Melanoma patients with an unknown primary tumor site have a better outcome than those with a known primary following therapeutic lymph node dissection for macroscopic (clinically palpable) nodal disease.

Background: Several reports in the literature suggest a difference in outcome between melanoma patients with macroscopic (clinically palpable) nodal disease from an unknown primary (MUP) and a known primary (MKP). The purpose of this study was to compare the outcomes for MUP and MKP patients after therapeutic lymph node dissection (TLND) for macroscopic nodal disease.
Methods: From a large, prospective, single-institution database, the details of melanoma patients who first presented with macroscopic nodal disease and underwent TLND between 1971 and 2010 were extracted and analyzed.
Results: There were 287 MUP patients and 264 MKP patients who fulfilled the study selection criteria. MUP patients had better disease-free, distant metastasis-free, and melanoma-specific survival after their TLND than MKP patients (all p < 0.001). Extranodal melanoma extension, >3 positive lymph nodes, and administration of adjuvant radiotherapy were all independent predictors of reduced disease-free and melanoma-specific survival (all p < 0.05). MUP patients also had a better prognosis than MKP patients whose primary melanoma had regression (p = 0.001).
Conclusions: The occurrence and improved outcome of MUP patients may be due to immune-induced total regression of the primary tumor and better immunologic prevention or control of distant metastatic disease. Alternatively, in some MUP patients, melanoma may not be metastatic but may originate de novo from nevus cells in lymph nodes, with the more favorable prognosis attributable to their primary nodal origin and complete surgical resection.