Cellular cohesion as a prognostic factor in malignant melanoma: a retrospective study with up to 12 years follow-up

Malignant melanomas have a high metastatic potential. Although the depth of tumour invasion is the single most important histological prognostic factor, in clinical practice this correlation is frequently challenged. In this study, we assessed the cohesion of malignant melanocytes in the dermal component of all primary melanomas in vertical growth phase with tumour thickness >0.76 mm diagnosed in our Department between 1990 and 1995. The rationale behind this morphological evaluation was based on the hypothesis that a change in the adhesion molecule profile of melanoma cells may manifest visually discrete changes in the way that cells group together in dermal aggregates. We used a dyscohesion score based on the proportion of invasive tumour occupied by dyscohesive neoplastic cells and assessed its clinical significance by correlating it with the incidence of recurrence, regional and distant metastases and survival of the patients. Follow-up was up to 12 years. We found that the degree of melanoma cell dyscohesion was associated with the probability of local recurrence or metastasis. This correlation was particularly significant when dyscohesion involving an area smaller than 25% (dyscohesion score 1) of the dermal component was compared to dyscohesion involving a larger area (scores 2-4). Melanomas in the latter group had significantly increased likelihood of recurrence or metastasis (P<0.025, log-rank test). This was particularly the case in T1-T3 melanomas (P<0.005). Similarly, T1-T3 melanomas with dyscohesion score 1 had a significantly higher survival rate (P<0.025). In the same cohort, both disease-free survival and survival were not significantly correlated to thickness, probably due to the limited number of cases. Finally, we showed that extent of dyscohesion was independent of Breslow thickness or tumour regression. We believe that estimation of melanoma cell dyscohesion is a reliable histological prognostic factor that may be appropriate in clinical practice. Modern Pathology (2010) 23, 502-510; doi:10.1038/modpathol.2009.171; published online 19 February 2010