title: Fibrin-associated EBV-positive Large B-Cell Lymphoma: An Indolent Neoplasm With Features Distinct From Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation.
abstract: Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.5 years with a M:F ratio of 3. In all 12 cases, the lymphoma was an incidental microscopic finding involving atrial myxomas (n=3), thrombi associated with endovascular grafts (n=3), chronic hematomas (n=2), and pseudocysts (n=4). All cases tested were nongerminal center B-cell origin, type III EBV latency, and were negative for MYC rearrangements and alternative lengthening of telomeres by FISH. Most showed high CD30, Ki67, and PD-L1, and low to moderate MYC and p53 expression. Among 11 patients with detailed follow-up, 6 were treated surgically, 3 with cardiac or vascular lesions had persistent/recurrent disease at intravascular sites, and 4 died of causes not directly attributable to lymphoma. Reports of previously published fibrin-associated cases showed similar features, whereas traditional DLBCL-CI cases with a mass lesion had significantly higher lymphoma-associated mortality. Fibrin-associated EBV+ large B-cell lymphoma is clinicopathologically distinct from DLBCL-CI, warranting separate classification. Most cases, particularly those associated with pseudocysts, behave indolently with the potential for cure by surgery alone and may represent a form of EBV+ lymphoproliferative disease rather than lymphoma. However, primary cardiac or vascular disease may have a higher risk of recurrence despite systemic chemotherapy.
authors.affiliation: *Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI †Department of Pathology, The James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Harvard Medical School, Boston ‡‡Department of Pathology, North Shore Medical Center, Salem, MA ‡Department of Anatomical Pathology, St Vincent's Hospital, Melbourne, Vic., Australia §Institut Universitaire de Pathologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ∥Department of Laboratory Medicine, University of Washington, Seattle, WA ¶Department of Pathology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea #Herbert Wertheim College of Medicine, Florida International University, Miami, FL **Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN ††Department of Pathology, Holmes Regional Medical Center, Melbourne, FL §§NeoGenomics Laboratories, Aliso Viejo, CA ∥∥Department of Pathology, Johns Hopkins University School of Medicine, Baltimore ¶¶Laboratory of Pathology, Hematopathology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Boyer
authors.forename: Penelope A
authors.initials: PA
authors.lastname: McKelvie
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.forename: Kerstin L
authors.initials: KL
authors.lastname: Edlefsen
authors.forename: Young-Hyeh
authors.initials: YH
authors.lastname: Ko
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Aberman
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Kovach
authors.forename: Aneal
authors.initials: A
authors.lastname: Masih
authors.forename: Ha T
authors.initials: HT
authors.lastname: Nishino
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.forename: Valentina
authors.initials: V
authors.lastname: Nardi
authors.forename: Maryknoll
authors.initials: M
authors.lastname: Palisoc
authors.forename: Lina
authors.initials: L
authors.lastname: Shao
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Judith A
authors.initials: JA
authors.lastname: Ferry
authors.forename: Nancy Lee
authors.initials: NL
authors.lastname: Harris
authors.forename: Aliyah R
authors.initials: AR
authors.lastname: Sohani
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D005337:Fibrin