An Update on the Histology of Pheochromocytomas: How Does it Relate to Genetics?

Oudijk, Lindsey; Gaal, José; Koopman, Karen; Krijger, Ronald R. de

doi:10.1055/a-0672-1266

Cited by 6 publications

(7 citation statements)

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“…25 Inactivation of SDHB reduces function of the succinate dehydrogenase complex, leading to activation of the hypoxia-inducible pathway and a pseudohypoxic state characterised by increased angiogenesis, growth and expression of mitogenic factors, 26 but also to DNA hypermethylation, which is believed to provide a further drive to metastatic progression. 27 At least 35% of PPGLs result from germline mutations of over 18 tumour-susceptibility genes identified to date, [28][29][30][31][32][33] with those resulting in stabilisation of hypoxia-inducible factors 1a and 2a (HIF1a and HIF2a) carrying a higher risk of metastatic disease than those due to other mutations (supplementary Table S4, available at https://doi.org/10. 1016/j.annonc.2020.08.2099).…”

Section: Molecular Biologymentioning

confidence: 99%

Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up

et al. 2020

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Section: Molecular Biologymentioning

confidence: 99%

Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up

et al. 2020

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“…In addition, germline mutations have been identified, but they comprise <1% of PCC/PGL. EPAS1/HIF2 alpha mutations are also linked to polycythemia and somatostinoma [30,31,32].…”

Section: Geneticsmentioning

confidence: 99%

Pheochromocytomas and Paragangliomas: New Developments with Regard to Classification, Genetics, and Cell of Origin

Koopman

Gaal

Krijger

2019

Cancers

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Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors that arise in the adrenal medulla and in extra-adrenal locations, such as the head, neck, thorax, abdomen, and pelvis. Classification of these tumors into those with or without metastatic potential on the basis of gross or microscopic features is challenging. Recent insights and scoring systems have attempted to develop solutions for this, as described in the latest World Health Organization (WHO) edition on endocrine tumor pathology. PCC and PGL are amongst the tumors most frequently accompanied by germline mutations. More than 20 genes are responsible for a hereditary background in up to 40% of these tumors; somatic mutations in the same and several additional genes form the basis for another 30%. However, this does not allow for a complete understanding of the pathogenesis or targeted treatment of PCC and PGL, for which surgery is the primary treatment and for which metastasis is associated with poor outcome. This review describes recent insights into the cell of origin of these tumors, the latest developments with regard to the genetic background, and the current status of tumor classification including proposed scoring systems.

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“…27 PPGL susceptibility genes can be further defined by syndromic patterns and anatomical distributions, (discussed in several recent reviews). [28][29][30][31] For example, most individuals with SDHD-related PPGLs have HNPGLs, which are predominantly biochemically silent and multifocal. 28,32 In contrast, SDHB-related PPGLs are more likely to be sympathetic extra-adrenal PGLs and, whilst less likely to be multifocal, have a high risk of metastatic spread.…”

Section: Mutation Frequency In Ppglsmentioning

confidence: 99%

“…PPGL susceptibility genes can be further defined by syndromic patterns and anatomical distributions, (discussed in several recent reviews) 28‐31 . For example, most individuals with SDHD ‐related PPGLs have HNPGLs, which are predominantly biochemically silent and multifocal 28,32 .…”

Section: Introductionmentioning

confidence: 99%

PET detectives: Molecular imaging for phaeochromocytomas and paragangliomas in the genomics era

Ryder

Love

Duncan

et al. 2020

Clinical Endocrinology

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Phaeochromocytomas and paragangliomas (PPGLs) are rare tumours that arise from the adrenal medulla or extra‐adrenal sympathetic or parasympathetic paraganglia. Recent advances in genetics have greatly enhanced understanding of the pathogenesis and molecular physiology of PPGL. Concomitantly, advances in molecular imaging mean four techniques are now available for use in PPGLs: [123I]‐MIBG coupled with SPECT/CT; [18F]‐ FDG, [68Ga]‐DOTATATE and [18F]‐FDOPA coupled with PET/CT. Each modality relies on unique cellular uptake mechanisms that are contingent upon the tumour's molecular behaviour—which, in turn, is determined by the tumour's genetic profile. This genotype‐phenotype correlation means the appropriate choice of radiotracer may depend on the known (or suspected) underlying genetic mutation, in addition to the clinical indication for the scan—whether confirming diagnosis, staging disease, surveillance or determining eligibility for radionuclide therapy. Given these rapid recent changes in genetic understanding and molecular imaging options, many clinicians find it challenging to choose the most appropriate scan for an individual with PPGL. To this end, recent guidelines published by the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging (EANM/SNMMI) have detailed the preferred radiotracer choices for individuals with PPGL based on their genotype and/or clinical presentation, providing timely clarity in this rapidly moving field. The current review summarizes the implications of the genotype‐phenotype relationship of PPGL, specifically relating this to the performance of molecular imaging modalities, to inform and enable practising endocrinologists to provide tailored, personalized care for individuals with PPGL.

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An Update on the Histology of Pheochromocytomas: How Does it Relate to Genetics?

Cited by 6 publications

References 84 publications

Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up

Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up

Pheochromocytomas and Paragangliomas: New Developments with Regard to Classification, Genetics, and Cell of Origin

PET detectives: Molecular imaging for phaeochromocytomas and paragangliomas in the genomics era

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