Adam I Kaplan, Trisha Dwight, Catherine Luxford, Diana E Benn, Roderick J Clifton-Bligh
{"title":"与 SDHA 相关的嗜铬细胞瘤和副神经节瘤:综述和临床治疗。","authors":"Adam I Kaplan, Trisha Dwight, Catherine Luxford, Diana E Benn, Roderick J Clifton-Bligh","doi":"10.1530/ERC-24-0111","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466202/pdf/","citationCount":"0","resultStr":"{\"title\":\"SDHA-related phaeochromocytoma and paraganglioma: review and clinical management.\",\"authors\":\"Adam I Kaplan, Trisha Dwight, Catherine Luxford, Diana E Benn, Roderick J Clifton-Bligh\",\"doi\":\"10.1530/ERC-24-0111\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":93989,\"journal\":{\"name\":\"Endocrine-related cancer\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466202/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrine-related cancer\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1530/ERC-24-0111\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine-related cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1530/ERC-24-0111","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/1 0:00:00","PubModel":"Print","JCR":"","JCRName":"","Score":null,"Total":0}
SDHA-related phaeochromocytoma and paraganglioma: review and clinical management.
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.