Xie Bin, Li Qi, Ma Qiang, Huang Ying, Wu Ze, Hu Zhongliang, Feng Junming, Tong Kuo
Department of Pathology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410078, Hunan, China.
Department of Pathology, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, Chongqing, 402760, China.
Virchows Arch. 2025 Apr 30. doi: 10.1007/s00428-025-04111-8.
Low-grade oncocytic fumarate hydratase-deficient renal cell carcinoma (FHdRCC), resembling succinate dehydrogenase-deficient RCC morphologically, is a recently described uncommon variant of FHdRCC. We report five additional cases to enhance the understanding of this rare tumor type. These tumors had variably thick fibromuscular capsules with frequent intracapsular invasions and had prominently compact nests and/or tubules. The tumor cells were characterized by abundant dense eosinophilic cytoplasm imparting a ground glass-like appearance and by variable bubbly cytoplasm. Despite a predominantly low histology grade, focal nuclear pleomorphism was observed in two cases. Two cases showed FH negativity and 2SC positivity, while the remaining cases exhibited both FH and 2SC positivity. All cases were positive for PAX8, Vimentin, P504s, and SDHB, but negative for CD117, CA9, CK20, ALK, and cathepsin-K. CK7 and TFE3 positivity were seen in 2 and 4 of 5 cases, respectively. The whole exome sequencing and multiplex PCR-based next generation sequencing identified pathogenic or likely pathogenic FH mutations in three cases and failed in one case showing the FH-negative and 2SC-positive immunophenotype. The remaining case exhibiting both FH and 2SC positivity had a germline FH mutation of uncertain significance and single copy loss of chromosomes 1, 14, and 18. None of three cases who underwent FISH detections had TFE3 translocations. Follow-up time for the 5 cases ranged from 7 to 94 months (median 46 months; mean 52 months). All cases were alive without disease, except for case 4 being alive with a stable contralateral renal mass. While low-grade oncocytic FHdRCC has a relatively better prognosis than conventional FHdRCCs, further research is required to confirm this in the future.
低级别富马酸水合酶缺乏的嗜酸性肾细胞癌（FHdRCC）在形态学上类似于琥珀酸脱氢酶缺乏的肾细胞癌，是一种最近才被描述的不常见的FHdRCC变异类型。我们报告另外5例病例，以增进对这种罕见肿瘤类型的了解。这些肿瘤具有厚度不一的纤维肌肉包膜，常有包膜内浸润，并有明显的致密巢状和/或管状结构。肿瘤细胞的特征是具有丰富的致密嗜酸性细胞质，呈现毛玻璃样外观，以及形态各异的泡沫状细胞质。尽管组织学分级主要为低级别，但在2例病例中观察到局灶性核异型性。2例病例显示FH阴性和2SC阳性，其余病例则同时显示FH和2SC阳性。所有病例PAX8、波形蛋白、P504s和SDHB均为阳性，但CD117、CA9、CK20、ALK和组织蛋白酶K均为阴性。5例病例中分别有2例和4例CK7和TFE3呈阳性。全外显子测序和基于多重PCR的下一代测序在3例病例中鉴定出致病性或可能致病性的FH突变，1例显示FH阴性和2SC阳性免疫表型的病例未检测到突变。其余同时显示FH和2SC阳性的病例有一个意义不确定的种系FH突变以及1号、14号和18号染色体单拷贝缺失。3例行FISH检测的病例均未发现TFE3易位。5例病例的随访时间为7至94个月（中位时间46个月；平均52个月）。除病例4有对侧肾脏稳定肿块且仍存活外，所有病例均存活且无疾病。虽然低级别嗜酸性FHdRCC的预后相对优于传统FHdRCC，但未来仍需进一步研究加以证实。
