NF2-mutated Renal Carcinomas Have Common Morphologic Features Which Overlap With Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma: A Comprehensive Study of 14 Cases. Am J Surg Pathol 2022 May 01;46(5):617-627
Date
01/17/2022Pubmed ID
35034039DOI
10.1097/PAS.0000000000001846Scopus ID
2-s2.0-85124100970 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Genetic alterations involving NF2 occur at low frequencies in renal cell carcinoma across all of the major histologic subtypes and have been associated with adverse outcomes. To better characterize tumors harboring these alterations, we identified 14 cases with NF2 mutations that had been previously diagnosed as papillary renal cell carcinoma; renal cell carcinoma, unclassified; or translocation associated renal cell carcinoma. These tumors were characterized by a tubulopapillary architecture, sclerotic stroma, microscopic coagulative necrosis, and psammomatous calcifications. All the cases displayed eosinophilic cytology as well as a high nuclear grade (World Health Organization/International Society of Urological Pathology [WHO/ISUP] grade 3 to 4) in all but 1 case. A subset of cases shared features with the recently described biphasic hyalinizing psammomatous renal cell carcinoma. Next-generation sequencing demonstrated mutations involving NF2 gene in all cases. In 10 cases, this was paired with the loss of chromosome 22. Additional mutations involving PBRM1 were found in 5 cases that were associated with a more solid growth pattern. Eight patients presented with metastatic disease including all 5 with PBRM1 mutations. Despite the aggressive disease course seen in many of the patients in our series, 2 patients exhibited a dramatic response to immunotherapy. Our results support the existence of a distinct group of cases of renal cell carcinoma characterized by distinct although admittedly nonspecific morphology, an aggressive disease course, and NF2 mutations, often paired with the loss of chromosome 22.
Author List
Paintal A, Tjota MY, Wang P, Fitzpatrick C, Wanjari P, Stadler WM, Gallan AJ, Segal J, 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
Biomarkers, TumorCarcinoma, Renal Cell
Female
Genes, Neurofibromatosis 2
Humans
Kidney Neoplasms
Male
Meningeal Neoplasms
Meningioma
Neurofibromin 2
