A Case of Age-Related Epstein–Barr Virus (EBV)-Associated B Cell Lymphoproliferative Disorder, so-called Polymorphous Subtype, of the Mandible, with a Review of the Literature

Abstract

Epstein-Barr virus (EBV) is known to be associated with the development of lymphomas in immunocompromised patients. Recently, age-related immune impairment has been recognized as a predisposing factor in the development of EBV-driven lymphoproliferative disorders (LPDs) in elderly patients without any known immunodeficiency or prior lymphoma. In approximately 70 % of reported cases, the affected sites have been extranodal, such as the skin, lung, tonsil and stomach. However, age-related EBV-associated B cell (EBV ? B cell) LPD is extremely rare in the oral cavity. Here we report a 71-year-old Japanese man who developed an EBV ? B cell LPD resembling classical Hodgkin lymphoma (CHL)-so-called polymorphous subtype-of the mandible. Histopathologically, infiltration of large atypical lymphoid cells including Hodgkin or Reed-Sternberg-like cells into granulation tissue with marked necrosis was found in the mandibular bone. Immunohistochemical analysis revealed that the large atypical Hodgkin or ReedSternberg-like cells were CD3-, CD15-, CD20?, CD30? and Epstein-Barr virus (EBV)-latent infection membrane protein-1 (LMP-1)?. In situ hybridization (ISH) demonstrated EBV-encoded small RNA (EBER) ? in numerous Hodgkin or Reed-Sternberg-like cells. EBNA-2 was detected by polymerase chain reaction (PCR) using an extract from the formalin-fixed, paraffin-embedded specimen. To our knowledge, this is the first reported case of the polymorphous subtype of age-related EBV ? B cell LPD affecting the mandible.

Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity

“…Tumor cells of Age-EBV-LPD [21] or plasma cells from tonsillitis tissue were used as overexpression-positive controls for EBV-encoded small RNA (EBER) and LMP-1. Germinal center B cells from tonsillitis tissue were used as normal positive controls for EBER and LMP-1.…”

“…Briefly, for detection of EBV, we used a fluoresceinconjugated EBV peptide nucleic acid (PNA) probe (Dako, Glostrup, Denmark). Age-EBV-LPD was used as a positive control for EBER [21].…”

“…Moreover, EBVassociated lymphoproliferative disorders are known to occur through EBV reactivation due to decreased immunity of the host in situations such as infectious diseases [16], organ transplantation [17], drug use [18], and aging [19]. In fact, we have previously reported EBV-associated B cell lymphoproliferative disorders arising in the oral cavity [20][21][22]. Many EBVassociated epithelial carcinomas such as those of the nasopharynx [23], stomach [24][25][26][27][28][29][30], salivary gland [31][32][33], breast [34][35][36][37][38], bladder [39], kidney [40], uterine cervix [41], colon [42], and lung [43] have been described.…”

Epstein–Barr virus (EBV)-associated epithelial and non-epithelial lesions of the oral cavity

“…5a,b) or as failure of extraction sockets to heal (Fig. 5c,d) [23], [24], [109]. The affected patients are believed to be immunosuppressed, a condition that causes reactivation of EBV.…”

“…Moreover, EBV-associated lymphoproliferative disorders (EBV-LPDs) are known to occur through EBV reactivation due to decreased immunity of the host in situations such as infectious diseases [19], organ transplantation [20], drug use [21] and aging [22]. In fact, we have previously reported EBV-associated B-cell LPDs arising in the oral cavity [23], [24]. Various EBV-associated epithelial carcinomas such as those of the nasopharynx [25], stomach [26], [27], [28], [29], [30], [31], [32], salivary gland [33], [34], [35], breast [36], [37], [38], [39], [40], [41], [42], [43], bladder [44], kidney [45], uterine cervix [46], colon [47], and lung [48] have been described.…”