Kolling Institute of Medical Research, The University of Sydney, Sydney, Australia.
Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia.
Endocr Relat Cancer. 2024 Sep 21;31(10). doi: 10.1530/ERC-24-0111. Print 2024 Oct 1.
Phaeochromocytomas and paragangliomas (collectively termed PPGL) are rare yet highly heritable neuroendocrine tumours, with over one-third of cases associated with germline pathogenic variants (PVs) in numerous genes. PVs in the succinate dehydrogenase subunit-A gene (SDHA) were initially implicated in hereditary PPGL in 2010, and SDHA has since become an important susceptibility gene accounting for up to 2.8% of cases. However, it remains poorly understood, particularly regarding the clinical nature of SDHA PPGL, rates of recurrence and metastasis, and the nature of metastatic disease. We present a narrative review of SDHA-related PPGL, covering pathophysiology, relevance to current clinical practice, and considerations for clinical genetics. We analyse a pool of 107 previously reported cases of SDHA-associated PPGL to highlight the spectrum of SDHA-related PPGL. Our analysis demonstrates that SDHA PPGL occurs across a wide age range (11-81 years) and affects men and women equally. SDHA PPGL typically presents as single tumours (91%), usually occurring in the head and neck (46%) or abdomen (43%, including 15% with phaeochromocytomas). Metastatic disease was reported in 25.5% of cases, with bone (82%) and lymph nodes (71%) being the most common sites of metastasis, often identified many years after the initial diagnosis. A family history of SDHA-related neoplasia was rare, reported in only 4% of cases. Understanding the clinical nature and risks associated with SDHA PVs is essential for facilitating the optimal management of patients and their families.
嗜铬细胞瘤和副神经节瘤（统称为 PPGL）是罕见但高度遗传性的神经内分泌肿瘤，超过三分之一的病例与许多基因中的种系致病性变异（PVs）有关。2010 年，琥珀酸脱氢酶亚单位-A 基因（SDHA）中的 PVs 最初被认为与遗传性 PPGL 有关，此后，SDHA 已成为一个重要的易感基因，占病例的 2.8%。然而，其仍知之甚少，特别是关于 SDHA PPGL 的临床性质、复发和转移率以及转移性疾病的性质。我们对 SDHA 相关的 PPGL 进行了叙述性综述，涵盖了病理生理学、与当前临床实践的相关性以及临床遗传学的考虑因素。我们分析了一组 107 例先前报道的 SDHA 相关 PPGL 病例，以突出 SDHA 相关 PPGL 的范围。我们的分析表明，SDHA PPGL 发生在广泛的年龄范围内（11-81 岁），男女发病率相等。SDHA PPGL 通常表现为单发肿瘤（91%），通常发生在头颈部（46%）或腹部（43%，包括 15%的嗜铬细胞瘤）。转移性疾病在 25.5%的病例中被报道，骨（82%）和淋巴结（71%）是最常见的转移部位，通常在初始诊断多年后才被发现。仅有 4%的病例报告了 SDHA 相关肿瘤的家族史。了解与 SDHA PVs 相关的临床性质和风险对于促进患者及其家属的最佳管理至关重要。
