Multiple Myeloma Concomitant with AL Amyloidosis: Histopathological Aspects of the Common Plasma Cell Spectrum

Concurrent multiple myeloma (MM) and AL amyloidosis is associated with the poorest outcomes among plasma cell dyscrasias and has dramatically reduced median overall survival. Despite their clinical significance, comprehensive systematic histopathological studies, characterizing multiorgan involvement and lesion severity are remarkably scarce. This study includes 24 autopsies (of 18 women and six men; median age-68 years) with MM-AL. Immunohistochemical (IHC) typing was performed with an expanded antibody panel targeting the amyloid precursor protein; anti-human CD138 antibody was used to identify plasma cells in bone marrow sections. Clinical diagnosis of MM with monoclonal G-lambda secretion, Durie-Salmon Stages II-III, was established in 17 (71%) patients; MM with monoclonal G-kappa secretion, Stage III, in five (21%); and non-secreting MM in two (8%). Systemic amyloidosis was revealed during life in only 15 (62.5%) patients. In all cases, extensive amyloid deposits were observed in the myocardium, lungs and kidneys, establishing the morphological basis for multiorgan failure. IHC typing of amyloids confirmed 18 (75%) cases of AL-lambda amyloidosis and six (25%) of AL-kappa amyloidosis. Our results clarify MM-AL morphogenesis and underscore that AL is frequently underdiagnosed in MM patients. Comprehensive histopathological studies with IHC typing are necessary to confirm the diagnosis, refine the prognosis, and optimize the therapeutic strategies.