BAP1-Mutated Clear Cell Renal Cell Carcinoma. Am J Clin Pathol 2021 Apr 26;155(5):718-728
Date
11/20/2020Pubmed ID
33210135DOI
10.1093/ajcp/aqaa176Scopus ID
2-s2.0-85105763697 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
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 high-grade 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 therapeutics, and distinction from other RCC subtypes such as Xp11 translocation RCC.
Author List
Gallan AJ, Parilla M, Segal J, Ritterhouse L, Antic TAuthor
Alexander J. Gallan MD Assistant Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedCarcinoma, Renal Cell
Gene Expression Regulation, Neoplastic
Humans
Kidney Neoplasms
Male
Middle Aged
Mutation
Nuclear Proteins
Phenotype
Prognosis
Transcription Factors
Tumor Suppressor Proteins
Ubiquitin Thiolesterase