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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

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

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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

Malignant PG 37 20 PGS (SDHD) 15 y HM DM, distant metastases; PC, pheochromocytoma; PG, paraganglioma; n, no; y, yes; PGS, paraganglioma syndrome; LM, liver metastases; LN, lymph node metastases; LG, lung metastases; BN, bone metastases; P, peritoneum; HM

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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

unknown ( Neumann et al . 2002 , Adler et al . 2008 ). Approximately 10% of pheochromocytoma cases are malignant ( DeLellis et al . 2004 ); however, this malignant potential cannot be determined histologically, and there is currently no diagnostic test

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Esther Korpershoek, Claudia K Stobbe, Francien H van Nederveen, Ronald R de Krijger, and Winand N M Dinjens

8.7 cm (range 0.7–15 cm) for the malignant series. Patient characteristics and clinical data are summarized in Table 1 . Table 1 Clinical data of pheochromocytoma and extra-adrenal sympathetic paraganglioma patients Patient Gender Age (years) Other

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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

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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

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WenQi Yuan, WeiQinq Wang, Bin Cui, TingWei Su, Yan Ge, Lei Jiang, WeiWei Zhou, and Guang Ning

similar to those detected by CGH analysis. The most obvious was the gain of erythroblastic leukemia viral oncogene homolog 2 ( ERBB-2 ) oncogene located on chromosome 17q that was more common in malignant pheochromocytomas. Moreover, we analyzed the ERBB

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N B Kiss, J Geli, F Lundberg, C Avci, D Velazquez-Fernandez, J Hashemi, G Weber, A Höög, T J Ekström, M Bäckdahl, and C Larsson

included in the present study, which is focused on catecholamine-secreting tumors of the abdomen (in the following referred to as ‘pheochromocytomas’ and ‘paragangliomas’). These tumors are morphologically and functionally similar, although malignant

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R Vassilopoulou-Sellin

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.

Acknowledgemnts

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.

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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