The Significance of Central Pathology Review in Clinical Studies of Transitional Cell Carcinoma in Situ

PURPOSE: The causes of interobserver variation in the pathological diagnosis of urothelial neoplasia were studied. MATERIALS AND METHODS: A central review was performed on pathological specimens in a multi-institutional clinical study of patients with in situ transitional cell carcinoma of the bladder. RESULTS: A significant discrepancy in pathological diagnosis was noted between the original report and the central review in 60 of 159 biopsies (38%) and in 73 of 217 cytology specimens (34%). Biopsy discrepancies were almost equally divided between upgrades and downgrades, whereas 89% of cytology discrepancies involved an upgrade in diagnosis by the central reviewer. The most significant factor causing variability in biopsy diagnoses was the multiplicity of classifications used by the originating pathologists. Other factors included fixation and biopsy artifacts. Cell degeneration secondary to treatment was the most important factor resulting in cytology under grading. At originating institutions the correlation of diagnoses between concurrent biopsy and cytology specimens was poor. CONCLUSIONS: The lack of a well accepted standard for the histopathological diagnosis of transitional cell carcinoma in situ poses a major problem for multi-institutional studies of this disease. Organizers must include a histopathological standard in the study plan and publicize it to all participants, particularly pathologists. Central review of pathological specimens is essential to maintain data integrity.