EBV-positive cutaneous B-cell lymphoproliferative disease after imatinib mesylate

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Abstract
The woman had previously been treated with 1000 mg hydroxyurea twice daily, resulting in stable disease. However, upon development of a leg ulcer, hydroxyurea was discontinued and ambulant compression therapy in combination with 2 × 200 mg/d pentoxyfilline (PTX) and 100 mg/d ascal was initiated. Her CML progressed, and 500 mg/d imatinib mesylate was started. Subsequently, her leukocyte count decreased from 9.9 × 109/L before treatment to 1.3 × 109/L after 2 months of treatment. Shortly after starting imatinib mesylate she noticed a rapidly growing, ulcerating tumor on her head (Figure 1A). A biopsy showed a diffuse proliferation of large, atypical, immunoblastic B cells (Figure 1B) that strongly expressed CD79a and CD30 and were monotypic immunoglobulin G (IgG) lambda-positive. Most large atypical cells stained positive for EBV-encoded RNA 1 (EBER-1), mRNAs, and latent membrane protein 1 (LMP-1) and EBV nuclear antigen 1 (EBNA1) proteins, whereas focal expression was found for BamHI fragment Z left frame 1 (BZLF1). There was no expression for EBV early antigen (EA), EBV viral capsid antigen (VCA), and membrane antigen (MA). RNA in situ hybridization showed expression of EBER-1 and EBER-2. EBV serology (enzyme-linked immunosorbent assay [ELISA]; Biotest, Dreieich, Germany) demonstrated IgG, against EBV-VCA, EBV-NA (nuclear antigen), and EBV-EA. After spontaneous resolution of the tumor, the IgG EBV-EA levels gradually lowered, but IgG VCA and NA remained stable. An immunoblot assay and synthetic peptide ELISA test demonstrated a strong IgG response against VCA (p18 en p40) and the lytic switch protein Zebra. There was a high IgA response against VCA (P18), without significant reactivity to other EBV antigens. Combined, these findings are consistent with EBV-related lymphoproliferation due to EBV reactivation and persistent EBV replication.