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Bone marrow biopsy is common in patients suspected of having systemic AL amyloidosis. However, little is known about the incidence, morphology and clinical phenotype of non-AL amyloid types in bone marrow. We retrospectively identified  N  = 1469 bone marrow amyloid biopsies typed using a proteomics-based method between 2008–2020. Frequency of amyloid types ( N  = 1469), distribution of amyloid deposits ( N  = 139), and clinical phenotypes ( N  = 355), with particular emphasis on cardiac involvement, were assessed. The amyloid types were: AL ( N  = 1172; 79.8%), ATTR ( N  = 240; 16.3%), AH ( N  = 38; 2.6%), AA ( N  = 17; 1.2%), and Aβ2M ( N  = 2; 0.1%). Although there were characteristic morphologic features, including periosteal soft tissue and/or vascular involvement in ATTR, interstitial vascular involvement in AA, and variable anatomic compartment involvement in AL, none were pathognomonic. Most patients with both an M-spike and cardiac involvement had AL amyloid in their BM, but in over 10% the amyloid type was ATTR. Compared to AL patients, ATTR patients had higher stage cardiac amyloidosis and lower overall survival, which was mainly due to advanced cardiac stage. ATTR amyloid is common in bone marrow and its morphologic distribution overlaps with AL. Amyloid typing is critical as over 10% of patients with bone marrow amyloid, cardiac amyloidosis, and an M-spike have ATTR amyloidosis.

Bone marrow amyloid: a comprehensive analysis of 1,469 samples, including amyloid type, clinical features, and morphologic distribution