Germline mutations in BAP1 predispose to melanocytic tumors.

Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.

Natural history of invasive cutaneous melanoma in Styria, Austria 2001-2003.

BACKGROUND: Rising melanoma incidences have created the need of assessment of epidemiological and clinical data. PATIENTS AND METHODS: We investigated the natural history of invasive cutaneous melanoma in Styria, a province of Austria, in the years 2001-2003. 1082 patients, 511 men and 571 women, mean age 58.2 +/- 16.7 years, were collected. Besides basic melanoma data, special histologic features such as regression structures, ulceration, microsatellites and vascular invasion were investigated. Furthermore, lymph node pathology in case of sentinel node biopsy and/or lymph node dissection was recorded. RESULTS: Mean annual incidence (crude rate) was 28.6 per 100,000 inhabitants, age standardized rate 24.5 per 100,000 (95 % CI 22.4-26.6). Cumulative risk (0- 74 years) was 1.92, lifetime risk 1 in 52. Superficial spreading melanoma was the most common type in both sexes, men on the trunk and women on the extremities. Only 11 % of all melanomas were in easily visible areas. Median tumor thickness was 0.75 mm, ranging between 0.2 and 50.0 mm. Sentinel node biopsy was performed in 158 melanomas (14.6 %),and was positive in 22 %.Primary therapeutic lymph node dissection was performed in 19 patients, showing metastases in 18 patients. CONCLUSIONS: The investigation revealed an unclear high melanoma incidence for invasive melanomas in our province, requiring further investigation.

Clinical epidemiology of invasive cutaneous malignant melanoma in the Austrian province Styria in the years 2001-2003 and its relationship with local geographical, meteorological and economic data.

BACKGROUND: Melanoma incidence rates vary within Europe. The highest incidences are reported in Scandinavia, the lowest in the southern parts, but incidences themselves also vary within the different countries. OBJECTIVE: We investigated the incidence of invasive cutaneous melanoma in Styria, a province of Austria, in the years 2001-2003. METHODS: Data from 1,082 patients, 511 males and 571 females (mean age 58.2 years) with primary melanoma were collected. For each patient, information regarding residence was available, and therefore the geographic distribution of melanoma on district level was investigated with particular reference to the mean number of sun hours, mean altitude, number of companies with more than 200 employees and median income. RESULTS: The mean annual incidence (age-standardized rate) was 24.5 per 100,000 (95% CI: 22.4-26.6), lifetime risk 1 in 52. Districts with a higher number of sun hours and higher altitude showed lower melanoma incidences. Higher median income was associated with higher melanoma incidence (p<0.001). CONCLUSION: The high incidence of invasive melanoma in Styria is unclear and a causal relationship between higher income and melanoma incidence remains speculative. Further investigations, especially concerning lifestyle and environmental factors, may unravel additional causative factors.