CYTOPA

THOLO

GY-7

DR

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AH

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L-SED

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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.

Pre-malignant & malignant criteria

Neoplasm

Cell growth has escaped from normal regulatory mechanisms

Benign Malignant

Benign

Dysplasia

Insitu

Malignancy

Metastasis

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.

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.

Dysplasia:

Premalignant condition.

Increased cell growth.

Cellular atypia.

Altered differentiation.

Can range from mild to severe.

Sites : cervix - bladder - stomach.

In-situ malignancy:

Epithelial neoplasm with features of malignancy.

Altered cell growth.

Cytological malignant changes.

BUT-no invasion through basement membrane.

Benign Benign

Benign Dysplasia

Benign Dysplasia In-situ

Benign Dysplasia In-situ Invasive

Dysplasia In-situ Invasive

In-situ InvasiveInvasive Invasive

POSSIBLE EVENTS

Key to the diagnosis of neoplasia is to determine that the "lesion" is not inflammatory and is not a normal structure.

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.

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

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.

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).

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.

N/C ratio is markedly increased

Nuclear size variation

Hyperchromatism

Multi-nucleation with two, three, four, or more nuclei is a common finding in many cells

Multinucleation

Prominent nucleoli

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.

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.

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.

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.

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.

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.

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).

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.

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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