Paraneoplastic Syndromes Mimicking Dermatomyositis and Remitting Seronegative Symmetrical Synovitis With Pitting Edema (RS3PE) Syndrome in Cancer of Unknown Primary Origin: A Case Report.

A 70-year-old male patient presented with fever, polyarthritis, systemic muscle weakness and pain, and skin rash, initially suspected to be an autoimmune disorder. Imaging revealed right supraclavicular and paratracheal lymphadenopathy, and a right supraclavicular lymph node biopsy confirmed squamous cell carcinoma. Still, the primary site remained unidentified, leading to a diagnosis of cancer of unknown primary origin (CUP). Laboratory tests showed no positive autoantibodies such as anti-Jo-1, anti-ribonucleoprotein (RNP), anti-Smith (Sm), and anti-SS-A antibodies, and a skin biopsy of the back indicated panniculitis with neutrophilic infiltration. Given the absence of infectious or autoimmune causes, the symptoms were attributed to paraneoplastic syndrome (PNS) associated with CUP, mimicking dermatomyositis and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Treatment with prednisolone (15 mg/day) led to the rapid resolution of joint pain, rash, and fever. Chemotherapy with carboplatin and paclitaxel for CUP was initiated with minimal adverse effects, allowing for continued outpatient management. This case highlights the importance of considering PNS when collagen disease-like symptoms are present in malignancy, particularly in CUP. Early recognition and corticosteroid therapy can improve performance status, enabling timely cancer treatment. Identifying atypical PNS presentations in CUP remains challenging, but a multidisciplinary approach can aid in diagnosis and management.