The molecular-based differentiation of Heck's disease from its mimics including oral condyloma and white sponge nevus

Heck's disease (focal or multifocal epithelial hyperplasia) is a benign, rare condition of the skin and mucous membranes induced by human papillomavirus (HPV) infection. Other entities that can induce large papillomatous lesions that involve the mucous membranes and skin include condyloma acuminatum, which is sexually transmitted, and white sponge nevus, often due to a mutation of cytokeratin 4 or 13. Six cases diagnosed as either Heck's disease (n = 2) or white sponge nevus (n = 4) and 6 oral condyloma were compared on histologic grounds and analyzed in situ for HPV DNA, including HPVs 6,11, and 13, as well as cytokeratins 4 and 13. Each case showed marked acanthosis, and para/hyperkeratosis. More variable histologic findings included rete ridge elongation, keratinocyte degeneration, and perinuclear halos. High copy HPV 13 DNA was evident in the squamous cells towards the surface in the two cases diagnosed as Heck's disease and in two cases diagnosed as white sponge nevus on clinical grounds. HPV 6/11 was found in each of the six condyloma. Marked decrease in either cytokeratin 4 or 13 was evident in the two cases diagnosed as white sponge nevus that were HPV DNA negative. It is concluded that in situ hybridization analyses including HPVs 6, 11, and 13 as well as immunohistochemistry for cytokeratins 4 and 13 can differentiate Heck's disease from condyloma and white sponge nevus, which can be difficult to differentiate on clinical and histologic grounds.