Head and neck paragangliomas: clinical and molecular genetic classification

Abstract

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.

Malignant Vagal Paraganglioma

“…CT and MRI with angiography provide valuable information to aid diagnosis and preoperative planning [6]. Vagal PGs tend to cause anterior displacement of the internal and external carotid arteries, as seen in this case.…”

“…The classic MRI feature of flow voids gives the tumor a ''salt and pepper'' appearance. 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy can be used to detect occult or metastatic PGs [6]. Histologic features of PGs include chief cells surrounded by sustentacular cells in a ''nest of cells'' pattern [6].…”

“…123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy can be used to detect occult or metastatic PGs [6]. Histologic features of PGs include chief cells surrounded by sustentacular cells in a ''nest of cells'' pattern [6]. Atypical histologic findings such as cytologic atypia, mitotic activity, necrosis, and infiltrative growth are not predictors of malignancy in isolation as, they can be seen in tumors that behave in clinically benign fashion.…”

“…Atypical histologic findings such as cytologic atypia, mitotic activity, necrosis, and infiltrative growth are not predictors of malignancy in isolation as, they can be seen in tumors that behave in clinically benign fashion. When present, they do suggest a higher risk of malignant behavior [6]. However, malignancy is classically defined by the gross or microscopic evidence of regional or distant metastatic disease [1,3,8].…”

Molecular and Therapeutic Advances in the Diagnosis and Management of Malignant Pheochromocytomas and Paragangliomas

“…Parasympathetic PGLs are a distinct subgroup predominantly found in the head and neck region, 95% of which are nonsecretory. These PGLs present in an alternative fashion that may be dictated by their specific location, such as tinnitus and hearing loss in patients with tympanic PGLs or cranial nerve deficits in those with jugular PGLs [16,17].…”