Small cell variant of chromophobe renal cell carcinoma: Clinicopathologic and molecular-genetic analysis of 10 cases.

Joanna Rogala,Kristyna Pivovarcikova,Kvetoslava Michalova,Levente Kuthi,Boris Bartovic,Delia Perez Montiel,Stela Bulimbasic,Nikola Ptakova,Adriena Bartos Vesela,Olga Dolejsova,Michal Michal,Ondrej Hes,Reza Alaghehbandan,Leila Ali,Maryna Slisarenko,Ana Bravc,Fumiyoshi Kojima

doi:10.17305/bjbms.2021.6935

Abstract

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 analyzed, using morphologic parameters, immunohistochemistry, and next-generation sequencing testing. Patients were five males and five females, with age ranging from 40 to 78 years. 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 expands on 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.

Highlights

Several morphologic variations of chromophobe renal cell carcinoma (ChRCC) have been reported since Thoenes and Storkel [1,2] first described it
Cases with morphology that differs from the typical solid-alveolar architecture seen in classic or eosinophilic ChRCC have been well-documented in the literature, including adenomatoid pigmented ChRCC, ChRCC with neuroendocrine differentiation, oncocytic ChRCC, multicystic ChRCC, and ChRCC with papillary architecture [3-9]
We focused on cases with true neuroendocrine differentiation, which were excluded after the initial immunohistochemical staining for synaptophysin, chromogranin, and CD56

Summary

Introduction

Several morphologic variations of chromophobe renal cell carcinoma (ChRCC) have been reported since Thoenes and Storkel [1,2] first described it. Cases with morphology that differs from the typical solid-alveolar architecture seen in classic or eosinophilic ChRCC have been well-documented in the literature, including adenomatoid pigmented ChRCC, ChRCC with neuroendocrine differentiation (or with neuroendocrine-like differentiation), oncocytic ChRCC, multicystic ChRCC, and ChRCC with papillary architecture [3-9]. The small-cell variant of renal oncocytoma (RO) is a well-defined morphologic subtype of a common renal tumor [10-12]. ChRCC and RO are thought to be closely related tumors derived from the intercalated cells. Small-cell variant of ChRCC has not been described. We selected a group of ChRCCs with a small-cell component forming from 10 to 80% of the tumor volume. Clinicopathologic, morphologic, immunohistochemical, and molecular genetic analysis of 10 cases were performed

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Results

Conclusion