Introduction of hereditary extraadrenal paraganglioma
Paragangliomas are rare tumors of the parasympathetic system composed of neural crest-derived chief cells. Tumors of the head and neck region occur most often in the carotid bodies, which sense hypoxia and may stimulate increase in heart rate and ventilation. Other locations include jugular, vagal, tympanic, and mediastinal paraganglia. Both parasympathetic paraganglioma and sympathetic, extraadrenal pheochromocytomas may occur around the abdominal aorta, mainly in the upper abdomen, and in the organ of Zuckercandl at the aortic bifurcation. Paragangliomas are thought to be hereditary in 50%, with an autosomal predisposition for development of tumors mainly in other parasympathetic ganglia. Some families may develop tumors in sympathetic paraganglia, as extraadrenal pheochromocytoma, and some families have combinations of these two entities, and adrenal pheochromocytomas.

Genetics of paraganglioma
The enzyme complex succinate dehydrogenase (SDH) is part of the mitochondrial complex II with an important role in the mitochondrial respiratory chain. Proteins SDHA and SDHB form the catalytic core of the enzyme complex, while SDHD and SDHC forms to anchor complex II to the inner mitochondrial membrane. The mitochondrial complex is thought to play a role in the oxygen sensing of the carotid body. Germ-line mutations in the mitochondrial complex II genes, SDHD at chromosome 11q23, SDHB at chromosome 1p36, and SDHC at chromosome 1q21-23, is reported to cause hereditary paraganglioma. SDHD gene mutations (PGL1) are revealed in a majority (50%) of families with hereditary head and neck parasympathetic paraganglioma, and in cases with both parasympathetic and sympathetic paraganglioma. SDHD act as a tumor suppressor gene, and in PGL1 families the disease is expressed only with mutation transmitted by the father, indicating imprinting of the maternal gene. Germ-line SDHB mutations (PGL2) are reported in 20% of families with head and neck paragangliomas. SDHB mutations are more common in families with adrenal or extraadrenal sympathetic paragangliomas, with or without parasympathetic paragangliomas. Both maternal and paternal imprinting has been demonstrated for SDHB mutations. In some families the SDHB positive parent had not presented with disease although the proband had manifested disease at an early age, indicating a variably penetrant gene. It is claimed to be important to test for SDHB mutations in patients with pheochromocytoma, with or without associated paragangliomas, especially in families where the proband is young and no parent has evidence of disease. Co-occurrence of head and neck or extraadrenal paraganglioma or pheochromocytomas, in the same person or other family members, indicates germ-line mutations in mitochondrial complex II genes. Germ-line SDHC gene mutations (PGL3) have been exceedingly rare.

Treatment of paraganglioma
Paragangliomas should be surgically resected if possible. The most common carotid body paraganglioma does generally not involve the internal carotide artery. Larger paragangliomas, especially in the abdomen, may be locally invasive and require extensive surgery for removal.