Epstein-Barr virus-infected cells in IgG4-related lymphadenopathy with comparison with extranodal IgG4-related disease.
IgG4-related lymphadenopathy with increased numbers of Epstein-Barr virus (EBV)-infected cells has been reported but not fully described. We analyzed 31 cases of IgG4-related lymphadenopathy and 24 cases of extranodal IgG4-related diseases for their possible relationship with EBV. Other types of reactive lymph nodes (22) and angioimmunoblastic T-cell lymphoma (AITL) (10) were also studied for comparison. EBV-encoded RNA (EBER) in situ hybridization revealed EBER(+) cells in 18 of 31 cases (58%) of IgG4-related lymphadenopathy. Increased EBER(+) cells were found in only 4 of 22 (18.1%) non-IgG4-related reactive lymphoid hyperplasia in patients of a similar age (P=0.002) and in only 5 of 24 (21%) extranodal IgG4-related biopsies (P=0.006). Interestingly, all patients with EBER(+) progressively transformed germinal center-type IgG4-related lymphadenopathy had systemic lymphadenopathy and/or extranodal involvement. AITL also is associated with EBV, and IgG4-related lymphadenopathy sometimes mimics the morphology of AITL; however, the number of IgG4(+) cells in AITL was significantly less than that in IgG4-related lymphadenopathy (P<0.001). Increased numbers of regulatory T cells are seen in IgG4-related disease; however, there was not a significant difference between the EBER(+) and EBER(-) cases. In conclusion, the presence of increased numbers of EBV-infected cells in IgG4-related lymphadenopathy, compared with other reactive lymphadenopathy or extranodal IgG4-related disease, suggests that there may be a relationship at least between nodal IgG4-related disease and EBV. It is important to avoid overdiagnosing these cases as malignant lymphomas or EBV-related lymphoproliferative disorders.
Departments of *Pathology ∥Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama ‡Center for Antibody and Vaccine, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo §Department of Pathology, Okazaki City Hospital, Okazaki ¶Department of Otolaryngology, Himeji Red Cross Hospital, Himeji †Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe Departments of #Clinical Laboratory **Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan ††Department of Pathology, Division of Hematopathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Mai
M
Takeuchi
Yasuharu
Y
Sato
Hiroshi
H
Yasui
Hiroaki
H
Ozawa
Kyotaro
K
Ohno
Katsuyoshi
K
Takata
Yuka
Y
Gion
Yorihisa
Y
Orita
Tomoyasu
T
Tachibana
Tomoo
T
Itoh
Naoko
N
Asano
Shigeo
S
Nakamura
Steven H
SH
Swerdlow
Tadashi
T
Yoshino
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008206:Lymphatic Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000302:isolation & purification; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000821:virology
D007074:Immunoglobulin G; D012367:RNA, Viral