Paraganglioma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2]

Overview

On gross pathology, sharply circumscribed polypoid red vascular masses with firm to rubbery in consistency are characteristic of paragangliomas. On microscopic inspection, the tumor cells are readily recognized. Individual tumor cells are polygonal to oval and are arranged in distinctive cell balls, called Zellballen. These cell balls are separated by fibrovascular stroma and surrounded by sustentacular cells.

Pathophysiology

Paragangliomas arise from the glomus cells, which are special chemoreceptors located along blood vessels that have a role in regulating blood pressure and blood flow. The main concentration of glomus cells is found in the carotid body (located in the upper neck at the branching of the common carotid artery), and the aortic bodies (located near the aortic arch). The glomus cells are part of the paraganglionic nervous system that composed of the extra-adrenal paraganglia of the autonomic nervous system, derived from the embryonic neural crest. Thus, paragangliomas are a type of neuroendocrine tumor, they are closely related to pheochromocytomas. Although all paragangliomas contain neurosecretory granules, only about 1-3% have clinical evidence of oversecretion.

Mutations of the genes SDHD (previously known as PGL1), PGL2, and SDHC (previously PGL3) have been identified as causing familial head and neck paragangliomas. Mutations of SDHB play an important role in familial adrenal pheochromocytoma and extra-adrenal paraganglioma (abdomen and thorax), although there is considerable overlap in the types of tumors associated with SDHB and SDHD gene mutations.

Gross Pathology

The paragangliomas appear grossly as sharply circumscribed polypoid masses and they have a firm or rubbery consistency. They are highly vascular tumors and may have a deep red color.

Microscopic Pathology

On microscopic inspection, individual tumor cells are polygonal to oval and are arranged in distinctive cell balls, known as a Zellballen pattern. These cell balls are separated by fibrovascular stroma and surrounded by sustentacular cells.

• Immunohistochemistry

• In paraganglioma the chief cells are positive for chromogranin, synaptophysin, neuron specific enolase, serotonin and neurofilament; they are S-100 protein negative.

• Histochemistry

• The paraganglioma cells are argyrophilic, periodic acid Schiff negative, mucicarmine negative, and argentaffin negative.