To describe patients with sporadic inclusion body myositis (sIBM) and interstitial amyloid deposition.

Intracellular congophilic inclusions, although nonspecific, are one of the pathological hallmarks of sIBM. Intramuscular interstitial amyloid deposits, on the other hand, are the canonical findings of amyloid myopathies, which occur with or without systemic amyloidosis.  Interstitial amyloidosis in sIBM muscle has not been reported.

We reviewed the myopathology database (1998-2018) to identify patients with sIBM and intramuscular interstitial amyloid deposition.

We identified 4 sIBM patients (2 clinicopathologically-defined and 2 clinically-defined) with interstitial amyloid deposits on muscle biopsy. Two patients were anti-cN1A antibody-positive. Age at diagnosis ranged from 68 to 84 years (median 71 years). All had the classic sIBM pattern of weakness without associated sensory or autonomic symptoms. None had clinical or electrophysiological evidence of peripheral neuropathy. Only 1/4 patients had an IgM-λ monoclonal gammopathy but normal bone marrow biopsy.  Congo red-stained fat pad aspirate and echocardiogram were normal in 3 and 2 patients (including the patient with monoclonal gammopathy), respectively. Two of 3 patients without monoclonal gammopathy had normal TTR sequencing and one had also normal ANO5 and DYSF analysis. These 2 patients underwent muscle mass spectrometry-based analysis: one had amyloid chaperone proteins without known amyloidogenic proteins while the other had insufficient congophilic material for analysis. Median duration of follow-up was 8 months (range 3 weeks to 5 years). The patient with monoclonal gammopathy died of pneumosepsis 5 years after diagnosis. Autopsy revealed multi-organ amyloid deposition, including heart. Immunohistochemical studies showed positive transthyretin immunoreactivity within the congophilic deposits, consistent with ATTR amyloidosis.

Detection of muscle interstitial amyloidosis should trigger an aggressive search for systemic amyloidosis independently from other associated muscle structural abnormalities.  Amyloid subtyping is important for early therapy and mortality prevention. An isolated monoclonal gammopathy should not halt search for non-hematological causes of systemic amyloidosis.