Background: The need for novel molecular prognostic markers that can supplement validated clinicopathologic correlates for cutaneous malignant melanoma is well recognized. Proteins that mediate the epithelialmesenchymal transition, the process by which a cancer cell disengages from its parent tumor, are important candidates. Methods: The prognostic relevance of E-cadherin, N-cadherin, and P-cadherin, calcium-dependent transmembrane glycoproteins that regulate cell-cell adhesion, and their adaptors, A-catenin, B-catenin, and p120-catenin, was evaluated on a cohort of 201 primary and 274 metastatic melanoma tumors using fluorescencebased immunohistochemical methods and Automated Quantitative Analysis of protein expression on digitally captured photomicrographs. Results: Increasing levels of N-cadherin expression improved overall survival (log-rank = 7.31; P = 0.03) but did not retain significance following adjustment for established clinicopathologic correlates (P = 0.50). Higher levels of E-cadherin approached significance for favorable prognosis on both univariate (P = 0.13)

Basal keratinocyte lysis is the hallmark histopathological finding of epidermolysis bullosa simplex (EBS), a group of rare heritable mechanobullous disorders characterized by intraepidermal blister formation and skin fragility. Over 100 mutations, found predominantly in the genes encoding keratins 5 and 14 (KRT5, KRT14), have been described to account for a variety of clinical subtypes. EBS with mottled pigmentation (EBS‐MP) is a rare variant featuring childhood‐onset reticulate hyperpigmentation and focal palmoplantar keratoderma, typically associated with a P25L KRT5 mutation. In this report, we present the case of a 77‐year‐old woman with a history of palmoplantar keratoderma who developed a transient EBS‐MP‐like phenotype associated with bexarotene treatment for cutaneous T‐cell lymphoma. Genetic sequencing revealed a heterozygous G138E KRT5 variant, present in approximately 10% of the European population and only rarely associated with pathology. Bexarotene, which has been reported to alter keratin synthesis, caused vesiculobullous reactions with similar frequency in clinical trials. We propose that the cumulative effect of drug treatment and underlying G138E polymorphism resulted in transient basal keratinocyte lysis in our patient and provides a plausible explanation for this unusual bexarotene side effect. Trufant JW, Kreizenbeck GM, Carlson KR, Muthusamy V, Girardi M, Bosenberg MW. A transient epidermolysis bullosa simplex‐like phenotype associated with bexarotene treatment in a G138E KRT5 heterozygote.