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The ability to distinguish cancer cells from normal epithelial cells by light microscopy is fundamental for accurate cytological diagnosis. The principal morphological features which distinguish benign from malignant epithelial cells are summarised in the Table below.
| Benign Cells | Cancer Cells | |
|---|---|---|
| Cell size and shape | Within physiological limits reflecting normal cell division and maturation of the epithelium. | Variation in size and shape reflecting abnormal cell division and maturation. |
| Nuclear size | Within normal limits reflecting normal cell division and maturation. | Significant variation in nuclear size (anisonucleosis) reflecting abnormal cell division and maturation. |
| Nuclear shape | Generally round, oval or bean shaped. | Abnormal shape. |
| Structure of chromatin in interphase nucleus | Finely granular chromatin evenly distributed throughout nucleus. | Coarse granular chromatin unevenly distribution throughout nucleus. |
| Chromatin content of interphase nucleus | Normal amount of chromatin for diploid cells evenly distributed in all cells. | Chromatin often increased but the amount and distribution of chromatin varies from one nucleus to another due to abnormal cell division. |
| Hyperchromasia | Rarely seen, if present reflects regenerative change. | Common reflecting increased chromatin content or rapid cell turnover or both. |
| Multinucleation | Not normally found. If present nuclei are of even size. | Not uncommon. Nuclei vary is size and shape. |
| Nucleoli | Small, even size, few in number. | Large, irregular variable in size and shape and in number. |
| Cohesiveness | Well formed cell junctions. | Loss of cohesiveness. |
| Mitoses | Occasionally seen in basal layer of epithelium. | Abnormal mitoses frequently found throughout epithelium. |
- The differences outlined in the table above reflect the abnormal growth patterns of cancer cell which have the ability to evade the controls on cell division and maturation which determine the structure of normal epithelium.
- Cancer cells acquire the ability to divide a property which is normally present only in the basal layers (germinal layers) of the epithelium. In consequence the cancer cells outgrow and displace the normal epithelial cells to form tumours. Recent studies have shown that tumours often create their own blood supply – a process termed tumour angiogenesis. However when tumour growth exceeds blood supply the tumour become necrotic and ulcerated and infection supervenes.
- Rapid growth of cancer cells often results in errors in mitosis (cell division). This leads to uneven distribution of the chromatin between daughter cancer cells which in turn is reflected morphologically in the variation in nuclear size, shape and chromatin content seen in cancer cells in cervical smears and histological sections.
- Cancer cell also lose normal cell cohesiveness which enables them to migrate and invade. As a result of loss of cohesiveness the cancer cells are exfoliated much more readily than normal epithelial cells which accounts for the sensitivity of exfoliative cytology as a method of detecting cancerous and precancerous lesions in cervical smears.
Relationship between precancerous (CIN) and invasive squamous carcinoma of the cervix
- The current concept of squamous carcinoma of the cervix is that the invasive squamous cancer of the cervix is preceded by the development of precancerous changes in the squamous epithelium of the transformation zone. These precancerous lesions are known collectively as Cervical Intraepithelial Neoplasia (CIN). CIN may be present in the cervix for many years before an invasive lesion develops.
- The precancerous changes associated with Cervical Intraepithelial Neoplasia incorporate a continuous spectrum of morphological change ranging from a mild deviation from normal epithelium to marked epithelial dysplasia.
- The morphological changes in cancer cells described in the table above are also present in the precancerous cells of CIN. The morphological distinction between normal, precancerous and cancerous epithelium provides the basis for the Pap test.
Three grades of change are recognised histologically – CIN1 (also known as mild dysplasia), CIN2 (moderate dysplasia) and CIN3 (severe dysplasia/carcinoma in situ).