HEOCHROMOCYTOMA AND PARAganglioma are tumors of the autonomic nervous system. Terminology in science and clinical practice is divergent. Herein, we use the term pheochromocytoma for location in the adrenal glands, extraadrenal abdominal, and thoracic locations (eg, where nearly all tumors are endocrinologically active). In contrast, the term paraganglioma is only used for tumors in the head and neck area where most tumors are nonfunctioning. All these tumors have been described as sporadic and as hereditary entities. [1][2][3] Estimated yearly incidence of

ARAGANGLIOMA SYNDROME(PGL) is a clinical term that has been introduced to describe a group of diseases in which patients may have neoplasias of several paraganglia. 1,2 For at least 4 decades, it has been known that such conditions may be heritable. 3 In addition, thoracic, retroperitoneal, and adrenal lo-cations (eg, extra-adrenal or adrenal pheochromocytomas) are also wellrecognized components of PGL. 4,5 Thus, Author Affiliations and a complete list of the members of the European-American Paraganglioma Study Group appear at the end of this article.

Paragangliomas of the head and neck (HNP) represent rare tumors of neural crest origin. They are highly vascular neoplasms that are benign in the majority of cases. The site of origin defines the name given those tumors. In the head and neck, they most commonly occur at the carotid bifurcation, where they are referred to as carotid body tumors (CBT). Other common sites of origin are the jugular bulb (jugular paraganglioma; JP), the tympanic plexus on the promontory (tympanic paraganglioma; TP) and the vagal nerve (vagal paraganglioma; VP). Patients with cervical paragangliomas frequently present with a painless, slowly enlarging mass in the lateral neck. In many patients with TP and JP, tinnitus and hearing loss are early symptoms. JP patients often suffer from lower cranial nerve deficits. Evaluation by an imaging modality is necessary to establish the diagnosis. Imaging procedures frequently used include B-mode sonography with color-coded Doppler sonography, computed tomography (CT), magnetic resonance imaging (MRI) and digital substraction angiography (DSA). Debate exists in the literature regarding the different treatment modalities for paragangliomas which include surgery, radiotherapy and stereotactic radiosurgery. The role of preoperative angiography and embolization has also been a matter of discussion. The diagnostic work up and the different treatment options for patients with head and neck paragangliomas will be presented and discussed.

The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.

Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs fUS$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for

Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I–III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.

Purpose Radionuclide imaging of phaeochromocytomas (PCCs) and paragangliomas (PGLs) involves various functional imaging techniques and approaches for accurate diagnosis, staging and tumour characterization. The purpose of the present guidelines is to assist nuclear medicine practitioners in performing, interpreting and reporting the results of the currently available SPECT and PET imaging approaches. These guidelines are intended to present information specifically adapted to European practice. Methods Guidelines from related fields, issued by the European Association of Nuclear Medicine and the Society of Nuclear Medicine, were taken into consideration and are partially integrated within this text. The same was applied to the relevant literature, and the final result was discussed with leading experts involved in the management of patients with PCC/PGL. The information provided should be viewed in the context of local conditions, laws and regulations. Conclusion Although several radionuclide imaging modalities are considered herein, considerable focus is given to PET imaging which offers high sensitivity targeted molecular imaging approaches.

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors belonging to the family of pheochromocytoma/paraganglioma neoplasms. Despite advances in understanding the pathogenesis of these tumors, the growth potential and clinical outcome of individual cases remains largely unpredictable. Over several decades, surgical resection has long been the treatment of choice for HNPGLs. However, increasing experience in various forms of radiosurgery has been reported to result in curative-like outcomes, even for tumors localized in the most inaccessible anatomical areas. The emergence of such new therapies challenges the traditional paradigm for the management of HNPGLs. This review will assist and guide physicians who encounter patients with such tumors, either from a diagnostic or therapeutic standpoint. This review will also particularly emphasize current and emerging knowledge in genetics, imaging, and therapeutic options as well as the health-related quality of life for patients with HNPGLs.