cytopathology-7 dr. maha al-sedik. objectives: 1- neoplasm. 2- stages of carcinoma. 3- differences...
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CYTOPA
THOLO
GY-7
DR
. M
AH
A A
L-SED
IK
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Objectives:1- Neoplasm.
2- Stages of carcinoma.
3- Differences between benign and malignant
neoplasm.
4- Dysplasia.
5- Carcinoma in situ.
6- Nuclear changes in malignancy.
7- Cytoplasmic changes in malignancy.
8- Determination of cell type.
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Pre-malignant & malignant criteria
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Neoplasm
Cell growth has escaped from normal regulatory mechanisms
Benign Malignant
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Benign
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Dysplasia
Insitu
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Malignancy
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Metastasis
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Stages of malignancy:Stage 1:
• One cell acquire mutation of repeated cell division.
• One of the cells acquire mutation to start tumor.
Stage 2:
• One cell acquire mutation to produce proteinase enzyme.
Stage 3:
• Tumor is formed but at its place without invasion of the
basement membrane ( carcinoma in situ ).
Stage 4:
• Cancer cell invade the blood and lymphatic vessels.
Stage 5:
• Tumor cells ( metastatic ) appear in another place.
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Benign neoplasm:
• Cells grow as a compact mass and remain at
their site of origin ( cells are normal ).
Malignant neoplasm:
• Growth of malignant cells is uncontrolled.
• Cells can spread into surrounding tissue and
spread to distant sites.
• Cancer = a malignant growth.
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Dysplasia:
Premalignant condition.
Increased cell growth.
Cellular atypia.
Altered differentiation.
Can range from mild to severe.
Sites : cervix - bladder - stomach.
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In-situ malignancy:
Epithelial neoplasm with features of malignancy.
Altered cell growth.
Cytological malignant changes.
BUT-no invasion through basement membrane.
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Benign Benign
Benign Dysplasia
Benign Dysplasia In-situ
Benign Dysplasia In-situ Invasive
Dysplasia In-situ Invasive
In-situ InvasiveInvasive Invasive
POSSIBLE EVENTS
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Key to the diagnosis of neoplasia is to determine that the "lesion" is not inflammatory and is not a normal structure.
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Neoplasia usually is recognized cytologically by the
presence of cells that are neither inflammatory nor
normally expected from the site of collection.
For example, the presence of squamous epithelial
cells in a lymph node aspirate is highly suggestive of
metastatic neoplasia.
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CYTOLOGICAL CRITERIA OF MALIGNANCY
A)Nuclear Changes:
1-Nuclear hypertrophy: nuclear enlargement that leads
to increased N/C ratio.
2-Nuclear size variation
3-Nuclear shape variation
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4- Hyperchromatism and chromatin irregularity:
refers to increased chromatin materials. It is
distributed as coarse, clumps. This is different from
normal cells, which have evenly distributed
chromatin.
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5- Multinucleation: Malignant cells may contain more
than one nucleus. However, some normal cells such
as hepatocytes and histiocytes may contain more
than one nucleus. Multinucleated malignant cells
differ from nonmalignant multinucleated cells by the
fact that the nuclei of malignant cells are unequal in
size (in contrast to that of normal cells).
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6-Irregularity of the nuclear membrane.
7-Irregular and prominent nucleoli: giant nucleoli or
multiple nucleoli may be present that differ in their
sizes and shapes. It should be remembered,
however, that normal columnar and goblet cells may
contain 2 nucleoli.
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N/C ratio is markedly increased
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Nuclear size variation
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Hyperchromatism
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Multi-nucleation with two, three, four, or more nuclei is a common finding in many cells
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Multinucleation
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Prominent nucleoli
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B) Cytoplasmic Changes:
1- Decrease of size of cytoplasm: in consequence to the
high N/C ratio.
2- Cytoplasmic boundaries: sharp and distinct in
Squamous cell carcinomas and indistinct in
undifferentiated carcinomas.
3- Variation in size .
4- Variation in Shape.
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5- Cytoplasmic inclusions: e.g. melanin pigments in
melanoma.
6- Cytoplasmic and nuclear membrane relationship:
cytoplasmic borders of malignant cells could be tightly
molded against the nucleus, touching it in more than
one place.
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Summary: Cytologic criteria for
malignancy:
1. Pleomorphic population of mononuclear cells with few
or no inflammatory cells.
2. Large cells (find an inflammatory cell or a red blood
cell for a size reference).
3. Variation in size and shape of nuclei, nucleoli and
cytoplasm.
4. High nuclear to cytoplasmic ratio - large nuclei.
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5. Nuclear abnormalities:
Multiple nuclei, varying numbers.
Macronuclei.
Variation in shape and size.
Lobation, cleaving, molding, angulation.
Irregular clumping and dark chromatin.
6. Nucleolar abnormalities: different numbers, sizes,
and shapes per nucleus; macronucleoli.
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IMPORTANT NOTES: The more neutrophils you see, the more likely the lesion
is inflammatory and not a tumor.
True, neutrophils can infiltrate tumors and be present,
but your rule is still the same – the greater the
inflammation, the less likely there is a neoplasm.
If the preparation is cellular and no neutrophils are
present one of your first differentials is neoplasia. Keep
it simple, e.g. a mass in the skin or subcutaneous
tissues and there are no neutrophils and there are lots
of nucleated cells….. diagnosis: neoplasia.
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Determination of cell type:
The shape of the cells and their nuclei is the main
criteria used in attempting to classify the cell type of
a neoplasm.
If the shape of the cell cannot be determined from
visualization of cytoplasm then a good estimation
can be made from the shape of the nuclei.
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Epithelial cells
• usually exfoliate easily (numerous cells seen) and
tend to be shed in clusters. Cell shape may reflect
that of the specific epithelial type (squamous,
cuboidal, columnar), but these characteristics are
often lost in poorly differentiated tumors.
• The key to recognition of an epithelial tumor is to
see clusters, acini or aggregates of cells that
represent their pattern of growth due to cell to cell
adhesion (desmosomes, hemidesmosomes).
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Mesenchymal (connective tissue) cells
Tend to exfoliate poorly (low cell numbers) and are
more prone to exfoliate individually (although groups
of cells may be closely apposed in highly cellular
specimens).
Cell shape is elongated (spindle-shaped) and nuclei
are oval or elongated.
Cytoplasm is seen it tends to “stream” at the end of
the cell making a tail or point. More specific
characterization as to cell type may not be possible
unless evidence of a cell product can be found.
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Round cell tumors
also exfoliate discrete cells, usually lots of them,
but they lack the elongated shape common among
connective tissue cells and they don’t form balls or
morulae like epithelial tumors.
The amount of cytoplasm varies with the tumor
type.
Nuclei are characteristically round and often quite
uniform. Lymphoma, mast cell tumor, histiocytoma
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THANK YOU