Intracellular light chain crystals in myeloma

Zane G. Staubach and J. Blake Rodman

A 72-year-old man presented for follow-up of worsening back pain and a history of monoclonal gammopathy. Serum electrophoresis showed an M spike of 2.1 g; immunofixation showed an immunoglobulin A λ monoclonal protein. Peripheral smear showed extensive rouleau formation. Core biopsy showed large aggregates of plasma cells, multinucleated plasma cells, and elongated crystals replacing the normal marrow architecture (panel A; hematoxylin and eosin stain, original magnification ×40). Aspirate smears showed numerous plasma cells with rectangular, elongated, tetragonal crystals. Intracellular crystals ranged in size from small to very large, with distorted plasma cell membrane entirely enveloping (panels B-D; Wright-Giemsa stain; original magnification ×20 [B]; original magnification ×100 [C]; original magnification ×40 [D]). Immunostaining for light chains showed the plasma cells to be λ light chain restricted, and the crystals stained positively with anti-λ immunoperoxidase (panels E-F; anti-κ–light chain immunohistochemistry [IHC], original magnification ×20 [E]; anti-λ–light chain IHC, original magnification ×20 [F]).

Inclusions, rarely including crystals, have been identified within plasma cell myeloma (PCM). Crystals often fail to stain with anti–light chain IHC. Crystal deposition resolved in subsequent bone marrow biopsy after treatment. The large crystals with enveloping cell membranes seem to indicate that crystals form intracellularly and subsequently grow beyond confines and lyse plasma cells. The prognostic significance of crystal formation in PCM has not been well described.


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