Predicting the clinical behavior and trajectory of chromophobe renal cell carcinoma (ChRCC) by histologic features has so far proven to be challenging. It is known that ChRCC represents a heterogeneous group of neoplasms demonstrating variable, yet distinctive morphologic and genetic profiles. In this international multi-institutional study, we aimed to assess the impact of histologic diversity in ChRCC (classic/eosinophilic versus rare subtypes) on survival outcome. This is an international multi-institutional matched case-control study including 14 institutions, examining the impact of histologic subtypes of ChRCC on survival outcome. The study group (cases) included 89 rare subtypes of ChRCC. The control group consisted of 70 cases of ChRCC including classic and eosinophilic features, age- and tumor size-matched. Most of the rare subtypes were adenomatoid cystic/pigmented ChRCC (66/89, 74.2%), followed by multicystic ChRCC (10/89, 11.2%), and papillary ChRCC (9/89, 10.1%). In the control group, there were 62 (88.6%) classic and 8 (11.4%) eosinophilic ChRCC. There were no statistically significant differences between the study and control groups for age at diagnosis, gender distribution, tumor size, presence of tumor necrosis, presence of sarcomatoid differentiation, and adverse outcomes. No statistically significant differences were found in clinical outcome between the rare subtypes and classic/eosinophilic groups by tumor size, necrosis, and sarcomatoid differentiation. Further, no statistically significant differences were found in clinical outcome between the two groups, stratified by tumor size, necrosis, and sarcomatoid differentiation. Our findings corroborated previous studies that both sarcomatoid differentiation and tumor necrosis were significantly associated with poor clinical outcome in classic/eosinophilic ChRCC, and this was proven to be true for ChRCC with rare histologic subtypes as well. This study suggests that rare morphologic patterns in ChRCC without other aggressive features play no role in determining the clinical behavior of the tumor.

Department of Laboratory Medicine and Pathology University of Washington Seattle WA USA

Department of Pathology Alpha Medical Pathologia Bratislava Slovakia

Department of Pathology Bellvitge Hospital Barcelona Spain

Department of Pathology Centro Medico Mexico City Mexico

Department of Pathology Charles University Faculty of Medicine and University Hospital in Plzen Plzen Czech Republic

Department of Pathology Faculty of Medicine University of British Columbia Royal Columbian Hospital Vancouver BC Canada

Department of Pathology Institute Nacional de Cancerologia Mexico City Mexico

Department of Pathology Sestre milosrdnice University Hospital Center Department of Pathology and Scientific Centre of Excellence for Reproductive and Regenerative Medicine School of Medicine University of Zagreb Croatia

Department of Pathology Stradin's University Riga Latvia

Department of Pathology University Hospital Zagreb Croatia

Department of Pathology University of Sarajevo Faculty of Health Sciences Sarajevo Bosnia and Herzegovina

Department of Pathology University of Split Croatia

Department of Pathology University of Vienna Vienna Austria

Department of Urology Charles University Faculty of Medicine and University Hospital in Plzen Plzen Czech Republic

Departments of Pathology and Urology Emory University School of Medicine Atlanta GA USA

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