Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients.

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

Metastatic renal cell carcinoma to the urinary bladder: a report of 11 cases.

Metastatic renal cell carcinoma (RCC) to the urinary bladder is rarely seen. Herein, we report the histologic subtypes, immunohistochemical characteristics, and prognosis of 11 patients with metastatic RCC to the urinary bladder. The mean age at the time of diagnosis of metastatic RCC to the bladder was 66 years (range, 58 to 79 y). There were 9 male and 2 female patients. Four patients presented with hematuria, 2 with urinary retention/obstruction, and 1 with bladder calculi. Four patients were asymptomatic and presented for surveillance cystoscopy, wherein they were found to have bladder masses. Nine patients had prior histories of RCC. The remaining 2 patients presented with metastatic clear cell RCC to the bladder and were subsequently found to have renal masses. The average time between nephrectomy and metastasis to the bladder was 20.7 months (range, 0 to 87 mo). Of the 10 patients with radical/partial nephrectomy, 7 cases were clear cell (2 with sarcomatoid features), 2 papillary, and 1 chromophobe with histologic fidelity between the primary and metastasis. Of cases with available data, the primaries' ISUP nucleolar grades were 2 (n=2), 3 (n=4), and 4 for the 2 cases with sarcomatoid features. In 8 cases, the bladder RCC undermined overlying urothelium with extensive urothelial denudation, and in 3 cases the RCC was free floating without attachment to the urothelium. The 1 chromophobe RCC metastasized with pagetoid spread to a preexisting urothelial papilloma. PAX8 immunohistochemistry was used to confirm the diagnosis in 2 cases. Three patients have no evidence of disease (7, 9, and 13 mo). Two are alive with disease after chemotherapy (30, 37 mo). Six patients are dead of disease with multiorgan metastases; 4 are dead after therapy (5, 8, 25, 28 mo), and two died without radiation or chemotherapy at 10 and 71 months. Metastatic RCC to the urinary bladder is uncommon, with most cases clear cell RCC. In some cases, evidence supports "drop metastases" as the mechanism of spread and patients have relatively long survival. However, in other cases spread to the bladder is in the setting of metastases to other sites, and these patients tended to die relatively shortly after their bladder metastases.