A Case Illustrative of Phenotypic Heterogeneity and Challenges in the Management of Paraganglioma
Introduction: Paragangliomas (PGLs) are extra-adrenal, usually benign, highly vascularized tumors that originate from neural-crest-derived chromaffin cells. These tumors are subdivided as either sympathetic or parasympathetic, depending on their location and catecholamine production. Sympathetic PGLs are situated along the abdominal sympathetic trunk and usually produce catecholamines, whereas parasympathetic PGLs are located in the head and neck, and these usually do not produce catecholamines. PGLs may present as sporadic or inherited tumor syndrome, including MEN 2, with RET germline mutations, von Hippel-Lindau (VHL) disease due to germline mutations in VHL gene, and pheochromocytoma-PGL syndrome. The latter is frequently a hereditary condition and is caused by germline mutations in the SDHB, SDHC, or SDHC genes. Patients with familial PGLs may present at a younger age, often as multifocal tumors, with an increased risk of recurrence and a higher frequency of malignancy in those with SDHB mutations. SDH mutations induce angiogenesis and tumorogenesis through the inhibition of hypoxia-inducible factors (HIF)-propyl hyroxylase. A younger age at onset, malignancy, and a positive family history are clinical parameters of high specificity, but low sensitivity for diagnosis. Genetic analysis for mutations in SDH genes for the patient and family members, and surveillance for the affected patient and family members, are necessary where there are no clear clinical or family indicators for the syndrome. We present a case of a large abdominal malignant PGL in a 20-year-old pt. that went on without clinical detection for at least three years.
Aim(s): To present a young individual with a large abdomino-pelvic malignant paraganglioma with disseminated metastases that was functionally largely quiescent for catcoholamine excess, and that had harbored SDHB mutation. The aim is to underscore phenotypic heterogeneity of the disease and the attendant therapeutic challenges.
Materials and methods: A 20-year-old single male was referred with a 3-year history of a large skull occipital mass and a large abdominal incidentaloma. He had a core biopsy of the abdominal mass done at an external hospital, with a diagnosis of paraganglioma. Under our observation, the patient had frequent round-the-clock blood pressure monitoring for eight weeks. Imaging studies consisted of CT scans of the abdomen, chest and pelvis, CT of the head and neck, 1-123 MIBG scan, Octreoscan, whole body bone scan, skeletal survey, and abdominal angiogram in preparation for repeated tumor embolization preoperatively to decrease tumor vascularity. Hormonal and biochemical studies were done afterward: 24-h urinary metanephrine and normetanephrine determinations x3, urinary epinephrine, norepinephribe, dopamine, serum-free catecholamies, and dopamine, chromogranin A (CGA), calcitonin, CEA antigen, CBC, liver and kidney function tests. Molecular genetic studies for mutations in SHDB, SHDC and SDHD, VHL, RET were also carried out.
Conference: 7th Annual ENETSConcerence (2010)
Presenting Author: Ahmed D
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