Morphological differences between normal epithelial cells and cancer cells

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 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).