Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours

Lam, Alfred King‐Yin

doi:10.1007/s12022-017-9484-5

Cited by 367 publications

(317 citation statements)

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“…Sympathetic PGLs are derived from sympathetic paraganglia in the chest, abdomen or pelvis. PCC are PGLs located in the adrenal medulla . HNPGLs are derived from parasympathetic paraganglia.…”

Section: Introductionmentioning

confidence: 99%

Clinical implications of the oncometabolite succinate in SDHx‐mutation carriers

et al. 2019

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Succinate dehydrogenase (SDH) mutations lead to the accumulation of succinate, which acts as an oncometabolite. Germline SDHx mutations predispose to paraganglioma (PGL) and pheochromocytoma (PCC), as well as to renal cell carcinoma and gastro-intestinal stromal tumors. The SDHx genes were the first tumor suppressor genes discovered which encode for a mitochondrial enzyme, thereby supporting Otto Warburg's hypothesis in 1926 that a direct link existed between mitochondrial dysfunction and cancer. Accumulation of succinate is the hallmark of tumorigenesis in PGL and PCC. Succinate accumulation inhibits several α-ketoglutarate dioxygenases, thereby inducing the pseudohypoxia pathway and causing epigenetic changes. Moreover, SDH loss as a consequence of SDHx mutations can lead to reprogramming of cell metabolism. Metabolomics can be used as a diagnostic tool, as succinate and other metabolites can be measured in tumor tissue, plasma and urine with different techniques. Furthermore, these pathophysiological characteristics provide insight into therapeutic targets for metastatic disease. This review provides an overview of the pathophysiology and clinical implications of oncometabolite succinate in SDHx mutations. K E Y W O R D S oncometabolites, paraganglioma, pheochromocytoma, SDH mutation, succinate 1 | INTRODUCTION Mutations of genes encoding for the succinate dehydrogenase (SDH) complex, associated with familial paraganglioma (PGL) and pheochromocytoma (PCC), lead to accumulation of succinate, which disturbs the metabolic regulation of the cell. Nowadays metabolic dysregulation is recognized as one of the eight hallmarks of cancer. 1 Although germline mutations in SDHx genes are predominantly linked to PGL and PCC, these mutations also predispose to renal cell carcinoma (RCC), gastrointestinal stromal tumors (GISTs) and, possibly, pituitary adenomas. PCC, PGL and head and neck PGL (HNPGL) are rare neuroendocrine tumors arising from chromaffin cells that can synthesize and release catecholamines. Sympathetic PGLs are derived from sympathetic paraganglia in the chest, abdomen or pelvis. PCC are PGLs located in the adrenal medulla. 2 HNPGLs are derived from parasympathetic paraganglia. Common locations for HNPGLs include the carotid body and the middle ear, as well as the vagus nerve and internal jugular vein. While parasympathetic PGLs are most often non-functional tumors, PCC and sympathetic PGL release catecholamines into the circulation and can

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Section: Introductionmentioning

confidence: 99%

Clinical implications of the oncometabolite succinate in SDHx‐mutation carriers

et al. 2019

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“…During a mean of 44 months of follow up, no recurrence was observed. However, all the pheochromocytomas, especially large ones, are considered to have malignant potential . If an oncologically satisfactory removal cannot be achieved during a laparoscopic procedure, conversion to an open procedure should not be delayed.…”

Section: Discussionmentioning

confidence: 99%

Transperitoneal versus retroperitoneal laparoscopic adrenalectomy for large pheochromocytoma: Comparative outcomes

et al. 2018

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Objectives To evaluate operative and oncological outcomes of laparoscopic adrenalectomy through a transperitoneal approach and retroperitoneal approach for large (>5 cm in diameter) pheochromocytomas. Methods We retrospectively compared the results of a transperitoneal approach with those of a retroperitoneal approach in 22 patients (mean age 57.5 years, range 38–76 years) with unilateral large pheochromocytomas (12 right, 10 left). The mean body mass index, operation time, pneumoperitoneum time, estimated blood loss, fluctuation in blood pressure and complication rate were compared between the two approaches. Results The mean tumor diameter (range) was 7.0 cm (range 5.2–15.5 cm), and no significant differences were observed between the transperitoneal approach and retroperitoneal approach in any baseline clinical parameter. For right‐sided procedures, significant differences were found for operation time (113 vs 85 min), pneumoperitoneum time (93 vs 64 min) and estimated blood loss (96 vs 23 mL; P < 0.05, transperitoneal approach and retroperitoneal approach, respectively). No open conversion or recurrence was reported, but one right transperitoneal approach case required blood transfusion. No difference in these parameters was noted on the left side. Conclusions For right side procedures, the retroperitoneal approach is feasible, safer and faster than the transperitoneal approach for large pheochromocytomas. Early transection of the feeding artery is beneficial for managing the tumor and reducing the risk of bleeding.

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“…(4-й пересмотр), к ФХ относится опухоль, возникающая из хром-аффинных клеток мозгового слоя надпочеч-ников, к ПГ -вненадпочечниковая опухоль из параганглиев [5]. На долю ФХ приходится примерно 80-85% всех катехоламин-сек-ретирующих нейроэндокринных опухолей, оставшиеся 10-15% -симпатические ПГ, реже -с локализацией в области головы и шеи.…”

Section: Introductionunclassified

Personalized diagnostics of chromaffin tumors (pheochromocytoma, paraganglioma) in oncoendocrinology

et al. 2018

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Central Military Clinical Hospital named after P.V. Mandryko, Moscow, Russian FederationФеохромоцитомы и параганглиомы (ФХ/ПГ) -редкие катехоламин-секретирующие нейроэндокринные опухоли, почти в 40% случаев имеющие наследственную природу. Заболеваемость колеблется от 2 до 8 случаев на 1 млн человек в год, с пиком заболеваемости в 30-50 лет. Согласно последней классификации, хромаффинные опухоли отнесены к злокачественным новообразованиям. Частота метастазирования ФХ -10%, ПГ -25%. Клинические проявления ФХ и ПГ обусловлены избытком катехоламинов. Известно более 20 наследуемых генов, мутации в которых провоцируют развитие ФХ/ПГ. С точки зрения молекулярной клеточной патофизиологии известный на сегодня пул мутаций можно разделить на два кластера: первый (SDHх, SDHAF2 -фактор сборки SDH, FH, MDH2) нарушает функционирование цикла Кребса и энергетической транспортной цепи митохондрий, второй (RET, NF1, TMEM127, MAX) -мутации генов рецепторов трансмембранных белков-протеинкиназ (тирозинкиназ), активирующие внутриклеточные сигнальные пути (PI3K-AKT-mTOR и MYC), ответственные за клеточный рост, регуляцию роста и дифференцировку клеток. В итоге происходят стабилизация HIF-транскрипционных факторов (оксидативный стресс), изменение метилирования ДНК, приводящие в итоге к глубоким нарушениям экспрессии генов и опухолевой трансформации клетки. Выделяют три основных секреторно-биохимических фенотипа ФХ/ПГ: норадренергический, адренергический и допаминергический. В зависимости от типа секреции опухоли, возраста пациента и семейного анамнеза назначаются комплементарные генетические исследования и методы молекулярной визуализации. В клинической практике биохимический фенотип опухоли, стадия, семейный анамнез и особенно генетический "паспорт" опухоли позволяют подобрать оптимальный алгоритм молекулярной визуализации (ОФЭКТ/ПЭТ) в целях персонализации тактики лечения и клинического прогноза.Ключевые слова : хромаффинные опухоли, феохромоцитома, параганглиома, радионуклидная диагностика, молекулярная визуализация, генетика, эндокринология, онкология, радиология, онкоэндокринология. Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting neuroendocrine tumours, up to 40% of which occur in the setting of a hereditary syndrome. The incidence is 2 to 8 per million persons per year. The peak incidence occurs in the third to fifth decades of life. According to the most recent classification, chromaffin tumours refer to malignant neoplasms. The incidence of metastasis in pheochromocytomas is 10%; in paragangliomas it is 25%. Clinical manifestations of PPGLs are caused by the excess of catecholamines. More than 20 hereditary gene mutations are known to result in PPGLs development. According to the molecular and cellular pathophysiology, all currently known mutations can be divided intoThe article can used under the CC BY-NC-ND 4.0 license. Статья может быть использована на условиях международной лицензии CC BY-NC-ND 4.0.

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Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours

Cited by 367 publications

References 113 publications

Clinical implications of the oncometabolite succinate in SDHx‐mutation carriers

Clinical implications of the oncometabolite succinate in SDHx‐mutation carriers

Transperitoneal versus retroperitoneal laparoscopic adrenalectomy for large pheochromocytoma: Comparative outcomes

Personalized diagnostics of chromaffin tumors (pheochromocytoma, paraganglioma) in oncoendocrinology

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