Life sciences · Journal article
Frontiers in Oncology · October 26, 2026
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Objective Lymphedema as the initial symptom poses significant challenges in the early diagnosis of underlying malignancies masquerading as rheumatic diseases. Methods This study retrospectively analyzed six patients who were hospitalized at Beijing Shijitan Hospital between October 2015 and October 2025 with paraneoplastic rheumatic syndromes (PRS) presenting with lymphedema as the initial manifestation. Data on clinical manifestation, laboratory and imaging findings, diagnoses, treatments, and prognosis were collected. Results Six patients (3 males, 3 females; median age 66 years) presented with lymphedema as the initial manifestation of PRS. The initial rheumatologic diagnoses were leukocytoclastic vasculitis (n=2), undifferentiated connective tissue disease (n=2), Sjögren’s syndrome (n=1), and anti-synthetase syndrome (n=1). The median interval from lymphedema onset to rheumatic diagnosis was 5.5 months. All patients received glucocorticoids, and four received immunosuppressants; none achieved durable benefit. The median interval from rheumatic diagnosis to therapy failure was 1 month, and from therapy failure to cancer diagnosis was 1 month. The underlying malignancies included lymphoma (n=3), lung adenocarcinoma (n=2), and gastric adenocarcinoma (n=1). During a follow-up of 1 to 13 months, two patients showed significant improvement in lymphedema, whereas the remaining four died. Conclusion Malignancies may present with lymphedema as the initial symptom, mimicking rheumatic diseases. Underlying malignancy should be highly suspected, particularly when there is a poor response to immunosuppressive therapy. Early recognition and screening for malignancies are crucial for improving patient outcomes.