Lymphoepithelioma-like Carcinoma of the Skin

The term lymphoepithelioma-like carcinoma identifies a group of nasopharingeal epithelial tumors characterized by aggregates of malignant undifferentiated cells surrounded by a dense reactive lymphoplasmacellular infiltrate. Primary cutaneous localization is rare, with approximately 30 cases reported in literature. We describe a case of primary lymphoepithelioma-like carcinoma of the skin in a 92-year-old woman. Immunohistochemical examination was positive for cytokeratine (KL1 and EMA) as regards epithelial cells, while the lymphocitic infiltrate was positive for LCA and CD3. In situ hybridization for Epstein Barr virus in tumor cells was negative. Electron microscopy showed rounded and occasionally spindle-shaped poorly-differentiated squamous epithelial cells, and a lymphoid stroma consisting mostly of normal-appearing small lymphocytes. Examination of the nasopharynx did not show any tumoral mass and after a 7 years follow-up the patient is free of local and distant recurrences. This tumor affects people aged over 50 years and is localized to the face, but scalp, shoulder and forearm may be involved. Research of Epstein-Barr virus is always negative in this tumor, unlike nasopharingeal epithelial carcinoma. The differential diagnosis of lymphoepithelioma-like carcinoma of the skin may present some difficulties and includes squamous cell carcinoma. Lymphoepithelioma-like carcinoma of the skin is a malignant neoplasm which tends to relapse locally and has a moderate tendency to metastatize.

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Direct Evidence for the Presence of Epstein-Barr Virus DNA and Nuclear Antigen in Malignant Epithelial Cells from Patients with Poorly Differentiated Carcinoma of the Nasopharynx

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.71.12.4737 ◽

1974 ◽

Vol 71 (12) ◽

pp. 4737-4741 ◽

Cited By ~ 255

Author(s):

G. Klein ◽

B. C. Giovanella ◽

T. Lindahl ◽

P. J. Fialkow ◽

S. Singh ◽

...

Keyword(s):

Epithelial Cells ◽

Epstein Barr Virus ◽

Direct Evidence ◽

Nuclear Antigen ◽

Barr Virus ◽

Poorly Differentiated Carcinoma ◽

Poorly Differentiated ◽

Epstein Barr

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Localization of Epstein–Barr Virus DNA in the Epithelial Cells of Oral Hairy Leukoplakia by in Situ Hybridization on Tissue Sections

New England Journal of Medicine ◽

10.1056/nejm198906083202315 ◽

1989 ◽

Vol 320 (23) ◽

pp. 1559-1560 ◽

Cited By ~ 48

Keyword(s):

In Situ Hybridization ◽

Epithelial Cells ◽

Epstein Barr Virus ◽

Barr Virus ◽

Tissue Sections ◽

Oral Hairy Leukoplakia ◽

Hairy Leukoplakia ◽

Epstein Barr

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Detection of Epstein-Barr virus infection in the epithelial cells and lymphocytes of non-neoplastic tonsils by in situ hybridization and in situ PCR

Archives of Virology ◽

10.1007/s007050050332 ◽

1998 ◽

Vol 143 (4) ◽

pp. 803-813 ◽

Cited By ~ 22

Author(s):

R. Kobayashi ◽

H. Takeuchi ◽

M. Sasaki ◽

M. Hasegawa ◽

K. Hirai

Keyword(s):

In Situ Hybridization ◽

Epithelial Cells ◽

Virus Infection ◽

Epstein Barr Virus ◽

Epstein Barr Virus Infection ◽

In Situ Pcr ◽

Barr Virus ◽

Epstein Barr ◽

Barr Virus Infection

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Epstein–Barr virus replication in tongue epithelial cells

Journal of General Virology ◽

10.1099/0022-1317-83-12-2995 ◽

2002 ◽

Vol 83 (12) ◽

pp. 2995-2998 ◽

Cited By ~ 31

Author(s):

Kathrin Herrmann ◽

Phroso Frangou ◽

Jaap Middeldorp ◽

Gerald Niedobitek

Keyword(s):

Epithelial Cells ◽

Epstein Barr Virus ◽

Infectious Virus ◽

Terminally Ill Cancer Patients ◽

Barr Virus ◽

Hairy Leukoplakia ◽

Cellular Source ◽

Epstein Barr ◽

Infrequent Event

Epstein–Barr virus (EBV) persistently infects B-cells in humans and can be shed into the saliva. The cellular source of infectious virus is uncertain. Hairy leukoplakia, an AIDS-associated lesion of the tongue, supports EBV replication in epithelial cells. However, the general significance of this observation has remained doubtful. Using immunohistochemistry and in situ hybridization, we demonstrate evidence of EBV replication in tongue epithelial cells in 4 of 168 samples from 84 autopsy cases. Thus, in patients who do not have AIDS, squamous epithelial cells of the tongue rarely support EBV replication. However, all individuals with evidence of EBV replication were either on immunosuppressive therapy or were terminally ill cancer patients, suggesting that an impairment of the immune system may have allowed EBV replication to occur at this site. Thus, our findings are consistent with the idea that EBV replication in oropharyngeal epithelial cells is an infrequent event.

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Virus–host interactions in carcinogenesis of Epstein-Barr virus-associated gastric carcinoma: Potential roles of lost ARID1A expression in its early stage

PLoS ONE ◽

10.1371/journal.pone.0256440 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0256440

Author(s):

Hiroyuki Abe ◽

Akiko Kunita ◽

Yuya Otake ◽

Teru Kanda ◽

Atsushi Kaneda ◽

...

Keyword(s):

Gastric Mucosa ◽

Epithelial Cells ◽

Gastric Carcinoma ◽

Epstein Barr Virus ◽

Cancer Tissue ◽

Host Interactions ◽

Barr Virus ◽

Epstein Barr

Epstein–Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct molecular subtype of gastric cancer characterized by viral infection and cellular abnormalities, including loss of AT-rich interaction domain 1A (ARID1A) expression (lost ARID1A). To evaluate the significance of lost ARID1A in the development of EBVaGC, we performed in situ hybridization of EBV-encoded RNA (EBER) and immunohistochemistry of ARID1A in the non-neoplastic gastric mucosa and intramucosal cancer tissue of EBVaGC with in vitro infection analysis of ARID1A-knockdown and -knockout gastric cells. Screening of EBER by in situ hybridization revealed a frequency of approximately 0.2% EBER-positive epithelial cells in non-neoplastic gastric mucosa tissue samples. Six small foci of EBV-infected epithelial cells showed two types of histology: degenerated (n = 3) and metaplastic (n = 3) epithelial cells. ARID1A was lost in the former type. In intramucosal EBVaGC, there were ARID1A-lost (n = 5) and -preserved tumors (n = 7), suggesting that ARID1A-lost carcinomas are derived from ARID1A-lost precursor cells in the non-neoplastic mucosa. Lost ARID1A was also observed in non-neoplastic mucosa adjacent to an ARID1A-lost EBVaGC. In vitro experiments using siRNA knockdown and the CRISPR/Cas9-knockout system demonstrated that transient reduction or permanent loss of ARID1A expression markedly increased the efficiency of EBV infection to stomach epithelial cells. Taken together, lost ARID1A plays a role in initiating EBV-driven carcinogenesis in stomach epithelial cells, which develop to a distinct subtype of EBVaGC within the proper mucosal layer. Lost ARID1A is one of the constituents of virus–host interactions in the carcinogenesis of EBVaGC.

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Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge

Vaccines ◽

10.3390/vaccines9030285 ◽

2021 ◽

Vol 9 (3) ◽

pp. 285

Author(s):

Xinle Cui ◽

Zhouhong Cao ◽

Yuriko Ishikawa ◽

Sara Cui ◽

Ken-Ichi Imadome ◽

...

Keyword(s):

Epithelial Cells ◽

B Lymphocytes ◽

Neutralizing Antibodies ◽

Epstein Barr Virus ◽

Lethal Dose ◽

Envelope Proteins ◽

Humanized Mice ◽

Target Cells ◽

Barr Virus ◽

Epstein Barr

Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes and epithelial cells, suggesting these proteins could induce antibodies that prevent EBV infection. We previously reported that the immunization of rabbits with recombinant EBV gH/gL or trimeric gB each induced markedly higher serum EBV-neutralizing titers for B lymphocytes than that of the leading EBV vaccine candidate gp350. In this study, we demonstrated that immunization of rabbits with EBV core fusion machinery proteins induced high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, and EBV gH/gL in combination with EBV trimeric gB elicited strong synergistic EBV neutralizing activities. Furthermore, the immune sera from rabbits immunized with EBV gH/gL or trimeric gB demonstrated strong passive immune protection of humanized mice from lethal dose EBV challenge, partially or completely prevented death respectively, and markedly decreased the EBV load in peripheral blood of humanized mice. These data strongly suggest the combination of EBV core fusion machinery envelope proteins gH/gL and trimeric gB is a promising EBV prophylactic vaccine.

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