Molecular and genetic mechanisms in melanoma.

Recent studies have indicated an increasing incidence of melanoma worldwide. Although UV signature mutations are found rarely in melanoma cells, there is some evidence that intense intermittent exposure to sunlight can induce melanocyte tumorigenesis, and this is also observed after UV irradiation in some animals. The purpose of this paper is to review some of the most important mechanisms involved in the pathogenesis of this tumor. Genetic studies showed the familiar melanoma is linked to the mutation or deletion of the suppressor gene CDKN2A, and perhaps to CDK4. Studies showed that BRAF mutation is frequent in primary and metastatic melanoma cells but also in naevocytic nevi. This mutation activates the RAF/MEK pathway. Exposure to UV radiation induces immunosuppression. Recent investigations showed that chemokines, angiogenesis, metalloproteinases can play a role in the mechanism of metastasis. In spite of these advances the initiating events are still not completely understood. In conclusion, the pathogenesis of melanoma is very complex because numerous genetic and epigenetic factors are implicated in its development and progression, but some of the showed mechanisms can be targets for new therapies.

Phytophotodermatitis in Rijeka region, Croatia.

Contact with plants can cause phototoxic or rarely photoallergic reactions. Phototoxic dermatitis (photophytodermatitis) occurs after contact or ingestion of plants containing furocumarins i.e. psoralens and followed by sun exposure. Skin lesions develop usually after 24-48 hours with erythema, bulla formation, itch or pain, followed by a long lasting hyperpigmentation. Furocumarins can be linear i.e. psoralens (5-MOP, 8-MOP), or angular like angelicin and pimpinellin. Their binding to DNA causes cellular damage. This can happen in florists, gardeners, farmers, horticulturists, food handlers, and botanists. The plants causing phototoxic reaction can vary with the local flora but are commonly a member of the family apiaceae (formerly umbelliferae), family rutaceae, leguminosae and moraceae. The authors give special consideration to the phytophotodermatitis that appeared in their region in spring and summer during a three year period.

Occupational skin diseases caused by solar radiation.

UV radiation is present in sunlight and can be emitted from numerous artificial sources. Outdoor workers are exposed to sunlight in a wide variety of occupations like sailors, fishers, construction workers, farmers, and other. Presented are the skin diseases caused by sunlight exposure. They may be of little medical importance such as stigmata or create problems like photoaging, skin carcinoma, melanoma, phototoxic and photoallergic reactions. Shown are briefly data on skin cancer in the Rijeka region in outdoor occupations, the legislation and necessity for prevention. Psoriatic patients need particular caution because they are exposed to UVR, tars, and immunosuppressive drugs during the treatment.

HPV 6-positive giant keratoacanthoma in an immunocompetent patient.

Keratoacanthoma (KA) is a clinically distinct, rapidly growing lesion that generally presents as a solitary crateriform nodule in sun-exposed areas in elderly, fair-skinned individuals. A KA larger than 20-30 mm is referred to as giant keratoacanthoma, a relatively rare lesion especially in young patients. Such lesions grow rapidly with possible destruction of underlying tissues. In addition to ultraviolet exposure, KAs have also been associated with chemical carcinogens, chemical peels, genetic factors, chronic skin conditions that produce scarring, trauma and thermal burns. Immunosuppressed patients, especially after transplantation, also develop KAs. A viral etiology has been suggested but not confirmed. We encountered a case of giant keratoacanthoma (greater than 50 mm in diameter) with induration of underlying structures on the upper lip of a 39-year-old male sailor. The patient reported sudden appearance and rapid enlargement of the lesion in only three weeks. Biopsy of the cutaneous lesion and the characteristic clinical history suggested the diagnosis of keratoacanthoma. Total excision with primary closure of the defect by a nasolabial advancement flap was performed. Histological examination of the tumor mass confirmed the diagnosis of KA with infiltrative growth and perineural invasion. Immunosuppression was excluded by blood analyses, as were HIV, syphilis and hepatitis infections. Only low-risk genital HPV type 6 was detected in the lesion, suggesting a possible cocarcinogenic effect of HPV and UV light in a chronically sun-exposed patient.