Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup.

BACKGROUND: Multiple primary melanoma (MPM), in concert with a positive family history, is a predictor of cyclin-dependent kinase (CDK) inhibitor 2A (CDKN2A) germline mutations. A rule regarding the presence of either 2 or 3 or more cancer events (melanoma and pancreatic cancer) in low or high melanoma incidence populations, respectively, has been established to select patients for genetic referral. OBJECTIVE: We sought to determine the CDKN2A/CDK4/microphthalmia-associated transcription factor mutation rate among Italian patients with MPM to appropriately direct genetic counseling regardless of family history. METHODS: In all, 587 patients with MPM and an equal number with single primary melanomas and control subjects were consecutively enrolled at the participating centers and tested for CDKN2A, CDK4, and microphthalmia-associated transcription factor. RESULTS: CDKN2A germline mutations were found in 19% of patients with MPM versus 4.4% of patients with single primary melanoma. In familial MPM cases the mutation rate varied from 36.6% to 58.8%, whereas in sporadic MPM cases it varied from 8.2% to 17.6% in patients with 2 and 3 or more melanomas, respectively. The microphthalmia-associated transcription factor E318K mutation accounted for 3% of MPM cases altogether. LIMITATIONS: The study was hospital based, not population based. Rare novel susceptibility genes were not tested. CONCLUSION: Italian patients who developed 2 melanomas, even in situ, should be referred for genetic counseling even in the absence of family history.

Sentinel lymph node dissection in stage I/II melanoma patients: surgical management and clinical follow-up study.

Selective sentinel lymph node (SLN) dissection is widely used in the management of cutaneous melanoma patients without clinical evidence of nodal metastases. A series of 274 consecutive melanoma patients who underwent melanoma primary excision and SLN mapping at our institutions since 1998, and were thereafter followed up and eventually treated, is reported in this prospective study. The aim was to analyse the parameters associated with a higher risk of occult nodal metastases, to evaluate the clinical outcome of melanoma patients who underwent SLN procedure, and to identify by means of multivariate analysis the prognostic parameters with independent predictive value on disease-free survival (DFS) in node-positive and negative patients. The SLN was tumour-negative in 228 patients (83.2%). A disease progression occurred in 25 (10.9%); among them, 10 patients in whom the initially identified SLN had been negative, developed a clinically and histologically evident positive lymph node in the same basin during follow-up. Five-year DFS and overall survival were 75% and 82%, respectively. In 46 patients (16.8%), the SLN proved to be tumour positive. The percentage of SLN-positive patients varied according to the primary thickness, from 11.8% in patients with Breslow of 2 mm or lower, to 34.7% in patients with Breslow from 2 to 4 mm, up to 55.9% in patients with Breslow greater than 4 mm (P<0.001). Only two patients with Breslow thickness lower than 1 mm had positive SLN biopsy. Five-year DFS and overall survival (OS) were 42 and 69%, respectively, significantly lower than those of negative SLN-patients (P<0.001). Multivariate analyses showed that the parameters with prognostic independent value on DFS were SLN status (micrometastases or macrometastases; P=0.0001), and to a lesser extent, Breslow thickness (P=0.04). In conclusion, our data support the clinical usefulness of SLN dissection as a reliable and accurate staging method in patients with cutaneous melanoma. SLN-positive patient OS (5-year survival 69%) seems to be superior to that historically reported for stage III patients treated with curative nodal dissection only after the clinical evidence of palpable adenopathies (5-year survival 36%). The prognostic relevance of the pattern of SLN invasion (micrometastases/macrometastases) could be the basis for the planning of adjuvant treatment trials on selected groups of patients.