Malignancy Risk and Predictors in Dermatomyositis and Polymyositis: A Large Population-Based Study

<i>Background and Objectives</i>: Idiopathic inflammatory myopathies (IIMs) are rare autoimmune diseases with extra-muscular manifestations. A firm association with malignancy, mainly observed in dermatomyositis (DM) is well established and several predictors of malignancy were previously published. However, given the low prevalence of IIMs, large population-based studies are scarce, hindering a comprehensive understanding of site-specific cancer patterns and risk factors. This study aimed to evaluate malignancy patterns and predictors, in a large, diverse cohort of patients with DM and PM. <i>Materials and Methods</i>: This retrospective cohort study used the Clalit Health Services electronic database, including 1557 DM patients and 528 PM patients diagnosed between 2002 and 2018, along with age-, sex-, and residence-matched controls at a 1:5 ratio. The incidence and risk of malignancies were assessed using Cox proportional hazards models, and predictors of solid and hematologic malignancies within the PM/DM cohort were analyzed using adjusted logistic regression. <i>Results:</i> In our cohort, DM was associated with an increased risk of both solid and hematologic malignancies (HR 1.89, 95%CI 1.47-2.41), whereas in PM the association was less pronounced and limited to solid malignancies (HR 1.50, 95%CI 1.06-2.11). In DM, higher risks were observed for breast cancer (HR 1.86) and chronic leukemia (HR 5.02). Across both subtypes, older age at diagnosis, the presence of specific autoantibodies were associated with increased malignancy risk. Significant markers included antiphospholipid antibodies (OR 2.28), lupus anticoagulant (OR 2.29), anti-Mi2 (OR 2.09), any of the antinuclear antibodies (OR 2.37), and individually anti-RNP/Sm (OR 1.70), anti-Ro/La (OR 1.79), anti-Scl-70 (OR 1.60), and anti-DNA (OR 1.97). <i>Conclusions:</i> Our study demonstrates an increased risk of malignancy in both DM and PM, with the relationship being stronger and broader in DM, involving both solid and hematologic cancers. Older age at diagnosis, and a distinct serological profile, particularly antiphospholipid antibodies and various antinuclear antibodies, identify patients at highest risk, warranting heightened clinical vigilance.