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Non Hodgkin-Lymphoma
Phenogenomic heterogeneity of post-transplant plasmablastic lymphomas
Rebecca J. Leeman-Neill,1 Craig R. Soderquist,1,2 Francesca Montanari,3 Patricia Raciti,4 David Park,1 Dejan Radeski,5 Mahesh M. Mansukhani,2 Vundavalli V. Murty,6 Susan Hsiao,2 Bachir Alobeid1 and Govind Bhagat1
1Department of Pathology and Cell Biology, Division of Hematopathology, Columbia University Irving Medical Center, NY Presbyterian Hospital, New York, NY, USA; 2Department of Pathology and Cell Biology, Division of Personalized Genomic Medicine, Columbia University Irving Medical Center, NY Presbyterian Hospital, New York, NY, USA; 3Department of Pathology and Cell Biology, Division of Hematology/Oncology, Columbia University Irving Medical Center, NY Presbyterian Hospital, New York, NY, USA; 4Department of Pathology, Greenwich Hospital, Greenwich, CT, USA; 5Department of Haematology, Sir Charles Gairdner Hospital, Perth, Australia; 6Department of Medicine, Division of Cytogenetics, Columbia University Irving Medical Center, NY Presbyterian Hospital, New York, NY, USA
ABSTRACT
Plasmablastic lymphoma (PBL) is a rare and clinically aggressive neo- plasm that typically occurs in immunocompromised individuals, including those infected with human immunodeficiency virus (HIV) and solid organ allograft recipients. Most prior studies have focused on delineating the clinico-pathological features and genetic attributes of HIV- related PBL, in which MYC deregulation, Epstein-Barr virus (EBV) infec- tion and, more recently, mutations in JAK/STAT, MAP kinase, and NOTCH pathway genes have been implicated in disease pathogenesis. The phenotypic spectrum of post-transplant (PT)-PBL is not well charac- terized and data on underlying genetic alterations are limited. This led us to perform comprehensive histopathological and immunophenotypic evaluation and targeted sequencing of 18 samples from 11 patients (8 males, 3 females; age range, 12-76 years) with PT-PBL; eight de novo and three preceded by other types of post-transplant lymphoproliferative dis- orders. Post-transplant PBL displayed morphological and immunopheno- typic heterogeneity and some features overlapped those of plasmablastic myeloma. Six (55%) cases were EBV positive and five (45%) showed MYC rearrangement by fluorescence in situ hybridization. Recurrent muta- tions in epigenetic regulators (KMT2/MLL family, TET2) and DNA damage repair and response (TP53, mismatch repair genes, FANCA, ATRX), MAP kinase (KRAS, NRAS, HRAS, BRAF), JAK/STAT (STAT3, STAT6, SOCS1), NOTCH (NOTCH1, NOTCH3, SPEN), and immune surveillance (FAS, CD58) pathway genes were observed, with the mutational profiles of EBV+ and EBV– cases exhibiting both similarities and differences. Clinical outcomes also varied, with survival ranging from 0-15.9 years after diag- nosis. Besides uncovering the biological heterogeneity of PT-PBL, our study highlights similarities and distinctions between PT-PBL and PBL occurring in other settings and reveals potentially targetable oncogenic pathways in subsets of the disease.
Introduction
Plasmablastic lymphoma (PBL) is an uncommon and aggressive B-cell non- Hodgkin lymphoma characterized by a proliferation of cells with immunoblastic or plasmablastic morphology, occasionally with a component of mature plasma cells, and an immunophenotype indicative of terminal B-cell differentiation.1 PBL usually occurs in the context of immune dysregulation, which may be due to human immunodeficiency virus (HIV) infection, iatrogenic (e.g., after organ transplantation), congenital, or age-related (immune senescence).2 Prior studies of mostly HIV-associ-
Ferrata Storti Foundation
Haematologica 2022 Volume 107(1):201-210
Correspondence:
REBECCA LEEMAN-NEILL
rjl2165@cumc.columbia.edu
GOVIND BHAGAT
gb96@cumc.columbia.edu
Received: July 17, 2020. Accepted: November 25, 2020. Pre-published: December 3, 2020.
https://doi.org/10.3324/haematol.2020.267294 ©2022 Ferrata Storti Foundation
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