The morphologic diversity of chromophobe renal cell carcinoma (ChRCC) is well-known. Aside from typical morphology, pigmented adenomatoid, multicystic and papillary patterns have been described. Ten cases of CHRCC composed of small cell population in various percentages were analysed, using morphologic parameters, immunohistochemistry and next-generation sequencing (NGS) testing. Patients were five males and five females, with age ranging from 40 to 78years. The size of tumors ranged from 2.2 cm to 11 cm (mean 5.17 cm). Small cell component comprised 10 to 80% of the tumor volume, while the remaining was formed by cells with classic ChRCC morphology. The immunohistochemical profile of the small cell component was consistent with typical ChRCC immunophenotype, with CD117 and CK7 positivity. Neuroendocrine markers were negative. Mutations of 13 genes were found: DCIER1, FGFR3, JAK3, SUFO, FAM46C, FANCG, MET, PLCG2, APC, POLE, EPICAM, MUTYH and AR. However, only the PLCG2 mutation is considered pathogenic.The small cell variant of ChRCC further highlights and expand upon existing morphologic heterogeneity spectrum. Recognition of small cell variant of CHRCC is not problematic in tumors, where the "classic" CHRCC component is present. However, in limited material (i.e., core biopsy), this may present a diagnostic challenge. Based on the limited follow-up data available, it appears that the small cell tumor component had no impact on prognosis, since there was no aggressive behavior documented. Awareness of this unusual pattern and applying additional sections to find classic morphology of ChRCC, as well as excluding neuroendocrine nature by immunohistochemistry, may help resolve difficult cases.

Department of Biology and Medical Genetics 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Czech Republic

Department of Human Pathology Wakayama Medical University Wakayama Japan

Department of Pathology 'Carol Davila' University of Medicine and Pharmacy Bucharest Romania

Department of Pathology Charles University Prague Faculty of Medicine in Plzeň Pilsen Czech Republic

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

Department of Pathology General Hospital Slovenj Gradec Slovenia

Department of Pathology Institute Nacional de Cancerologia Mexico City Mexico

Department of Pathology University Hospital Centre Zagreb Zagreb Croatia

Department of Pathology University of Szeged Szeged Hungary

Department of Urology Charles University Prague Faculty of Medicine in Plzeň Pilsen Czech Republic

Departmnet of Pathology Cytopathos Bratislava Slovakia

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