title: An analysis of MYC and EBV in diffuse large B-cell lymphomas associated with angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified.
abstract: Composite diffuse large B-cell lymphomas (DLBCLs) with peripheral T-cell lymphomas (PTCLs) are rare co-occurrences with poorly understood pathologic features. Herein, we describe 15 distinct cases of DLBCL occurring in association with PTCL, including angioimmunoblastic T-cell lymphoma (AITL; n = 12) and PTCL, not otherwise specified (n = 3). Sheets of large B cells were seen in all cases, with Hodgkin/Reed-Sternberg-like (HRS-L) cells present in 6 cases. When compared to cases of AITL without DLBCL, HRS-L cells were more frequently seen in cases of AITL with DLBCL (P = .02). Epstein-Barr virus (EBV) expression was seen in 10 of 15 cases, and in those with HRS-L cells, EBV expression was detected invariably in at least a subset of the HRS-L cells. MYC gene rearrangements were consistently absent, although 6 of the 10 cases showed MYC overexpression by immunohistochemistry in the neoplastic B cells; a frequency significantly increased compared to other cases of DLBCL not associated with a T-cell lymphoma: 29 of 166 (P = .005). In addition, when MYC was overexpressed in DLBCL, it was also weakly present in the HRS-L cells. The increased and frequent morphologic presence of HRS-L cells in association with this composite lymphoma raises a possible link between their occurrence and DLBCLs in PTCLs; furthermore, the frequent detection of MYC protein expression and EBV infection in these cases suggests a possible role of these pathways in B-cell lymphomagenesis.
authors.affiliation: Stanford University, Stanford, CA 94305. Electronic address: jcheng35@stanford.edu.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Hoffmann
authors.affiliation: Seattle Children's Hospital, Seattle, WA 98105.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Chisholm
authors.affiliation: Stanford University, Stanford, CA 94305.
authors.forename: Athena
authors.initials: A
authors.lastname: Cherry
authors.affiliation: Harvard University, Boston, MA 02138.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chen
authors.affiliation: Stanford University, Stanford, CA 94305.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Arber
authors.affiliation: Stanford University, Stanford, CA 94305.
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
authors.affiliation: Stanford University, Stanford, CA 94305.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Warnke
authors.affiliation: Stanford University, Stanford, CA 94305. Electronic address: rohgami@stanford.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Ohgami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000453:epidemiology*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000473:pathology* / Q000821:virology; D016399:Lymphoma, T-Cell / Q000150:complications / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000150:complications / Q000473:pathology* / Q000821:virology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D046888:Tissue Array Analysis; D014412:Tumor Virus Infections / Q000150:complications / Q000453:epidemiology*
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc
keywords: Angioimmunoblastic T-cell lymphoma; Composite lymphoma; Diffuse large B-cell lymphoma; EBV; Hodgkin/Reed-Sternberg–like cells; MYC; Peripheral T-cell lymphoma