Renal cell carcinoma associated with TFEB gene rearrangement: a clinicopathological and molecular study of 8 cases
10.3760/cam.j.cn112151-20221019-00875
- VernacularTitle:TFEB重排肾细胞癌8例临床病理及分子生物学特征
- Author:
Yalan YANG
1
;
Linmao ZHENG
;
Xiaoxue YIN
;
Mengxin ZHANG
;
Yuyan WEI
;
Mengni ZHANG
;
Ling NIE
;
Ni CHEN
;
Xueqin CHEN
;
Qiao ZHOU
Author Information
1. 四川大学华西医院病理科，成都 610041
- Keywords:
Carcinoma, renal cell;
Molecular biology;
Pathology, clinical;
Prognosis
- From:
Chinese Journal of Pathology
2023;52(3):236-242
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the clinicopathological features, immunophenotype, molecular genetic characteristics and prognosis of renal cell carcinoma associated with TFEB gene rearrangement (TFEBr-RCC).Methods:Eight cases of TFEBr-RCC diagnosed at the West China Hospital of Sichuan University from 2014 to 2022 were collected for clinicopathological, immunohistochemical, fluorescence in situ hybridization and RNA sequencing analyses, with review of literature.Results:Six patients were male and two were female. The patient ages ranged from 25 to 50 years (mean: 34 years, median: 32 years). The tumors were present in the right kidney (3 cases) or the left kidney (5 cases). The maximum diameters of the tumors ranged from 4.0 cm to 18.5 cm, with an average of 8.5 cm. Histologically, majority of the cases (5/8) showed typical biphasic "pseudorosette" structure, while the remaining three cases demonstrated atypical morphology that was similar to epithelioid angiomyolipoma or clear cell renal cell carcinoma. Immunohistochemical study showed positivity of TFEB (8/8), PAX8 (8/8), MART-1 (7/7), and HMB45 (5/6). Interestingly, PD-L1 was variably expressed in all five tested cases. Staining for TFE3 in all cases was negative. TFEB translocation was verified in all 8 cases using TFEB fluorescence in situ hybridization. RNA sequencing showed MALAT1-TFEB gene fusion in 4 of the 5 tested cases (two of which showing novel MALAT1-TFEB fusion sites), and one case with a novel ACTB-TFEB gene fusion. Patient follow-ups ranged from 5 to 96 months (average 47 months). All patients were alive without recurrence or metastasis.Conclusions:TFEBr-RCC tends to occur in young adults and has a good prognosis. Histologically, most of the cases show characteristic biphasic structure, and some cases show epithelioid angiomyolipoma-like or clear cell RCC-like morphology. Immunohistochemical reactivity to TFEB, melanocytic markers and PD-L1 is characteristic. MALAT1-TFEB gene fusion is the most common molecular change, with variable fusion sites.
