However there are rare reports seen in neonates and infants. These lymphocytes differ from a pertussis infection as they are predominantly of B cell lineage but share similar morphological features such as high N/C ratio, mature chromatin and nuclear clefting. Neoplastic lymphocytosis with cleaved nuclei

Mature B cell lineage leukemias/lymphomas

A number of neoplastic disorders may cause lymphocytosis with morphological features similar to our current case. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a common cause for lymphocytosis in the adult population. The cells are typically small to slightly larger than a normal lymphocyte and contain mature, coarse chromatin. (Figure 3) Occasional cases may have neoplastic lymphoid cells with cleaved, indented nuclei. A characteristic finding in circulating follicular lymphoma cells is nuclear folding, irregularity and cleaving. (Figure 4) Follicular lymphoma cells are small to slightly larger than a normal lymphocyte and contain scant to moderate cytoplasm with moderately clumped chromatin and occasional small nucleolus. Mantle cell lymphoma is another B cell lineage lymphoma composed of lymphoma cells which are small to medium in size. (Figure 5) These lymphoma cells have moderately clumped chromatin and nuclei which may be folded or cleaved.

10

Figure 3. Chronic Lymphocytic Leukemia Figure 4. Follicular Lymphoma

Figure 5. Mantle cell Lymphoma

T cell lineage lymphomas

T cell lymphomas are less common than B cell lymphomas; however they should also be considered in the differential diagnosis of a non-activated lymphocytosis with cleaved/irregular nuclei. The lymphoma cells in Sezary Syndrome are typically small with condensed chromatin and convoluted nuclei imparting a “cerebriform” appearance. A more uncommon lymphoma known as adult T cell leukemia/lymphoma contains lymphoma cells with markedly irregular, lobulated nuclear membranes. Acute lymphoblastic leukemia

An important differential to consider in our current pediatric case is acute B or T lymphoblastic leukemia. Lymphoblasts may be difficult to distinguish from normal lymphoid cells when they are small in size, contain mature appearing moderately granular chromatin, lack distinguishable nucleoli and have round to irregular nuclei. (Figure 6) However, even in these cases, occasional lymphoblasts with more typical morphology such as larger size, finer chromatin and distinct nucleoli will be seen. Thus, it is helpful to scan the slide on low power to evaluate the entire range of lymphoid morphology.

11

Figure 6: T lymphoblastic leukemia blasts Figure 7: Bordetella pertussis lymphocyte

It may be difficult to morphologically distinguish a benign lymphocyte from a lymphoma or a blast cell, thus it is helpful to take several key features into account. It is important to correlate the lymphocytosis with other CBC parameters. Does the patient also have low hemoglobin and/or platelet levels? Acute lymphoblastic leukemias typically have associated cytopenias, while pertussis patients may have a neutrophilia and a monocytosis. An important distinguishing factor is the patient’s age. The lymphomas mentioned above would be a rare finding in the pediatric population, while reactive conditions and acute lymphoblastic leukemia would be more common causes for a lymphocytosis. Correlation with patient’s clinical symptoms and serology testing will also aid in the proper identification of the lymphoid cells. In the current case the patient had a severe cough which prompted serological testing for Bordetella pertussis. (Figure 7) For patients with persistent lymphocytosis without an underlying etiology flow cytometric analysis is very useful for identifying the cell lineage (B versus T cell), as well as distinguishing a benign lymphoid cell from a blast or lymphoma cell.

REFERENCES

1. Hudnall SD, Molina CP. Marked increase in L-selectin-negative T cells in neonatal pertussis. The lymphocytosis explained? Am J Clin Pathol. 2000;114(1):35-40.

2. Hodge G, Hodge S, Markus C, Lawrence A, Han P. A marked decrease in L-selectin expression by leukocytes in infants with Bordetella pertussis infection: leucocytosis explained? Respirology. 2003;8(2):157-62.

3. Foucar K, Reichard K, Czuchlewski D. Bone Marrow Pathology. 3rd ed. Chicago, IL: ASCP Press; 2010. 4. Glassy E, ed. Color Atlas of Hematology. Northfield, IL: CAP Press; 1998. 5. Kjeldsberg C. Practical Diagnosis of Hematologic Disorders. 4th ed. Chicago, IL: ASCP Press; 2006. 6. Forbes B, Sahm D, Weissfeld A. Bailey & Scott’s Diagnostic Microbiology. 12th ed. Mosby Elsevier; 2007.

Kathryn Rizzo, DO, PhD Hematology and Clinical Microscopy Committee

13

Cell Identification

Case History This peripheral blood smear is from a 25-year-old male with a one-week history of sudden bruising of the lower and upper extremity; bleeding per mouth, nose, and rectum; fevers; and headaches. Laboratory data include: WBC = 108 x 109/L; HGB = 11.7 g/dL; HCT = 33.2%; MCV = 89.3 fL; RDW = 13.9; Platelet = 11 x 109/L; FISH for PML/RAR fusion: Positive. (PERIPHERAL BLOOD, WRIGHT-GIEMSA)

VP

BS

-08


Neutrophil 966 92.3 Educational Neutrophil, toxic 60 5.7 Educational

The image represents a segmented neutrophil, accurately identified by 92.3% of participants. Segmented neutrophils have multi-lobated nuclei connected by a thin chromatin filament. The identified cell has three distinct nuclear lobes. The cytoplasm is pale pink and contains fine lilac (secondary or specific) granules. The clearly segmented nucleus and color of the granules and cytoplasm help distinguish it from other white blood cells.

14

Case History

This peripheral blood smear is from a 25-year-old male with a one-week history of sudden bruising of the lower and upper extremity; bleeding per mouth, nose, and rectum; fevers; and headaches. Laboratory data include: WBC = 108 x 109/L; HGB = 11.7 g/dL; HCT = 33.2%; MCV = 89.3 fL; RDW = 13.9; Platelet = 11 x 109/L; FISH for PML/RAR fusion: Positive. (PERIPHERAL BLOOD, WRIGHT-GIEMSA)

VP

BS

-09


Platelet 1040 99.4 Educational

The image is of a platelet, correctly identified by 99.4% of participants. Platelets are usually small, anuclear fragments of megakaryocytic cytoplasm that contain small inconspicuous granules. In scanning through this blood smear, it is evident that the platelet number is decreased. Occasional platelets in the smear are larger in size than the platelet that was identified by the arrow.

15


VP

BS

-10


Neutrophil, promyelocyte abnormal with/without Auer rod(s)

343 32.9 Educational

Myeloblast with Auer rod 627 60.2 Educational Blast Cell 10 1.0 Educational

The image is of an abnormal promyelocyte with an Auer rod, a cell that can also be appropriately classified as a myeloblast with an Auer rod. This cell was correctly identified by 93.1% of participants. This promyelocyte is part of acute promyelocytic leukemia (APL). Abnormal promyelocytes are identified by their large size and bi-lobed or reniform nucleus. Scanning of this peripheral smear shows that many cells lack prominent granulation and are characteristic of the microgranular morphologic variant of APL. The promyelocyte indicated by the arrow, however, has a few dark pink (primary) granules, as well as an Auer rod. Auer rods are abnormal collections of primary granules that coalesce to form a rod-like structure. Their presence indicates a neoplastic myeloid process, usually acute myelogenous leukemia (AML). In some AMLs, some cells may have multiple Auer rods that stack upon each other. These are called faggot cells. Promyelocytes in APL are considered “blast equivalents”, similar to promonocytes, in the diagnosis of AML.

16


VP

BS

-11


Lymphocyte 984 94.2 Educational Lymphocyte, reactive 20 1.9 Educational

The image represents a lymphocyte, correctly identified by 94.2% of participants. This normal lymphocyte is slightly larger than the surrounding red cells and contains a small round nucleus with condensed chromatin. The cytoplasm is a thin rim that is slightly basophilic and lacks granules. Lymphocytes may show a range of morphologic features and some forms may be larger than the lymphocyte identified here. The larger forms often have round to slightly oval nuclei with slightly less condensed chromatin, occasional chromocenters and more abundant cytoplasm. Some lymphocytes may have a few small pink granules present in the cytoplasm.

17


VP

BS

-12


Eosinophil 1037 99.1 Educational

The image is of an eosinophil, correctly identified by 99.1% of participants. Eosinophils are round to oval cells that contain a segmented nucleus with two to three lobes connected by a thin filament of chromatin. The chromatin is dense, compact and lacks nucleoli. The cytoplasm is filled by characteristic coarse spherical red-orange refractile granules. The cell indicated by the arrow shows a small area of clear faint pink cytoplasm, a normal finding that reflects partial degranulation of the eosinophil. The characteristic orange-red granules help to differentiate eosinophils from segmented neutrophils.

Sherrie Perkins, MD and Luke R. Shier, MD Hematology and Clinical Microscopy Resource Committee

18

Acute Promyelocytic Leukemia This case represents the microgranular variant of acute promyelocytic leukemia (APL). Acute leukemias are clonal neoplasms of immature hematopoietic cells whose primary characteristics are rapid unregulated proliferation and lack of normal maturation. Acute myeloid leukemias (AML) include a special subset with specific

recurrent cytogenetic abnormalities that impact patient prognosis. APL with the translocation t(15;17) PML-RAR

is one of this subset of AML, and has a number of distinctive characteristics in terms of its biology, its clinical behavior, and in its morphology and laboratory findings. APL is particularly important to identify as its unique biologic and clinical features require that it be treated differently from the other subtypes of AML. APL comprises between 5 and 20% of all new cases of AML, and is seen predominantly in middle-aged adults. The most characteristic presentation for APL is that of severe bleeding and pancytopenia. In contrast to most acute leukemias, the peripheral blood often shows marked leukopenia. However, in some cases such as the current one, the white count can also be high due to increased numbers of neoplastic promyelocytes; this is particularly true in the microgranular variant. In blood and marrow differential counts, leukemic promyelocytes should be identified as blasts, so that their significance is clear to aid in making a diagnosis of AML. In the peripheral blood, leukemic promyelocytes can sometimes be mistaken as reactive myeloid precursors if they are not scrutinized closely. However, their morphology is often quite characteristic and easily identified in blood smears and marrow aspirates. Nuclei are reniform or bilobed, sometimes described as butterfly shaped. In the classic morphologic subtype of APL, the neoplastic cells will have cytoplasm that is densely packed with abundant azurophilic granules, which can be so heavy as to obscure nuclear detail. Auer rods, abnormal polymers of primary granules, are invariably present. Cells containing bundles of numerous Auer rods, termed “faggot cells” can be found in most cases, more often in the marrow. The term “faggot” is an old British noun meaning a bundle or cord of sticks used for kindling, which the bundles of Auer rods resemble. While neither Auer rods nor faggot cells are specific to APL, classic APL will contain an abundance of faggot cells not seen in any other form of AML. The microgranular (or hypogranular) variant of APL comprises approximately 20% of cases and is represented in the current case. While the more common hypergranular APL usually presents with pancytopenia, the microgranular variant typically presents with a high white count. These promyelocytes also have reniform or bilobed nuclei, but their granulation is so fine as to appear absent on light microscopy. Microgranular variant promyelocytes can be mistaken for monocytes due to their indented or bilobed nucleus and relatively abundant cytoplasm, but rare cells containing Auer rods, more prominent granulation and even faggot cells are usually still present upon careful examination, as in this case. Cytochemical staining for myeloperoxidase (MPO) or Sudan Black (SB) is also strongly positive in microgranular APL, as it is in the more common classic hypergranular form, and non-specific esterase (NSE) is negative or only very weak. This will distinguish microgranular APL from monocytic cells, in which MPO and SB are negative or weak, and NSE is more strongly positive. Nearly all cases of APL are associated with bleeding or ecchymosis (bruising). The bleeding diathesis of APL is in excess of what is attributable to thrombocytopenia due to bone marrow replacement alone. Rather, this is due to disseminated intravascular coagulopathy (DIC), a consumptive coagulopathy which arises from unregulated activation and clearance of coagulation factors, and is reflected in prolongation of the INR and PTT. In APL, even a minor elevation in the INR can indicate the presence of early DIC, which is confirmed by the finding of an abnormally low fibrinogen level, due to secondary fibrinolysis. In addition, the formation of microthrombi in vessels leads to consumption of platelets and disruption of red cells by shearing, causing a microangiopathic hemolytic

19

anemia. Thus, platelets are usually significantly decreased and red cells may show evidence of microangiopathic hemolysis, including fragmented red cells (schistocytes). The initiation of DIC is believed to be secondary to release of bioactive substances contained in the granules of the neoplastic promyelocytes. This has treatment implications as therapy may cause lysis of the leukemic cells and release of granules containing procoagulant activity and a marked increase in DIC. Most cases of APL have a balanced translocation between chromosomes 15 and 17, which creates a fusion

transcript linking the PML and RAR genes. The PML (promyelocytic leukemia) gene on chromosome 15 codes

for a nuclear regulatory factor named for its identification in association with APL. The RAR gene on

chromosome 17 codes for retinoic acid receptor , whose function is important in the normal maturation of

granulocytic cells. The PML-RAR fusion protein that results from the t(15;17) translocation both inhibits

differentiation of granulocytic precursors beyond the promyelocyte stage, and promotes the survival of these leukemic promyelocytes. The translocation can be identified on conventional karyotyping with G-banding, by RT-PCR for the RNA fusion transcript, and by fluorescence in-situ hybridization (FISH) using fluorescence labeled

probes for the PML and RAR genes. Identification of the translocation by RT-PCR or karyotyping and FISH is

essential to confirm the diagnosis of APL.

A minority of APL (less than 10%) have variant translocations in which the RAR gene is partnered with genes

other than PML on 15q22, including PLZF-RAR t(11;17), NPM-RAR t(5;17), NuMA-RAR t(11;17), BCOR-

RAR t(X;17), and STAT5b-RAR , del(17)(q11q12). It is important to identify cases that harbor variant

translocations as they may not respond to therapy in the same manner as cases with t(15;17). Because APL is invariably associated with mutations that disrupt the gene for the retinoic acid receptor, it was hypothesized that super-physiologic doses of retinoic acid (vitamin A) could overcome the receptor dysfunction, and this is indeed the case. All-trans retinoic acid (ATRA) induces differentiation and maturation of leukemic promyelocytes into mature neutrophils, which then no longer proliferate and undergo normal apoptosis. During this differentiation, maturing neutrophils containing Auer rods can be seen in the peripheral blood. The most important feature of the ATRA-induced promyelocyte differentiation is that the primary granules, which contain the procoagulant proteins, are lost during maturation. Thus, apoptosis of the mature cells will not lead to increased DIC. If APL is treated with standard AML therapy without or before ATRA, apoptosis of the neoplastic promyelocytes will lead to extensive DIC. In the past, many patients died from the bleeding complications, particularly brain hemorrhages, due to worsening coagulopathy with chemotherapy. The incidence of severe hemorrhage is markedly decreased by addition of ATRA to initial therapy. Treatment with ATRA alone is insufficient for cure, since patients treated in this fashion almost always relapse. Clinical trials have demonstrated that the combination of ATRA with chemotherapy is superior to either ATRA or chemotherapy alone. Because the best outcomes occur when ATRA therapy is initiated early, it is critical to identify and confirm the diagnosis of APL urgently. Whereas most other forms of AML are treated with a standard induction chemotherapy protocol, the diagnosis of APL requires that ATRA therapy be initiated as quickly as possible. All translocations

identified with APL involve the RAR gene, and almost all cases of APL with t(15;17) are sensitive to ATRA

therapy. While the majority of patients do well with standard therapy, a small proportion relapse. Recent data has demonstrated excellent responses to arsenic trioxide (ATO) in relapsed APL. In fact, because APL is so responsive to ATO, its use during induction or consolidation therapy is currently under evaluation. Amongst the rare variant translocations, only some appear responsive to ATRA. The role of ATO in these variants is at present unknown.

20

Without treatment, APL is a highly aggressive leukemia with a median survival of less than one month. With current therapies, however, APL has the highest long-term survival of all types of AML. Despite this excellent prognosis, fatalities still occur. A significant portion of the mortality in APL occurs on presentation or early in treatment, due to fatal bleeding complications such as intra-cerebral or pulmonary hemorrhage. Vigilance for DIC and bleeding complications together with appropriate supportive care provide patients with the best opportunity to survive this highly malignant but curable disease. It is essential to identify and confirm the diagnosis of APL as early as possible. In contrast to all other forms of AML, APL must receive differentiation therapy with all-trans retinoic acid (ATRA) in addition to chemotherapy. Early recognition of this unique leukemia, expedient confirmation of the diagnosis, early initiation of appropriate therapy, and vigilance for bleeding complications, will provide patients with APL the best chance for survival and long-term remission.

REFERENCES

1. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and

Lymphoid Tissues. 4th ed. IARC Press, Lyon; 2008. 2. Wang ZY, Chen Z. Acute promyelocytic leukemia: from fatal to highly curable. Blood. 2008;111(5):2505-

2515. 3. Glassy E, ed. Myeloblast/promyelocyte with Auer rod(s). Color Atlas of Hematology. Northfield, IL: CAP

Press; 1998. 4. Tallman M, Altman J. How I treat acute promyelocytic leukemia. Blood. 2009;114(25):5126-5135.

Luke R Shier, MD and Sherrie L Perkins, MD PhD Hematology and Clinical Microscopy Resource Committee

Documents

Cell Identificationwebapps.cap.org/apps/docs/committees/hematology/... · lymphocytes with occasional large granular lymphocytes. Persistent polyclonal B cell lymphocytosis has distinctive