Extra-adrenal and adrenal pheochromocytomas associated with a germline SDHC mutation

Department of Hypertension at the Institute of Cardiology, Warsaw, Poland.
Nature Clinical Practice Endocrinology &#38 Metabolism (Impact Factor: 7.55). 03/2008; 4(2):111-5. DOI: 10.1038/ncpendmet0726
Source: PubMed

ABSTRACT A 46-year-old man presented with headaches, paroxysmal palpitations, anxiety and hypertension. The patient had undergone surgery for a retroperitoneal tumor at the age of 31 years, when histological examination revealed an extra-adrenal pheochromocytoma. The patient's 68-year-old mother had a history of a carotid body tumor, which had been resected when she was 34 years old. She was diagnosed with a meningioma at 54 years of age and a jugular paraganglioma at 68 years of age.
A 24h urine catecholamine assay was performed. CT imaging of the abdomen and (123)I-labeled metaiodobenzylguanidine scintigraphy revealed a right pheochromocytoma and left adrenal incidentaloma. An inherited neoplasia syndrome was suspected and molecular genetic analyses were performed.
Right adrenal pheochromocytoma and left adrenal nonfunctioning incidentaloma, as part of a familial pheochromocytoma-paraganglioma syndrome associated with a germline mutation in SDHC (gene encoding succinate dehydrogenase complex, subunit C, integral membrane protein, 15 kDa).
Predictive testing, with genetic counseling. Management included surgical resection of the existing pheochromocytoma. The patient continues to be monitored with MRI scans of the neck, thorax, abdomen and pelvis every 1-2 years and an annual 24h urine collection for the measurement of metanephrines and catecholamines.

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    ABSTRACT: EinleitungGlomus-caroticum-Tumoren sind seltene Paragangliome (Inzidenz 0,012%), die von sympathischen Fasern im Bereich der Karotisbifurkation ausgehen und ein sehr langsames Wachstum haben. Symptomatisch werden sie durch lokale mechanische Kompression benachbarter Gefäß- und Nervenstrukturen. Ziel dieser Arbeit ist es, Diagnostik, Therapie und Verlauf der an der Universität Düsseldorf behandelten Patienten mit Glomustumoren darzustellen und anhand einer Nachuntersuchung, Aussagen über die Rezidivhäufigkeit und Dignität in der Langzeitbeobachtung zu treffen. Patienten und MethodenEingeschlossen in diese retrospektive Studie wurden alle Patienten, die von Januar 1988 bis Juni 2008 an einem Glomustumor behandelt wurden. Zur Nachuntersuchung wurde bei den Patienten eine aktuelle Anamnese, eine Sonographie und Duplexsonographie durchgeführt. Zudem wurde der standardisierte Fragebogen EORTC QLQ-C30 in Verbindung mit dem Zusatzbogen EORTC QLQ-H&N35 ausgefüllt. ErgebnisseIn dem untersuchten Patientenkollektiv von 36 Patienten (36% Männer, 64% Frauen; durchschnittliches Lebensalter 48,33Jahre, Spannweite 17–78Jahre) fand sich eine lokale Schwellung am Hals als Hauptsymptom bei 16 Patienten; Schluckbeschwerden bzw. Heiserkeit traten bei jeweils 5 Patienten auf. Bei einem Patienten bestand präoperativ ein Horner-Syndrom. Insgesamt fanden sich 22 Glomustumoren auf der rechten Seite (52,38%) und 20 Tumoren auf der linken Halsseite (47,62%). Bei 6Patienten (16,67%) bestand beidseitig ein Glomustumor, von denen 3 im Verlauf beidseitig resiziert wurden und weitere 3Patienten in der Verlaufskontrolle sind, sodass bei 36 Patienten insgesamt 39 Glomustumoren operativ behandelt wurden. Bei allen 39Operationen (Primäroperation n=34, Rezidivoperationen n=5) wurden die Glomustumoren makroskopisch in toto reseziert. Vagusanteile wurden in 3Fällen (7,69%, ShamblinII n=1, ShamblinIII n=1) mitreseziert, Gefäßresektionen waren bei 10Operationen notwendig. Die Überlebensraten der dokumentierten Patienten lagen nach einem Jahr bei 100%, nach 2Jahren bei 96,3% und nach 5 Jahren bei 92,6%. Bei 2Patienten wurde ein lokales Rezidiv diagnostiziert; ein Patient wurde nachoperiert und bei einem Patienten besteht eine seit 14Jahren nicht größenprogrediente Schwellung in der Karotisgabel, die bisher konservativ belassen wurde. Die periphere Nervenschädigung betrug im Langzeitverlauf 12,0% (3/25). Anamnestische oder klinische Hinweise für eine lokale oder periphere Metastase eines Glomustumors haben sich bei keinem Patienten ergeben. SchlussfolgerungenDie operative Exstirpation bleibt der einzige kurative Heilungsansatz bei Glomus-caroticum-Tumoren mit einer perioperativen Letalität von 0%. Die Morbidität mit Auftreten eines zentral-neurologischen Defizits ist unter Ausnutzung gefäßchirurgischer Techniken gering (2,56%). Die Radikalität der Resektion findet Ausdruck in der Häufigkeit perioperativer peripher-neurologischer Defizite von 64,10%. Im Langzeitverlauf senkt sich die permanente periphere Nervenbeteiligung auf 12,0%. Aufgrund eines potenziell infiltrierenden und metastatischen Wachstums sind Glomus-caroticum-Tumoren als semimaligne einzuschätzen und damit eine operative Indikationsstellung bei Diagnosestellung indiziert. Ob die Inzidenz dieses seltenen Karotisgabeltumors aufgrund zunehmender Routinediagnostik der Kopf- und Halsregion durch Ultraschall und Schnittbilddiagnostik ansteigt, bleibt abzuwarten. IntroductionTumors of the carotid body are rare paragangliomas (incidence 0.012%) originating from sympathetic fibres of the carotid bifurcation. Growth is slow and they frequently become symptomatic through local mechanical compression of neighboring vascular and neural structures. The aim of this study is to present the diagnosis, therapy and course in patients with a carotid body tumor treated at our department of the Düsseldorf University Hospital and to discuss rates of recurrence and also dignity during the long-term follow-up. Patients and methodsIncluded in this retrospective study were all patients treated for a carotid body tumor between January 1988 and June 2008. At follow-up examination the current history was recorded and a physical examination, sonography and duplex sonography were carried out. Furthermore each patient completed the questionnaires QLQ-C30 of the European Organisation for Research and Treatment of Cancer (EORTC) and the module for head and neck QLQ-H&N35 to assess quality of life. ResultsIn our collective of 36 patients consisting of 13 men (36%) and 23 women (64%) with an average age of 48.33 years (range 17–78 years), 16 patients presented with a local neck swelling and 5 patients each had difficulties swallowing or hoarseness, respectively. Preoperatively Horner’s syndrome was found in one patient. A total of 22 tumors were found on the right side of the neck (52.38%), 20 were found on the left side (47.62%) and 6 patients showed a bilateral carotid body tumor (16.67%), 3 of which were bilaterally excised. The other 3 patients are still under surveillance without surgery. Altogether surgery of 39 carotid body tumors was performed in 36 patients. In all 39 cases (primary surgery n=34, recurrence surgery n=5) the tumors were macroscopically excised in toto. Parts of the vagus nerve had to be resected in 3 patients (7.69% Shamblin type II n=1, Shamblin type III n=1) and resection of blood vessels was necessary during 10 operations. The survival rate after 1 year was 100%, after 2 years 96.3% and after 5 years 92.6%. A local recurrence was diagnosed in 2 patients (5.13%). In one patient a second operation was necessary and in the other patient there was a non-progressive swelling in the carotid bifurcation which had existed for 14 years and which was conservatively left untreated. Peripheral neural lesions could be found in 12% (3/25) at long-term follow-up. None of the patients showed evidence of local or remote metastasization of a carotid body tumor. ConclusionsSurgical extirpation of carotid body tumors can be regarded as the only curative option with an overall mortality of 0%. Morbidity is low when applying vascular surgical techniques (2.56% for central lesions). The incidence of peripheral nervous lesions is high reflecting the radicality of the resection (64.10%) but is outweighed by the benefits. In the long-term follow-up the rate of permanent peripheral neural lesions decreased to 12%. Due to a potentially infiltrating and disseminating growth, carotid body tumors should be regarded as semi-malignant and should therefore be indicated for surgery at the time of diagnosis. Whether the incidence of carotid body tumors will rise due to increased routine diagnostic examination of the head and neck region using sonography and tomography remains to be seen.
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