Introduction: Paragangliomas are rare vascular tumors located most commonly in the head and neck (H&N) region at the carotid bifurcation as a carotid body tumor (CBT). They are mostly sporadic, but may be familial where it has an autosomal dominant inheritance. The role of preoperative embolization is evolving. Hence, we studied its implication in the management of H&N paragangliomas.
Methods: All paragangliomas of the H&N were studied in non-familial and familial kindred. Patients underwent clinical evaluation, computed tomography and/or magnetic resonance imaging (CT/MRI) and selective carotid angiogram. The last twenty-three patients underwent preoperative embolization 24 hours prior to the operation with injection of polyvinyl alcohol particles, covered stent placement and/or coil(s). All resection was performed by a single H&N oncologic surgeon along with a vascular surgeon. All familial patients with tumors and other asymptomatic family members underwent DNA analysis.
Results: Twenty-five patients with non-familial and eight patients with familial paragangliomas were studied with a total of forty-two paragangliomas. Ages ranged from 28 to 84 years with a male to female ratio of 3:5. For familial paragangliomas, all 8 patients had at least one CBT: 2 with unilateral, 5 were bilateral, and 1 was multicentric. Of the bilateral CBT patients, two patients also had vagal, jugular and sympathetic paragangliomas. Twenty-two non familial paragangliomas had unilateral CBT. The other three had vagal, glomus jugulare and sympathetic paragangliomas (Table 1). Patients with preoperative embolization undergoing resection alone had an estimated blood loss (EBL) of <50 to 400 mL with operative time of 1.5 to 3.8 hours. Those without preoperative embolization had an EBL of 100 to 4000 mL with an operative time of 3.5 to 8 hours. Based on tumor size evaluation on CT/MRI compared to pathology specimen measurements, a volume reduction of 0.6 to 66 cm3 (4 to 89%) was appreciated in patients treated with pre-operative embolization. There were no carotid related neurologic complications with embolization or surgery.
Genetic study showed deletion of promotor regions, P1 or P2 of the c-myc proto-oncogene in 7 patients with familial CBT and 6 asymptomatic patients of the same family kindred. No HER-2/neu oncogenes were detected in any patients tested. Pedigree analysis indicated the deletion was transmitted to children of the affected males only. No children of the affected females have a deletion of P1 or P2 promotor regions of the c-myc oncogenes (Table 2). Only two patients, one familial and one non-familial, were diagnosed with malignant CBT with nodal metastasis. Both patients are still alive.
Conclusions: In the management of H&N paragangliomas, surgical resection remains the most successful treatment. Familial paragangliomas in three generations with both sons and daughters being equally affected suggests of an autosomal dominant mode of inheritance. Genetic analysis confirms the paternal imprinting of familial paragangliomas and suggests that deletion of the promotor region of the c-myc oncogene may be a useful screening test for asymptomatic family members. Surgical resection within 24 hours after preoperative embolization dramatically reduces the operative time, EBL and complications.
