Biology of melanogenesis

s24

Symposium

S13. Pathogenesis

and treatment

suggested that a number of vitamins and antioxidants may be effective in preventing NMSC, but only few actual human trials have been carried out. Retinol (25000 iu daily), ttetinoin in combination with systemic therapy and acitretin have been shown to have some preventive potential in human studies. Skin resurfacing techniques have also shown promise although surgery may be considered more therapeutic than preventive.

of cutaneous

pigmentaty

disorders

long-term remissions are rare mostly therapy in this stage is best described as palliative.

Pathogenesisand treatment of cutaneouspigmentary disorders

s13.

S13-1 Biology of melanogenesis S12-6 Photodynamic therapy for non-melanoma skin cancer R. Kaufmann. Department Goethe-University,

Frankfurt

of Dermatology, .I. W am Main, Germany

Because of the easy accessibility of superficial skin cancers a vast array of therapeutic options have evolved for their management. Recent interest has focussed on the use of photodynamic therapy (PDT). Most experience has been gained with a topical approach employing the heme precursor 5-delta-aminolevulinic acid as a sensitizer avoiding prolonged skin photosensitivity of earlier systemic application trials. Moreover, high-power polychromatic red light systems have substituted laser light sources in ‘most dermatological indications. Especially in skin cancer precursors (acitinic keratosis) or in in-situ lesions (e.g. Bowen’s disease) as well as in superficial basal cell carcinomas topical PDT has been demonstrated to be a safe and feasable alternative to other destructive techniques. A major drawback is a buming sensation, making the procedure painful in most patients. However, local anesthetics are required only in few cases, in larger lesions or in delicate areas. The procedure should be considered especially in patients not suitable for surgery, but also in multiple lesions or those in critical sites. The recent development of new light sources along with the availability of alternative sensitizers will certainly help to make PDT a more popular approach.

S12-7 Modern concept in the management of Merkel cell carcinoma W. Hartschuh. Universitltls-Hautklinik,

Heidelberg,

Germany

Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine tumor of the skin with features of epithelial differentiation. The tumor arises mostly in elderly persons in the head/neck region. Its biologically aggressive behavior is documented by a high rate of local recurrences and distant metastases and, therefore, demands an early and actuate diagnosis which comprises immunohistochemistry to detect cytokeratin 20, neurofilarnents and neuroendocrine marker substances like NSE and chromogranin A. MCC should be treated aggressively with wide excision of the primary lesion. Preliminary data suggest that sentinel lymph node biopsy may be a useful1 adjunct to identify a population of high risk patients who could benefit from further lymphadenectomy, eventually in combination with radiotherapy to the primary site and to the lymph node station. A beneficial effect of adiuvant chemo-/immunotherapy so far has not been established due to the rarity of the tumor. In non-resectable tumors multimodal therapeutic concepts including radiotherapy, chemo- and immunotherapy are applied. However, since

B. Gilchrest. Boston

MA,

USA

Studies in mice have revealed > 100 gene products whose loss influences pigmentation; and in cultured human melanocytes, numerous paracrine regulatory factors, cell surface receptors, signal transduction pathways, and nuclear transcription factors that modulate melanogenesis have been identified. Remarkably, despite this progress, the molecular determinants of human skin and hair color, as well as alterations leading to common pigmentary disorders remain incompletely understood. Recent insights will be discussed. S13-2

Mutant mouse models for normal and abnormal human pigmentation

D.C. Bennett. St. George’s Terrace,

London

Hospital SW1 7 ORE, UK

Medical

School,

Cranmer

There are currently 88 known genetic loci in mice, mutations at which affect the pigmentation of the hair, skin and/or eyes. These provide a rich resource for molecular studies of the normal and abnormal pigmentation of humans. 25 of these genes have been cloned to date. Human homologues are known for most of them, and include 13 loci for pigmentary disorders. The mammalian colour genes can be classified into four main groups. The first group control primarily melanocyte function; their products include melanosomal proteins like tyrosinase. Their mutations can produce albinism, and hair-colour variation. The second group, when mutated, produce pigmentary defects with bleeding and lysosomal storage disorders, such as Herman&y-Pudlak syndrome. These genes control protein routing and organelie biogenesis. A third group have systemic functions like copper transport. Lastly a large group of genes controls the development of melanocytes. These encode transcription factors, receptors and their ligands. Their mutations cause piebaldism and a wide range of disorders, often affecting other neural crest derivatives, as in Hirschsprung and Waardenburg syndromes. In this short review, emphasis will be on recently-cloned genes, and those for which there is progress in understanding function.

S13-3 Silvery hair syndromes: An update J.M. Naeyaert, J. Lambert, G. Van Coillie. University Gent,

Hospital,

Belgium

The presence of silvery hair in an infant indicates one of three syndromes: Griscelli (G), ChCdiak-Higashi (C-H) or Elejalde (E) syndrome. All three are characterized by partial albinism and, in G and C-H, variable immunodeficiency. Neurologic defects can also be present (E Z- G > C-H). Diagnosis is