Fibrin-associated EBV-positive Large B-Cell Lymphoma: An Indolent Neoplasm With Features Distinct From Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation

Am J Surg Pathol. 2017 Mar;41(3):299-312. doi: 10.1097/PAS.0000000000000775.

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.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Chronic Disease
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / metabolism
  • Epstein-Barr Virus Infections / pathology
  • Female
  • Fibrin / metabolism*
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / virology
  • Lymphoma, B-Cell / diagnosis
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology*
  • Lymphoma, B-Cell / virology*
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Fibrin