BAP1-Mutated Clear Cell Renal Cell Carcinoma A Clinicopathologic Characterization of 14 Molecularly Confirmed Tumors

Objectives: While aberrations in the VHL gene and chromosome 3p resulting in clear cell renal cell carcinoma (CCRCC) are well established we know that additional mutations in chromatin remodeling genes PBRM1, SETD2, and BRCA1-associated protein 1 (BAP1) contribute to pathogenesis in some cases. Given the known aggressive clinical behavior of BAP1-mutated CCRCC, we sought to define the pathologic phenotype of BAP1-mutated CCRCC. Methods: We identified 14 cases of molecularly proven BAP1-mutated CCRCC and investigated their clinicopathologic features. Results: BAP1-mutated CCRCC frequently showed papillary, tubulopapillary, or expanded nested architecture; demonstrated granular to diffusely eosinophilic cytoplasm with prominent eosinophilic globules; and contained highgrade nuclei. This morphology demonstrates significant overlap with Xp11 translocation renal cell carcinoma (RCC). Immunohistochemistry notably demonstrates loss of BAP1 expression in almost all tumors, in addition to strong p504S expression. A conventional CCRCC component was frequently present adjacent to the characteristic BAP1 areas and showed retained BAP1 expression and only patchy p504S. Approximately two-thirds of BAP1-mutated CCRCCs were stage pT3, renal vein invasion was common, and 50% developed metastases. Conclusions: Herein, we describe the histologic and immunohistochemical findings in BAP1-mutated CCRCC, which has important implications for utilization of molecular testing prognosis, future therapeutic.g and distinction from other RCC subtypes such as Xp11 translocation RCC.

Automated summary

The study identifies the pathological features of BAP1-mutated CCRCC, which exhibit overlapping morphological characteristics with other subtypes of renal cell carcinoma and specific immunohistochemical patterns. BAP1-mutated CCRCCs are often aggressive, with a high likelihood of invasion and metastasis.