P. Perlea, D. M. Albulescu, M. J. Țuculină, A. G. Nicola, R. V. Georgescu, C. Petcu, C. N. Cumpătă, D. Terzea, A. Valea, M. Carsote
Abstract: Pheochromocytoma (PHEO) and paraganglioma (PGL) are catecholamines (norepinephrine, epinephrine, and dopamine) producing neuroendocrine neoplasia (NEN) of chromaffin cells with adrenal and extra-adrenal location, respectively. Histological/immunohistochemistry report is provided after tumor removal; adrenal biopsy being prohibited in PHEOs. PHEO/PGL grading is different from other NENs scores like lung or gastro-entero-pancreatic. Metastatic disease (15% of all cases, 15% of PHEOs, 60% of PGLs, 5% of bilateral PHEOs, 10% of pediatric PHEOs) means tumor spreading at an organ with non-chromaffin cells. Lifelong follow-up is required since recurrence has been reported even in cases that were initially considered benign. The previous benign/malign features based on PASS (Pheochromocytoma of the Adrenal Gland Scale Score) system which exclusively takes into consideration hematoxylin-eosin assays has been replace by GAPP (Grading of Adrenal Pheochromocytoma and Paraganglioma) since 2017. It incorporates Ki67 immunostain and secretor profile type, categorizing the tumors in well/moderately/poorly differentiated, each associating a certain malignant potential. Alternatively, ASES (Age, Size, Extra-Adrenal Location, and Secretory Type) and COPPS (Composite Pheochromocytoma/paraganglioma Prognostic Score) score include tumor size, and patient’ age at diagnosis for ASES. 12 hereditary syndromes and more than 15 non-syndromic mutations are related to PHEP/PGL which increase the risk of malignant potential, especially SDHB (succinate dehydrogenase) mutations (5-year survival rate of 50%). COPPS model includes SDHB status, as well as M-GAPP (Modified-GAPP). The genetic status is a key player in outcome. Emerging immunstaining involves biomarkers like glutamine metabolism – related proteins GLS1, angiogenesis elements as CD31, expression of Snail, galectin-3, PDK1; their role in malignant prediction needs to be evaluated in addition to metabolomics assessments (for instance, succinate accumulations in SDHx mutations or products caused by mutations at the level of fumarate hydratase or malate dehydrogenase). There is no single element to serve as a strong, independent predictor factor of malignant behavior in PHEO/PGL due to the complexity of these highly heterogeneous tumors while none of current score grading systems represent a gold standard. Keywords: pheochromocytoma, malignant pheochromocytoma, poorly differentiated pheochromocytoma, adrenal tumor, Ki67, adrenalectomy, paraganglioma, metastases, neuroendocrine tumor, cathecolamines, pheochromocytoma with malignant potential.
 and paraganglioma (PGL) are catecholamines (norepinephrine, epinephrine, and dopamine) producing neuroendocrine neoplasia (NEN) of chromaffin cells with adrenal and extra-adrenal location, respectively. Histological/immunohistochemistry report is provided after tumor removal; adrenal biopsy being prohibited in PHEOs. PHEO/PGL grading is different from other NENs scores like lung or gastro-entero-pancreatic. Metastatic disease (15% of all cases, 15% of PHEOs, 60% of PGLs, 5% of bilateral PHEOs, 10% of pediatric PHEOs) means tumor spreading at an organ with non-chromaffin cells. Lifelong follow-up is required since recurrence has been reported even in cases that were initially considered benign. The previous benign/malign features based on PASS (Pheochromocytoma of the Adrenal Gland Scale Score) system which exclusively takes into consideration hematoxylin-eosin assays has been replace by GAPP (Grading of Adrenal Pheochromocytoma and Paraganglioma) since 2017. It incorporates Ki67 immunostain and secretor profile type, categorizing the tumors in well/moderately/poorly differentiated, each associating a certain malignant potential. Alternatively, ASES (Age, Size, Extra-Adrenal Location, and Secretory Type) and COPPS (Composite Pheochromocytoma/paraganglioma Prognostic Score) score include tumor size, and patient’ age at diagnosis for ASES. 12 hereditary syndromes and more than 15 non-syndromic mutations are related to PHEP/PGL which increase the risk of malignant potential, especially SDHB (succinate dehydrogenase) mutations (5-year survival rate of 50%). COPPS model includes SDHB status, as well as M-GAPP (Modified-GAPP). The genetic status is a key player in outcome. Emerging immunstaining involves biomarkers like glutamine metabolism – related proteins GLS1, angiogenesis elements as CD31, expression of Snail, galectin-3, PDK1; their role in malignant prediction needs to be evaluated in addition to metabolomics assessments (for instance, succinate accumulations in SDHx mutations or products caused by mutations at the level of fumarate hydratase or malate dehydrogenase). There is no single element to serve as a strong, independent predictor factor of malignant behavior in PHEO/PGL due to the complexity of these highly heterogeneous tumors while none of current score grading systems represent a gold standard.&redirect_uri=http://rjlm.ro/index.php/arhiv/945)