Immunoglobulin-containing vacuoles in CLL Free

A 52-year-old man with chronic lymphocytic leukemia (CLL) with unmutated IGHV, a TP53 splice-site mutation (variant allele frequency 4%), and a 13q deletion was treated with obinutuzumab and presented for follow-up bone marrow (BM) evaluation. The BM aspirate revealed atypical small lymphoid cells with prominent cytoplasmic vacuolation (panel A: Wright-Giemsa stain, original magnification ×100). Oil Red O stain was negative (panel A [inset]: histochemical stain, original magnification ×100). Core biopsy showed a hypercellular marrow with small lymphocyte infiltration exhibiting both interstitial and nodular patterns (panel B: hematoxylin and eosin stain, original magnification ×4). Flow cytometry and immunohistochemical studies confirmed CLL, positive for CD5, CD20, CD23, and κ (dim to negative) (panel C), and negative for cyclin D1. Vacuolation was visible on sections with hematoxylin and eosin stain (panel D: hematoxylin and eosin stain, original magnification ×100). Immunostaining demonstrated vacuoles containing κ (panel E: immunohistochemical stain, original magnification ×100), immunoglobulin M (IgM) (panel G: immunohistochemical stain, original magnification ×100), and IgG4 (panel H: immunohistochemical stain, original magnification ×100), but not λ (panel F: immunohistochemical stain, original magnification ×100; inset shows a λ-positive reactive plasma cell on the same slide), IgG (panel I: immunohistochemical stain, original magnification ×100; inset shows an IgG⁺ plasma cell on the same slide), IgD, IgA, or IgE. Peripheral blood showed normocytic hypochromic anemia without vacuolated lymphocytes. However, vacuolated lymphocytes could be observed in the peripheral blood before obinutuzumab treatment (panel J: Wright-Giemsa stain, original magnification ×100).

Although various cytoplasmic inclusions, such as globular, crystalline, azurophilic Auer rod–like, and lipid type, as well as intranuclear inclusions induced by herpes simplex virus, have been reported in CLL cells, this case highlights cytoplasmic inclusions that resemble lipid content in peripheral blood and aspirate smears but are Ig⁺ on core biopsy of the bone marrow.

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