{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:42:59Z","timestamp":1790048579346,"version":"4.0.1"},"reference-count":94,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,13]],"date-time":"2018-09-13T00:00:00Z","timestamp":1536796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Paragangliomas are neuroendocrine neoplasms, derived from paraganglia of the sympathetic and parasympathetic nervous systems. They are most commonly identified in the head and neck, being most frequent in the carotid body, followed by jugulotympanic paraganglia, vagal nerve and ganglion nodosum, as well as laryngeal paraganglia. Abdominal sites include the well-known urinary bladder tumors that originate in the Organ of Zuckerkandl. However, other unusual sites of origin include peri-adrenal, para-aortic, inter-aortocaval, and paracaval retroperitoneal sites, as well as tumors in organs where they may not be expected in the differential diagnosis of neuroendocrine neoplasms, such as thyroid, parathyroid, pituitary, gut, pancreas, liver, mesentery, lung, heart and mediastinum. The distinction of these lesions from epithelial neuroendocrine neoplasms is critical for several reasons. Firstly, the determination of clinical and biochemical features is different from that used for epithelial neuroendocrine tumors. Secondly, the genetic implications are different, since paragangliomas\/pheochromocytomas have the highest rate of germline susceptibility at almost 40%. Finally, the characterization of metastatic disease is unique in these highly syndromic lesions. In this review, we summarize updated concepts by outlining the spectrum of anatomic locations of paragangliomas, the importance of morphology in establishing the correct diagnosis, the clinical implications for management, and the impact of genetics on the distinction between multifocal primary tumors compared with malignant disease.<\/jats:p>","DOI":"10.3390\/jcm7090280","type":"journal-article","created":{"date-parts":[[2018,9,13]],"date-time":"2018-09-13T11:46:04Z","timestamp":1536839164000},"page":"280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":142,"title":["The Diagnosis and Clinical Significance of Paragangliomas in Unusual Locations"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8418-5054","authenticated-orcid":false,"given":"Sylvia L.","family":"Asa","sequence":"first","affiliation":[{"name":"Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Endocrine Oncology Site, Princess Margaret Cancer Center, Toronto, ON M5G 2MG, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shereen","family":"Ezzat","sequence":"additional","affiliation":[{"name":"Endocrine Oncology Site, Princess Margaret Cancer Center, Toronto, ON M5G 2MG, Canada"},{"name":"Department of Medicine, Division of Endocrinology, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozgur","family":"Mete","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Endocrine Oncology Site, Princess Margaret Cancer Center, Toronto, ON M5G 2MG, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rindi, G., Klimstra, D.S., Abedi-Ardekani, B., Asa, S.L., Bosman, F.T., Brambilla, E., Busam, K.J., de Krijger, R.R., Dietel, M., and El-Naggar, A.K. (2018). A common classification framework for neuroendocrine neoplasms: An international Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod. Pathol.","DOI":"10.1038\/s41379-018-0110-y"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lack, E.E. (2007). Tumors of the Adrenal Gland and Extraadrenal Paraganglia. Armed Forces Institute of Pathology. Atlas of Tumor Pathology, American Registry of Pathology Press.","DOI":"10.55418\/9781881041016"},{"key":"ref_3","unstructured":"Kovacs, K., and Asa, S.L. (1998). The adrenal medulla and extra-adrenal paraganglia. Functional Endocrine Pathology, Blackwell Science."},{"key":"ref_4","unstructured":"Mete, O., and Asa, S.L. (2016). Adrenal medulla and extra-adrenal paraganglia. Endocrine Pathology, Cambridge University Press."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.mpdhp.2014.06.002","article-title":"Head and neck paragangliomas: What does the pathologist need to know?","volume":"20","author":"Hayashi","year":"2014","journal-title":"Diagn. Histopathol."},{"key":"ref_6","unstructured":"Mills, S.E. (2018). Paraganglia. Histology for Pathologists, Wolters Kluwer. in press."},{"key":"ref_7","unstructured":"Lack, E.E. (1997). Tumors of the Adrenal Gland and Extra-Adrenal Paraganglia. AFIP Atlas of Tumor Pathology, Armed Forces Institute of Pathology."},{"key":"ref_8","first-page":"234","article-title":"The Spectrum and Clinical Features of Paragangliomas","volume":"98","author":"Mete","year":"2018","journal-title":"Lab. Investig."},{"key":"ref_9","first-page":"103","article-title":"Emil Zuckerkandl and his delightful little organ","volume":"18 Pt 1","author":"Ober","year":"1983","journal-title":"Pathol. Annu."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1177\/1066896917720750","article-title":"Functional Ulnar Nerve Paraganglioma: First Documented Occurrence in the Extremity With Hitherto Undescribed Associated Extensive Glomus Cell Hyperplasia and Tumorlet Formation","volume":"26","author":"Chow","year":"2018","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"523","DOI":"10.5858\/2005-129-523-GPACRW","article-title":"Gallbladder paraganglioma: A case report with review of the literature","volume":"129","author":"Mehra","year":"2005","journal-title":"Arch. Pathol. Lab Med."},{"key":"ref_12","first-page":"244","article-title":"Gallbladder paraganglioma","volume":"31","author":"Ece","year":"2015","journal-title":"Ulus. Cerrahi. Derg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1111\/jgh.12254","article-title":"Hepatobiliary and pancreatic: A huge liver paraganglioma","volume":"28","author":"Koh","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e0293","DOI":"10.1097\/MD.0000000000010293","article-title":"Primary functioning hepatic paraganglioma mimicking hepatocellular carcinoma: A case report and literature review","volume":"97","author":"Liao","year":"2018","journal-title":"Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1227\/00006123-199305000-00021","article-title":"Paragangliomas of the sellar region: Report of two cases","volume":"32","author":"Steel","year":"1993","journal-title":"Neurosurgery"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1097\/00006123-199602000-00034","article-title":"Intrasellar paraganglioma: Report of a case in a sibship of von Hippel-Lindau disease","volume":"38","author":"Scheithauer","year":"1996","journal-title":"Neurosurgery"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s002340050573","article-title":"Primary paraganglioma simulating pituitary macroadenoma: A case report and review of the literature","volume":"40","author":"Mokry","year":"1998","journal-title":"Neuroradiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"429","DOI":"10.5858\/1999-123-0429-IPPANP","article-title":"Intrasellar paraganglioma presenting as nonfunctioning pituitary adenoma","volume":"123","author":"Sambaziotis","year":"1999","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00234-005-1422-4","article-title":"Suprasellar paraganglioma: A case report and review of the literature","volume":"47","author":"Naggara","year":"2005","journal-title":"Neuroradiology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s00701-006-0895-1","article-title":"Intrasellar paraganglioma: A case report and review of the literature","volume":"148","author":"Boari","year":"2006","journal-title":"Acta Neurochir."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/j.1440-1789.2008.00885.x","article-title":"Paraganglioma in pituitary fossa","volume":"28","author":"Egilmez","year":"2008","journal-title":"Neuropathology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.jocn.2007.03.029","article-title":"Malignant paraganglioma of the sellar region mimicking a pituitary macroadenoma","volume":"15","author":"Sinha","year":"2008","journal-title":"J. Clin. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s11102-008-0099-1","article-title":"A rare case of paraganglioma of the sella with bone metastases","volume":"12","author":"Haresh","year":"2009","journal-title":"Pituitary"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1097\/00000478-199707000-00002","article-title":"Thyroid paraganglioma: A clinicopathologic and immunohistochemical study of three cases","volume":"21","author":"LaGuette","year":"1997","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1089\/thy.2006.0284","article-title":"Paraganglioma of the thyroid: Report of a male case with ultrasonographic imagings, cytologic, histologic, and immunohistochemical features","volume":"17","author":"Yano","year":"2007","journal-title":"Thyroid"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.humpath.2011.08.022","article-title":"Thyroid paraganglioma. Report of 3 cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary thyroid carcinoma, based on complementary DNA array results","volume":"43","author":"Castelblanco","year":"2012","journal-title":"Hum. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.5858\/arpa.2013-0703-RS","article-title":"Thyroid Paraganglioma","volume":"139","author":"Lee","year":"2015","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s12022-015-9380-9","article-title":"Thyroid Paraganglioma: \u201cNaked\u201d Nuclei as a Clue to Diagnosis on Imprint Cytology","volume":"26","author":"Taweevisit","year":"2015","journal-title":"Endocr. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s12105-016-0745-2","article-title":"The Management of Locally Invasive Primary Thyroid Paraganglioma: A Case Report and Review of the Literature","volume":"11","author":"Navaratne","year":"2017","journal-title":"Head Neck Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s12105-009-0157-7","article-title":"Primary paraganglioma of the parathyroid: A case report and clinicopathologic review","volume":"4","author":"Levy","year":"2010","journal-title":"Head Neck Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1477-7819-12-74","article-title":"Superior mediastinal paraganglioma associated with von Hippel-Lindau syndrome: Report of a case","volume":"12","author":"Takahashi","year":"2014","journal-title":"World J. Surg. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.athoracsur.2014.09.068","article-title":"Rare Middle Mediastinal Paraganglioma Mimicking Metastatic Neuroendocrine Tumor","volume":"100","author":"Mehta","year":"2015","journal-title":"Ann. Thorac. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s11604-015-0436-z","article-title":"Mediastinal paraganglioma","volume":"33","author":"Takashima","year":"2015","journal-title":"Jpn J. Radiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s12022-013-9296-1","article-title":"Functional Cardiac Paraganglioma Associated with a Rare SDHC Mutation","volume":"25","author":"Millar","year":"2014","journal-title":"Endocr. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s12022-013-9258-7","article-title":"Endobronchial gangliocytic paraganglioma: Not all keratin-positive endobronchial neuroendocrine neoplasms are pulmonary carcinoids","volume":"25","author":"Gucer","year":"2014","journal-title":"Endocr. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e1271","DOI":"10.1097\/MD.0000000000001271","article-title":"Primary Pulmonary Paraganglioma: A Case Report and Review of Literature","volume":"94","author":"Huang","year":"2015","journal-title":"Medicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s13256-015-0639-z","article-title":"Primary paraganglioma of the lung: A case report","volume":"9","author":"Fiorentino","year":"2015","journal-title":"J. Med. Case Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/jso.24818","article-title":"Primary mediastinal paraganglioma associated with a familial variant in the succinate dehydrogenase B subunit gene","volume":"117","author":"Samuel","year":"2018","journal-title":"J. Surg. Oncol."},{"key":"ref_39","first-page":"259","article-title":"Paraganglioma mimicking a pancreatic neoplasm","volume":"12","author":"Lightfoot","year":"2011","journal-title":"J. Pancreas"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.3748\/wjg.v21.i3.1036","article-title":"Primary pancreatic paraganglioma: A report of two cases and literature review","volume":"21","author":"Meng","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jacob, N.C., Howard, M., Kelly, M., and Hale, P.C. (2012). Mesenteric paraganglioma\u2019s: An important differential diagnosis in intra-abdominal tumours. BMJ Case Rep.","DOI":"10.1136\/bcr.02.2012.5726"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4240\/wjgs.v5.i3.62","article-title":"Mesenteric paraganglioma: Report of a case","volume":"5","author":"Fujita","year":"2013","journal-title":"World J. Gastrointest. Surg."},{"key":"ref_43","first-page":"183","article-title":"Pheochromocytoma","volume":"Volume 10","author":"Lloyd","year":"2017","journal-title":"WHO Classification of Tumours of Endocrine Organs"},{"key":"ref_44","first-page":"190","article-title":"Extra-adrenal paragangliomas","volume":"Volume 10","author":"Lloyd","year":"2017","journal-title":"WHO Classification of Tumours of Endocrine Organs"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.surg.2016.05.050","article-title":"SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma","volume":"161","author":"Assadipour","year":"2017","journal-title":"Surgery"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1210\/jc.2010-1946","article-title":"Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: Primary tumor size and primary tumor location as prognostic indicators","volume":"96","author":"Feng","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1046\/j.1365-2265.2001.01268.x","article-title":"Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) isoform expression in ectopic acromegaly","volume":"55","author":"Othman","year":"2001","journal-title":"Clin. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1046\/j.1365-2559.1999.00595.x","article-title":"Sustentacular cells in pulmonary neuroendocrine tumours","volume":"34","author":"Gosney","year":"1999","journal-title":"Histopathology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ctrv.2016.05.003","article-title":"Diagnosis and management of gastrointestinal neuroendocrine tumors: An evidence-based Canadian consensus","volume":"47","author":"Singh","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1242\/dev.02553","article-title":"Gata3 participates in a complex transcriptional feedback network to regulate sympathoadrenal differentiation","volume":"133","author":"Moriguchi","year":"2006","journal-title":"Development"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1309\/AJCP5UAFMSA9ZQBZ","article-title":"Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: A useful immunomarker for breast and urothelial carcinomas","volume":"138","author":"Liu","year":"2012","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1097\/PAP.0b013e3182a28a68","article-title":"Value of GATA3 immunostaining in tumor diagnosis: A review","volume":"20","author":"Ordonez","year":"2013","journal-title":"Adv. Anat. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/modpathol.2013.76","article-title":"GATA3 expression in paragangliomas: A pitfall potentially leading to misdiagnosis of urothelial carcinoma","volume":"26","author":"So","year":"2013","journal-title":"Mod. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1016\/j.humpath.2014.08.013","article-title":"Thymic neuroendocrine tumors (paraganglioma and carcinoid tumors): A comparative immunohistochemical study of 46 cases","volume":"45","author":"Weissferdt","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/PAS.0b013e3182a0218f","article-title":"GATA3: A multispecific but potentially useful marker in surgical pathology: A systematic analysis of 2500 epithelial and nonepithelial tumors","volume":"38","author":"Miettinen","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mete, O., Kefeli, M., \u00c7ali\u015fkan, S., and Asa, S.L. (2018). GATA-3 Immunoreactivity Expands The Transcription Factor Profile of Pituitary Neuroendocrine Tumors. Mod. Pathol., submitted.","DOI":"10.1038\/s41379-018-0167-7"},{"key":"ref_57","first-page":"373","article-title":"Immunocytochemical demonstration of the catecholamine-synthesizing enzymes and neuropeptides in the catecholamine-storing cells of human fetal sympathetic nervous system","volume":"25","author":"Hervonen","year":"1980","journal-title":"Adv. Biochem. Psychopharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s12022-011-9188-1","article-title":"Diagnostic tests and biomarkers for pheochromocytoma and extra-adrenal paraganglioma: From routine laboratory methods to disease stratification","volume":"23","author":"Eisenhofer","year":"2012","journal-title":"Endocr. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.5858\/2008-132-1272-PAEPU","article-title":"Pheochromocytoma and extra-adrenal paraganglioma: Updates","volume":"132","author":"Tischler","year":"2008","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"182","DOI":"10.5858\/arpa.2012-0551-OA","article-title":"Protocol for the examination of specimens from patients with pheochromocytomas and extra-adrenal paragangliomas","volume":"138","author":"Mete","year":"2014","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1373\/clinchem.2010.153320","article-title":"Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma","volume":"57","author":"Eisenhofer","year":"2011","journal-title":"Clin. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1210\/jc.2014-1498","article-title":"Pheochromocytoma and paraganglioma: An endocrine society clinical practice guideline","volume":"99","author":"Lenders","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1530\/EJE-17-0077","article-title":"Plasma methoxytyramine: Clinical utility with metanephrines for diagnosis of pheochromocytoma and paraganglioma","volume":"177","author":"Rao","year":"2017","journal-title":"Eur. J. Endocrinol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1515\/cclm-2015-0631","article-title":"Dopamine concentration in blood platelets is elevated in patients with head and neck paragangliomas","volume":"54","author":"Osinga","year":"2016","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrc3648","article-title":"Pheochromocytoma and paraganglioma pathogenesis: Learning from genetic heterogeneity","volume":"14","author":"Dahia","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ccell.2017.01.001","article-title":"Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma","volume":"31","author":"Fishbein","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrendo.2016.185","article-title":"Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas","volume":"13","author":"Toledo","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/his.13402","article-title":"Pathology and genetics of phaeochromocytoma and paraganglioma","volume":"72","author":"Turchini","year":"2018","journal-title":"Histopathology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/pcmr.12006","article-title":"A cryptic BAP1 splice mutation in a family with uveal and cutaneous melanoma, and paraganglioma","volume":"25","author":"Wadt","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"E1352","DOI":"10.1210\/jc.2013-4375","article-title":"Rare germline mutations identified by targeted next-generation sequencing of susceptibility genes in pheochromocytoma and paraganglioma","volume":"99","author":"Welander","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1002\/gcc.22267","article-title":"Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene","volume":"54","author":"Juhlin","year":"2015","journal-title":"Gene Chromosome Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Remacha, L., Curras-Freixes, M., Torres-Ruiz, R., Schiavi, F., Torres-P\u00e9rez, R., Calsina, B., Let\u00f3n, R., Comino-M\u00e9ndez, I., Rold\u00e1n-Romero, J.M., and Montero-Conde, C. (2018). Gain-of-function mutations in DNMT3A in patients with paraganglioma. Genet. Med.","DOI":"10.1038\/s41436-018-0003-y"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Calsina, B., Curras-Freixes, M., Buffet, A., Pons, T., Contreras, L., Let\u00f3n, R., Comino-M\u00e9ndez, I., Remacha, L., Calatayud, M., and Obispo, B. (2018). Role of MDH2 pathogenic variant in pheochromocytoma and paraganglioma patients. Genet. Med.","DOI":"10.1038\/s41436-018-0068-7"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.humpath.2017.10.013","article-title":"The utility of SDHB and FH immunohistochemistry in patients evaluated for hereditary paraganglioma-pheochromocytoma syndromes","volume":"71","author":"Udager","year":"2018","journal-title":"Hum. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"E1472","DOI":"10.1210\/jc.2011-1043","article-title":"SDHA immunohistochemistry detects germline SDHA gene mutations in apparently sporadic paragangliomas and pheochromocytomas","volume":"96","author":"Korpershoek","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/modpathol.2015.41","article-title":"SDHB\/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: A multicenter interobserver variation analysis using virtual microscopy: A Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T)","volume":"28","author":"Papathomas","year":"2015","journal-title":"Mod. Pathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"E287","DOI":"10.1210\/jc.2014-1870","article-title":"SDHD immunohistochemistry: A new tool to validate SDHx mutations in pheochromocytoma\/paraganglioma","volume":"100","author":"Menara","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1210\/js.2017-00135","article-title":"Case Report of a Prolactinoma in a Patient With a Novel MAX Mutation and Bilateral Pheochromocytomas","volume":"1","author":"Roszko","year":"2017","journal-title":"J. Endocr. Soc."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/bjc.2012.538","article-title":"Immunohistochemical markers of the hypoxic response can identify malignancy in phaeochromocytomas and paragangliomas and optimize the detection of tumours with VHL germline mutations","volume":"108","author":"Pinato","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1097\/PAT.0b013e32835f45c5","article-title":"Precursor lesions of endocrine system neoplasms","volume":"45","author":"Mete","year":"2013","journal-title":"Pathology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e200","DOI":"10.1200\/JCO.2010.32.2156","article-title":"Bilateral adrenal medullary hyperplasia associated with an SDHB mutation","volume":"29","author":"Grogan","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"E308","DOI":"10.1210\/jc.2014-2473","article-title":"Penetrance and clinical features of pheochromocytoma in a six-generation family carrying a germline TMEM127 mutation","volume":"100","author":"Toledo","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00428-015-1755-2","article-title":"Familial pheochromocytoma and renal cell carcinoma syndrome: TMEM127 as a novel candidate gene for the association","volume":"466","author":"Hernandez","year":"2015","journal-title":"Virchows Arch."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s12022-016-9460-5","article-title":"Pathological and Genetic Characterization of Bilateral Adrenomedullary Hyperplasia in a Patient with Germline MAX Mutation","volume":"28","author":"Romanet","year":"2017","journal-title":"Endocr. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1210\/er.2017-00062","article-title":"New Perspectives on Pheochromocytoma and Paraganglioma: Toward a Molecular Classification","volume":"38","author":"Crona","year":"2017","journal-title":"Endocr. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3888","DOI":"10.1158\/1078-0432.CCR-14-2751","article-title":"Superiority of [68Ga]-DOTATATE PET\/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma","volume":"21","author":"Janssen","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s00259-017-3896-9","article-title":"Superiority of (68)Ga-DOTATATE over (18)F-FDG and anatomic imaging in the detection of succinate dehydrogenase mutation (SDHx)-related pheochromocytoma and paraganglioma in the pediatric population","volume":"45","author":"Jha","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/00000478-200205000-00002","article-title":"Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: A clinicopathologic and immunophenotypic study of 100 cases","volume":"26","author":"Thompson","year":"2002","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1530\/ERC-13-0494","article-title":"Phaechromocytoma Study Group in Japan. Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma","volume":"21","author":"Kimura","year":"2014","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/cen.13434","article-title":"Outcomes of patients with metastatic phaeochromocytoma and paraganglioma: A systematic review and meta-analysis","volume":"87","author":"Hamidi","year":"2017","journal-title":"Clin. Endocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"E1386","DOI":"10.1210\/jc.2015-2689","article-title":"Succinate Dehydrogenase (SDH)-Deficient Pancreatic Neuroendocrine Tumor Expands the SDH-Related Tumor Spectrum","volume":"100","author":"Niemeijer","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_92","unstructured":"Mete, O., and Asa, S.L. (2016). Thyroid. Endocrine Pathology, Cambridge University Press."},{"key":"ref_93","first-page":"246","article-title":"Hereditary endocrine tumor syndromes: The clinical and predictive role of molecular hoistopathology","volume":"22","author":"Duan","year":"2017","journal-title":"AJSP Rev. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/his.13277","article-title":"Succinate dehydrogenase (SDH)-deficient neoplasia","volume":"72","author":"Gill","year":"2018","journal-title":"Histopathology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/7\/9\/280\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:20:20Z","timestamp":1760196020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/7\/9\/280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,13]]},"references-count":94,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["jcm7090280"],"URL":"https:\/\/doi.org\/10.3390\/jcm7090280","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,13]]}}}