Introduction: Intracellular congophilic inclusions within muscle fibers, although nonspecific, are one of the pathological hallmarks of sporadic inclusion body myositis (sIBM). Extracellular amyloid deposits in muscle, on the other hand, are the canonical findings of amyloid myopathies, which occur with or without systemic amyloidosis.

Methods: We reviewed the muscle biopsy database (1998- 2020) to identify sIBM patients with extracellular amyloid deposits. Clinical and laboratory data were reviewed.

Results: We identified 5 sIBM patients (3 clinicopathologically-defined and 2 clinically-defined) with extracellular amyloid deposits in muscle. Mean age at diagnosis was 74.8 years (range 68-84 years). All patients had a typical sIBM pattern of weakness without associated sensory or autonomic symptoms. None had electrophysiological evidence of peripheral neuropathy. Only one patient had a monoclonal gammopathy (IgM-λ) with normal bone marrow biopsy. This patient with monoclonal gammopathy and three other patients underwent abdominal fat pad aspirate and were negative for amyloid. Cardiac evaluation was unrevealing in the 4 patients tested. Three patients without monoclonal gammopathy had normal transthyretin gene sequencing and inconclusive mass spectrometry-based analysis. The patient with monoclonal gammopathy died of pneumosepsis 5 years after diagnosis and autopsy revealed multi-organ transthyretin amyloidosis.

Discussion: Detection of extracellular amyloid deposition in muscle should trigger an aggressive search for systemic amyloidosis independently from other associated myopathological abnormalities. Amyloid subtyping is crucial for early therapy and mortality prevention. An isolated monoclonal gammopathy should not halt a search for non-hematological causes of systemic amyloidosis.