Paragangliomas of the Head and Neck: An Overview from Diagnosis to Genetics

Abstract

Paragangliomas (PGL) develop from the parasympathetic system in the head and neck (HN) and arise primarily in four distinct areas: Carotid body, vagal, middle ear, and larynx. Globally, the diagnosis and morphologic features are the same regardless of anatomic site, however the incidence, frequency of genetic alterations/syndromes and differential diagnosis vary. It is now recognized that nearly 40% of all HN PGLs are hereditary, including a significant subset without a known family history. Now pathologists are central to the evaluation for diagnosis and further management of patients with HNPGLs. Specifically, SDHB immunohistochemical evaluation is an excellent screening tool to detect tumors with alterations in the SDH family of genes that represent the majority of hereditary cases in HNPGL. Similarly, SDHB immunohistochemical analysis allows for screening of PGL syndrome associated tumors (gastrointestinal stromal tumor (GIST), renal cell carcinoma (RCC), and pituitary adenomas) that have now been linked by their overlapping gene alterations. Awareness of the spectrum of these syndromes, and their associated tumors, positions the pathologist to augment patient care and surveillance.

Keywords: Carotid body tumour; Paraganglioma; Paraganglioma syndromes; SDHB; SDHD; Zellballen.

Fig. 1

Paragangliomas are characterized by chief cells forming variable size clusters ‘zellballen’ (H&E, 200x) (a); Supporting sustentacular cells surrounding the zellballen structures are highlighted by S100 (400x) (b); The sclerosing variant of paraganglioma shows rare clusters of paraganglioma cells (within dotted circles) in dense collagenous background (H&E 200x) (c); Paraganglioma cells may also show vacuolization/clear cell change (H&E 400X) (d)

Fig. 2

Histologic features in paraganglioma do not predict behavior (H&E 200x): a tumor irregular edge, b bone involvement, c cellular atypia, d tumor around nerve

Fig. 3

Metastatic paraganglioma and SDHB immunohistochemical evaluation. a A metastatic paraganglioma is present in a lymph node (H&E 10x); b the morphology in metastasis is the same as in primary paragangliomas, showing prominent vascularization (H&E 200x). c Immunohistochemical evaluation for SDHB expression in a sporadic paraganglioma shows diffuse expression in tumor cells (normal pattern)(400x) compared to d SDHB expression loss in a hereditary paraganglioma (note internal control in vascular cells is present)(400x)