Fumarate hydratase (FH) deficiency is a rare, yet impactful metabolic disorder caused by mutations in the FH gene, affecting the Krebs cycle, leading to the accumulation of fumarate and pseudohypoxic states. This metabolic shift promotes cell signaling alterations that can drive tumorigenesis, as heterozygous germline mutations in the FH gene, resulting in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. FH-deficient uterine leiomyomas show peculiar histological features that may lead to misdiagnosis STUMP (smooth muscle tumor of uncertain malignant potential) and uLMS (uterine leiomyosarcoma). Definitive diagnosis involves clinical evaluation, imaging, and histopathological examination, with immunohistochemistry for FH protein being a key diagnostic tool. Management of FH-deficient leiomyomas may involve conventional treatments like surgery and hormonal therapy but also requires careful monitoring and genetic counseling for associated malignancies. High-intensity focused ultrasound (HIFU) has emerged as a promising treatment option for fibroids, although long-term efficacy remains a concern also because of its inability to obtain tissue for a pathological diagnosis. Fumarate hydratase deficiency (FHD) represents a significant challenge in gynecologic oncology due to its association with an increased risk of hereditary leiomyomatosis and renal cell carcinoma. Nevertheless, to the best of our knowledge, there is a lack of studies demonstrating the potential role of FH deficiency in increased risk of leiomyosarcomatosus transformation. Early detection, genetic screening, and personalized treatment approaches are critical for improving patient outcomes. The aim of this review is to develop a narrative overview of the implications of FHD in gynecological diseases and its correlation with cancer risk. For the first time, this review offers an overview of the necessity for studies to address the possible correlation between FH deficiency and the risk of developing leiomyosarcoma, focusing on new perspectives that can be explored in the field of better FH deficiency knowledge and cancer risk.
延胡索酸水合酶（FH）缺乏症是一种罕见但影响深远的代谢性疾病，由FH基因突变引起，影响克雷布斯循环，导致延胡索酸积累和假性缺氧状态。这种代谢转变促进细胞信号传导改变，从而驱动肿瘤发生，如FH基因杂合种系突变导致的遗传性平滑肌瘤病和肾细胞癌（HLRCC）综合征。FH缺乏的子宫平滑肌瘤表现出独特的组织学特征，可能导致误诊为恶性潜能未定的平滑肌瘤（STUMP）和子宫平滑肌肉瘤（uLMS）。明确诊断需结合临床评估、影像学和组织病理学检查，其中FH蛋白的免疫组化染色是关键诊断工具。FH缺乏平滑肌瘤的治疗可能包括手术和激素治疗等常规方法，但也需要对相关恶性肿瘤进行密切监测和遗传咨询。高强度聚焦超声（HIFU）已成为治疗肌瘤的一种有前景的选择，尽管其长期疗效仍受关注，部分原因在于无法获取组织进行病理诊断。延胡索酸水合酶缺乏症（FHD）因其与遗传性平滑肌瘤病和肾细胞癌风险增加相关，在妇科肿瘤学中构成重大挑战。然而，据我们所知，目前缺乏研究证明FH缺乏在增加平滑肌肉瘤转化风险中的潜在作用。早期检测、遗传筛查和个性化治疗方法对于改善患者预后至关重要。本综述旨在系统阐述FHD在妇科疾病中的影响及其与癌症风险的相关性。首次综述了研究FH缺乏与发生平滑肌肉瘤风险之间可能相关性的必要性，重点关注在深化FH缺乏认识和癌症风险领域可探索的新视角。
肿瘤(癌症)患者之家