Hairy Leukoplakia Workup

Updated: Jun 11, 2021
  • Author: James E Cade, DDS, FACD; Chief Editor: Jeff Burgess, DDS, MSD  more...
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Laboratory Studies

In most cases of oral hairy leukoplakia (OHL), the diagnosis is established on clinical basis, while a definitive diagnosis requires both an appropriate histopathological appearance and the demonstration of Epstein-Barr virus (EBV) DNA, RNA, or protein within the epithelial cells of the lesion.

Several immunohistochemical and in situ hybridization kits are commercially available for this purpose. [26] Tissue biopsy is indicated only if the lesions are unusual in appearance or ulcerated and suggest cancer.

Oral hairy leukoplakia may occur when CD4 counts are 200-300 cells/µL or lower. [27]



It is important to differentiate hairy leukoplakia from other, more serious, oral lesions that may have a similar clinical appearance. In some cases, biopsy and histologic examination are required to exclude cancer.


Histologic Findings

The histopathology of oral hairy leukoplakia (OHL) is characterized by the following five major features:

  • Hyperkeratosis of the upper epithelial layer that represents an altered pattern of keratin expression in the squamous epithelial cells: This hyperkeratosis is largely responsible for the characteristic shaggy or "hairy" gross appearance of the lesion. Superficial infections of the hyperkeratinized epithelium with bacteria or Candida may also be seen.

  • Parakeratosis of the superficial epithelial layer: This abnormal persistence of cell nuclei in the superficial epithelial layers may represent incomplete squamous differentiation.

  • Acanthosis of the stratum spinosum in the epithelial mid layer: This abnormal expansion of cells occurs with foci or layers of ballooning koilocyte-like cells. The nuclei have a homogenous ground-glass appearance and may contain Cowdry type A intranuclear inclusions.

  • Minimal or no inflammation in the epithelial and subepithelial tissues

  • Histologically normal basal epithelial layer

Although these characteristic histologic features of hairy leukoplakia are highly suggestive of the diagnosis, none is unique to the lesion. Thus, a definitive diagnosis of hairy leukoplakia requires both an appropriate histologic/cytologic appearance and demonstration of Epstein-Barr virus (EBV) DNA, RNA, or protein within the epithelial cells of the lesion.