Recent Advances in Histopathological and Molecular Diagnosis in Pheochromocytoma and Paraganglioma: Challenges for Predicting Metastasis in Individual Patients

Yamazaki, Yuto; Gao, Xin; Pecori, Alessio; Nakamura, Yasuhiro; Tezuka, Yuta; Omata, Kei; Ono, Yoshikiyo; Morimoto, Ryo; Satoh, Fumitoshi; Sasano, Hironobu

doi:10.3389/fendo.2020.587769

Cited by 19 publications

(18 citation statements)

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“…Hence, the clinical presentation combined with radiological and biochemical findings may serve as a guide to the appropriate genetic testing. PPGLs display considerable heterogeneity and are classified into three different groups according to patient outcome and underlying genetics [36,42]. Each subgroup is associated with distinct biochemical and clinical phenotype (Table 1) [12].…”

Section: Genetics Of Ppglsmentioning

confidence: 99%

“…Each subgroup is associated with distinct biochemical and clinical phenotype (Table 1) [12]. The most prevalent subtype is the 'pseudohypoxia' group which is characterized by somatic or germline mutations in genes involved in the tricarboxylic acid cycle, including succinate dehydrogenase subunits SDHx, fumarate hydratase (FH), von Hippel-Lindau (VHL), endothelial PAS domain 1 (EPAS1), also known as hypoxia-inducible factor 2 (HIF2A)), and in polyhydroxylases PHD1 and PHD2 [36,42]. PPGLs in this cluster are mainly extra-adrenal and aggressive, and particularly those related to SDHB mutations, are associated with the highest proportion of metastatic disease [72,73].…”

Section: Genetics Of Ppglsmentioning

confidence: 99%

“…The second subtype is the 'kinase signaling' group that is associated with genetic or somatic mutations in the RET proto-oncogene (syndrome MEN 2A, 2B), neurofibromin 1 (NF1), transmembrane protein 127 (TMEM127), MYC-associated factor X (MAX), kinesinlike protein (KIF1BB), receptor tyrosine kinase (MET), GTPase, and Harvey rat sarcoma viral oncogene homolog (HRAS) [36,42]. PPGLs in this group are predominately located in the adrenals and rarely develop metastatic disease [72].…”

Section: Genetics Of Ppglsmentioning

confidence: 99%

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A Critical Appraisal of Contemporary and Novel Biomarkers in Pheochromocytomas and Adrenocortical Tumors

Tsoli

Daskalakis

Kassi

et al. 2021

Biology

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Pheochromocytomas/Paragangliomas (PPGLs) and adrenocortical tumors are rare neoplasms with significant heterogeneity in their biologic and clinical behavior. Current diagnostic and predictive biomarkers include hormone secretion, as well as histopathological and genetic features. PPGL diagnosis is based on biochemical measurement of catecholamines/metanephrines, while histopathological scoring systems have been proposed to predict the risk of malignancy. Adrenocortical tumors are mostly benign, but some can be malignant. Currently, the stage of disease at diagnosis and tumor grade, appear to be the most powerful prognostic factors. However, recent genomic and proteomic studies have identified new genetic and circulating biomarkers, including genes, immunohistochemical markers and micro-RNAs that display high specificity and sensitivity as diagnostic or prognostic tools. In addition, new molecular classifications have been proposed that divide adrenal tumors in distinct subgroups with different clinical outcomes.

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Section: Genetics Of Ppglsmentioning

confidence: 99%

Section: Genetics Of Ppglsmentioning

confidence: 99%

Section: Genetics Of Ppglsmentioning

confidence: 99%

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A Critical Appraisal of Contemporary and Novel Biomarkers in Pheochromocytomas and Adrenocortical Tumors

Tsoli

Daskalakis

Kassi

et al. 2021

Biology

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“…At least 10% of pheochromocytomas and up to 25% of PGLs are metastatic, although rates of malignancy vary depending on the anatomical site of origin (for example, 2-4% jugulotympanic, 4-6% carotid body, or 10-19% vagal tumours) and the genetic context [1,30]. Considering the latter, mutations in the succinate dehydrogenase B (SHDB) gene are at a highest risk of metastatic disease (up to 50% of affected patients) [31,32]. Mutations leading to stabilization of hypoxia-inducible factor 2α (HIF2α) and downstream pseudohypoxic signalling are also associated with a higher risk of metastatic disease (in 30% of the cases) [33].…”

Section: Epidemiologymentioning

confidence: 99%

Special situations in pheochromocytomas and paragangliomas: pregnancy, metastatic disease, and cyanotic congenital heart diseases

et al. 2021

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The aim of our study was to describe the epidemiology, diagnosis, and treatment of the most complex pheochromocytoma and paraganglioma (PGL) cases, including pheochromocytoma/PGL during pregnancy, in cyanotic congenital heart diseases (CCHDs), and metastatic pheochromocytoma. The English and Spanish literature was thoroughly evaluated searching for articles reporting clinical studies, case reports, or reviews of pheochromocytoma/PGL in pregnancy and in CCHD and metastatic pheochromocytoma/PGL. Particular settings in the diagnosis and management of pheochromocytoma and PGLs remain challenging. Those special situations include the diagnosis during pregnancy or in the context of CCHD since the typical clinical features of pheochromocytoma may be confounded with preeclampsia during pregnancy and with the complications commonly observed in CCHD. In addition, although some clinical and genetic features have been associated with higher risk of metastatic pheochromocytoma, the detection and prediction of the development of metastatic disease involve another complex situation that may require special hormonal determinations as plasmatic 3-methoxytyramine and nuclear medicine studies including 18 FDG PET-CT or 18 F-FDOPA PET-CT, among others. Furthermore, the selection of the most appropriate treatment in these situations, as well as the moment to carry it out, requires special care as limited evidence is available. This article reviews the epidemiology, diagnosis, and treatment of the pheochromocytoma/PGL during pregnancy, metastatic pheochromocytoma/PGL, and pheochromocytoma/PGL in CCHD. The diagnosis, and especially the treatment, of metastatic pheochromocytomas and pheochromocytoma/PGL during pregnancy and in CCHD is challenging. Thus, these cases should be management in reference centres by multidisciplinary teams specialized in the pheochromocytoma/PGL treatment.

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“…Pheochromocytoma is a catecholamine-producing tumor in the adrenal medulla and is often accompanied by hypertension, hyperglycemia, hypermetabolism, headache, and hyperhidrosis. It is classified as benign and malignant pheochromocytoma, and histological grading of pheochromocytoma is usually evaluated with pheochromocytoma of the adrenal gland scaled score (PASS) (1)(2)(3)(4)(5)(6). In malignant pheochromocytoma, distant metastasis and/or infiltration into surrounding tissues are observed.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Malignant Pheochromocytoma Without Hypertension Accompanied by Increment of Serum VEGF Level and Catecholamine Cardiomyopathy

et al. 2021

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IntroductionPheochromocytoma is a catecholamine-producing tumor in the adrenal medulla and is often accompanied by hypertension, hyperglycemia, hypermetabolism, headache, and hyperhidrosis, and it is classified as benign and malignant pheochromocytoma. In addition, persistent hypertension is often observed in subjects with malignant pheochromocytoma.Case PresentationA 52-year-old Japanese male was referred and hospitalized in our institution. He had a health check every year and no abnormalities had been pointed out. In addition, he had no past history of hypertension. In endocrinology markers, noradrenaline level was as high as 7,693 pg/ml, whereas adrenaline level was within normal range. Abdominal contrast-enhanced computed tomography revealed a 50-mm hyper-vascularized tumor with calcification in the right adrenal gland and multiple hyper-vascularized tumors in the liver. In 131I MIBG scintigraphy, there was high accumulation in the right adrenal gland and multiple accumulation in the liver and bone. In echocardiography, left ventricular ejection fraction was as low as 14.3%. In coronary angiography, however, there was no significant stenosis in the coronary arteries. Based on these findings, we finally diagnosed him as malignant pheochromocytoma accompanied by multiple liver and bone metastases and catecholamine cardiomyopathy. However, blood pressure was continuously within normal range without any anti-hypertensive drugs. Right adrenal tumor resection was performed together with left hepatic lobectomy and cholecystectomy. Furthermore, serum levels of vascular endothelial growth factor (VEGF) and parathyroid (PTH)-related protein were very high before the operation but they were markedly reduced after the operation.ConclusionsThis is the first report showing the time course of serum VEGF level in a subject with malignant pheochromocytoma, clearly showing that malignant pheochromocytoma actually secreted VEGF. In addition, this case report clearly shows that we should bear in mind once again that malignant pheochromocytoma is not necessarily accompanied by hypertension.

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Recent Advances in Histopathological and Molecular Diagnosis in Pheochromocytoma and Paraganglioma: Challenges for Predicting Metastasis in Individual Patients

Abstract: time. Therefore, we herein review recent advances in relevant studies, including histopathological and molecular analyses, to summarize the current status of potential prognostic factors in patients with PHEO/PGL.

Cited by 19 publications

References 97 publications

A Critical Appraisal of Contemporary and Novel Biomarkers in Pheochromocytomas and Adrenocortical Tumors

A Critical Appraisal of Contemporary and Novel Biomarkers in Pheochromocytomas and Adrenocortical Tumors

Special situations in pheochromocytomas and paragangliomas: pregnancy, metastatic disease, and cyanotic congenital heart diseases

Case Report: Malignant Pheochromocytoma Without Hypertension Accompanied by Increment of Serum VEGF Level and Catecholamine Cardiomyopathy

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