British Journal of Dermatology 2000; 143: 1091±1096. Huriez syndrome: case report with a detailed analysis of skin dendritic cells C.GUERRIERO, C.ALBANESI,* G.GIROLOMONI,* C.DE SIMONE, R.CAPIZZI, P.AMERIO AND A.TULLI Department of Dermatology, Catholic University of the Sacred Heart, Largo A.Gemelli 8, 00168 Rome, Italy *Istituto Dermopatico dell'Immacolata, IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy Accepted for publication 4 May 2000 Summary We report a 60-year-old man with familial scleroatrophic syndrome of Huriez who developed squamous cell carcinomas on the affected skin of the right palm. Immunohistochemical analysis showed a marked reduction in the number of CD1a1, Lag1 and S1001 epidermal Langerhans cells, but not of CD1b1 and factor XIIIa1 dermal dendritic cells, limited to palmoplantar skin. The Langerhans cell depletion was not associated with an abnormal skin content of mRNA for factors involved in Langerhans cell development or recruitment in the epidermis, including granulocyte/macrophage colony-stimulating factor, transforming growth factor-b 1 and macrophage inflammatory protein-3a . The results indicate that other as yet unknown mechanisms may account for the reduced number of Langerhans cells in the affected skin of such patients. Key words: Huriez syndrome, immunohistochemistry, Langerhans cells, squamous cell carcinoma In 1963, Huriez and coworkers first identified a new congenital syndrome that they termed `ge Ânodermatose scle Âroatrophiante et ke Âratodermique des extre Âmite Âs' in several members of two families from northern France, which they subsequently described in more detail. 1±4 To our knowledge, since the initial description, nine families with Huriez syndrome have been reported to date. 1±12 This rare autosomal dominant genoderma- tosis is characterized by a triad of clinicopathological manifestations, including diffuse scleroatrophy of the hands with sclerodactyly, lamellar keratoderma of the palms and, to a lesser extent, of the soles, and ridging, clubbing or hypoplasia of the nails. Hypo- hidrosis is usually associated with the disorder. The disease appears at birth or in the first years of life, and persists unchanged in adult life. 13±15 A distinctive feature of the syndrome is the risk of development of a squamous cell carcinoma on the scleroatrophic skin. 3,4 This skin neoplasm seems to be particularly aggressive in these patients, and the often poor grade of differentiation may account for the high rate of metastasis, which is unusual in cutaneous squamous cell carcinomas. An approximately 13% risk of skin cancer and 5% mortality in affected individuals have been calculated by some authors. 11 Although earlier studies suggested linkage with MNSs blood group, 4 recent investigations refuted this association. 16 Immunohistochemical and ultrastructural studies per- formed by Hamm et al. revealed an almost complete absence of epidermal Langerhans cells (LCs) in involved skin. 11 The crucial part played by these cells in the recognition and presentation of tumour-associated antigens and in cutaneous immunosurveillance against incipient neoplasms is well documented. 17,18 Based on these data, the authors suggested that the proneness of the scleroatrophic skin to malignant degeneration could be due to the absence of epidermal LCs. We report a patient with Huriez syndrome who developed squamous cell carcinomas on the affected skin. An extensive analysis of epidermal LCs and dermal dendritic cells (DCs) confirmed a marked reduction in the number of CD1a1, Lag1 and S1001 epidermal LCs, but not of CD1b1 and factor XIIIa1 dermal DCs in palmoplantar skin. In addition, the LC depletion was not associated with an abnormal mRNA expression of factors involved in LC development or recruitment in the epidermis, including granulocyte/ macrophage colony-stimulating factor (GM-CSF), transforming growth factor (TGF) -b1 and macrophage inflammatory protein (MIP)-3a. q 2000 British Association of Dermatologists 1091