title: EBV-negative monomorphic B-cell post-transplant lymphoproliferative disorders are pathologically distinct from EBV-positive cases and frequently contain TP53 mutations.
abstract: Monomorphic post-transplant lymphoproliferative disorder commonly resembles diffuse large B-cell lymphoma or Burkitt lymphoma, and most are Epstein-Barr virus (EBV) positive. We retrospectively identified 32 cases of monomorphic post-transplant lymphoproliferative disorder from two institutions and evaluated EBV in situ hybridization; TP53 mutation status; p53, CD30, myc, and BCL2 expression by immunohistochemistry; proliferation index by Ki67; and germinal center vs non-germinal center immunophenotype by Hans criteria. Post-transplant lymphoproliferative disorder arose after hematopoietic stem cell transplant in five and solid organ transplant in 27 patients, a median of 4 and 96 months after transplant, respectively (overall median latency 71 months, range 2-295). The most common morphology was diffuse large B-cell lymphoma (28 cases), with three cases of Burkitt lymphoma, and one case of plasmablastic lymphoma. Ten cases (31%) were EBV negative. Of those with the morphology of diffuse large B-cell lymphoma, the EBV-negative cases were more frequently TP53-mutated (P<0.001), p53 positive by immunohistochemistry (P<0.001), CD30 negative (P<0.01), and of germinal center immunophenotype (P=0.01) compared with EBV-positive cases. No statistically significant difference in overall survival was identified based on EBV, TP53 mutation status, germinal center vs non-germinal center immunophenotype, or other immunohistochemical parameters evaluated. Patients who died of post-transplant lymphoproliferative disorder were older with a longer latency from time of transplant to diagnosis (P<0.05). Our study demonstrates that diffuse large B-cell lymphoma-related immunohistochemical prognostic markers have limited relevance in the post-transplant setting and underscores differences between EBV-positive and EBV-negative post-transplant lymphoproliferative disorder in terms of immunophenotype and TP53 mutation frequency, supporting an alternative pathogenesis for EBV-negative post-transplant lymphoproliferative disorder.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Courville
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Yohe
authors.affiliation: The James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, and The Department of Pathology, Harvard Medical School, Boston, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chou
authors.affiliation: The James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, and The Department of Pathology, Harvard Medical School, Boston, MA, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nardi
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Lazaryan
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Beenu
authors.initials: B
authors.lastname: Thakral
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Nelson
authors.affiliation: The James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, and The Department of Pathology, Harvard Medical School, Boston, MA, USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Ferry
authors.affiliation: The James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, and The Department of Pathology, Harvard Medical School, Boston, MA, USA.
authors.forename: Aliyah R
authors.initials: AR
authors.lastname: Sohani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects; D000069293:Plasmablastic Lymphoma / Q000235:genetics / Q000473:pathology* / Q000821:virology; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53