Case Presentation: A 61-year-old male with a history of tobacco use was admitted for two months of progressive muscle weakness. He denied constitutional, respiratory, or dermatologic symptoms. Exam confirmed symmetric proximal muscle weakness by Oxford strength grading. Labs revealed an elevated alanine aminotransferase (ALT) at 318 U/L (reference range: 3-44 U/L) and aspartate aminotransferase (AST) at 319 U/L (reference range: 0-40 U/L). Alkaline phosphatase, total bilirubin, and gamma-glutamyl transferase were normal. Creatine kinase (CK) was elevated at 11,693 U/L (reference range: 10-205), C-reactive protein at 31.1 mg/L (reference range: ≤5), and erythrocyte sedimentation rate at 40 mm/hr (reference range: ≤17). Workup for inflammatory myopathy, including infectious serologies, autoantibody panels (myositis-specific, paraneoplastic, antinuclear antibody, rheumatoid factors), complement, thyroid, and methylmalonic acid, was unremarkable. Electromyography demonstrated irritative myopathy. Muscle biopsy of the right thigh showed myonecrosis, myophagocytosis, and regenerating fibers without significant inflammation.Findings were consistent with seronegative immune-mediated necrotizing myopathy (IMNM). Given known associations with malignancy, CT imaging was done and revealed a left upper-lobe mass with bilateral hilar and peribronchial lymphadenopathy. Fine-needle aspiration of a left supraclavicular lymph node confirmed non-small cell lung carcinoma (NSCLC).High-dose methylprednisolone (1 gram daily x five days) and intravenous immunoglobulin (30 grams daily) were initiated. CK improved to 3,282 U/L, and strength gradually returned. The patient was discharged for oncology and neuromuscular follow-up for coordinated cancer and myopathy management.
Discussion: This case describes paraneoplastic seronegative IMNM secondary to NSCLC. IMNM is a rare idiopathic inflammatory myopathy characterized by progressive, symmetric proximal muscle weakness, markedly elevated CK levels, and biopsy findings of myonecrosis with minimal inflammatory infiltrate (1). Seronegative IMNM is difficult to diagnose due to the absence of specific autoantibodies and overlap with statin- and steroid-induced myopathies, endocrine disorders, and inclusion body myositis.Although seronegative IMNM rarely occurs as a paraneoplastic syndrome, prior cases typically presented with systemic symptoms of malignancy (2-5). The absence of overt cancer-related signs in this case posed a significant diagnostic challenge.This case highlights the importance of considering a paraneoplastic process even in the absence of malignancy symptoms. Recognizing that the elevated ALT and AST were secondary to muscle rather than hepatic injury, in the context of proximal weakness, elevated CK, and inflammation, was crucial for timely biopsy, malignancy screening, and immunotherapy. For hospitalists, recognizing this distinction can quickly orient the diagnostic approach toward myopathic processes and facilitate timely multidisciplinary evaluation.
Conclusions: Seronegative paraneoplastic IMNM, though rare, may be the initial presentation of an occult malignancy, especially when a patient presents with unexplained, progressive proximal weakness and CK elevation. Early identification and collaboration with neurology, rheumatology, and oncology can facilitate prompt immunotherapy and cancer management, preserving function and preventing irreversible muscle damage.