High discordance rate in assessing sentinel node positivity in cutaneous melanoma: Expert review may reduce unjustified adjuvant treatment

Introduction: Identification of sentinel node (SN) metastases can set the adjuvant systemic therapy indication for patients with stage III melanoma. Studies re-evaluating the diagnosis of initially positive SN biopsies are scarce. Materials and methods: Dutch patients with melanoma who underwent SN biopsy between 2003 and 2014 were selected from PALGA, the Dutch Pathology Registry. Histopathological slides of SN-positive patients were retrieved for review. A random sample was reassessed by an expert melanoma pathologist. Recurrence-free survival (RFS) of patients who were misclassified (false-positive) was compared with those with a true positive SN status. For comparison, a group of SN-negative patients was included. Multivariable logistic analysis was performed to assess clinicopathological characteristics associated with misclassification of SN status. Results: Diagnosis was downgraded from melanoma metastasis to nodal nevus in 38 of the 322 reviewed patients (11.8%). Considering the inclusion criteria of phase III adjuvant trials, at least 4.3% of patients would have falsely qualified for adjuvant therapy. In multivariable analysis, patients with a low SN tumour burden and subcapsular SN tumour location had a significantly higher chance of being misclassified. The five-year RFS of the 38 downgraded patients was 86.7% (95% confidence interval [CI] = 72.6–96.6), similar to the 85.9% (95% CI = 84.9–86.8, p = 0.18) for 6413 SN-negative patients and better than the 53.2% (95% CI = 47.2–59.9, p = 0.009) of 284 patients who were truly SN positive upon review. Conclusion: More than 10% of originally positive SN biopsies of patients with melanoma concern misclassified nodal nevi. We advocate that when adjuvant treatment is considered in patients with stage III melanoma, SN biopsies should be reassessed by an expert melanoma pathologist.