Alterations of 9p21 analysed by FISH and MLPA distinguish atypical spitzoid melanocytic tumours from conventional Spitz’s nevi but do not predict their biological behaviour

Cesinaro A M, Schirosi L, Bettelli S, Migaldi M & Maiorana A (2010) Histopathology 57, 515–527 Alterations of 9p21 analysed by FISH and MLPA distinguish atypical spitzoid melanocytic tumours from conventional Spitz’s nevi but do not predict their biological behaviour Aim:  The aim of this study was to investigate whether 9p21 status influence the prognosis of the spitzoid melanocytic tumours, peculiar lesions whose biological behaviour cannot be predicted by histopathological criteria alone. Methods and results:  Twenty-eight atypical spitzoid tumours, 12 conventional Spitz’s nevi and one congenital Spitz’s nevus were studied by fluorescent in-situ hybridization (FISH) and multiple ligation-dependent probe amplification (MLPA) for the presence of 9p21 deletion. The 28 patients were aged 3–56 years (mean 32, median 35), and follow-up ranged between 4 and 156 months (mean 51, median 48). Eight patients (28.5%) experienced lymph node metastasis (three cases with macrometastasis and five with micrometastasis). Of those with macrometastasis, two are alive after 159 and 26 months, whereas a third developed widespread metastases and died after 26 months. All of the other patients are alive. Statistically, the thickness (P = 0.01) and the diameter (P = 0.009) of the lesions significantly correlated with metastasis. Deletion of 9p21 by FISH analysis was observed in eight spitzoid tumours (28.5%), and MLPA demonstrated alterations of 9p21, particularly deletion of CDKN2A, in the same lesions, whereas all Spitz’s nevi, except the congenital one, were of unaltered 9p21 status (P < 0.0001). Deletion of 9p21/CDKN2A did not correlate with the presence of metastasis. Conclusion:  Alterations at 9p21 locus are significantly more frequent in spitzoid tumours than in Spitz’s nevi, but do not predict their biological behaviour.