HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Metastatic pheochromocytomas and paragangliomas: proceedings of the MEN2019 workshop

Dahia, Patricia L.M.; Clifton‐Bligh, Roderick; Gimenez-Roqueplo, A.-P.; Robledo, Mercedes; Jiménez, Camilo

doi:10.1530/erc-19-0435

Cited by 37 publications

(36 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further studies and newer treatment modalities are urgently needed. New guidelines regarding the management and research opportunities of sporadic and hereditary PPGLs have recently been published ( 76 , 129 ).…”

Section: Discussionmentioning

confidence: 99%

Metastatic Pheochromocytomas and Abdominal Paragangliomas

Granberg

Juhlin

Falhammar

2021

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

Context Pheochromocytomas and paragangliomas (PPGLs) are believed to harbor malignant potential; about 10% to 15% of pheochromocytomas and up to 50% of abdominal paragangliomas will exhibit metastatic behavior. Evidence Acquisition Extensive searches in the PubMed database with various combinations of the key words pheochromocytoma, paraganglioma, metastatic, malignant, diagnosis, pathology, genetic, and treatment were the basis for the present review. Data Synthesis To pinpoint metastatic potential in PPGLs is difficult, but nevertheless crucial for the individual patient to receive tailor-made follow-up and adjuvant treatment following primary surgery. A combination of histological workup and molecular predictive markers can possibly aid the clinicians in this aspect. Most patients with PPGLs have localized disease and may be cured by surgery. Plasma metanephrines are the main biochemical tests. Genetic testing is important, both for counseling and prognostic estimation. Apart from computed tomography and magnetic resonance imaging, molecular imaging using 68Ga-DOTATOC/DOTATATE should be performed. 123I-MIBG scintigraphy may be performed to determine whether 131I-MIBG therapy is a possible option. As first-line treatment in patients with metastatic disease, 177Lu-DOTATATE or 131I-MIBG is recommended, depending on which shows best expression. In patients with very low proliferative activity, watch-and-wait or primary treatment with long-acting somatostatin analogues may be considered. As second-line treatment, or first-line in patients with high proliferative rate, chemotherapy with temozolomide or cyclophosphamide + vincristine + dacarbazine is the therapy of choice. Other therapies, including sunitinib, cabozantinib, everolimus, and PD-1/PDL-1 inhibitors, have shown modest effect. Conclusions Metastatic PPGLs need individualized management and should always be discussed in specialized and interdisciplinary tumor boards. Further studies and newer treatment modalities are urgently needed.

show abstract

Section: Discussionmentioning

confidence: 99%

Metastatic Pheochromocytomas and Abdominal Paragangliomas

Granberg

Juhlin

Falhammar

2021

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

show abstract

“…Biochemical and imaging diagnosis of PPGL followed the Endocrine Society guideline recommendations 1 . Moreover, metastatic PPGL was defined by the presence of tumour in nonchromaffin tissues 4 . The TNM staging system for mPPGL developed for the American Joint Committee on Cancer was employed 12…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, metastatic PPGL (mPPGL) is defined by the presence of tumours in nonchromaffin tissues. Approximately 15%–20% of adult individuals with PPGL develop metastasis 4 . Metastatic disease ranged from 12% to 47% among children 5 .…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 15%-20% of adult individuals with PPGL develop metastasis. 4 Metastatic disease ranged from 12% to 47% among children. 5 Pamporaki et al 6 recently showed that 49.5% of 95 children with PPGL were diagnosed with metastatic disease.…”

Section: Introductionmentioning

confidence: 99%

“…Patients and Methods: This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The median time of follow-up was 145 months.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Genetic and clinical aspects of paediatric pheochromocytomas and paragangliomas

Petenuci

Guimarães

Fagundes

et al. 2021

Clinical Endocrinology

View full text Add to dashboard Cite

Objective Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL. Patients and Methods This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4‐19). The median time of follow‐up was 145 months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation‐dependent probe amplification and/or target next‐generation sequencing panel. Results Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline VHL pathogenic variants, SDHB, SDHD, RET and negative genetic investigation, respectively. Children with germline VHL missense pathogenic variants were younger than those with SDHB or SDHD genetic defects [median (range), 12 (4‐16) vs. 15.5 (14‐19) years; P = .027]. Moreover, 10 of 11 cases with VHL pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline SDHB pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with SDHD pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL. Conclusions Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with VHL being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.

show abstract