Morphological & biological characteristics of  CIN

• In all cases of CIN, the normal epithelium of the cervix is replaced by abnormal epithelial cells showing varying degrees of differentiation.
• Undifferentiated  neoplastic cells of basaloid or parabasaloid appearance may occupy the whole  thickness of the epithelium (CIN3) or they may differentiate as they approach they approach the surface (CIN1,CIN2)
• The nuclei of the  undifferentiated cells are large, irregular and vary in size and shape. The chromatin content is increased and abnormal in structure and the nuclear/cytoplasmic ratio is high.
• As the basaloid  or parabasaloid neoplastic cells differentiate    the amount of cytoplasm increases. Nuclear irregularity, pleomorphism and anisonucleosis persist although there is usually a decrease in nuclear size.
• Mitotic  activity is no longer confined to the basal layers of the epithelium and atypical mitoses may be seen at any level
• It is not uncommon for  foci of CIN1,CIN2 and CIN3 to be present in the same cervix

CIN1	CIN2	CIN3

The abnormal cells  found in the smear are derived from the surface of the CIN lesion. The abnormal cells appear  singly or in streaks or in sheets. They can be distinguished from normal cells by the following diagnosis:

1. Disproportionate nuclear enlargement resulting in alteration of normal nuclear/cytoplasmic ratio.
2. variation in nuclear size and shape.
3. irregularity of nuclear outline
4. hyperchromasia of nucleus  and abnormal chromatin pattern
5. large irregular and sometimes multiple nuclei (not in CIN1)

The grade of CIN (CIN 1, 2 or 3) can be deduced from the degree of nuclear enlargement and alteration of n/c ratio.

Cytological diagnosis of CIN1 (encompassing LSIL and mild dysplasia) Show Cytological diagnosis of CIN2 (encompassing HSIL and moderate dysplasia) Show Cytological diagnosis of CIN3 (encompassing HSIL, severe dysplasia and carcinoma in situ) Close The Bethesda System definition CIN 3 (HSIL) Cells occur singly or grouped in sheets or in syncytial-like clusters Abnormal nuclei  generally found in cells with “immature”, delicate or dense  cytoplasm; occasionally the cytoplasm is heavily keratinised Nuclear enlargement is three or more times the area of normal intermediate nuclei* The cytoplasmic area is decreased. For this reason, in a cell with very high nuclear/cytoplasmic ratio, the dimension of the nucleus can be smaller than in LSIL Overall cell size is often ksmaller than in LSIL Nuclei are hyperchromatic usually  with granular coarse chromatin Nuclear borders are irregular and  anisonucleosis is a prominent feature When the abnormal cells occur in sheets ,the nuclei are crowded and overlapping and mitotic figures may be seen *The WHO cytological definition of CIN 3 requires that the nucleus occupies more than two thirds of the area of the cell. Cytological presentation of CIN 3 (HSIL).