Increased Risk of Second Primary Hematologic and Solid Malignancies in Patients with Mycosis Fungoides

Importance: Mycosis fungoides (MF) is a rare, generally indolent non-Hodgkin T-cell lymphoma of the skin. It has previously been associated with increased risk of second hematologic malignancies and melanoma, but the association with second solid malignancies has not been well characterized.

Objective: This retrospective analysis seeks to assess the risk of developing a second primary hematologic or solid malignancy in patients with MF.

Design: We performed (1) an analysis of patients diagnosed with MF from 2000-2014 in the 18 population-based United States cancer registries of the Surveillance, Epidemiology, and End Results Program (SEER-18), and (2) a retrospective cohort study of patients with MF treated at the University of Minnesota (UMN) from 2005-2017 with a control group of patients with seborrheic dermatitis.

Setting: This study is a combination of population-based data and a single-center cohort.

Participants: SEER-18 consists of a population-based sample of patients across the United States with a diagnosis of MF (n=6196). The UMN cohort included a cohort of 172 patients with MF treated at the UMN from 2005-2017.

Results: In the SEER-18 cohort, relative risks were estimated using the standardized incidence ratios (SIR). Of the 6196 patients in the MF cohort there were 514 (8.3%) second cancer events (SIR 7.3, 95% confidence interval [CI] 6.7-7.9). Patients with MF were at substantially increased risk for both. non-Hodgkin (SIR 46.51, CI 39.16-55.0) and Hodgkin lymphoma (SIR 69.8, CI 34.8-124.9). MF patients were also at higher risk of melanoma (SIR 7.2, CI 4.5-10.9), lung (SIR 6.2, CI 4.8-7.8), female breast (SIR 8.0, CI 5.8-10.6), prostate (SIR 4.1, CI 3.1-5.2), bladder (SIR 3.6, CI 2.0-5.8), colon (SIR 5.2, CI 3.7-7.2) and renal (SIR 3.9, CI 1.8-7.3) cancers.

In the UMN cohort, patients with MF were significantly more likely to develop a second malignancy than patients with seborrheic dermatitis (relative risk [RR] 8.1, p<0.0005, CI 5.1-13.2). Patients with tumor stage MF were more likely to develop a second malignancy than those with patch/plaque stage disease (RR 3.2 p<0.01, CI 2.6-10.4). Similarly, patients with stage IIB or higher were significantly more likely than those with early stage disease (RR 3.0, p<0.003, CI 3.1-13.5) to develop a second malignancy. Analysis of treatments and imaging undergone by each patient revealed no significant difference in systemic, topical, radio- or phototherapy, or number of CT scans between patients who did and did not develop second malignancies.

Conclusions and Relevance: Patients with MF are at increased risk of developing second malignancies, particularly those with advanced stage disease or tumors. These findings warrant the development of targeted screening strategies for patients with MF.