Clinical Presentations, Biochemical Phenotypes, and Genotype-Phenotype Correlations in Patients with<i>Succinate Dehydrogenase Subunit B</i>-Associated Pheochromocytomas and Paragangliomas

Timmers, Henri J L M; Kozupa, Anna; Eisenhofer, Graeme; Raygada, Margarita; Adams, Karen T.; Solis, D.; Lenders, Jacques W.M.; Pacák, Karel

doi:10.1210/jc.2006-2315

Cited by 253 publications

(277 citation statements)

References 35 publications

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“…According to the genetic testing algorithm recommended by experts at the First International Symposium on Pheochromocytoma (26), testing for SDHB and SDHD mutations is suggested for patients who present with bilateral extra-adrenal tumors. SDHB mutations have been associated with malignant disease (27), extra-adrenal paragangliomas (28), and other extra-paraganglial tumors, for example renal cell carcinoma (29). A preponderance of head and neck paragangliomas and multifocal disease has been reported in SDHD mutations (23,25), as in the present patient.…”

Section: Dopamine-secreting Paragangliomassupporting

confidence: 72%

Dopamine-secreting Carotid Body Paragangliomas-Biochemical Control with Radiotherapy

Soh

Kek

2012

Intern. Med.

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Head and neck paragangliomas that are exclusively or predominantly dopamine-secreting are rare. Surgery and/or radiotherapy are modalities for locoregional tumoral control. Little is known about the efficacy of radiotherapy for biochemical control in such tumors. We report a 62-year-old Chinese man with bilateral carotid body tumors which were exclusively dopamine secreting. The left-sided tumor invaded the skull base and encased the left carotid artery. Surgery was not performed due to high risk of morbidity and mortality. The patient received external beam radiotherapy to bilateral neck regions. Progressive decline and eventual normalization of urinary dopamine excretion was seen together with a slight reduction in tumor size. This is the first report demonstrating the efficacy of radiotherapy for both biochemical and locoregional control of functioning carotid body paragangliomas.

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Section: Dopamine-secreting Paragangliomassupporting

confidence: 72%

Dopamine-secreting Carotid Body Paragangliomas-Biochemical Control with Radiotherapy

Soh

Kek

2012

Intern. Med.

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“…These germline mutations in the SDH subunit genes were found in individuals with GIST without a personal or family history of paraganglioma. Three of the four SDHB and SDHC germline mutations identified in these patients with GIST have previously been reported to occur in individuals with paragangliomas (12,20,27,28). Like the majority of SDHB mutations associated with paraganglioma, the identified SDHB mutations in these patients with WT GIST are missense mutations in highly conserved amino acids (12,22).…”

Section: Discussionmentioning

confidence: 81%

Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations

Janeway

Kim

Lodish

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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539

471

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Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction of complex II of the electron transport chain. We evaluated the role of defective cellular respiration in sporadic GIST lacking mutations in KIT or PDGFRA (WT). Thirty-four patients with WT GIST without a personal or family history of paraganglioma were tested for SDH germline mutations. WT GISTs lacking demonstrable SDH genetic inactivation were evaluated for SDHB expression by immunohistochemistry and Western blotting and for complex II activity. For comparison, SDHB expression was also determined in KIT mutant and neurofibromatosis-1-associated GIST, and complex II activity was also measured in SDH-deficient paraganglioma and KIT mutant GIST; 4 of 34 patients (12%) with WT GIST without a personal or family history of paraganglioma had germline mutations in SDHB or SDHC. WT GISTs lacking somatic mutations or deletions in SDH subunits had either complete loss of or substantial reduction in SDHB protein expression, whereas most KIT mutant GISTs had strong SDHB expression. Complex II activity was substantially decreased in WT GISTs. WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating SDH mutations. Testing for germline mutations in SDH is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis.genetic predisposition | sarcoma | pediatric

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“…As Gimenez-Roqueplo et al (2003) first reported that an extra-adrenal site, recurrence and malignancy were strongly associated with SDHB mutations and suggested that the presence of SDHB mutants should be considered a high-risk factor for malignancy or recurrence, genotype-phenotype correlations in patients with SDHB-associated PHEO/PGL have been closely studied in cases of malignant PHEO/PGL (Timmers et al 2007). A malignant PGL was documented in 37.5% of SDHB carriers, 3.1% of SDHD carriers and none of the SDHC mutation carriers (Burnichon et al 2009 reported loss of SDHB protein immunoreactivity in tumours with HPPS with a sensitivity of 100% and a specificity of 84%.…”

Section: Figurementioning

confidence: 99%

Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma

Kimura

Takayanagi

Takizawa

et al. 2014

Endocrine-Related Cancer

269

207

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Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. A total of 163 tumours, including 40 metastatic tumours, collected by the Phaeochromocytoma Study Group in Japan (PHEO-J) were analysed using a system called grading system for adrenal phaeochromocytoma and paraganglioma (GAPP). The tumours were scored based on GAPP criteria as follows: histological pattern, cellularity, comedo-type necrosis, capsular/ vascular invasion, Ki67 labelling index and catecholamine type. All tumours were scored from 0 to 10 points and were graded as one of the three types: well-differentiated (WD, 0-2 points), moderately differentiated (MD, 3-6 points) and poorly differentiated (PD, 7-10 points). GAPP scores of the non-metastatic and metastatic groups were 2.08G0.17 and 5.33G0.43 (meanGS.E.M., P!0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (rZK0.438, P!0.01). The mean number of years until metastasis after the initial operation was 5.5G2.6 years. The study included 111 WD, 35 MD and 17 PD types. The five-year survival of these groups was 100, 66.8 and 22.4% respectively. In addition, negative immunoreactivity for succinate dehydrogenase gene subunit B (SDHB) was observed in 13 (8%) MD or PD tumours and ten of the 13 (77%) had metastases. Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.

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Clinical Presentations, Biochemical Phenotypes, and Genotype-Phenotype Correlations in Patients withSuccinate Dehydrogenase Subunit B-Associated Pheochromocytomas and Paragangliomas

Cited by 253 publications

References 35 publications

Dopamine-secreting Carotid Body Paragangliomas-Biochemical Control with Radiotherapy

Dopamine-secreting Carotid Body Paragangliomas-Biochemical Control with Radiotherapy

Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations

Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma

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