The keratotic tumors of Cowden's disease: an electronmicroscopic study

Cowden's disease is characterized by multiple hamartomas of the skin, breast, thyroid, and gastrointestinal tract. In the past, a viral hypothesis for the keratotic lesions of the skin has led to much controversy. The present study describes the results of a detailed fine structural analysis of 10 hyperkeratotic extremity lesions and 2 keratotic lesions from the face of a patient with Cowden's disease. Increases in the keratinocyte population were primarily confined to the basal and suprabasal regions. Differentiation products characteristic of keratinization were normal in both quantity and appearance. Nuclear remnants and numerous lipid droplets, markers of abnormal keratinization, were noted within horny cells. However, viral particles and/or virus-like particles were not observed in keratinocytes. Melanocytes and Langerhans cells were numerous. The latter contained membrane-bound pigment vacuoles in addition to the characteristic Birbeck granules. These unusual Langerhans cells were observed in the dermis as well as the epidermis. A large number of fully granulated "resting" mast cells was uniformly distributed throughout the dermis, associated with a prominent cellular infiltrate. Our observations do not support the concept of a viral etiology for these tumors.