Cytopathology-8 DR. MAHA AL-SEDIK

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

Cell growth has escaped from normal regulatory mechanisms Neoplasm Cell growth has escaped from normal regulatory mechanisms Benign Malignant

Benign neoplasm Malignant neoplasm Cells grow as a compact mass and remain at their site of origin. Malignant neoplasm Growth of 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 atypia. Altered differentiation. BUT-no invasion through basement membrane.

POSSIBLE EVENTS Benign Benign Benign Dysplasia Benign Dysplasia In-situ Benign Dysplasia In-situ Invasive Dysplasia In-situ Invasive In-situ Invasive Invasive Invasive

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 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 in different from normal cells, which have evenly distributed chromatin.

5- Multinucleation: malignant cells may contain more than one nucleus 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

myeloma cells . 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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