Crystal-Storing Histiocytosis as a Red Herring in Multiple Myeloma

Multiple myeloma (MM) is a clonal plasma cell disorder characterized by aberrant immunoglobulin deposition causing end-organ damage (Jones et al. in Hum Pathol 30:1441-1448, 1999). Rarely, paraproteins crystallize within histiocytes, resulting in crystal-storing histiocytosis (CSH) (Jones et al. in Hum Pathol 30:1441-1448, 1999). The coexistence of MM, CSH, and amyloidosis is exceedingly uncommon (Takahashi et al. in Pathol Int 37:141-154, 1987). A 56-year-old male presented with chronic low back pain and elevated creatinine (~ 2.05 mg/dL). Myeloma workup revealed elevated beta-2 microglobulin (8.34 mg/L), an M-band (~ 1.75 g/dL), an abnormal free light chain ratio (~ 31.28), and increased IgG (~ 3272 mg/dL). Peripheral blood smear showed rouleaux formation. Bone marrow aspirate demonstrated 8% plasma cells and histiocytes with cytoplasmic crystals (Fig. 1A-C) Biopsy and immunohistochemistry confirmed CD138+interstitial plasma cell clusters (20-25%) and sheets of CD68+/CD163+crystal-laden histiocytes (Fig. 1D-L). Congo red-positive amyloid deposits were detected in blood vessels (Fig. 1M, N). This case highlights a rare triad of pathologies arising from paraprotein dyscrasia. This case underscores the significance of recognizing masquerading features such as CSH, which can result in an underestimation of plasma cells. The Patient was started on bortezomib based chemotherapy and is in very good partial response (VGPR) post 3-cycles of therapy.Fig. 1A-N Morphological and immunohistochemical features in myeloma with CSH. A BMA showing small mature plasma cells(Red arrow)(MGG 60x); B, C BMA showing histiocytes with foamy cytoplasm and intracytoplasmic grey blue crystals(white arrows) and scattered plasma cells (red arrows) (B;MGG 100x,C;MGG 60x) D BMBx showing sheets of histiocytes (H & E, 10x); E Eosinophilic Crystal laden histiocytes (H&E, 40x) and F clusters of plasma cells (H&E, 40x); G CD138 positive plasma cell aggregates (IHC, 10x); H cytoplasmic Kappa light chain positive in plasma cells (IHC, 10x); I Lambda light chain negative(IHC, 10x); J CD163 positive histiocytes in sheets (IHC, 10x); K CD68 positive histiocytes (IHC, 10x); L S-100 negative (IHC, 10x). M BMBX showing extracellular eosinophilic deposits (Congo red, 10x); N Eosinophilic deposits showing apple green birefringe under polarized light (10x). BMA bone marrow aspirate; BMBx bone marrow biopsy; H&E hematoxylin & eosin; CD cluster of differentiation; IHC immunohistochemistry.