Upload
dr-suvarna-nalapat
View
227
Download
0
Embed Size (px)
Citation preview
7/31/2019 Neoplasia3 [Compatibility Mode]
1/80
Neoplasia
Dr Suvarna Nalapat
7/31/2019 Neoplasia3 [Compatibility Mode]
2/80
Alterations in cell growth physiologic (normal responses to stimuli) or
pathologic. alterations of cell growth are potentially reversible and include:
Hypertrophy: increase in cell size. Increase inskeletal muscle fiber size is a physiologic responseto exercise, but the cardiac hypertrophy above is a
pathologic response to abnormally elevated blood pressure.
Hyperplasia: a increase in number of cells.Postpartum breast lobules undergo hyperplasia for lactation, endometrial hyperplasia in
postmenopausal woman is abnormal
7/31/2019 Neoplasia3 [Compatibility Mode]
3/80
Growth disturbances
increase in tissue size isnot necessarily neoplasia
increase in the size of themyocardial fibers inresponse to an increased
pressure load fromhypertension
cells increase in size, butnot in number
7/31/2019 Neoplasia3 [Compatibility Mode]
4/80
large fronds of endometrium are a resultof hyperplasia. resultedfrom increased estrogen.With hyperplasia, there isincrease in cell numberscells are normal inappearance. Sometimeshyperplasias can be"atypical" and the cells not
completely normal. Suchconditions can be premalignant.
7/31/2019 Neoplasia3 [Compatibility Mode]
5/80
cellular transformation.
The two forms of cellular transformation that are potentially reversible, but may be steps toward aneoplasm, are
metaplasia: the exchange of normal epithelium for another type of epithelium. Metaplasia isreversible when the stimulus for it is taken away.
Dysplasia: a disordered growth and maturation of an epithelium, which is still reversible if thefactors driving it are eliminated
7/31/2019 Neoplasia3 [Compatibility Mode]
6/80
metaplasia of normalrespiratory laryngealepithelium on the rightto squamousepithelium on the leftin response to chronicirritation of smoking
7/31/2019 Neoplasia3 [Compatibility Mode]
7/80
biopsy of the lower esophagus in a patientwith chronicgastroesophageal refluxdisease shows columnar metaplasia (Barrett'sesophagus), and the gobletcells are typical of anintestinal type of epithelium. Squamous
epithelium typical of thenormal esophagus appearsat the right
7/31/2019 Neoplasia3 [Compatibility Mode]
8/80
next step towardneoplasia. Here, there isnormal cervical squamousepithelium at the left, but
dysplastic squamousepithelium at the right.Dysplasia is a disorderlygrowth of epithelium, butstill confined to the
epithelium. Dysplasia isstill reversible
7/31/2019 Neoplasia3 [Compatibility Mode]
9/80
the normal cervicalsquamous epitheliumat the left merges intothe dysplasticsquamous epitheliumat the right in whichthe cells are moredisorderly.
7/31/2019 Neoplasia3 [Compatibility Mode]
10/80
Some epithelia areaccessible, such as thecervix, that cancer screening can be done bysampling some of the cells
and sending them to thelaboratory. cervical Papsmear in which dysplasticcells are present that havelarger and darker nucleithan normal squamouscells with small nuclei andlarge amounts of cytoplasm
7/31/2019 Neoplasia3 [Compatibility Mode]
11/80
When entire epithelium isdysplastic and no normalepithelial cells are left, the
process is beyonddysplasia and is neoplasia.If the basement membraneis still intact, as shownhere, then the process iscalled "carcinoma in situ"
because the carcinoma is
still confined to theepithelium.
7/31/2019 Neoplasia3 [Compatibility Mode]
12/80
This is a neoplasm. Neoplasia is uncontrollednew growth. Note mass of abnormal tissue on surfaceof cervix. term "tumor"used synonymously withneoplasm, but "tumor" canmean any mass effect,whether inflammatory,hemodynamic, or
neoplastic. Once aneoplasm, it is notreversible.
7/31/2019 Neoplasia3 [Compatibility Mode]
13/80
microscopic appearanceof neoplasia, or uncontrolled newgrowth. Here, theneoplasm is infiltratinginto the underlyingcervical stroma. Of course, there can becarcinoma in situ inwhich a full-fledged
neoplasm is present, buthas not yet invaded
7/31/2019 Neoplasia3 [Compatibility Mode]
14/80
squamous cellcarcinoma. Note thedisorderly growth of the squamousepithelial cells in theselarge nests with pink keratin in the centers
7/31/2019 Neoplasia3 [Compatibility Mode]
15/80
neoplasms can be benignas well as malignant,.Here is a benign lipomaon the serosal surface of
the small intestine. It hasthe characteristics of a
benign neoplasm: it is wellcircumscribed, slowgrowing, and resembles
the tissue of origin (fat).
7/31/2019 Neoplasia3 [Compatibility Mode]
16/80
At low power magnification, a lipoma of the stomach is seen to bewell demarcated from themucosa at the lower center-right. Thisneoplasm is so well-differentiated that, exceptfor its appearance as alocalized mass, it is
impossible to tell fromnormal adipose tissue
7/31/2019 Neoplasia3 [Compatibility Mode]
17/80
Here is the lipoma athigh magnification.This is a goodexample of how a
benign neoplasmmimics the tissue of origin.
7/31/2019 Neoplasia3 [Compatibility Mode]
18/80
Benign neoplasms can bemultiple, leiomyomas of
varying size, but all benign and well-
circumscribed firm whitemasses. most commonneoplasm is a benign
nevus (pigmented mole)of the skin, and most
people have several. As a
general rule, benignneoplasms do not give riseto malignant neoplasms.
7/31/2019 Neoplasia3 [Compatibility Mode]
19/80
microscopicappearance of aleiomyoma indicatesthat the cells do notvary greatly in sizeand shape and closelyresemble normalsmooth muscle cells.
7/31/2019 Neoplasia3 [Compatibility Mode]
20/80
Multiple adenomatous polyps of the cecumare seen here in a caseof familial polyposis
7/31/2019 Neoplasia3 [Compatibility Mode]
21/80
This schwannoma wasresected from a nerve.
Note thecircumscribed nature
of this benignneoplasm.
7/31/2019 Neoplasia3 [Compatibility Mode]
22/80
schwannoma is seenmicroscopically to becomposed of spindlecells (like most
neoplasms of mesenchymal origin),
but the cells are fairlyuniform and there is
plenty of pink cytoplasm.
7/31/2019 Neoplasia3 [Compatibility Mode]
23/80
small fibroadenoma of the breast, a benign neoplasmmore commonly found inyounger women of
reproductive age. The bluedye was injected during aradiographic procedure tomark the location of theneoplasm so the surgeon
could find it.
7/31/2019 Neoplasia3 [Compatibility Mode]
24/80
the most commonneoplasm is a benignnevus (pigmented mole)of the skin, and most
people have several, asseen here over the skin of the chest. As a generalrule, benign neoplasms donot give rise to malignant
neoplasms
7/31/2019 Neoplasia3 [Compatibility Mode]
25/80
small hepatic adenoma, anuncommon benignneoplasm, but one thatshows how well-demarcated an benignneoplasm is. It alsoillustrates how function of the normal tissue ismaintained, because theadenoma is making bile
pigment, giving it a greencolor.
7/31/2019 Neoplasia3 [Compatibility Mode]
26/80
In contrast, thishepatocellular carcinomais not as wellcircumscribed (note the
infiltration of tumor off tothe lower right) nor asuniform in consistency. Itis also arising in acirrhotic (nodular) liver.
7/31/2019 Neoplasia3 [Compatibility Mode]
27/80
renal cell carcinomademonstrates distortionand displacement of therenal parenchyma by the
tumor mass in the lower pole. This malignantneoplasm is variegated oncut surface, with yellow towhite to red to brown
areas.
7/31/2019 Neoplasia3 [Compatibility Mode]
28/80
excision of skindemonstrates amalignant melanoma,which is much larger and more irregular than a benign nevus.
7/31/2019 Neoplasia3 [Compatibility Mode]
29/80
example of metastases tothe liver. Note that the tan-white masses are multipleand irregularly sized. Likemany large metastaticlesions, there is centralnecrosis. A primaryneoplasm is more likely to
be a solitary mass. The presence of metastases arethe best indication that aneoplasm is malignant.
7/31/2019 Neoplasia3 [Compatibility Mode]
30/80
This abdominal CT scandemonstrates multiplevariegated mass lesions,some with dark central
necrosis, in a patient withwidespread metastaticcarcinoma. A normal sizedspleen is seen at the lower left.
7/31/2019 Neoplasia3 [Compatibility Mode]
31/80
metastaticadenocarcinoma isseen in a lymph nodehere. It is common for
carcinomas tometastasize to lymphnodes. The first nodesinvolved are thosedraining the site of the
primary neoplasm
7/31/2019 Neoplasia3 [Compatibility Mode]
32/80
Both lymphatic andhematogenous spreadof malignantneoplasms is possibleto distant sites. Here, a
breast carcinoma hasspread to a lymphaticin the lung.
7/31/2019 Neoplasia3 [Compatibility Mode]
33/80
chest radiographreveals the presence of multiple roundedmasses in all lungfields. These aremetastases.
7/31/2019 Neoplasia3 [Compatibility Mode]
34/80
Neoplasms can spread byseeding along bodycavities, and this pattern ismore typical for
carcinomas than other neoplasms. Note themultitude of small tantumor nodules seen over the peritoneal surface of
the mesentery shown here.
7/31/2019 Neoplasia3 [Compatibility Mode]
35/80
microscopic evidenceof the spread of a
carcinoma via bodycavities. A focus of
metastatic breastcarcinoma is present
along the pleuraoverlying the lung.
7/31/2019 Neoplasia3 [Compatibility Mode]
36/80
small focus of metastaticcarcinoma to theepicardium .key feature of neoplasms--angiogenesis.
Note the proliferation of many small capillariesadjacent to the neoplasticcells. Neoplasms can
produce factors that promote vascular growthto provide a vascular supply and continueduncontrolled growt
7/31/2019 Neoplasia3 [Compatibility Mode]
37/80
Malignant neoplasmsare also characterized
by the tendency toinvade surroundingtissues. Here, a lungcancer is seen to bespreading along the
bronchi into the
surrounding lung.
7/31/2019 Neoplasia3 [Compatibility Mode]
38/80
squamous cellcarcinoma of the lung.It is a bulky mass thatextends intosurrounding lung
parenchyma.
7/31/2019 Neoplasia3 [Compatibility Mode]
39/80
chest CT scandemonstrates a largesquamous cell carcinomaof the right upper lobe that
extends around the rightmain bronchus and alsoinvades into themediastinum and involveshilar lymph nodes.
7/31/2019 Neoplasia3 [Compatibility Mode]
40/80
infiltrating ductalcarcinoma of the breastsurrounding breast.centralwhite area is very hardand gritty, because theneoplasm is producing adesmoplastic reaction withlots of collagen. This isoften called a "scirrhous"appearance. There is alsofocal dystrophiccalcification leading to thegritty areas
7/31/2019 Neoplasia3 [Compatibility Mode]
41/80
the infiltrating ductalcarcinoma extendsirregularly through thetissue as cords and
nests of neoplasticcells with interveningcollagen. There is a
purplishmicrocalcification at
the lower center right.
7/31/2019 Neoplasia3 [Compatibility Mode]
42/80
the infiltrating ductalcarcinoma of breasthas pleomorphic cellsinfiltrating through thestroma.
7/31/2019 Neoplasia3 [Compatibility Mode]
43/80
invadingadenocarcinoma can
be seen here. Normalgastric epithelium at
the left merges into thecarcinoma at the right,and irregular neoplastic glandsinfiltrate downward
into the submucosa.
7/31/2019 Neoplasia3 [Compatibility Mode]
44/80
Branches of peripheralnerve are invaded bynests of malignantcells. This is oftenwhy pain associatedwith cancers isunrelenting
7/31/2019 Neoplasia3 [Compatibility Mode]
45/80
The concept of differentiation isdemonstrated by this smalladenomatous polyp of the
colon. Note the differencein staining quality between the epithelialcells of the adenoma at thetop and the normalglandular epithelium of the colonic mucosa below.
7/31/2019 Neoplasia3 [Compatibility Mode]
46/80
normal colonic epitheliumat left contrasts withatypical epithelium of adenomatous polyp(tubular adenoma) at right.
Nuclei darker moreirregularly sized closer
together in theadenomatous polyp thanin normal mucosa. overalldifference between themis not great, so this benignneoplasm mimics normal
tissue and is, well-differentiated.
7/31/2019 Neoplasia3 [Compatibility Mode]
47/80
colonoscopy of adenocarcinoma colon.
bulky mass spreads over colonic mucosal surface. Ithas red areas because it is
bleeding, and this led to positive occult blood instool (screening methodfor detection). Neoplasmsmay not maintain thestructure of normaltissues, there is irregular growth with necrosis and
hemorrhage, in larger aggressive neoplasms.
7/31/2019 Neoplasia3 [Compatibility Mode]
48/80
The infiltrating glands of this colonicadenocarcinomademonstrate lessdifferentiation than theadenomatous polyp,although they stillresemble glands. Ingeneral, lessdifferentiation of aneoplasm means a greater likelihood of malignant
behavior. This is the basisfor grading.
7/31/2019 Neoplasia3 [Compatibility Mode]
49/80
gastric adenocarcinoma is positive for cytokeratin byimmunoperoxidase.typical staining reactionfor carcinomas and helpsto distinguish carcinomas
from sarcomas andlymphomas.Immunoperoxidasestaining helpful todetermine cell type of neoplasm when degree of
differentiation, or morphology, does notallow exact classification
7/31/2019 Neoplasia3 [Compatibility Mode]
50/80
By electron microscopy,features of carcinoma
seen. adenocarcinomademonstrates severalfeatures typical of neoplasm of epithelialorigin, including
junctional complex (tight junction at the asterisk andthe desmosomes atcrosses). The mucingranule (M) and lumenalmicrovilli at upper rightalso typical for adenocarcinoma.
7/31/2019 Neoplasia3 [Compatibility Mode]
51/80
normal squamousepithelium at left mergesinto squamous cellcarcinoma at right,
infiltrating downward.neoplastic squamous cellsare still similar to normalsquamous cells, but areless orderly. This is awell-differentiatedsquamous cell carcinoma.
7/31/2019 Neoplasia3 [Compatibility Mode]
52/80
a moderatelydifferentiated squamouscell carcinoma in whichsome, but not all, of the
neoplastic cells in nestshave pink keratin. Ingeneral, neoplasms withless differentiation aremore aggressive.
7/31/2019 Neoplasia3 [Compatibility Mode]
53/80
At high magnification,
squamous cell carcinomademonstrates enoughdifferentiation to tell thatcells are of squamousorigin. cells are pink and
polygonal with
intercellular bridges (seenas desmosomes or "tight
junctions" by electronmicroscopy). neoplasticcells show pleomorphism,with hyperchromaticnuclei. A mitotic figure
present near center.
7/31/2019 Neoplasia3 [Compatibility Mode]
54/80
Features of a carcinomaare seen in this electronmicrograph. Thissquamous cell carcinoma
demonstrates manydesmosomes, along withcytoplasmic tonofilamentsstreaming to the left.
7/31/2019 Neoplasia3 [Compatibility Mode]
55/80
This neoplasm is so poorlydifferentiated that it isdifficult to tell what thecell of origin is. It is
probably a carcinoma
because of the polygonalnature of the cells. Notethat nucleoli are numerousand large in this neoplasm.
Neoplasms with nodifferentiation are said to
be anaplastic.
7/31/2019 Neoplasia3 [Compatibility Mode]
56/80
Neoplasia in the pediatricage range is not common.Childhood malignanciesare rare, but those that
occur often have theappearance of primitive"small round blue celltumors" such as theneuroblastoma seen here
Childh d li
7/31/2019 Neoplasia3 [Compatibility Mode]
57/80
Childhood Malignancy
Leukemia
Neuroblastoma
Medulloblastoma
Retinoblastoma
Wilms tumor
Ewing sarcoma
Blood, marrow, lymphnodes Adrenal, extra-adrenal
ganglia Cerebellum Eye
Kidney
bone
7/31/2019 Neoplasia3 [Compatibility Mode]
58/80
Aneuploidy by flow cytometry-ca breast
7/31/2019 Neoplasia3 [Compatibility Mode]
59/80
A mitotic figure in center,surrounded by poorly
differentiated squamouscell carcinoma with pleomorphic cells thathave minimal pink keratinization incytoplasm., mitoses are
more likely to be seen inmalignant neoplasms.Remember,, that normallycells are actively dividingin many tissues of body,including skin, bonemarrow, gonads, andgastrointestinal tract.
7/31/2019 Neoplasia3 [Compatibility Mode]
60/80
Here are three abnormalmitoses. Mitoses bythemselves are notindicators of malignancy.However, abnormal
mitoses are highlyindicative of malignancy.The marked
pleomorphism andhyperchromatism of surrounding cells alsofavors malignancy.
7/31/2019 Neoplasia3 [Compatibility Mode]
61/80
large fleshy mass inretroperitoneum Sarcomasarise from mesenchymaltissues. "malignant fibroushistiocytoma" awastebasket term for sarcomas that do notresemble striated muscle(rhabdomyosarcoma),
smooth muscle(leiomyosarcoma), fat(liposarcoma), bloodvessels (angiosarcoma),
bone (osteosarcoma),cartilage(chondrosarcoma).Sarcomas tend to be bigand bad.
7/31/2019 Neoplasia3 [Compatibility Mode]
62/80
computed tomographic(CT) scan of the abdomenat the level of the kidneysin which there is a largemass in theretroperitoneum that
proved to be a sarcoma.The mass is just anterior to the right kidney andmedial to the right lower lobe of liver.
7/31/2019 Neoplasia3 [Compatibility Mode]
63/80
fleshy mass arising in thesoft tissues of the lower leg. The tibia and thefibula are seen in crosssection. This neoplasm
proved to be a malignantfibrous histiocytoma.Sarcomas tend to invadelocally, as can be seenhere by the ill-definedmargins of the mass.
7/31/2019 Neoplasia3 [Compatibility Mode]
64/80
Sarcomas tend to havea spindle cell pattern.
Note that some of thecells are much larger and very pleomorphic.
7/31/2019 Neoplasia3 [Compatibility Mode]
65/80
sarcoma seen at mediummagnification is composedof very pleomorphic cells.The cell of origin of sarcomas is often difficultto determine because of their tendency to be poorlydifferentiated or evenanaplastic.
7/31/2019 Neoplasia3 [Compatibility Mode]
66/80
magnetic resonanceimaging (MRI) scan of the left leg, with alarge sarcoma arising
posterior to the knee,seen here at the levelof the lower femur.
7/31/2019 Neoplasia3 [Compatibility Mode]
67/80
7/31/2019 Neoplasia3 [Compatibility Mode]
68/80
Vimentin-infiltrating to normalmuscle is a sarcoma
7/31/2019 Neoplasia3 [Compatibility Mode]
69/80
7/31/2019 Neoplasia3 [Compatibility Mode]
70/80
liposarcoma
7/31/2019 Neoplasia3 [Compatibility Mode]
71/80
large bizarre lipoblasts
7/31/2019 Neoplasia3 [Compatibility Mode]
72/80
Paraneoplastic syndromes
A paraneoplastic syndrome occurs when aneoplasm elaborates a substance that results in aneffect that is not directly related to growth,invasion, or metastasis. Most paraneoplasticsyndromes result from elaboration of hormone-like substances, but a variety of effects are
possible. Sometimes the paraneoplastic syndromemay precede diagnosis of the neoplasm and may
give a clue to its presence.
7/31/2019 Neoplasia3 [Compatibility Mode]
73/80
Syndrome
Cushing's
Mechanism
ACTH-like
Example
Lung (oat
Hypercalcemia
Parathormone-like
Lung(squamous
Hyponatremia InappropriateADH
Lung (oat
Polycythemia Erythropoietin-like
Renal cellcarcinoma
7/31/2019 Neoplasia3 [Compatibility Mode]
74/80
7/31/2019 Neoplasia3 [Compatibility Mode]
75/80
process of neoplasia begins with celltransformation. A variety of chemical carcinogensas diverse as benzene, cigarette smoke, and nitritescan initiate and/or promote this process. Radiation,either as low level long-term environmentalgamma rays or as higher dose therapeuticradiation, can also produce genetic mutations.Infectious agents such as human papillomavirus
can lead to cellular transformation as well
7/31/2019 Neoplasia3 [Compatibility Mode]
76/80
Genetic damage with DNA alterations leads to point mutations of genes, translocations of geneticmaterial between chromosomes, and genereduplication with amplification. These alterationstransform proto-oncogenes into oncogenes. The
proto-oncogenes may play a role in growth promotion and regulation in normal cells, perhapsin embryogenesis, but are typically "turned off" in
adults. They are "turned on" by transformation.
7/31/2019 Neoplasia3 [Compatibility Mode]
77/80
7/31/2019 Neoplasia3 [Compatibility Mode]
78/80
7/31/2019 Neoplasia3 [Compatibility Mode]
79/80
or uncontrolled cellular proliferation, canresult either from mutations that "turn on"the oncogenes that stimulate growth, or
from mutations that result in loss of tumor suppressor genes and their products thatinhibit growth.
7/31/2019 Neoplasia3 [Compatibility Mode]
80/80
Thank you