Cytopathology . 7

Dr. Maha Al-Sedik2015

CLS 422

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.

Objectives:

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.

Premalignant condition.

Increased cell growth.

Cellular atypia.

Can range from mild to severe.

Sites : cervix - bladder - stomach.

Dysplasia:

Epithelial neoplasm with features of malignancy.

Altered cell growth.

Cytological malignant changes.

BUT no invasion through basement membrane.

In-situ malignancy:

• Benign ---------------------------------------------- Benign• Benign ----------------------------------------------- Dysplasia• Benign ----------------Dysplasia ----------- --------In-situ• Benign -----------Dysplasia -----------In-situ -------Invasive• Dysplasia ------------- In-situ ------------------------Invasive• In-situ ------------------------------------- -----------Invasive• Invasive -------------------------------------------- ---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.

1. Increase in the number of 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.

Summary: Cytological criteria for malignancy:

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.

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.

IMPORTANT NOTES:

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.

Determination of cell type:

• 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).

Epithelial 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.

Mesenchymal (connective tissue) cells

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.

Round cell tumors

Reference:The Pathology of the Female Reproductive Tract John M. Craig, MD Boston Hospital for Women Harvard Medical School Boston, Massachusetts