Abstract Introduction Squamous cell carcinoma (SCC) can rarely trigger myositis as paraneoplastic syndrome, most commonly in the form of dermatomyositis. This phenomenon, termed cancer-associated myositis (CAM), is characterized by immune-mediated muscle inflammation that arises in temporal association with malignancy. Epidemiological studies confirm that patients with dermatomyositis have an increased risk of developing cancer compared to the general population, and the risk is highest within three years before or after myositis onset. Though this may be true, SCC is an uncommon underlying cancer type in these cases. Case Report A 58-year-old man initially presented with proximal muscle weakness and persistently elevated CK levels. Workup revealed inflammatory myositis with positive SSA antibodies and SIADH-related hyponatremia. Imaging demonstrated hilar and mediastinal adenopathy. He was started on a prednisone taper, mycophenolate, and trimethoprim-sulfamethoxazole for pneumocystis jirovecii (PJP) prophylaxis under rheumatology care. His initial workup included a CT chest which showed mediastinal lymphadenopathy. Follow-up CT chest showed enlarging mediastinal lymphadenopathy. Endobronchial ultrasound with biopsy (EBUS) was performed, and it showed non-small cell carcinoma consistent with squamous cell type (p40 positive, TTF-1 negative). Due to concern for exacerbating paraneoplastic inflammatory myositis, the plan would involve chemoradiation while avoiding immunotherapy after establishing definitive staging for a presumed lung malignancy. Discussion Cancer-associated myositis is a recognized paraneoplastic syndrome most frequently associated with adenocarcinomas of the ovary, breast, lung, and gastrointestinal tract. Reported cases involving squamous cell carcinoma (SCC) typically arise from the head and neck, cervix, or skin, with pulmonary SCC representing a rare trigger. The concurrent syndrome of inappropriate antidiuretic hormone secretion (SIADH) further supports a malignancy-driven immune process. Therapeutic management in such cases remains challenging, as immune checkpoint inhibitors may exacerbate autoimmune manifestations. In this patient, the decision to proceed with chemoradiation while withholding immunotherapy allowed for oncologic control with mitigation of paraneoplastic inflammation. Recognition of this uncommon association is essential, as new or recurrent myositis may herald underlying or relapsing malignancy. Conclusion This case highlights a rare presentation of paraneoplastic inflammatory myositis associated with thoracic cancer, likely pulmonary in origin. The temporal association between myositis onset and mediastinal lymphadenopathy underscores the importance of malignancy screening in adults presenting with new or treatment-refractory inflammatory myopathies. Early recognition of CAM facilitates timely cancer evaluation and therapeutic planning while addressing autoimmune complications. Ongoing surveillance remains critical, as recurrent myositis may serve as an early indicator of malignant relapse. This abstract is funded by: None
Naraparaju et al. (Fri,) studied this question.