Lymphoblastic lymphoma with mature b‐cell immunophenotype and MLL‐AF9 in a child (2011)

To the Editor: A distinct subset of acute lymphoblastic leukemia (ALL) characterized by a unique triad of non-L3 morphology, mature B-cell immunophenotype, and MLL gene rearrangement has been reported, especially in infancy 1-3. Although lymphoblastic lymphoma (LBL) and ALL share common morphological, biological, and molecular features, LBL with this triad has not been reported. A 3-year-old female presented with a tumor on the cheek. A biopsy was compatible with B-lineage LBL, with L1-morphology on the stamp preparation (Fig. 1). By flow cytometry, the blast cells were positive for CD19, CD22, and HLA-DR and negative for cytoplasmic CD3, terminal deoxytransferase (TdT), CD10, CD20, CD34, CD56, and myeloperoxidase. Notably, surface immunoglobulin M and λ-chain were clonally positive. Because rearrangement of CMYC and IgH were not demonstrated by FISH, we then examined frozen-stored tumor tissue by RT-PCR which amplifies minor/major BCR-ABL, TEL-AML1, E2A-PBX1, SIL-TAL, MLL-AF4, MLL-AF6, MLL-AF9, and MLL-ENL. A MLL-AF9 fusion was detected. The presence of MLL rearrangement was further confirmed by FISH. By conventional karyotyping, we obtained only two metaphases displaying no abnormalities. The imaging studies revealed a small metastatic nodule in the liver. Neither central nervous system nor bone marrow invasion was demonstrated. The patient was diagnosed with LBL with the Murphy stage III disease. We administered ALL-type multidrug chemotherapy, resulting in a rapid and complete response. The patient has maintained complete remission for 2 years since the end of the therapy. Microscopic appearance. A: May-Giemsa-stained stamp preparation of the skin tumor. The blastic cells were classified as L1-morphology by FAB classification. Cells with L3-morphology were not found. B: Hematoxylin-eosin stained, paraffin-embedded formalin-fixed specimen. The tumor cells had large, round to oval nuclei with prominent nucleoli and a small amount of cytoplasm and lacked “a starry-sky pattern”. The morphology was considered to be compatible with a diagnosis of LBL. Immunohistochemically, the tumor was positive for leukocyte common antigen and CD79a and negative for CD3, CD10, CD20, and TdT. LBL with a mature B-cell immunophenotype has been rarely reported. In 1987, Sheibani et al. 4 reported an elderly patient with precursor B-cell LBL that displayed surface light chain immunoglobulin restriction. In 1990, the authors reported an additional three cases with the same features and suggested that these cases formed a previously unrecognized variant of LBL 4, 5. Chromosomal karyotyping was not performed in the four cases. Only limited data are available for cytogenetic abnormalities in B-lineage LBL. To date, only 10 cases have been described with conventional karyotyping. In none of these, was there an 11q23 abnormality 6-9. Recently, Shafer et al. 10 reported two cases with cutaneous LBL with an early precursor B-cell immunophenotype. In one of the cases, MLL gene rearrangement was demonstrated by FISH on sections of paraffin-embedded formalin-fixed tissue, although the partner gene that formed the fusion gene with MLL was not verified. In the reported cases with ALL harboring the triad, t(9;11)(p22;q23) was most frequently observed; there were 10 cases with this translocation among 11 cases with karyotyping data. Notably, FISH or spectral karyotyping disclosed MLL gene rearrangement in 8 out of 11 cases, while conventional karyotyping (e.g., G-banding) was not able to demonstrate any abnormalities 1-3. These observations suggest the importance of molecular analysis together with conventional karyotyping for appropriately diagnosing ALL (or LBL) with this triad. We thus present a novel case of LBL with the triad of non-L3 morphology, a mature B-cell immunophenotype and MLL-AF9. LBL with this triad may form an uncommon but distinct subset of LBL.