title: Lymphoblastic transformation of follicular lymphoma: a clinicopathologic and molecular analysis of 7 patients.
abstract: Approximately 30% of patients with follicular lymphoma (FL) transform to a more aggressive malignancy, most commonly diffuse large B cell lymphoma. Rarely, FL transformation results in clinical findings, histology, and immunophenotype reminiscent of B-lymphoblastic leukemia/lymphoma. We report the largest series to date with detailed analysis of 7 such patients. Lymphoblastic transformation occurred on average 2 years after initial diagnosis of FL. Five patients had prior intensive chemotherapy. Two patients developed mature high-grade lymphoma, followed by the lymphoblastic transformation. FL had BCL2 gene rearrangement in 4 of 5 cases. High-grade transformation was accompanied by MYC gene rearrangement (5 of 5). Transformation was characterized by expression of TdT, loss of Bcl6, variable loss of immunoglobulin light chain, and persistence of Pax-5, Bcl2, and CD10. Whole-exome sequencing in 1 case revealed presence of several actionable mutations (CD79B, CCND3, CDK12). FL, aggressive mature B cell lymphoma, and lymphoblastic transformation were clonally related in 6 evaluable cases. After transformation, survival ranged from 1 to 14 months. Four patients died of disease, 2 were in remission after stem cell transplant, and 1 was alive with disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: jut9021@med.cornell.edu.
authors.forename: Julia Turbiner
authors.initials: JT
authors.lastname: Geyer
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Subramaniyam
authors.affiliation: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Ferry
authors.affiliation: Institut Universitaire de Pathologie, 1011 Lausanne, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.affiliation: Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Megan O
authors.initials: MO
authors.lastname: Nakashima
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Martin
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Mathew
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Tam
mesh_terms: D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D008213:Lymphocyte Activation / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D057089:Pathology, Molecular / Q000379:methods; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism
chemical_list: D051560:Proto-Oncogene Proteins c-bcl-6
keywords: Double hit lymphoma; Follicular lymphoma; Lymphoblastic transformation; MYC rearrangement; TdT staining