A Case of Epstein-Barr Virus (EBV)-Associated Thymic Carcinoid and Investigation of Existence of EBV-Infected Cells in Thymus and Thymic Tumors

Takeuchi, Hiroaki; Fujita, Hiroshi; Iwasaki, Fumio; Takeuchi, Takako; Imadome, Ken Ichi; Okumiya, Toshika; Matsui, Tomohiro; Takahashi, Mutsuo

doi:10.1128/jcm.42.6.2850-2854.2004

Cited by 10 publications

(11 citation statements)

References 24 publications

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“…Since the 80's several studies attempted to identify EBV nucleic acids in MG and non-MG thymomas producing contrasting results [ 27 – 31 ], likely because of the different approaches employed and the use of virus detection techniques that would not be considered sufficiently sensitive today. Nevertheless, some of them provided evidence of EBV presence in some thymoma cases: i) McGuire et al found EBV DNA in the 3 thymomas studied (2 with MG) [ 27 ]; ii) Chen et al found EBV signals in 8 out of 21 thymic carcinomas with lymphoepithelioma-like morphology, a subtype not included in the present histological WHO classification, but they did not specify whether EBV-positive tumors were from MG patients [ 30 ]; iii) Takeuchi et al analyzed 11 thymomas without MG and detected EBV-infected lymphocytes in one of them [ 31 ]. More recently, the search of potential pathogens in 18 MG thymomas was focused on human papillomavirus (HPV) and EBV; neither HPV nor EBV DNA were detected, but few details on EBV DNA detection protocol were provided [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Whether EBV is also involved in MG associated with thymoma is not known. Previous studies designed to investigate the potential association between EBV and thymoma produced contrasting results [ 18 , 27 – 31 ]. To better address this issue, we investigated the presence of EBV nucleic acids and proteins in MG and non-MG thymoma specimens by combining molecular, in situ hybridization and immunohistochemistry techniques.…”

Section: Introductionmentioning

confidence: 99%

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Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

et al. 2017

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The thymus plays a key role in myasthenia gravis (MG), a B cell-mediated autoimmune disorder affecting neuromuscular junction. Most MG patients have thymic abnormalities, including hyperplasia and thymoma, a neoplasm of thymic epithelial cells. Epstein-Barr virus (EBV) is associated with autoimmune diseases and tumors. Recently, we showed EBV persistence and reactivation in hyperplastic MG thymuses, suggesting that EBV might contribute to intra-thymic B cell dysregulation in MG patients. Here, we investigated EBV involvement in thymoma-associated MG, by searching for EBV markers in MG (n=26) and non-MG (n=14) thymomas. EBV DNA and EBV-encoded small nuclear RNA (EBER) 1 transcript were detected in 14/26 (53.8%) and 22/26 (84.6%) MG thymomas, and only in 3 of 14 (21.4%) non-MG thymomas. Latent EBNA2 and late gp350/220 lytic transcripts were undetectable in all, but one, thymomas, and early lytic BZLF1 transcript was absent in all samples, suggesting that early infection events and EBV reactivation were very rare in thymomas. EBER1 and 2-positive cells were detected in MG, but not in non-MG, thymomas, as well as cells expressing EBV latency proteins (EBNA1, LMP1, LMP2A), that were mainly of B cell phenotype, indicating EBV association with MG rather than with thymoma. Toll-like receptor (TLR) 3 transcriptional levels were higher in MG than non-MG thymomas and positively correlated with EBER1 levels, suggesting a role for EBERs in TLR3 activation. Our findings show that EBV is commonly present in thymoma-infiltrating B cells of myasthenic patients, indicating a contribution of EBV to B cell-mediated autoreactivity in MG associated with thymic tumor.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

et al. 2017

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Besides nasopharyngeal carcinoma, EBV is frequently found in carcinomas arising in the lung, stomach, thymus, and salivary gland, but not in Lymphoepithelioma-like carcinoma of the urinary tract EF Tamas et al other locations. 2,4,6,7,9,13,15,16 These data confirm that EBV is not a prerequisite for development of lymphoepithelioma-like carcinoma. None of our cases showed any labeling for EBER by in situ hybridization.…”

Section: Discussionmentioning

confidence: 99%

“…Lymphoepithelioma-like carcinoma has been described in a variety of organs including salivary glands, thymus, lung, skin, stomach, uterine cervix, breast, prostate, and the urinary tract. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] In the urinary tract, they typically arise in the urinary bladder, although isolated cases have been reported in the renal pelvis, ureter, and urethra. 5,8 Lymphoepithelioma-like carcinoma of the urinary bladder, first reported by Zuckerberg et al in 1991, is uncommon with a reported incidence between 0.4 and 1.3% of all bladder carcinomas.…”

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confidence: 99%

Lymphoepithelioma-like carcinoma of the urinary tract: a clinicopathological study of 30 pure and mixed cases

et al. 2007

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We studied 28 cases of lymphoepithelioma-like carcinoma of the bladder, one case in the renal pelvis, and one in the urethra. The mean age of the patients was 67.6 years with 21 (70%) males. Seventeen cases (56.7%) were pure with the remaining mixed with other patterns of carcinoma, including invasive urothelial carcinoma (n ¼ 10), invasive adenocarcinoma (n ¼ 3), and squamous cell carcinoma (n ¼ 2). The surface demonstrated carcinoma in situ (CIS) in six cases, noninvasive high-grade papillary urothelial carcinoma in three cases, and in situ adenocarcinoma in one case. In 19/30 (66%) cases, there was a heavy lymphocytic infiltrate and in the remaining 11/30 (34%) cases a mixed inflammatory infiltrate. None of the 26 cases labeled for EBV-encoded RNA by in situ hybridization. Tumor stages at presentation were: seven cases T1 (23%); 14 cases T2 (47%); seven cases T3 (23%); and two cases T4 (7%). Treatment consisted of radical cystectomy in 13/30 cases (43%); partial cystectomy in 4/30 cases (13%); nephrectomy in one case (3%), and transurethral resection often followed by radiation or chemotherapy in 12/30 (40%) cases. The mean follow up for patients without progression was 31 months. Eight of 27 cases with follow-up (30%) cases had tumor recurrence, with seven patients having metastases. In cases treated with cystectomy, the 5-year actuarial recurrence-free risk was 59% (62 and 57%, for pure and mixed cases, respectively). Lymphoepithelioma-like carcinoma, whether in pure or mixed form, has a similar prognosis to ordinary urothelial carcinoma when treated by cystectomy. Of the three pure cases treated by chemotherapy, two were free of disease at 4 and 65 months and the third had recurrent disease at 17 months. Given the association of lymphoepithelioma-like carcinoma with urothelial carcinoma in 47% of our cases and its propensity for multifocality, partial cystectomy would typically be ill advised for lymphoepithelioma-like carcinoma.

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“…to the presence of a heavy lymphocytic intratumoral infiltrate. The majority of these tumors, particularly those originating from the nasopharynx [11] , salivary glands [2] , thymus [12] , lung and stomach [13] , show relevant pathogenetic similarities: a close etiopathogenetic linkage with EpsteinBarr virus (EBV) infection. At the immunohistochemical level, EBV expression in these tumors has been associated…”

Section: Introductionmentioning

confidence: 99%

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

Nemolato

Fanni²,

Naccarato³

et al. 2008

WJG

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A Case of Epstein-Barr Virus (EBV)-Associated Thymic Carcinoid and Investigation of Existence of EBV-Infected Cells in Thymus and Thymic Tumors

Cited by 10 publications

References 24 publications

Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

Lymphoepithelioma-like carcinoma of the urinary tract: a clinicopathological study of 30 pure and mixed cases

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

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