Isolated Hematogenous Dissemination in Malignant Melanoma

Background: Metastasis in malignant melanoma occurs via lymphatic or hematogenous pathways. While sentinel lymph node biopsy (SLNB) is the gold standard for staging the disease, a subset of patients develops isolated hematogenous metastasis despite negative nodal involvement. This study aims to investigate the risk factors associated with isolated hematogenous dissemination based on the "differential spread model." Materials and Methods: A retrospective analysis was conducted on 815 patients who underwent surgery and SLNB for malignant melanoma between 2008 and 2024. Patients with isolated hematogenous metastasis (distant organ metastasis without any prior or concurrent lymphatic involvement) were defined as the study group. The remaining patients with sufficient follow-up data formed the control group. Groups were compared regarding age, sex, primary tumor location, histopathologic subtype, Breslow thickness, ulceration, and regression. Results: Univariate analysis revealed that male sex, head and neck localization, increased Breslow thickness, presence of ulceration, and absence of regression were significantly associated with isolated hematogenous metastasis ( P <0.05). In the multivariate logistic regression model, male sex (OR=2.932, 95% CI: 1.082-7.946, P =0.034) and head and neck location (OR=5.301, 95% CI: 1.076-26.103, P =0.040) remained independent risk factors. Breslow thickness and ulceration lost their statistical significance in the multivariate analysis. Notably, regression was entirely absent in the hematogenous metastasis group. Conclusion: Isolated hematogenous dissemination in melanoma is independently driven by male sex and head and neck primary tumor location. The loss of significance for Breslow thickness in multivariate models might be related to the relatively small sample size. Furthermore, the absence of regression in these patients may indicate a failure in the host immune response. These findings may help identify high-risk patients who require more intensive systemic surveillance despite negative sentinel lymph nodes.