Histopathologic characterization of epidermolytic hyperkeratosis: a systematic review of histology from the National Registry for Ichthyosis and Related Skin Disorders.

BACKGROUND: The clinical condition generalized epidermolytic hyperkeratosis, also known as bullous congenital ichthyosiform erythroderma, is an autosomal dominant disorder and presents as a bullous disease of the newborn followed by an ichthyotic skin disorder throughout life. Clinical epidermolytic hyperkeratosis (cEHK) has characteristic histopathologic findings. Mosaic cEHK, which occurs without a family history, is a sporadic condition that clinically resembles epidermal nevi but demonstrates histopathologic findings similar to the generalized disorder; when a postzygotic mutation involves the germ line, the disease can occur in subsequent generations as generalized cEHK. Ichthyosis bullosa of Siemens (IBS) is similar histopathogically, but is clinically distinct from generalized cEHK, presenting with more superficial bullae. OBJECTIVES: It is well established that the clinical diagnoses generalized cEHK, mosaic cEHK, and IBS have similar histopathologic findings of epidermolysis with hyperkeratosis. We sought (1) to characterize the spectrum of histopathologic features and (2) to assess whether there were histopathologic differences between these clinically distinct disorders. METHODS: One hundred seventeen skin biopsy slides from the National Registry for Ichthyosis and Related Skin Disorders were reviewed, with those reviewers blinded to clinical information. All slides were systematically evaluated for a variety of features, including differences in the pattern of the epidermolysis and hyperkeratosis. Clinical predictions of whether the biopsy specimen was obtained from patients with generalized cEHK, mosaic cEHK, or IBS were made on the basis of histologic pattern of the epidermolysis and hyperkeratosis. RESULTS: Eighteen of the 117 slides revealed features sufficient to make a histologic diagnosis of epidermolytic hyperkeratosis (hEHK). One additional slide, for which a definitive histologic diagnosis was not possible, had features of both hEHK and acantholytic dyskeratosis. Two distinct patterns of the histopathologic changes were observed within the 18 slides diagnostic of hEHK: (1) continuous involvement of the entire horizontal epidermis and (2) focal involvement revealing skip areas of normal-appearing epidermis along the horizontal epidermis. Upon clinical correlation, all 12 of the slides with continuous involvement were from patients with generalized cEHK. One slide was from acral skin and had continuous involvement; this was from a patient with Vorner's palmoplantar keratoderma. Of the remaining 5 slides with focal involvement, two patterns were observed: focal involvement of both granular and spinous layers and focal involvement of only the granular layer. The 3 slides with focal involvement of the granular and spinous layers were from patients with mosaic cEHK. Of the two slides with focal involvement confined to the granular layer, one was from a patient with IBS and the other from a patient with generalized cEHK. LIMITATION: The sample pool is biased by who was enrolled in the Registry and therefore may not represent the full spectrum of the disease. CONCLUSION: The pattern of histologic involvement may be a useful predictor of the clinical phenotype of cEHK.

A range of histologic findings in infantile digital fibromatosis.

Infantile digital fibromatosis is a benign proliferation of myofibroblasts with characteristic eosinophilic intracytoplasmic inclusion bodies. Clinically, patients present in the first several years of life with asymptomatic, smooth, flesh-colored nodules located on the dorsal or lateral aspect of the fingers or toes. The lesions have a tendency for spontaneous regression and recur over 60% of the time following excision. Observation is often recommended, while surgery is reserved for cases of rapid growth or functional impairment. We report three patients, ranging in age from 8 months to 8 years, with infantile digital fibromatosis. All three patients presented with nodules on the hands or feet and all shared histologic findings of spindle cells with characteristic inclusion bodies. Pathologic features ranged from a haphazard arrangement of spindle cells with few inclusion bodies and numerous lymphocytes to a well-organized arrangement of spindle cells with abundant inclusion bodies and rare lymphocytes. All three patients underwent excision for diagnosis or treatment of their tumors with two of the patients experiencing a recurrence.

Multinucleated atypia of the vulva.

Multinucleated atypia of the vulva (MAV) is an entity with a distinctive histologic pattern of multinucleation in the basal and middle layers of the squamous epithelium that may mimic human papillomavirus (HPV)-related squamous atypias. MAV is rarely reported in the literature, and we believe it should be considered in the differential diagnosis of flesh-colored vulvar papules and vulvar epidermal atypias with multinucleated squamous cells. We describe the case of a 49-year-old patient with the diagnosis of MAV. Results of histopathologic examination revealed a focal area of multinucleation in the basal to middle epithelial layers of the vulvar squamous epithelium, accompanied by mild hyperkeratosis and chronic inflammation. HPV was not identified in the lesion by in situ hybridization techniques.

Localized cutaneous posttransplant Epstein-Barr virus-associated lymphoproliferative disorder.

Localized cutaneous posttransplant lymphoproliferative disorder is a rare complication of solid organ transplantation. Biopsies demonstrate diffuse dermal proliferations of atypical lymphocytes with variable Epstein-Barr virus latent membrane protein-1 expression. Extracutaneous involvement is absent.