Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, Kansas City, KS.
Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT.
Adv Anat Pathol. 2021 Nov 1;28(6):396-407. doi: 10.1097/PAP.0000000000000321.
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is typically considered a high-grade, aggressive subtype of RCC that frequently arises in the setting of hereditary leiomyomatosis-renal cell carcinoma (HLRCC) syndrome. Increasing experience with HLRCC-associated RCC and FH-deficient RCC has resulted in recognition of tumors with lower grade morphologic features, overlapping with those of succinate dehydrogenase-deficient RCC and other low-grade oncocytic tumors. In this review article, we report a previously unpublished case that was recently encountered in our practice and review cases in the current literature with an aim of getting a better understanding of these oncocytic tumors and their morphologic spectrum. The 13 cases reviewed were approximately equally distributed across males and females, occurred at a younger age, and were more frequently seen in the right kidney, with both unifocal and multifocal presentations. While most presented an exclusive, low-grade oncocytic morphology, in 4 cases they were associated with either separate high-grade tumors, or as a secondary pattern in an otherwise conventional high-grade FH-deficient RCC. Loss of FH and 2 succinyl cysteine (2SC) positivity by immunohistochemistry supported their diagnosis, and are recommended to be performed alongside CD117, CK7, and CK20 in to aid classification in challenging oncocytic tumors. When occurring in isolation, these tumors are distinctive from their high-grade counterparts, with no reported adverse outcomes in cases reported thus far. As such, accurate diagnosis of this low-grade pattern among FH-deficient RCCs is worthwhile not only due to its association with HLRCC and need of genetic counseling and surveillance, but also due to more favorable prognosis. Finally, increasing experience with the low-grade end of the morphologic spectrum of FH deficient RCC reiterates that not all tumors of this subtype of RCC have a uniformly aggressive outcome.
琥珀酸脱氢酶缺陷型肾细胞癌（FH-deficient RCC）通常被认为是一种高级别、侵袭性的 RCC 亚型，常发生于遗传性平滑肌瘤-肾细胞癌（HLRCC）综合征中。随着对 HLRCC 相关 RCC 和 FH 缺陷型 RCC 的经验不断增加，人们认识到这些肿瘤具有较低级别的形态特征，与琥珀酸脱氢酶缺陷型 RCC 和其他低级别嗜酸细胞瘤重叠。在这篇综述文章中，我们报告了一个最近在我们的实践中遇到的、以前未发表的病例，并回顾了当前文献中的病例，旨在更好地了解这些嗜酸细胞瘤及其形态谱。回顾的 13 例病例在男性和女性中的分布大致相等，发病年龄较小，更多见于右肾，既有单发病灶也有多发病灶。虽然大多数病例表现为单纯的低级别嗜酸细胞瘤形态，但在 4 例病例中，它们与单独的高级别肿瘤或在其他常规 FH 缺陷型 RCC 中作为次要模式相关。免疫组织化学检测 FH 和 2 个琥珀酰半胱氨酸（2SC）阳性支持其诊断，建议与 CD117、CK7 和 CK20 一起进行检测，以辅助在具有挑战性的嗜酸细胞瘤中进行分类。当孤立发生时，这些肿瘤与高级别肿瘤不同，迄今为止报告的病例均无不良预后。因此，在 FH 缺陷型 RCC 中准确诊断这种低级别形态不仅因为其与 HLRCC 相关，需要遗传咨询和监测，还因为其预后较好。最后，对 FH 缺陷型 RCC 形态学谱的低级别末端的不断增加的经验再次表明，并非所有此类 RCC 亚型的肿瘤都具有一致的侵袭性结局。
