Recurrent Tuberous Sclerosis Complex/Mammalian Target of Rapamycin Mutations Define Primary Renal Hemangioblastoma as a Unique Entity Distinct From Its Central Nervous System Counterpart.

Autor:	Wang XT; Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing., Fang R; Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing., He HY; Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing., Zhang W; Department of Pathology, the 971 Hospital of People's Liberation Army Navy, Qingdao., Li Q; Department of Pathology, the First People's Hospital of Changzhou, Changzhou., Sun SA; Department of Pathology, Huai'an First People's Hospital, Huai'an., Wang X; Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing., Zhang RS; Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing., Teng XD; Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou., Zhou XJ; Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing., Xia QY; Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing., Zhao M; Department of Molecular Pathology, Ningbo Clinical Pathology Diagnosis Center, Ningbo, China., Rao Q; Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing.
Jazyk:	angličtina
Zdroj:	The American journal of surgical pathology [Am J Surg Pathol] 2024 Jul 01; Vol. 48 (7), pp. 874-882. Date of Electronic Publication: 2024 Mar 19.
DOI:	10.1097/PAS.0000000000002211
Abstrakt:	Abstract: Renal hemangioblastoma (HB) is a rare subset of HBs arising outside of the central nervous system (CNS), with its molecular drivers remaining entirely unknown. There were no significant alterations detected in previous studies, including von Hippel-Lindau gene alterations, which are commonly associated with CNS-HB. This study aimed to determine the real molecular identity of renal HB and better understand its relationship with CNS-HB. A cohort of 10 renal HBs was submitted for next-generation sequencing technology. As a control, 5 classic CNS-HBs were similarly analyzed. Based on the molecular results, glycoprotein nonmetastatic B (GPNMB) immunohistochemistry was further performed in the cases of renal HB and CNS-HB. Mutational analysis demonstrated that all 10 renal HBs harbored somatic mutations in tuberous sclerosis complex 1 ( TSC1 , 5 cases), TSC2 (3 cases), and mammalian target of rapamycin (2 cases), with the majority classified as pathogenic or likely pathogenic. The CNS-HB cohort uniformly demonstrated somatic mutations in the von Hippel-Lindau gene. GPNMB was strong and diffuse in all 10 renal HBs and completely negative in CNS-HBs, reinforcing the molecular findings. Our study reveals a specific molecular hallmark in renal HB, characterized by recurrent TSC/mammalian target of rapamycin mutations, which defines it as a unique entity distinct from CNS-HB. This molecular finding potentially expands the therapeutic options for patients with renal HB. GPNMB can be considered for inclusion in immunohistochemical panels to improve renal HB identification. Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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