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A Leukemia/Lymphoma With Lymphoblastic Morphology And L3 Morphologic Relapse

High-grade lymphoid leukemias/lymphomas occasionally show inconsistent or discordant morphologic and immunophenotypic features that challenge diagnostic efforts. We present a case with fluctuating findings that illustrates such difficulties. A 20-year-old human immunodeficiency virus (HIV)-negative male presented with hepatosplenomegaly, leukemia (white blood cell [WBC] count 5.1 × 103/μL; 12% blasts; hemoglobin 7.5 g/dL; hematocrit 22.8%; platelets 20 × 103/μL), and no lymphadenopathy. The marrow had 96% FAB L1 leukemic blasts (Figure 1). Flow cytometry showed expression of CD10, CD19, and CD79a with surface and cytoplasmic immunoglobulin (cIg and sIg) light chain restriction and absence of CD34 and TdT. Immunohistochemical stains showed expression of CD43, BCL2, and Ki67 (52% positivity) and confirmed CD34 and TdT negativity. Marrow culture failure limited cytogenetic studies. Cyclophosphamide, doxorubicin, and etoposide (CAE) and intrathecal methotrexate were administered for treatment of a high-grade B-cell leukemia/lymphoma (BL/L) and led to a complete remission [1]. Disease recurred 23 weeks after presentation with 84% marrow blasts of L3 morphology (Figure 1). Oil red O stains were negative. The Ki-67 immunostain marker showed 73% positivity. An Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) immunostain was uninterpretable. The relapsed disease showed persistent CD43, BCL2, and cIg expression with absence of CD34 and sIg and gain of TdT (Table 1). The marrow yielded 5 metaphase cells including 2 with trisomy 21. A second relapse sample revealed a third MYC signal in 15 of 300 (5%) cells by fluorescence in situ hybridization (FISH). Ifosfamide, carboplatin, and etoposide (modified ICE) and highdose methotrexate was administered. This patient’s WBC count reached 63.2 × 103/μL with 91% blasts before he expired about 1 year after presentation. The presenting findings were most consistent with acute lymphoblastic leukemia (ALL). Most ALL cases express CD34 or TdT, but absence of both is possible. Also, many ALL cases express CD43. Rare ALL cases express sIg, but most of these are TdT positive [2–4]. Leukemic BL/L is rare but characteristically associated with advanced disease or HIV infection [5]. Also, the proliferation rate (52% Ki-67 positivity) was inadequate for diagnosis of BL/L. No MYC abnormalities were identified, but up to 10% of BL/L