Expanding the Histologic Spectrum of Oral Pseudoperineurioma: A Retrospective Study of 21 Cases

Oral pseudoperineurioma (OPP) is a recently recognized peripheral nerve-associated lesion characterized by pseudo-onion bulb-like perineurial cell proliferations surrounding axon-Schwann cell units. Although now is included in the current World Health Organization (WHO) Classification of Head and Neck Tumors within the spectrum of neuromas, it remains underrecognized and is frequently misdiagnosed as other neural lesions, particularly traumatic neuroma. The full histopathologic spectrum of OPP has not yet been well defined.

Following Institutional Review Board approval, a retrospective review of University of Florida Oral Pathology Biopsy Service archives was performed to identify lesions meeting WHO-defined diagnostic criteria for OPP. Cases were retrieved through re-evaluation of lesions originally diagnosed as traumatic neuroma, intraneural perineurioma, or related peripheral nerve lesions. Hematoxylin and eosin-stained slides were reviewed and immunohistochemical studies (EMA, GLUT-1, CD56, and S-100) were performed. Clinical and pathologic data were recorded, and lesions were subclassified based on architectural growth patterns. Descriptive statistics were used for analysis.

Twenty-one cases of oral pseudoperineurioma were identified. Patients ranged in age from 14 to 73 years (mean 36 years), with a slight female predominance (52%). The tongue was the most commonly affected site (86%), followed by the lip (14%). Lesions were small, measuring 0.3-1.5 cm, with most measuring ≤ 1.0 cm. None were clinically suspected to represent a neural lesion, and the majority were originally diagnosed as traumatic neuroma. Histologically, cases demonstrated a spectrum of architectural patterns, including serpiginous and non-serpiginous forms, as well as papillary growth and distinctive intraneural and extraneural perineurial proliferations not previously described. Immunohistochemistry showed a uniform profile, with EMA and GLUT-1 positivity in all cases, frequent CD56 positivity, and absence of S-100 expression in perineurial cells.

OPP is an uncommon benign peripheral nerve lesion with a strong predilection for the tongue and a highly reproducible immunophenotype. The identification of previously undescribed morphologic patterns expands the recognized histopathologic spectrum of OPP and highlights the importance of awareness of this entity to avoid diagnostic misclassification.