Imaging Work-Up for Screening of Paraganglioma and Pheochromocytoma in<i>SDHx</i>Mutation Carriers: A Multicenter Prospective Study from the PGL.EVA Investigators

Gimenez-Roqueplo, Anne-Paule; Caumont-Prim, Aurore; Houzard, C.; Hignette, C.; Hernigou, A.; Halimi, P.; Niccoli, Patricia; Leboulleux, Sophie; Amar, Laurence; Borson‐Chazot, Françoise; Cardot-Bauters, Catherine; Delemer, Brigitte; Chabolle, F.; Coupier, Isabelle; Libé, Rossella; Peitzsch, Mirko; Peyrard, Séverine; Tenenbaum, Florence; Plouin, Pierre‐François; Châtellier, Gilles; Rohmer, V.

doi:10.1210/jc.2012-2975

Cited by 134 publications

(122 citation statements)

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“…Germline mutations of genes encoding subunits of succinate dehydrogenase account for the majority of PGL in the head and neck. Their recognition promotes screening for associated tumors in affected patients and, conversely, recognition of associated tumors can lead to screening for paragangliomas [50]. Loss of immunohistochemical staining for SDHB protein is a valuable screening tool that can help to identify any succinate dehydrogenase gene mutation in most tumors.…”

Section: In Summary (Table 2)mentioning

confidence: 99%

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Paragangliomas

Williams

Tischler

2017

Head and Neck Pathol

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Section: In Summary (Table 2)mentioning

confidence: 99%

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Paragangliomas

Williams

Tischler

2017

Head and Neck Pathol

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“…Its use for standard evaluation of HNPGLs is limited, and it is more frequently employed to assess tumour avidity for the tracer if radionuclide therapy is planned. Somatostatin receptor (SSR) scintigraphy has a better sensitivity, lower than that of standard anatomical imaging but offers whole-body scanning (Timmers et al 2012, Gimenez-Roqueplo et al 2013. Positron-emission tomography (PET) has been used intensively as it can be used for the examination of the whole body with improved resolution, and it can detect small (Gabriel et al 2013) and SDH-related HNPGLs (King et al 2011).…”

Section: Diagnosismentioning

confidence: 99%

The management of head-and-neck paragangliomas

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Ntali

Karavitaki

et al. 2013

Endocrine-Related Cancer

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Paragangliomas (PGLs) are tumours originating from neural crest-derived cells situated in the region of the autonomic nervous system ganglia. Head-and-neck PGLs (HNPGLs) originate from the sympathetic and parasympathetic paraganglia, most frequently from the carotid bodies and jugular, tympanic and vagal paraganglia, and are usually non-catecholamine secreting. Familial PGLs are considered to be rare, but recently genetic syndromes including multiple PGLs and/or phaeochromocytomas have been more thoroughly characterised. Nowadays, genetic screening for the genes frequently implicated in both familial and sporadic cases is routinely being recommended. HNPGLs are mostly benign, generally slow-growing tumours. Continuous growth leads to the involvement of adjacent neurovascular structures with increased morbidity rates and treatment-related complications. Optimal management mostly depends on tumour location, local involvement of neurovascular structures, estimated malignancy risk, patient age and general health. Surgery is the only treatment option offering the chance of cure but with significant morbidity rates, so a more conservative approach is usually considered, especially in the more difficult cases. Radiotherapy (fractionated or stereotactic radiosurgery) leads to tumour growth arrest and symptomatic improvement in the short term in many cases, but the longterm consequences are unclear. Early detection is essential in order to increase the chance of cure with a lower morbidity rate. The constant improvement in diagnostic imaging, surgical and radiation techniques has led to a safer management of these tumours, but there are still many therapeutic challenges, and no treatment algorithm has been agreed upon until now. The management of HNPGLs requires a multidisciplinary effort addressing the genetic, surgical, radiotherapeutic, oncological, neurological and endocrinological implications. Further progress in the understanding of their pathogenesis will lead to more effective screening and earlier diagnosis, both critical to successful treatment.

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“…SDHx mutation carriers are at risk of developing multiple paraganglioma that can arise all along the embryonic migration way of neural crest cells, from the base of the skull to the pelvis (10). Moreover, the identification of SDHB gene mutations is of specific clinical importance as they predispose to malignant, particularly aggressive forms of the disease (11,12), and a genetic counseling is now recommended for all patients suffering from PPGL (1).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Detection of Succinate by Magnetic Resonance Spectroscopy as a Hallmark of SDHx Mutations in Paraganglioma

Lussey-Lepoutre

Bellucci

Morin

et al. 2016

Clinical Cancer Research

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International audiencePurpose: Germline mutations in genes encoding mitochon-drial succinate dehydrogenase (SDH) are found in patients with paragangliomas, pheochromocytomas, gastrointestinal stromal tumors, and renal cancers. SDH inactivation leads to a massive accumulation of succinate, acting as an oncometabolite and which levels, assessed on surgically resected tissue are a highly specific biomarker of SDHx-mutated tumors. The aim of this study was to address the feasibility of detecting succinate in vivo by magnetic resonance spectroscopy. Experimental Design: A pulsed proton magnetic resonance spectroscopy (1 H-MRS) sequence was developed, optimized, and applied to image nude mice grafted with Sdhb À/À or wild-type chromaffin cells. The method was then applied to patients with paraganglioma carrying (n ¼ 5) or not (n ¼ 4) an SDHx gene mutation. Following surgery, succinate was measured using gas chromatography/mass spectrometry, and SDH protein expression was assessed by immunohistochemistry in resected tumors. Results: A succinate peak was observed at 2.44 ppm by 1 H-MRS in all Sdhb À/À-derived tumors in mice and in all paragangliomas of patients carrying an SDHx gene mutation, but neither in wild-type mouse tumors nor in patients exempt of SDHx mutation. In one patient, 1 H-MRS results led to the identification of an unsus-pected SDHA gene mutation. In another case, it helped define the pathogenicity of a variant of unknown significance in the SDHB gene. Conclusions: Detection of succinate by 1 H-MRS is a highly specific and sensitive hallmark of SDHx mutations. This non-invasive approach is a simple and robust method allowing in vivo detection of the major biomarker of SDHx-mutated tumors. Clin Cancer Res; 22(5); 1120–9. Ó2015 AACR

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Imaging Work-Up for Screening of Paraganglioma and Pheochromocytoma inSDHxMutation Carriers: A Multicenter Prospective Study from the PGL.EVA Investigators

Abstract: In routine practice, the imaging work-up for screening SDHx mutation carriers should include thoraco-abdomino-pelvic computed tomography, head and neck magnetic angiography, and somatostatin receptor scintigraphy. Expert centralized image assessment is recommended.

Cited by 134 publications

References 40 publications

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Paragangliomas

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Paragangliomas

The management of head-and-neck paragangliomas

In Vivo Detection of Succinate by Magnetic Resonance Spectroscopy as a Hallmark of SDHx Mutations in Paraganglioma

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