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Accurate discrimination of benign oncocytoma and malignant renal cell carcinoma is useful for planning appropriate treatment strategies for patients with renal masses. Classification of renal neoplasms solely based on histopathology can be challenging, especially the distinction between chromophobe renal cell carcinoma and oncocytoma. In this study we develop and validate an algorithm based on genomic alterations for the classification of common renal neoplasms.Using TCGA renal cell carcinoma copy number profiles and the published literature, a classification algorithm was developed and scoring criteria were established for the presence of each genomic marker. As validation, 191 surgically resected formalin fixed paraffin embedded renal neoplasms were blindly submitted to targeted array comparative genomic hybridization and classified according to the algorithm. CCND1 rearrangement was assessed by fluorescence in situ hybridization.The optimal classification algorithm comprised 15 genomic markers, and involved loss of VHL, 3p21 and 8p, and chromosomes 1, 2, 6, 10 and 17, and gain of 5qter, 16p, 17q and 20q, and chromosomes 3, 7 and 12. On histological rereview (leading to the exclusion of 3 specimens) and using histology as the gold standard, 58 of 62 (93%) clear cell, 51 of 56 (91%) papillary and 33 of 34 (97%) chromophobe renal cell carcinomas were classified correctly. Of the 36 oncocytoma specimens 33 were classified as oncocytoma (17 by array comparative genomic hybridization and 10 by array comparative genomic hybridization plus fluorescence in situ hybridization) or benign (6). Overall 93% diagnostic sensitivity and 97% specificity were achieved.In a clinical diagnostic setting the implementation of genome based molecular classification could serve as an ancillary assay to assist in the histological classification of common renal neoplasms.

INTRODUCTION AND OBJECTIVES: Regressed testicular tumors (RTTs) account for a significant proportion of what were once considered to be extragonadal germ cell tumors (GCTs). The clinical presentation and outcomes of patients with “burned-out” primary tumors are poorly understood as are their pathologic characteristics. We describe our experience with this unique subset of testicular GCTs. METHODS: We reviewed our prospectively-maintained testicular cancer database for radical orchiectomies performed from 1977– 2009. Specimens without viable tumor were reviewed by dedicated genitourinary pathologists blinded as to whether or not the patient had received prior chemotherapy. Kaplan-Meier curves were generated to describe recurrence-free and overall survival. RESULTS: We identified 80 patients with testicular or extragonadal GCTs but with no viable tumor in the radical orchiectomy specimen. A total of 28 patients had not received prior chemotherapy. Pathologic findings at the time of retroperitoneal lymph node dissection or biopsy of a metastatic site included non-seminomatous GCT (NSGCT) in 11 (39%), seminoma in 6 (21%), unspecified GCT in 3 (11%), and sarcoma in 1 (4%). Benign disease was identified in the remaining 7 patients (25%). The 11 patients with NSGCT included 4 with embryonal carcinoma (14%), 2 with choriocarcinoma (7%), 2 with teratoma (7%), 2 with mixed NSGCT (7%), and 1 with yolk sac (4%). At presentation, the clinical stage was I in 3 patients (14%), II in 10 patients (45%), and III in 9 patients (41%). Based on the IGCCCG classification system, 10 were good risk (56%), 3 were intermediate risk (17%), and 5 were poor risk (28%). Intratubular germ cell neoplasia was identified in 8 patients (29%). Additional findings included hyalinization in 24 (86%), nodular scar in 22 (79%), Sertoli cell-only pattern in 21 (75%), interstitial fibrosis in 22 (79%), inflammation in 13 (46%), tubular calcification in 11 (39%), coarse calcification in 10 (36%), psammomatous calcification in 7 (25%), and necrosis in 1 (4%). Fiveyear recurrence-free, cancer-specific, and overall survival rates were 83% (95% CI: 61%, 93%), 96% (95% CI: 75%, 99%), and 96% (95% CI: 75%, 99%), respectively. CONCLUSIONS: To our knowledge, this is the largest published review of patients with RTT. We describe in detail the pathologic findings in this unique subset of testicular GCTs as well as their clinical presentation and outcomes.