Clear-cell acanthoma (CCA) has been reported to be a benign epidermal neoplasm; however, several authors have suggested alternative differentiation as well as other nosologic categories, including a reactive dermatosis. Fourteen CCAs, ten tricholemmomas, and seven cases of psoriasis were reviewed with conventional microscopy, periodic acid-Schiff stains, and immunohistochemical stains. Twelve of fourteen (86%) CCAs were associated with underlying or adjacent conditions. The CCAs stained immunohistochemically in a pattern similar to normal epidermis and psoriasis. Tricholemmomas stained in a distinctly different pattern with MNF116 and NGFR/p75. These cases demonstrate CCA in settings that reflect chronic inflammation, primarily scars and stasis dermatitis, and with an immunophenotype that parallels psoriasis. These findings support the contention that CCA does not show outer follicular sheath (tricholemmal) differentiation. Furthermore, these cases lend additional support to the contention that CCA represents a psoriasiform reaction pattern, which, in appropriately taken biopsies, usually has a demonstrable associated condition. Nonetheless, the precise nosology of this phenomenon has yet to be elucidated completely.

Immunohistochemical characterization of keratin expression in clear cell acanthoma.Br J Dermatol. 1995 Aug;133(2):186-93.

The nature of clear cell acanthoma has not been clarified, although many hypotheses have been proposed, including a benign neoplasm derived from epidermis or the acrosyringium, or a non-specific dermatosis. In this study, seven cases of clear cell acanthoma were analysed by immunohistochemical techniques, using various monoclonal antikeratin antibodies, and antibodies against filaggrin, involucrin and epithelial membrane antigen. Different immunoreactivities were noted between clear cell acanthoma and a normal eccrine gland, including the acrosyringium. Immunoreactivities of clear cell acanthoma were almost identical to those of normal epidermis, although some antibodies gave a different staining pattern between clear cell acanthoma and normal epidermis. The expression of cytokeratins in psoriatic epidermis has been reported to change as a result of abnormal differentiation or maturation. Clear cell acanthoma showed a similar staining pattern to inflammatory dermatoses such as psoriasis vulgaris, lichen planus and discoid lupus erythematosus. We speculate that clear cell acanthoma is a localized form of inflammatory dermatosis rather than a neoplasm.