Intranuclear Inclusions Correlate with the Ultrastructural Detection of Herpes-Type Virions in Oral Hairy Leukoplakia

Abstract
Hairy leukoplakia (HL) is an Epstein-Barr virus-associated lesion of the oral mucosa that occurs in persons infected with human immunodeficiency virus. Ultrastructural studies have demonstrated herpes-type virions in 63–100% of cases of HL. In this investigation, incisional biopsy specimens from 52 consecutive patients with oral lesions clinically suspicious for HL were analyzed by light and electron microscopy to determine which light microscopic features correlated best with the presence of herpes-type virions ultrastructurally. The predominant histopathologic features consisted of irregular hyperparakeratosis, acanthosis, koilocytoid cells, and an absence of significant inflammation. Candidal organisms and bacterial colonies were variable findings. Intranuclear inclusions, identical to Cowdry type A inclusions seen in other herpesvirus infections, were observed in 46 cases and demonstrated the best correlation with the presence of virions ultrastructurally (p < 0.0001). Koilocytoid cells also had a statistically significant correlation with the presence of virions (p < 0.001). We conclude that Cowdry type A inclusions are present in many cases of HL and that their presence, when combined with the other clinical and histologic findings in these lesions, is the most specific light microscopic feature of HL.