Focal acantholytic dyskeratosis (FAD), epidermolytic hyperkeratosis (EHK), and Hailey-Hailey-like acantholysis (HH) represent unique histology reaction patterns, which can be associated with defined phenotypic and genotypic alterations. Incidental microscopic foci demonstrating these patterns have been identified in skin and mucosal specimens in association with a gamut of disease processes. These changes, when secondary, are of unclear etiology and significance. The following study further analyzes the incidence and association of these histologic patterns in a routine pathology/dermatopathology practice. 1. Introduction A variety of incidental microscopic cutaneous changes have been described in skin and mucosal specimens. Whether these represent spurious changes of no consequence, or true manifestations of underlying cellular alterations, remains unclear. Incidental FAD, HH, and EHK have been reported in association with a wide variety of benign and malignant skin conditions. (Table 2) Some authors believe these changes represent markers for underlying widespread cellular damage, likely from prolonged sun/ultraviolet light exposure. Several studies show an association of these changes with preneoplastic lesions and malignancy, supporting this theory. However, others cite a variety of clinical and pathologic evidence to refute this. A potential association between EHK, and possibly FAD, with atypical/dysplastic nevus has also been reported, although not uniformly. 2. Material and Methods 247 consecutive skin specimens covering a three-month period (1/04-3/04) were reviewed by the author to identify incidental foci of Hailey-Hailey-like acantholysis (HH) and focal acantholytic dyskeratosis (FAD). Subsequently, 500 consecutive skin specimens were reviewed by the author (8/08-9/08) at a different institution to evaluate for incidental foci of epidermolytic hyperkeratosis (EHK). An incidental focus was defined as a minor histologic finding occurring within a biopsy or excision specimen demonstrating a separate, primary process. All cases in which these patterns comprised the primary process were excluded. HH, FAD, and EHK patterns were defined utilizing standard diagnostic criteria. (Table 1) All cases were formalin fixed, paraffin embedded, and hematoxylin and eosin stained as per standard protocol. Table 1 Table 2: Conditions reported in association with described incidental reaction patterns. 3. Results Six cases of incidental FAD and HH were identified in the 247 skin specimens reviewed, representing 2.4% of the total reviewed. Of the six cases, three
A. C. S. Hutcheson, P. J. Nietert, and J. C. Maize, “Incidental epidermolytic hyperkeratosis and focal acantholytic dyskeratosis in common acquired melanocytic nevi and atypical melanocytic lesions,” Journal of the American Academy of Dermatology, vol. 50, no. 3, pp. 388–390, 2004.
L. Requena, C. Schoendorff, and E. Sanchez Yus, “Hereditary epidermolytic palmo-plantar keratoderma (Vorner type)—report of a family and review of the literature,” Clinical and Experimental Dermatology, vol. 16, no. 5, pp. 383–388, 1991.
D. K. Goette and N. A. Lapins, “Epidermolytic hyperkeratosis as an incidental finding in normal oral mucosa. Report of two cases,” Journal of the American Academy of Dermatology, vol. 10, no. 2, part 1, pp. 246–249, 1984.
G. Brodsky, “Focal acantholytic dyskeratosis and epidermolytic hyperkeratosis of the oral mucosa adjacent to squamous cell carcinoma,” Oral Surgery Oral Medicine and Oral Pathology, vol. 59, no. 4, pp. 388–393, 1985.
C. Urmacher and M. H. Shiu, “Malignant melanoma in association with keratosis palmaris et plantaris (epidermolytic hyperkeratosis variant),” American Journal of Dermatopathology, vol. 7, pp. 187–190, 1985.
J. A. Carlson, D. Scott, J. Wharton, and S. Sell, “Incidental histopathologic patterns: possible evidence of 'field cancerization' surrounding skin tumors,” American Journal of Dermatopathology, vol. 23, no. 5, pp. 494–496, 2001.
C. B. Tannenbaum, R. C. Billick, and H. Srolovitz, “Multiple cutaneous malignancies in a patient with pityriasis rubra pilaris and focal acantholytic dyskeratosis,” Journal of the American Academy of Dermatology, vol. 35, no. 5, pp. 781–782, 1996.
G. Rodsky, “Focal acantholyic dyskeratosis and epidermolyic hyperkeratosis of the oral mucosa adjacent to squamous cell carcinoma,” Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, vol. 59, pp. 388–393, 1985.
M. L. Cintra and E. M. de Souza, “Focal acantholytic dyskeratosis: a snare for the pathologist. Report of two cases associated to psoriasis and fibrous papule of the nose,” Revista Paulista de Medicina, vol. 110, no. 5, pp. 237–240, 1992.
M. Vazquez Botet and J. L. Sanchez, “Vesiculation of focal acantholytic dyskeratosis in acral lentiginous malignant melanoma,” Journal of Dermatologic Surgery and Oncology, vol. 5, no. 10, pp. 798–800, 1979.