malignant pheochromocytoma. There are also no reliable histopathological methods for distinguishing benign from malignant tumors. Instead, malignancy requires evidence of metastases at non-chromaffin sites distant from that of the primary tumor. Although
Graeme Eisenhofer, Stefan R Bornstein, Frederieke M Brouwers, Nai-Kong V Cheung, Patricia L Dahia, Ronald R de Krijger, Thomas J Giordano, Lloyd A Greene, David S Goldstein, Hendrik Lehnert, William M Manger, John M Maris, Hartmut P H Neumann, Karel Pacak, Barry L Shulkin, David I Smith, Arthur S Tischler, and William F Young Jr
Jens Waldmann, Volker Fendrich, Julia Holler, Malte Buchholz, Ernst Heinmöller, Peter Langer, Annette Ramaswamy, Birgit Samans, Martin K Walz, Matthias Rothmund, Detlef K Bartsch, and Emily P Slater
and malignant pheochromocytoma (PC) compared with normal adrenal medulla Gene symbols Gene title/definition Gene ID Chromosomal location Fold change Direction MGST1 Microsomal glutathione S -transferase 1 4257 12p12.3-p12.1 61.98/131.73 Down GSTA3
Goswin Y Meyer-Rochow, Nicole E Jackson, John V Conaglen, Denis E Whittle, Muthusamy Kunnimalaiyaan, Herbert Chen, Gunnar Westin, Johanna Sandgren, Peter Stålberg, Elham Khanafshar, Daniel Shibru, Quan-Yang Duh, Orlo H Clark, Electron Kebebew, Anthony J Gill, Rory Clifton-Bligh, Bruce G Robinson, Diana E Benn, and Stan B Sidhu
and catecholamine-related markers such as chromogranin A are not reliable diagnostic markers of malignant pheochromocytoma ( Brouwers et al . 2005 , Strong et al . 2008 ). In addition, patients with malignant pheochromocytoma respond poorly to
Johanna Sandgren, Teresita Diaz de Ståhl, Robin Andersson, Uwe Menzel, Arkadiusz Piotrowski, Helena Nord, Martin Bäckdahl, Nimrod B Kiss, Michael Brauckhoff, Jan Komorowski, Henning Dralle, Ola Hessman, Catharina Larsson, Göran Åkerström, Carl Bruder, Jan P Dumanski, and Gunnar Westin
malignant pheochromocytomas have been reported to comprise up to 10% of all cases ( Bravo & Tagle 2003 , Elder et al . 2005 , Karagiannis et al . 2007 ). Malignant tumours occur, however, more frequently among abdominal paragangliomas, representing ∼20
Erwan Thouënnon, Alice Pierre, Yannick Tanguy, Johann Guillemot, Destiny-Love Manecka, Marlène Guérin, L'houcine Ouafik, Mihaela Muresan, Marc Klein, Jérôme Bertherat, Hervé Lefebvre, Pierre-François Plouin, Laurent Yon, and Youssef Anouar
, there is currently no means to identify, predict, or cure malignant pheochromocytomas. Despite distinction attempts based on biochemical measurements of dihydroxyphenylalanine (DOPA) and dopamine production, histological criteria such as tumor cell
L Fishbein, S Ben-Maimon, S Keefe, K Cengel, D A Pryma, A Loaiza-Bonilla, D L Fraker, K L Nathanson, and D L Cohen
screening bias given the increased risk of developing PCC/PGL and metastatic disease in mutation carriers. Table 1 Clinical characteristics of the malignant pheochromocytoma cohort. Characteristic Total cohort ( n ) 71
Background: Tumors of the paraganglionic system represent a distinct, albeit uncommon, clinical entity characterized by catecholamine hypersecretion and hemodynamic instability; initial pathologic examination often cannot predict benign vs malignant behavior. An analysis of the clinical outcome of patients with known malignant tumors may serve to enhance the initial evaluation and therapeutic plan of all patients presenting with pheochromocytoma or paraganglioma.
Methods: At the University of Texas M D Anderson Cancer Center, 30 patients with malignant abdominal paraganglioma and 20 patients with malignant pheochromocytoma were diagnosed between 1971 and 1995. Their medical records were reviewed with particular attention to clinical characteristics and disease outcome.
Results: Among the 30 patients with paraganglioma, 73% were men, and 90% were younger than 50 years at the time of diagnosis. Sixteen patients have remained alive with persistent disease 0.2 to 25 years after initial diagnosis while eight patients died of their disease within 0.8 to 32 years. Regional recurrence and skeletal metastases were the most prominent events. Among the 20 patients with pheochromocytoma, 60% were men and 70% were younger than 50 years at the time of diagnosis. Ten patients have remained alive with persistent disease 0.8 to 20 years after initial diagnosis while five patients died of their disease within 1.5 to 39 years. Hypertension was a prominent presenting feature and regional recurrence was the most frequent pattern of treatment failure.
Conclusions: Important clinical differences distinguish adrenal pheochromocytomas from extra-adrenal, abdominal paragangliomas. Patients with paragangliomas are, as a group, younger men, more likely to have malignant lesions and a more aggressive clinical course. Patients with malignant pheochromocytomas usually present with hypertension, are somewhat older, and have less aggressive disease.
We thank the staff of the Department of Medical Informatics for database retrieval and the clinical faculty who participated in the patients' care. We thank Teo Spear for expert preparation of the manuscript. We thank Terry Smith, biostatistician, for her critical review and suggestions.
Esther Korpershoek, Claudia K Stobbe, Francien H van Nederveen, Ronald R de Krijger, and Winand N M Dinjens
different areas of the tumor. Figure 3 LOH results of the malignant pheochromocytomas and extra-adrenal sympathetic paragangliomas. =no LOH, =loss of upper allele, =loss of lower allele, NI=not informative, x=no data, –=no tissue available, T1–T4=tumor
P N Span, J U Rao, S B J Oude Ophuis, J W M Lenders, F C G J Sweep, P Wesseling, B Kusters, F H van Nederveen, R R de Krijger, A R M M Hermus, and H J L M Timmers
Giordano TJ Greene LA Goldstein DS Lehnert H 2004 Malignant pheochromocytoma: current status and initiatives for future progress . Endocrine-Related Cancer 11 423 – 436 doi:10.1677/erc.1.00829 . Forsythe JA Jiang BH Iyer NV Agani F
Elizabeth Grubbs, Daniel Halperin, Steven G Waguespack, and Robert F Gagel
The multiple endocrine neoplasia (MEN) workshops had their beginnings at Queen’s University in Kingston, Ontario in June 1984. This initial meeting brought clinicians and scientists together to focus on mapping the gene for multiple endocrine neoplasia type 2 (MEN2). These efforts culminated in the identification of the RET protooncogene as the causative gene a decade later. Over the next 35 years there were a total of 16 international workshops focused on the several MEN syndromes. Importantly, these workshops were instrumental in efforts to define the molecular basis for multiple endocrine neoplasia type 1 (MEN1), MEN2, von Hippel-Lindau disease (VHL), Carney Complex, hereditary pheochromocytoma and hyperparathyroidism. In this same spirit some 150 scientists and clinicians met at MD Anderson Cancer Center, 27–29 March 2019, for the 16th International Workshop on Multiple Endocrine Neoplasia (MEN2019). Appropriate to its location in a cancer centre, the workshop focused on important issues in the causation and treatment of malignant aspects of the MEN syndromes: medullary thyroid carcinoma, pancreatic neuroendocrine tumours, malignant pheochromocytoma and parathyroid carcinoma. Workshops at the meeting focused on a better understanding of how the identified molecular defects in these genetic syndromes lead to transformation, how to apply targeted kinase inhibitors and immunotherapy to treat these tumours and important clinical management issues. This issue of Endocrine-Related Cancer describes these discussions and recommendations.