PHEOCHROMOCYTOMA – A NEW VIEW OF THE OLD PROBLEM Edited by Jose Fernando Martin Pheochromocytoma – A New View of the Old Problem Edited by Jose Fernando Martin Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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DepositPhotos First published December, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Pheochromocytoma – A New View of the Old Problem, Edited by Jose Fernando Martin p. cm. ISBN 978-953-307-822-9 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Pathophysiology 1. Anatomo-Pathological Aspects 1 Chapter 1 Macro and Microscopic Aspects 3 Fernando Candanedo-Gonzalez, Leslie Camacho-Rebollar and Candelaria Cordova-Uscanga Chapter 2 Phaechromocytoma with Histopathologic Aspects 15 Servet Guresci, Derun Taner Ertugrul and Gulcin Guler Simsek Part 2 Pathophysiology 2. Study Experimental Models 23 Chapter 3 Mouse Models of Human Familial Paraganglioma 25 Louis J. Maher III, Emily H. Smith, Emily M. Rueter, Nicole A. Becker, John Paul Bida, Molly Nelson-Holte, José Ignacio Piruat Palomo, Paula García-Flores, José López-Barneo and Jan van Deursen Chapter 4 Cell Differentiation Induction Using Extracellular Stimulation Controlled by a Micro Device 47 Yuta Nakashima, Katsuya Sato, Takashi Yasuda and Kazuyuki Minami Part 3 Pathophysiology 3. Signaling Pathways 63 Chapter 5 Phospholipase A 2 and Signaling Pathways in Pheochromocytoma PC12 Cells 65 Alexey Osipov and Yuri Utkin Chapter 6 Programmed Cell Death Mechanisms and Pheocromocytomas: Recent Advances in PC12 Cells 85 Davide Cervia and Cristiana Perrotta VI Contents Part 4 Clinical Presentation 101 Chapter 7 Headache in Pheochromocytoma 103 Masahiko Watanabe Chapter 8 Primary Cardiac Pheochromocytoma (Paraganglioma) 111 Iskander Al-Githmi Part 5 Diagnosis 117 Chapter 9 Diagnosis: Laboratorial Investigation and Imaging Methods 119 José Fernando Vilela-Martin and Luciana Neves Cosenso-Martin Part 6 Treatment and Clinical Cases 133 Chapter 10 Undiagnosed Pheochromocytoma Complicated with Perioperative Hemodynamic Crisis and Multiple Organ Failure 119 Anis Baraka Chapter 11 Familial Catecholamine-Secreting Tumors - Three Distinct Families with Hereditary Pheochromocytoma 149 Shirin Hasani-Ranjbar, Azadeh Ebrahim-Habibi and Bagher Larijani Preface Cardiovascular diseases are the major cause of mortality in developed and developing countries. Hypertension is the most prevalent of all cardiovascular diseases, the major risk factor for cardio and cerebrovascular injury and the third cause of disability. It is likely to be involved in 50% of the deaths due to cardiovascular diseases. Genetic and environmental factors are involved in more than 90% of cases, characterizing essential hypertension. About 5 to 10% of hypertension cases are represented by cases of secondary arterial hypertension. In this situation, pheochromocytoma, a catechomine- secreting tumor that is located in the adrenal medulla (pheochromocytoma) or in the extra adrenal paraganglionic tissue (paranganglioma) presents prevalence varying from 0.01% to 0.10% of the hypertensive population, and an incidence of two to eight cases per million people per year. When I received the invitation to be editor of a book on pheochromocytoma, a disease that represents small percentage of cases of secondary hypertension, I was worried with the development of the book and always wondered what would be the interest for the medical community. As the chapters were presented and developed by the authors, this worry has disappeared, because despite its rarity, pheochromocytoma presents a different clinical picture and several opportunities for clinical and basic research. Certainly, the level of the authors of this book also did make it an excellent topic to be discussed, in addition to chapters with new approaches about the clinical presentation and in the field of experimental research. The book is divided into 6 sections covering the main aspects of clinical practice and other issues related to translational research. I hope readers enjoy this book and I expect it is a reference in the area. Dr. Jose Fernando Vilela Martin, MD PhD, Head of Internal Medicine Division, Coordinator of Hypertension Clinic, State Medical School of São José do Rio Preto (FAMERP), Brazil [...]... nuclei are spheroidal and show slight pleomorphism 3 The paraganglia Sympathetic paraganglia (SP) are distributed along paraaxial regions of the trunk along the prevertebral and paravertebral sympathetic chains and in connective tissue in the walls of pelvic organs However parasympathetic paraganglia (PSP) are found along cranial and thoracic branches of the glossopharyngeal and vagus nerves Among SP the. .. PSP are similar at cellular level 4 Histopathology of phaeochromocytoma Sporadic phaeochromocytomas make up of about 50% of all phaeochromocytomas and are usually unilateral and unicentric while more than 50% of familial forms are bilateral and coexist with extraadrenal sympathetic and parasympathetic paragangliomas Patients with MEN type 2, VHL or NF type 1 are known to have an increased risk for pheochromocytoma. .. tumors that arise from chromaffin cells of sympathetic paraganglia The new World Health Organisation (WHO) classification of endocrine tumors has recommended to reserve the term phaeochromocytoma for intraadrenal tumors only and the others are defined as sympathetic or parasympathetic paragangliomas, further categorised by site Although it was the first adrenal tumor to be recognised, the term phaeochromocytoma... tumours of the adrenal glands 12 2 Pathology features 2.1 Macroscopy findings Nearly 90% of pheochromocytomas are usually confined to the adrenal gland, and may appear encapsulated In sporadic pheochromocytomas, even though lobulated, the tumour is actually a single neoplasm In contrast, familial tumours are often bilateral and usually multicentric 13 Pheochromocytomas are of variable size, ranging... intravascular attached tumour thrombi, and/ or tumour nests convered by endothelium identified in a capsular or extracapsular vessel †Defined as 3-4 times the size of a zellballen or the normal size of the medullary paraganglia nest Table 1 Pheochromocytoma of the Adrenal Gland Scoring Scale (PASS) 30 Additional markers that might be useful prognostic indicators in the pathological assessment of these... pheochromocytoma is composed of polygonal to spindled cells arranged in an alveolar, trabecular, or solid pattern, often with a typical Zellballen appearance Composite pheochromocytomas account for only 3% of both adrenal and extra-adrenal pheochromocytomas and can be associated with MEN 2A and phakomatoses 41,42 Composite pheochromocytoma is a rare tumour composed of typical pheochromocytoma and other components,... pheochromocytoma and ganglioneuroblastoma or neuroblastoma is variable Coexistence with No of cases % Ganglioneuroma 41 70 Ganglioneuroblastoma 7 11 Neuroblastoma 4 9 Schwannoma 4 7 Neuroendocrine carcinoma 1 2 Total 57 100 Table 2 Cases of composite pheochromocytoma of adrenal gland 43 6 New insights on pheochromocytoma The molecular events involved in the malignant transformation of pheochromocytoma are poorly... (30%) paraaortic region Urinary bladder, intrathoracic and cervical paragangliomas can occasionally be seen More than 25% of these tumors are functional and usually secrete norepinephrine Approximately 50% of extraadrenal tumors are malignant giving rise to metastases PSP seldomly produce cathecolamine excess Carotid body and jugulotympanic tumors are more common than aortic and vagal lesions Carotid... phaeochromocytoma and paraganglioma with features of ganglioneuroma, ganglioneuroblastoma, neuroblastoma or peripheral nerve sheath tumour There are fewer than 40 cases in the literature The tumour was combined with ganglioneuroma in 80%, and with ganglioneuroma in 20% of all reported cases They are usually seen in adults and symptoms are similar to typical phaeochromocytoma as with genetic abnormalities About... occur as part of several familial tumour syndromes It is now recognized that the frequency of germline mutations in apparently sporadic presentations is as high as 15 %–2 4% 11,20 However, the genetic basis of the majority of sporadic pheochromocytomas remains largely uncharacterized Macro and Microscopic Aspects 7 Familial pheochromocytomas are often multifocal or bilateral and generally present at an . 103 Masahiko Watanabe Chapter 8 Primary Cardiac Pheochromocytoma (Paraganglioma) 111 Iskander Al-Githmi Part 5 Diagnosis 117 Chapter 9 Diagnosis: Laboratorial Investigation and Imaging. 1. Anatomo-Pathological Aspects 1 Chapter 1 Macro and Microscopic Aspects 3 Fernando Candanedo-Gonzalez, Leslie Camacho-Rebollar and Candelaria Cordova-Uscanga Chapter 2 Phaechromocytoma with. seen. A true capsule does not usually separate the tumour from the adjacent adrenal but a pseudocapsule may be present, or the tumour may extend to the adrenal capsule. The border with the adjacent