Real-World Outcomes of Mycosis Fungoides and Site-Specific Nodal Involvement: A Registry-Based Study of 25 467 Patients.

Mycosis fungoides (MF) is a rare extranodal T-cell lymphoma with primary cutaneous involvement. While it is the most common primary skin lymphoma, large-scale real-world data defining survival benchmarks and the prognostic significance of specific nodal sites remain limited. To address this, we conducted a retrospective cohort study using the TriNetX global health research network and identified 25 467 patients with MF. The 5- and 10-year OS for the overall cohort was 83.4% and 74.7%, respectively. Patients with disease limited to the skin had 5- and 10-year OS rates of 86.1% and 78.0%, respectively. Nodal involvement at diagnosis was associated with significantly inferior survival [adjusted HR (aHR) = 1.60; 95% CI: 1.50-1.71; p < 0.001], exhibiting 5- and 10-year OS rates of 74.5% and 63.6%, respectively. Among patients with single-site lymphadenopathy, survival outcomes varied substantially by anatomical site, revealing a potential prognostic hierarchy: patients with inguinal/lower limb involvement exhibited the most favorable outcomes (5-year OS 80.2%), while those with visceral lymphadenopathy had the poorest prognosis (5-year OS 62.9%). In multivariable analysis, elevated LDH (aHR 3.06), lymphocytosis (aHR 1.37), and eosinophilia (aHR 1.29) were strong independent predictors of mortality, among others. To summarize, this study of over 25 000 MF patients represents the largest real-world analysis to date. Data suggest a potential prognostic divergence based on the anatomical site of nodal involvement. Additionally, our findings reinforce the prognostic value of LDH, eosinophils, lymphocytes and the hypopigmented and poikilodermatous variants as independent predictors of mortality, supporting their integration into routine risk stratification.