BILATERAL PRIMARY UVEAL MELANOMA - BAD LUCK OR BAD GENES

Background: The occurrence of bilateral primary uveal melanoma has bee n assumed to be a rare, random event. Bilaterality of a primary cancer is suggestive of an inherited cancer predisposition. The authors ther efore evaluated patients with bilateral primary uveal melanoma for suc h cancer predisposition. Methods: The charts of 4500 patients with uve al melanoma were reviewed for the presence of bilaterality, The clinic al profile of patients with bilateral primary uveal melanoma was studi ed. The presence of ocular melanocytosis, familial atypical mole and m elanoma syndrome, neurofibromatosis type 1, cutaneous melanoma, famili ar uveal melanoma, Li-Fraumeni syndrome, and second primary cancers al so was investigated. Results: Of 4500 patients with primary uveal mela noma, 8 (0.18%) were identified to have bilateral primary uveal melano ma. Using the annual incidence rate (Shammas and Watzke) and normal ap proximation to the binomial, the expected number of patients with prim ary bilateral uveal melanoma in the authors' series was calculated to be less than one person. Observation of eight patients with bilateral primary uveal melanoma represented greater than expected occurrence (P < 0.0001). The mean age at diagnosis in the first eye was 56 years. T he interval between the diagnosis of uveal melanoma in the two eyes ra nged from 2 to 32 years (median, 10.5 years). Two patients had bilater al ocular melanocytosis. Ocular melanocytosis was more common (2/8, 25 %) in patients with bilateral uveal melanoma compared with those with unilateral uveal melanoma (60/4492, 1.3%). This difference was statist ically significant (P = 0.001). No relation to familial atypical mole and melanoma syndrome, cutaneous melanoma, neurofibromatosis type 1, f amilial uveal melanoma, second primary cancers, or Li-Fraumeni syndrom e was observed. Conclusions: Bilateral primary uveal melanoma occurs m ore frequently than expected by chance, and may be associated with ocu lar melanocytosis. In the authors' series, there was no clinical evide nce of an inherited genetic predisposition for bilateral primary uveal melanoma. Unidentified germ-line mutations may be involved in pathoge nesis of bilateral primary uveal melanoma.