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Oral Verruciform Xanthomas

A previously healthy 22-year-old woman presented to the oral medicine clinic with a 3-month history of bumps on the right ventral surface of her tongue. She had no history of tobacco or alcohol use and was monogamous with one sexual partner. The lesions had been previously diagnosed as condyloma acuminatum. On physical examination, the bumps were observed to be pink papillomatous lesions measuring 3 to 8 mm in diameter (Panel A). Testing for human immunodeficiency virus infection and syphilis was negative. Histopathological analysis of an excised lesion revealed acanthotic, papillary, and parakeratinized epithelium (Panel B, black arrow) with an accumulation of large cells with foamy cytoplasm in the connective tissue (inset, yellow arrows). The foamy cells stained positive for CD68 on immunohistochemical analysis, which confirmed that they were macrophages. In situ hybridization for human papillomavirus infection was negative. A diagnosis of oral verruciform xanthomas — benign growths of the mucosa characterized by the presence of parakeratosis and foamy macrophages — was made. The cause of oral verruciform xanthomas is unknown, but they may result from trauma and chronic inflammation. Surgical excision is curative. In this case, surgical excision was offered, but the patient declined owing to the asymptomatic nature of the lesions. The lesions have remained stable in both number and size over 6 months of follow-up.
Gabriela Anaya-Saavedra, D.D.S., Ph.D. , and Marcela Vázquez-Garduño, D.D.S.
Published October 4, 2025
N Engl J Med 2025;393: e22
DOI: 10.1056/NEJMicm2504918
VOL. 393 NO. 14


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