A Novel Fusion Partner in a Case of Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement

Abstract

Abstract Introduction/Objective Myeloid/lymphoid neoplasms with rearrangement of FGFR1 are uncommon and heterogeneous group of hematological malignancies that may present as myeloproliferative neoplasm, acute myeloid leukemia, T or B lymphoblastic lymphoma/leukemia, or mixed phenotypic acute leukemia. Patients can present with lymphadenopathy, mediastinal mass, or systemic symptoms. Eosinophilia is common in peripheral blood or bone marrow. Several chromosomal rearrangements and fusion genes have been described with FGFR1 rearrangement and all of them encode an aberrant tyrosine kinase. Tyrosine kinase inhibitors may offer a prospective therapeutic approach although specific targeted therapies have yet to be established. Methods/Case Report We present a case of a 14-year-old male who presented with rapid neck pain and swelling. Imaging revealed a 15 x 8 x 6 cm neck mass extending into the anterior mediastinum. Laboratory evaluation revealed anemia, thrombocytopenia, and leukocytosis (41.7 K/mm3), with absolute eosinophilia and blasts of 50%. Flow cytometry of peripheral blood demonstrated a population of T-lymphoblasts comprising about 60% of the cellularity with dim CD45, cytoplasmic CD3, CD7, TdT, CD38, CD4, CD5, CD10, and CD15, supporting T-lymphoblastic leukemia/lymphoma. The patient received induction chemotherapy, and subsequent bone marrow biopsy showed morphologic remission. Six weeks from diagnosis, the patient developed a gluteal mass with an atypical T-cell infiltrate that was negative for TdT; and at 15 weeks from diagnosis, developed an enlarging abdominal mass, also with an atypical T-cell infiltrate also negative for TdT and CD1a. At that time molecular diagnostic studies of the abdominal wall mass discovered a previously unpublished ATG16L1-FGFR1 fusion, supporting myeloid/lymphoid neoplasm with FGFR1 rearrangement, T-lymphoblastic leukemia/lymphoma. Results (if a Case Study enter NA) NA. Conclusion Although a variety of translocations have been identified with FGFR1 rearrangement, the novel fusion partner ATG16L1 has not been previously reported. The case also illustrates an unusual extramedullary recurrence of the T-cell lymphoblastic leukemia/lymphoma with significant antigenic shift including loss of TdT and CD1a.