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Hematopoietic neoplasms with FGFR1 rearrangements are rare. Clinically, patients often present with a chronic myeloproliferative neoplasm with eosinophilia and an increased risk of transformation to acute leukemia. We report a patient who initially presented with B-cell acute lymphoblastic leukemia (B-ALL) with t(8;22)(p11.2;q11.2) and an additional derivative chromosome 22 [der(22)t(8;22)]. After induction chemotherapy, B-ALL blasts were eradicated; however, a chronic myeloproliferative process emerged showing persistent t(8;22) (p11.2;q11.2) but not der(22)t(8;22). Combined morphologic and fluorescence in situ hybridization revealed that both lymphoblasts and myeloid cells harbored t(8;22)(p11.2;q11.2); but only lymphoblasts carried the additional der(22)t(8;22). This case provides direct evidence to illustrate the clonal relationship of chronic phase and blast phase in myeloid neoplasms with FGFR1 rearrangement, and demonstrates that clonal cytogenetic evolution plays an important role in disease progression.

Although the association of pure red cell aplasia (PRCA) and aplastic anemia with thymoma is well-known, acquired amegakaryocytic thrombocytopenia (AAMT) is not a recognized paraneoplastic manifestation of thymoma. This report discusses a patient with recurrent thymoma complicated by myasthenia gravis, PRCA, and AAMT. Both PRCA and AAMT are diagnosed after a thymoma recurrence, 11 years after complete resection of the initial tumor and 9 months after chemotherapy for the relapsed disease. Both PRCA and AAMT responded to immunosuppression with cyclosporine, corticosteroid, and an abbreviated course of antithymocyte globulin, achieving a very good erythroid response and a complete remission for AAMT, suggesting that AAMT, although extremely rare, can be an immune-mediated paraneoplastic manifestation of thymoma.

T-cell large granular lymphocytic (T-LGL) leukemia after hematopoietic stem cell transplantation (SCT) is rare and its natural history and clinical outcome have not been well described. We report the clinical, morphologic, immunophenotypic, and molecular features of a case of donor-derived T-LGL leukemia in a 16-year-old man who received allogeneic SCT for peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). The patient presented with persistent neutropenia and splenomegaly 9 months after SCT when the chimerism study showed a 100% donor pattern. A splenectomy revealed T-LGL leukemia. Flow cytometric analysis showed an aberrant T-cell population positive for CD3, CD5 (dim, subset), CD7, CD8, CD16 (subset), CD57, CD94 (dim, partial), and T-cell receptor (TCR) αβ, and negative for CD4, CD26, CD56, and TCRγδ. Molecular studies showed monoclonal TCRβ and TCRγ gene rearrangements. Both the immunophenotype and molecular profile of the T-LGL leukemia were different from the pre-SCT PTCL. Sequencing analysis for STAT3 exon 21 did not reveal any mutation in both pre-SCT and post-SCT specimens. The patient did not receive any treatment for T-LGL leukemia; however, his count progressively increased after splenectomy, despite the presence of persistent T-LGL leukemia in the bone marrow. There was no evidence of recurrent PTCL. We propose an algorithm to diagnose this rare post-SCT neoplasm.

Acute promyelocytic leukemia (APL) is characterized by the fusion of retinoic acid receptor alpha (RARA) with promyelocytic leukemia (PML) or, rarely, other gene partners. This report presents a patient with APL with a novel fusion between RARA and the interferon regulatory factor 2 binding protein 2 (IRF2BP2) genes. A bone marrow examination in a 19-year-old woman who presented with ecchymoses and epistaxis showed morphologic and immunophenotypic features consistent with APL. PML oncogenic domain antibody was positive. Results of fluorescence in situ hybridization, conventional cytogenetics, reverse transcription–polymerase chain reaction (RT-PCR), and oligonucleotide microarray for PML-RARA and common APL variant translocations were negative. Next-generation RNA-sequencing analysis followed by RT-PCR and direct sequencing revealed distinct breakpoints within IRF2BP2 exon 2 and RARA intron 2. The patient received all-trans retinoic acid, arsenic, and gemtuzumab ozogamicin, and achieved complete remission. However, the disease relapsed 10 months later, 2 months after consolidation therapy. This is the first report showing involvement of IRF2BP2 in APL, and it expands the list of novel RARA partners identified in APL.

RNA-seq was used to identify the partner gene and confirm the presence of a BCR-PDGFRB fusion. Identification of this fusion product resulted in successful treatment and long-term remission of this myeloid neoplasm. Based on our results, we suggest that despite current WHO recommendations, screening for PDGFRB rearrangement in cases of leukocytosis with eosinophilia and no other etiologic explanation is necessary, even if the karyotype is normal.