Transaminitis Evaluation Leads to the Incidental Diagnosis of Familial Paraganglioma Due to SDHB Mutation

Abstract Background: Paragangliomas are rare neuroendocrine tumors. Patients with succinate dehydrogenase subunit B (SDHB) gene mutations are predisposed to developing paraganglioma/pheochromocytoma. We are presenting the case of an incidental finding of a paraganglioma during an evaluation for transaminitis. Clinical Case: A 23-year-old male with a medical history of right hydrocele repair as a teenager was evaluated with an ultrasound of the abdomen for elevated liver enzymes and right upper quadrant discomfort. The ultrasound revealed a large lobular solid vascular 13.8 x 8.1 x 11.3 cm mass in the mid abdomen. He underwent a CT of the chest, abdomen and pelvis which demonstrated a large retroperitoneal mass measuring 16 x 10 x 13.7 cm within the right mid abdomen. The mass was described as a large centrally necrotic peripherally enhancing right retroperitoneal mass displacing the IVC anteriorly. The patient subsequently underwent an image-guided biopsy of the mass and the pathology revealed it was a paraganglioma. The patient denied any history of hypertension, orthostasis, headaches or palpitations. Biochemical workup for plasma catecholamines, plasma metanephrines, 24-hour urine catecholamines and metanephrines and cortisol were unremarkable. His transaminitis also resolved. He underwent a retroperitoneal paraganglioma excision and the final pathology was consistent with paraganglioma and negative for capsular invasion. He was referred to a genetic counsellor for testing since paragangliomas can be inherited. He also mentioned a family history of breast cancer in his mother and HTN and prostate cancer in his father. His test revealed that he had a c.289A>T mutation in his SDHB gene. He was encouraged to share the information with his family to help them understand the implications of his genetic test result. He underwent a surveillance PET scan which showed multiple osseous lesions in his temporal calvarium, sphenoid, spine and sacrum suggestive of metastasis. Repeat imaging with a DOTATATE PET scan showed stable disease. His transaminitis was transient, and we did not find a correlation to his paraganglioma. His imaging tests showed no liver metastasis. A CT of the head showed no evidence of intracranial metastasis. The current plan is to continue surveillance. His older brother underwent a genetic testing. He tested positive for the same SDHB mutation and underwent biochemical and imaging tests which were unremarkable. He too will continue surveillance. Conclusions: Patients with a succinate dehydrogenase subunit B (SDHB) gene mutations are predisposed to developing paraganglioma/pheochromocytoma. The tumors produce catecholamines, but can be biochemically silent as in our patient. They are inherited in an autosomal dominant manner. Our case highlights the importance for genetic counseling which increases the chances of early screening and surveillance in affected family members for optimal multidisciplinary management of patients.

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Succinate dehydrogenase subunit B (SDHB) gene deletion associated with a composite paraganglioma/neuroblastoma

Journal of Medical Genetics ◽

10.1136/jmg.2008.060749 ◽

2008 ◽

Vol 46 (3) ◽

pp. 215-216 ◽

Cited By ~ 19

Author(s):

R Armstrong ◽

K L Greenhalgh ◽

E Rattenberry ◽

B Judd ◽

R Shukla ◽

...

Keyword(s):

Succinate Dehydrogenase ◽

Gene Deletion ◽

Sdhb Gene ◽

Succinate Dehydrogenase Subunit B ◽

Subunit B

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Paraganglioma of the Urinary Bladder Metastatic to the Lung in a Patient with SDHB Gene Mutation: A Case Report

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.065 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S32-S32

Author(s):

C P Onyenekwu ◽

K A Iczkowski ◽

Y Sheinin

Keyword(s):

Wedge Resection ◽

Lung Nodule ◽

Gene Mutations ◽

Pathogenic Mutation ◽

The Body ◽

Sustentacular Cells ◽

History Of ◽

Paraganglioma Syndrome ◽

Sdhb Gene ◽

Succinate Dehydrogenase Subunit B

Abstract Introduction/Objective Paragangliomas are tumors originating from the neural crest. Most tumors are benign and arise from various locations in the body. Extra-adrenal paragangliomas arise as sporadic cases in most settings or as part of heredofamilial syndromes in about one-quarter of cases. Succinate dehydrogenase subunit B (SDHB) gene mutations are associated with an aggressive clinical disease course of pheochromocytoma/paraganglioma. Methods We present a 41-year-old male former smoker with a history of a growing right upper lung nodule on chest imaging. He had no cough or respiratory symptoms. Twenty-seven months prior the patient underwent a cystoprostatectomy due to paraganglioma of the bladder. Genetic testing identified a pathogenic mutation in SDHB gene, c.166_170delCCTCA (p.Pro56Tyrfs*5). He underwent a wedge resection of the lung nodule. Results Sectioning of the lung wedge revealed a well circumscribed, firm tan nodule. Microscopically there were nests of large neoplastic cells with round nuclei and eosinophilic granular cytoplasm. Tumor cells were positive for synaptophysin and chromogranin and negative for pan-cytokeratin. S100 highlighted sustentacular cells. The pulmonary neoplasm was morphologically similar to the prior tumor of the bladder. These features are consistent with a metastatic urothelial paraganglioma to the lung, in a background of a hereditary paraganglioma syndrome. Conclusion Extra-adrenal paraganglioma occurring in a setting of hereditary paraganglioma syndrome has a higher risk of metastasis. Lifelong surveillance even after prompt resection of primary tumor with negative margins is required to ensure early detection of metastasis and prevention of complications associated with it.

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Lack of utility of SDHB mutation testing in adrenergic metastatic phaeochromocytoma

Acta Endocrinologica ◽

10.1530/eje-14-0756 ◽

2015 ◽

Vol 172 (2) ◽

pp. 89-95 ◽

Cited By ~ 7

Author(s):

Mariko Sue ◽

Victoria Martucci ◽

Florina Frey ◽

Jacques W M Lenders ◽

Henri J Timmers ◽

...

Keyword(s):

Metastatic Disease ◽

Primary Tumour ◽

Plasma Concentrations ◽

Gene Mutations ◽

Mutation Testing ◽

Sdhb Mutation ◽

Tumour Location ◽

Succinate Dehydrogenase Subunit B ◽

Design And Methods ◽

Subunit B

ObjectiveTesting for succinate dehydrogenase subunit B (SDHB) mutations is recommended in all patients with metastatic phaeochromocytomas and paragangliomas (PPGLs), but may not be required when metastatic disease is accompanied by adrenaline production. This retrospective cohort study aimed to establish the prevalence of SDHB mutations among patients with metastatic PPGLs, characterised by production of adrenaline compared with those without production of adrenaline, and to establish genotype–phenotype features of metastatic PPGLs according to underlying gene mutations.Design and methodsPresence of SDHB mutations or deletions was tested in 205 patients (114 males) aged 42±16 years (range 9–86 years) at diagnosis of metastatic PPGLs with and without adrenaline production.ResultsTwenty-three of the 205 patients (11%) with metastatic PPGLs had disease characterised by production of adrenaline, as defined by increased plasma concentrations of metanephrine larger than 5% of the combined increase in both normetanephrine and metanephrine. None of these 23 patients had SDHB mutations. Of the other 182 patients with no tumoural adrenaline production, 51% had SDHB mutations. Metastases in bone were 36–41% more prevalent among patients with SDHB mutations or extra-adrenal primary tumours than those without mutations or with adrenal primary tumours. Liver metastases were 81% more prevalent among patients with adrenal than extra-adrenal primary tumours.ConclusionSDHB mutation testing has no utility among patients with adrenaline-producing metastatic PPGLs, but is indicated in other patients with metastatic disease. Our study also reveals novel associations of metastatic spread with primary tumour location and presence of SDHB mutations.

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Malignant paraganglioma in an African patient associated with a succinate dehydrogenase subunit B (SDHB) mutation

South African Journal of Surgery ◽

10.17159/2078-5151/2018/v56n2a2391 ◽

2018 ◽

Vol 56 (2) ◽

pp. 64-66

Author(s):

Dennis Shone ◽

Jacqueline Goedhals ◽

Nicholas E Pearce

Keyword(s):

Succinate Dehydrogenase ◽

Sdhb Mutation ◽

Malignant Paraganglioma ◽

African Patient ◽

Succinate Dehydrogenase Subunit B ◽

Subunit B

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Resection of a functioning intrapericardial paraganglioma associated with succinate dehydrogenase B mutation

SAGE Open Medical Case Reports ◽

10.1177/2050313x19839530 ◽

2019 ◽

Vol 7 ◽

pp. 2050313X1983953 ◽

Cited By ~ 1

Author(s):

Dylan A Siejka ◽

Alexander F Vittorio ◽

Sameer Thakur ◽

John R Burgess ◽

Ashutosh Hardikar

Keyword(s):

Succinate Dehydrogenase ◽

Neuroendocrine Tumours ◽

Young Male ◽

Cardiac Anatomy ◽

Significant Challenge ◽

Catecholamine Excess ◽

History Of ◽

Succinate Dehydrogenase Subunit B ◽

Time Critical ◽

Subunit B

Functional paragangliomas are rare neuroendocrine tumours that secrete catecholamines and are infrequently found in the mediastinum. We report a case of a young male with symptoms of catecholamine excess and a personal and family history of the paraganglioma predisposing succinate dehydrogenase subunit B mutation. The lesion had anatomical intrapericardial juxtaposition to important cardiac anatomy and posed the significant challenge of dissection at surgery. The lesion was successfully resected via sternotomy on cardiopulmonary bypass and confirmed histopathologically as paraganglioma. Intrapericardial paraganglioma is rare and treatment is difficult and time critical considering the proximity of cardiac anatomy as well as malignant potential.

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Longest survive by the combination for radiation-therapy and resection in patient with metastatic spinal paragangliomas from primary-neck lesion with succinate dehydrogenase subunit B (SDHB) mutation

Endocrine Journal ◽

10.1507/endocrj.ej20-0292 ◽

2020 ◽

Author(s):

Takehiro Kitagawa ◽

Tatsuya Ohtonari ◽

Junkoh Yamamoto ◽

Nobuharu Nishihara ◽

Masakazu Nishigaki ◽

...

Keyword(s):

Radiation Therapy ◽

Succinate Dehydrogenase ◽

Sdhb Mutation ◽

Neck Lesion ◽

Succinate Dehydrogenase Subunit B ◽

Subunit B

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Hereditary pheochromocytoma/paraganglioma syndrome with a novel mutation in the succinate dehydrogenase subunit B gene in a Japanese family: two case reports

Journal of Medical Case Reports ◽

10.1186/s13256-021-02852-z ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Rei Hirose ◽

Yuya Tsurutani ◽

Chiho Sugisawa ◽

Kosuke Inoue ◽

Sachiko Suematsu ◽

...

Keyword(s):

Genetic Testing ◽

Succinate Dehydrogenase ◽

Novel Mutation ◽

Case Reports ◽

Site Mutation ◽

Japanese Family ◽

Paraganglioma Syndrome ◽

Succinate Dehydrogenase Subunit B ◽

Hereditary Pheochromocytoma ◽

Subunit B

Abstract Background Pheochromocytoma and paraganglioma caused by succinate dehydrogenase gene mutations is called hereditary pheochromocytoma/paraganglioma syndrome. In particular, succinate dehydrogenase subunit B mutations are important because they are strongly associated with the malignant behavior of pheochromocytoma and paraganglioma . This is a case report of a family of hereditary pheochromocytoma/paraganglioma syndrome carrying a novel mutation in succinate dehydrogenase subunit B. Case presentation A 19-year-old Japanese woman, whose father died of metastatic paraganglioma, was diagnosed with abdominal paraganglioma, and underwent total resection. Succinate dehydrogenase subunit B genetic testing detected a splice-site mutation, c.424-2delA, in her germline and paraganglioma tissue. Afterwards, the same succinate dehydrogenase subunit B mutation was detected in her father’s paraganglioma tissues. In silico analysis predicted the mutation as “disease causing.” She is under close follow-up, and no recurrence or metastasis has been observed for 4 years since surgery. Conclusions We detected a novel succinate dehydrogenase subunit B mutation, c.424-2delA, in a Japanese family afflicted with hereditary pheochromocytoma/paraganglioma syndrome and found the mutation to be responsible for hereditary pheochromocytoma/paraganglioma syndrome. This case emphasizes the importance of performing genetic testing for patients with pheochromocytoma and paraganglioma suspected of harboring the succinate dehydrogenase subunit B mutation (that is, metastatic, extra-adrenal, multiple, early onset, and family history of pheochromocytoma and paraganglioma) and offer surveillance screening to mutation carriers.

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