Faculty Bibliography

CONTEXT/BACKGROUND:- Serous carcinoma of the gynecologic tract often involves the external bladder wall and can occasionally mimic primary urothelial carcinoma of the bladder. OBJECTIVE:- To define the spectrum of morphologic and immunohistochemical features that characterize serous carcinoma involving the bladder wall and its distinction from urothelial carcinoma. DESIGN/METHODS:- We reviewed all cases of serous carcinoma secondarily involving the bladder wall from the University of California San Diego and Polytechnic Institute for histopathologic and immunohistochemical features. RESULTS:- We identified 20 cases of Müllerian high-grade serous carcinoma involving the bladder wall. Five cases were clinical mimics of urothelial carcinoma, including 2 cases that presented as a large, transmural, primary bladder mass without precedent gynecologic history in women younger than 60 years, and 3 cases presumed to be new bladder carcinoma occurring distant to a serous carcinoma diagnosis. A subset of cases were morphologic mimics of urothelial carcinoma, which showed nested growth patterns (2 of 20; 10%), squamouslike foci (2 of 20; 10%), spindled/sarcomatoid growth (2 of 20; 10%), basaloid morphology (3 of 20; 15%), and syncytial growth patterns (1 of 20; 5%). Immunohistochemical stains in 17 cases showed immunoreactivity for CK7 (17 of 17; 100%), WT1 (17 of 17; 100%), uroplakin (UP) II (1 of 17; 6%), p63 (2 of 17; 12%), GATA3 (2 of 17; 12%), and PAX8 (17 of 17; 100%). CONCLUSIONS:- A subset of serous carcinomas involving the bladder wall can mimic urothelial carcinoma. Awareness of this mimicker and use of an immunohistochemical panel that includes CK7, WT1, UPII, PAX8, p63, and GATA3 can be helpful in confirming the diagnosis.

Urothelial carcinoma of the bladder invasive into lamina propria on biopsy or transurethral resection of bladder tumor, termed "T1" disease, progresses to muscularis propria invasion in a subset of patients. Prior studies have proposed histopathologic metrics to predict progression, although methods vary widely and it is unclear which method is most robust. This poses a challenge since recent World Health Organization and American Joint Commission on Cancer editions encourage some attempt to substratify T1 disease. To address this critical problem, we analyzed T1 specimens to test which T1 quantification method is best to predict progression and to then establish the optimal cut-off. Progression was analyzed for all patients or for patients with definitive muscularis propria only. Multivariate analysis and outcomes modeling controlled for additional histopathologic features. Our results suggest that aggregate linear length of invasive carcinoma (ALLICA) measured by optical micrometer is far superior to other methods (P=3.067×10) and could be applied to 100% of specimens. ALLICA retained significance in multivariate analysis and eliminated contribution of other histopathologic features to progression. The best cut-off for ALLICA using a 30% false-positive threshold was 2.3 mm and using a 10% false-positive threshold at 25 mm, although the latter severely limited patients who could achieve this threshold. After comparison of all proposed methods of T1 quantification, we recommend the adoption of the ALLICA measurement and a cut-off of ≥2.3 mm as the best predictor of progression, acknowledging that additional nonhistopathologic methods may be required to increase broad applicability and further reduce the false-positive threshold.

Unclassified renal cell carcinoma is a diagnostic category for renal cell tumors not fitting into one of the established subtypes in our current classification system and includes a heterogeneous group of tumors with variable clinicopathologic features and biological behaviors. Unclassified renal cell carcinoma with high-grade histologic features represents a particularly challenging group of tumors for diagnosis and management, given their complex pathologic features, aggressive clinical attributes, and a lack of standard therapy. Using an example case of high-grade unclassified renal cell carcinoma, this review discusses the diagnostic approaches to these tumors in the context of the World Health Organization 2016 classification system and provides updates on the molecular characteristics of these tumors.