Catecholamine-Synthesizing Enzymes Are Expressed in Parasympathetic Head and Neck Paraganglioma Tissue

Abstract

Background/Aim: Increased dopamine production may be a feature of head and neck paraganglioma (HNPGL). ¹⁸F-fluorodihydroxyphenylalanine positron emission tomography scintigraphy has a high sensitivity for detecting HNPGLs. These observations strongly suggest that HNPGLs have the capacity for <smlcap>L</smlcap>-3,4-dihydroxyphenylalanine uptake and conversion towards dopamine. Therefore, our aim was to demonstrate the presence of catecholamine-synthesizing enzymes, i.e. tyrosine hydroxylase (TH), aromatic <smlcap>L</smlcap>-amino acid decarboxylase (AADC) and dopamine β-hydroxylase (DBH) in HNPGL tissue. Methods: A single-center study was performed among patients who underwent surgery for HNPGL at a single university referral center between 1994 and 2012. HNPGL tissue was immunohistochemically stained for TH, AADC and DBH. Data on paraganglioma-associated germline mutations, preoperative biochemical phenotype and imaging studies were retrieved. Catecholamine excess was defined as preoperative plasma and/or urinary levels of metanephrine, normetanephrine or 3-methoxytyramine above the upper reference limit. Results: Nineteen HNPGLs from 18 patients were evaluated. All tumor tissues (100%) stained positive for AADC, 6 (32%) for TH and 2 (11%) for DBH. Of 3 HNPGLs staining positive for DBH, 2 were also positive for AADC and TH. Catecholamine excess was only present in 1 patient (5%). The HNPGLs of this single patient only showed positive staining for AADC. Conclusions: Catecholamine-synthesizing enzymes, in particular AADC, are expressed in the majority of HNPGL tissues.

Pathology of Paraganglioma and Pheochromocytoma: Review of Articles and Updates in Pathology

“…However, majority of the researchers agree that head and neck paragangliomas are more common among the females [10,11]. Our data of the head and neck paragangliomas also showed a female to male ratio of 3.8:1 [7].…”

Pathology and genetics of phaeochromocytoma and paraganglioma

“…the ability to produce catecholamines or their metabolites, requires the expression of tyrosine hydroxylase (TH), the initial enzyme in catecholamine biosynthesis. Immunohistochemical stains for TH are positive in most sympathetic paragangliomas, but in only a minority of parasympathetic paragangliomas . A TH stain of a paraganglioma, particularly in the head or neck, can be useful because recurrence or persistence of catecholamine metabolites in a patient whose tumour is TH‐negative most probably indicates a second primary rather than recurrence or metastasis.…”

Emerging role of dopamine in neovascularization of pheochromocytoma and paraganglioma

“…We recently documented the presence of catecholamine‐synthesizing enzymes in parasympathetic head and neck PGL tissues (118). Elevated levels of 3‐MT in plasma or urine have been found in 19–28% of patients with head and neck PGL (119–121).…”