Abstract :
[en] Background: Epithelial maturation traditionally is used to grade CIN in histologic sections. However, in some an immature epithelium displays atypia that is low in proportion to the level of epithelial maturity. Although MIB1 and p16ink4 are helpul in establishing the diagnosis of CIN in this setting, classifying such lesions can be problematic. We analyzed a subset of these atypias, and this study summarizes a correlation between morphology and p16 and MIB1 immunostaining.
Design: Immature metaplastic atypias were divided into those with putative low (uniform nuclear spacing, minimal nuclear variation, absent or mild nuclear hyperchromasia) and high-grade (irregular nuclear spacing, heterogeneous nuclear morphology, increased nuclear chromasia) features. Immunohistochemical staining for p16 was classifi ed as patchy or diffuse (horizontally) and MIB-1 proliferation index was recorded as percentage of positive cells and location of elevated proliferative index as a function of basal, middle and superfi cial third of the epithelium. Staining patterns and histologic grade were correlated.
Results: Forty-three cases were classified without knowledge of the immunohistochemistry. Immature metaplastic low grade CINs exhibited strong and diffuse staining for p16 and but unlike High grade CINs, the proliferating (MIB1+) cells were concentrated in the more basal 1-2 thirds of the epithelium and the proliferative index was less than 30%. Variable columnar differentiation was observed in some, with strong staining of both the columnar and squamous cells by p16.
Conclusions: A distinct subset of immature CINs displays a uniform cell population and based on both cytology and proliferative index, warrants classifi cation as low grade CIN (CIN1). p16 immunohistochemistry, although helpful in the recognition of these lesions, will not distinguish them from higher grade CIN (CIN2/3). Attention to regularity in nuclear morphology with absence of noticeable differences in cell size and shape, combined with MIB1 staining, is helpful,. The presence of columnar differentiation, which also stains positive for p16 is consistent with bidirectional differentiation in the transformation zone epithelium. Further studies of this entity are warranted to precisely determine its biologic behavior.
