Distinct Longitudinal Patterns of Basal and Squamous Cell Carcinoma in Polycythemia Vera and Essential Thrombocythemia

Despite both being classified as NMSC, BCC [2] and SCC [3] differ substantially in biological behavior and clinical implications [4, 5]. However, data addressing subtype-specific temporal patterns of skin cancer occurrence across the MPN disease course remain limited, particularly with respect to malignancies arising before and after MPN diagnosis and the longitudinal evolution of distinct NMSC subtypes [6, 7]. To investigate subtype-specific NMSC patterns, we analyzed a longitudinal cohort of 1968 patients with polycythemia vera (PV) and essential thrombocythemia (ET) followed at Mayo Clinic between 1970 and 2024. Institutional review board approval was obtained from Mayo Clinic in accordance with the Declaration of Helsinki; informed consent was waived due to the retrospective nature of the study. The underlying PV/ET cohort has been previously reported in an analysis of autoimmune/inflammatory diseases (AID) and second malignancies [8]; the present study addresses a distinct question focused on subtype-specific longitudinal patterns of BCC and SCC before and after MPN diagnosis. Patients were classified according to the first post-MPN NMSC subtype, including first post-MPN BCC and SCC. Patients developing both subtypes during follow-up were assigned according to the subtype occurring first after MPN diagnosis. Prior malignancies, including BCC, SCC, and non-cutaneous cancers occurring before or at MPN diagnosis, were specifically recorded. Hydroxyurea exposure was evaluated in sensitivity analyses restricted to patients receiving hydroxyurea monotherapy or no cytoreductive therapy, excluding those treated with other cytoreductive agents or sequential/combination cytoreductive regimens. Cumulative incidence functions for post-MPN BCC and SCC were estimated accounting for death as a competing event. Factors associated with subtype-specific NMSC occurrence were evaluated using Fine-Gray competing-risk regression models, with MPN subtype included in multivariable analyses, and expressed as subdistribution hazard ratios (sHRs). Comparisons between groups were performed using Kruskal-Wallis tests for continuous variables and chi square or Fisher's exact tests for categorical variables. Statistical significance was defined as a two-sided p-value <0.05. All statistical analyses were performed using R version 4.4.3.