For flat lesion, dysplasia is not well-recognised now; either normal/hyperplasia versus CIS. A diagnosis of dysplasia needs comment:
An example:
From WHO: "Urothelial dysplasia shows cytological atypia that is thought to be neoplastic in nature but not definitive for the diagnosis of CIS. Although sometimes this terminology is necessary, some authors have emphasized that there is a lack of reproducible criteria to distinguish urothelial dysplasia from atypia of uncertain significance, undermining the accuracy and utility of the diagnosis of dysplasia"
The exact criteria for CIS is not established in WHO.
Cytological atypia: pleomorphic nuclei with hyperchromasia, irregular chromatin patterns, and loss of nuclear polarity, identifiable at low magnification. CIS diagnosis does not require full-thickness mucosal involvement; malignant cells can appear as pagetoid spread or undermining benign urothelium. Mitotic figures, though often present, are not necessary for diagnosis.
Reactive urothelial atypia: which shows milder nuclear enlargement, regular chromatin patterns, and preserved polarity.
Good news is that in practice a panel p53, CK20, and CD44 can help.
Immunohistochemistry in urothelial carcinoma in situ (CIS) often reveals:
Abnormal CK20: Full-thickness labeling, deviating from its normal restriction to umbrella cells.
Aberrant p53 expression: Either diffuse and strong positivity or complete negativity (null pattern).
Reduced CD44 labeling: Limited to the basal layer or entirely absent, contrasting with full-thickness labeling in reactive urothelium.
Don't do stains on papillary lesions and stains negative does not mean it's not dysplasia.
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