Journal of Pathology and Translational Medicine

Case Studies

Histopathological characteristics of Epstein-Barr virus (EBV)–associated encephalitis and colitis in chronic active EBV infection: Betty A Kasimo, James J Yahaya, Sun Och Yoon, Se Hoon Kim, Minsun Jung; J Pathol Transl Med. 2025;59(3):188-194. Published online April 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.02.21

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Abstract PDF: Chronic active Epstein-Barr virus (CAEBV) can induce complications in various organs, including the brain and gastrointestinal tract. A 3-year-old boy was referred to the hospital with a history of fever and seizures for 15 days. A diagnosis of encephalitis based on computed tomography (CT) and magnetic resonance imaging findings and clinical correlation was made. Laboratory tests showed positive serology for Epstein-Barr virus (EBV) and negative for Rotavirus antigen and IgG and IgM antibodies for cytomegalovirus, herpes simplex virus, and varicella zoster virus, respectively. Abdominal CT showed diffuse wall thickening with fluid distension of small bowel loops, lower abdomen wall thickening, and a small amount of ascites. The biopsy demonstrated positive Epstein-Barr encoding region in situ hybridization in cells within the crypts and lamina propria. The patient was managed with steroids and hematopoietic stem cell transplantation (HSCT). This case showed histopathological characteristics of concurrent EBV-associated encephalitis and colitis in CAEBV infection. The three-step strategy of immunosuppressive therapy, chemotherapy, and allogeneic HSCT should be always be considered for prevention of disease progression.

Uncommon granulomatous manifestation in Epstein-Barr virus–positive follicular dendritic cell sarcoma: a case report: Henry Goh Di Shen, Yue Zhang, Wei Qiang Leow; J Pathol Transl Med. 2025;59(2):133-138. Published online October 31, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.27

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Hepatic Epstein-Barr virus–positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) represents a rare form of liver malignancy. The absence of distinct clinical and radiological characteristics, compounded by its rare occurrence, contributes to a challenging diagnosis. Here, we report a case of a 54-year-old Chinese female with a background of chronic hepatitis B virus treated with entecavir and complicated by advanced fibrosis presenting with a liver mass found on her annual surveillance ultrasound. Hepatectomy was performed under clinical suspicion of hepatocellular carcinoma. Immunomorphologic characteristics of the tumor were consistent with EBV+ IFDCS with distinct non-caseating granulomatous inflammation. Our case illustrates the importance of considering EBV+ IFDCS in the differential diagnosis of hepatic inflammatory lesions. Awareness of this entity and its characteristic features is essential for accurately diagnosing and managing this rare neoplasm.

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Mesenchymal Tumors of the Liver: An Update Review
Joon Hyuk Choi, Swan N. Thung
Biomedicines.2025; 13(2): 479. CrossRef
EBV-positive inflammatory follicular dendritic cell sarcoma occurring in different organs: a case report and literature review
Wenhua Bai, Chunfang Hu, Zheng Zhu
Frontiers in Oncology.2025;[Epub] CrossRef
Spleen EBV-positive inflammatory follicular dendritic cell sarcoma: a case report and literature review
Yi Xiao, Lanlan Li, Xiumei Zhan, Juner Xu, Yewu Chen, Qiuchan Zhao, Yinghao Fu, Xian Luo, Huadi Chen, Hao Xu
Frontiers in Oncology.2025;[Epub] CrossRef
Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma of the liver: clinical features, imaging findings and potential diagnostic clues
Gui-Ling Huang, Man-Qian Huang, Yu-Ting Zhang, Hui-Ning Huang, Hong-Tao Liu, Xiao-Qing Pei
Abdominal Radiology.2025;[Epub] CrossRef
Epstein‑Barr virus+ inflammatory follicular dendritic cell sarcoma with clonal immunoglobulin heavy chain gene rearrangement: A case report and literature review
Qian Ye, Juan Zhao, Jiao He, Weishan Zhang
Oncology Letters.2025; 31(2): 1. CrossRef
Primary hepatic follicular dendritic cell sarcoma: A case study and literature review
Junjie Zhu, Ying Liang, Li Zhang, Bingqi Li, Danfeng Zheng, Hangyan Wang
Journal of International Medical Research.2025;[Epub] CrossRef

Intravascular NK/T-cell lymphoma: a case report and literature review: Ji Min Na, Wookjae Jung, Minhye Kim, Yun-Hong Cheon, Jong Sil Lee, Dae Hyun Song, Jung Wook Yang; J Pathol Transl Med. 2023;57(6):332-336. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.30

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Abstract PDF

Intravascular lymphoma is characterized by an exclusively intravascular distribution of tumor cells. Intravascular natural killer/T-cell lymphoma (IVNKTL) is extremely rare, highly aggressive, commonly Epstein-Barr virus (EBV)–positive, and predominantly affects the skin and central nervous system. Here we report a case of IVNKTL diagnosed in a 67-year-old female, presenting with persistent intermittent fever and skin rashes throughout the body. Incisional biopsy of an erythematous lesion on the chest exhibited aggregation of medium to large-sized atypical lymphoid cells confined to the lumen of small vessels that were positive for CD3, granzyme B, and CD56 on immunohistochemistry and EBV-encoded RNA in situ hybridization. EBV DNA was also detected in serum after diagnosis. With a review of 26 cases of IVNKTL to date, we suggest that active biopsy based on EBV DNA detection may facilitate early diagnosis of IVNKTL.

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Mimicry in the vasculature: a review of diagnostic clues in cutaneous intravascular lymphoid proliferations
MA Faraz, S Tu Zahra, F Ocampo-Gonzalez, SC Shalin, Aadil Ahmed
Diagnostic Histopathology.2026;[Epub] CrossRef
Intravascular Lymphoma: A Unique Pattern Underlying a Protean Disease
Mario Della Mura, Joana Sorino, Filippo Emanuele Angiuli, Gerardo Cazzato, Francesco Gaudio, Giuseppe Ingravallo
Cancers.2025; 17(14): 2355. CrossRef
Cutaneous Intravascular Hematolymphoid Entities: A Review
Emily Hatheway Marshall, Bethany Brumbaugh, Allison Holt, Steven T. Chen, Mai P. Hoang
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CD30- and CD56-positive atypical intravascular lymphocytes of the uterine cervix, mimicking intravascular lymphoma: A case report and review of the literature
Daisuke Yamashita, Munemichi Otani, Hayato Maruoka, Takuya Aoki, Shigeo Hara
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Original Article

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea: Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho; J Pathol Transl Med. 2023;57(3):166-177. Published online May 10, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.12

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Abstract PDF Supplementary Material

Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

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Case Study

Unsuspected systemic Epstein-Barr virus–positive T-cell lymphoma of childhood diagnosed at autopsy in a potential homicide case: Daniel J. Robbins, Erik A. Ranheim, Jamie E. Kallan; J Pathol Transl Med. 2023;57(2):123-127. Published online December 22, 2022; DOI: https://doi.org/10.4132/jptm.2022.10.31

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Abstract PDF

Systemic Epstein-Barr virus (EBV)–positive T-cell lymphoma of childhood (SETLC) is a rare, rapidly progressive, and often fatal disease of children and young adults characterized by monoclonal expansion of EBV-positive T cells in tissues or peripheral blood following infection with EBV. Its distinction from other EBV-positive T-cell lymphoproliferative disorders with overlapping features can be difficult, and particular diagnostic features may not be manifest until autopsy examination. We present the case of a 10-year-old boy with significant disability due to remote traumatic brain injury following non-accidental head trauma who died unexpectedly at home. Given the history of physical abuse and the potential for homicide charges, significant medicolegal implications arose with this case. Pathologic investigation ultimately revealed conclusive diagnostic features of SETLC including extensive proliferation of EBV-positive T cells in multiple organs. A natural manner of death was confirmed, thereby excluding delayed homicide related to complications of non-accidental head trauma.

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The ‘Oma’s of the Gammas—Cancerogenesis by γ-Herpesviruses
Anwesha Banerjee, Debashree Dass, Soumik Mukherjee, Mollina Kaul, R. Harshithkumar, Parikshit Bagchi, Anupam Mukherjee
Viruses.2024; 16(12): 1928. CrossRef

Review

Tumor immune response and immunotherapy in gastric cancer: Yoonjin Kwak, An Na Seo, Hee Eun Lee, Hye Seung Lee; J Pathol Transl Med. 2020;54(1):20-33. Published online November 1, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.08

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Abstract PDF

Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.

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Original Article

Multistaining Optimization for Epstein-Barr Virus–Encoded RNA In Situ Hybridization and Immunohistochemistry of Formalin-Fixed Paraffin-Embedded Tissues Using an Automated Immunostainer: Jae Nam Ko, Jin Kyoung Jung, Yun Ik Park, Hwa Jeong Shin, Jooryung Huh, Sol Back, Yu Jin Kim, Jae Ho Kim, Heounjeong Go; J Pathol Transl Med. 2019;53(5):317-326. Published online August 27, 2019; DOI: https://doi.org/10.4132/jptm.2019.08.06

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Abstract PDF Supplementary Material

Background
Single staining is commonly performed for practical pathologic diagnoses. However, this method is limited in its ability to specify cellular morphology and immunophenotype and often requires consumption of limited tissue. This study aimed to describe an optimized protocol for multiple in situ hybridization (ISH) and immunohistochemistry (IHC).
Methods
The quality of multistaining was evaluated by carefully changing each step of ISH and IHC in an angioimmunoblastic T-cell lymphoma (AITL) case on a Ventana BenchMark XT automated immunostainer. The optimized protocols were also performed using another immunostainer and in 15 cases of five Epstein-Barr virus (EBV)–associated malignancies using formalin-fixed paraffin-embedded tissue.
Results
The quality of various ISHIHC staining protocols was semi-quantitatively evaluated. The best EBV-encoded RNA (EBER)-ISH/double IHC staining quality, equivalent to single staining, was obtained using the following considerations: initial EBER-ISH application, use of protease and antigen retrieval reagent (cell conditioning 1 [CC1] treatment time was minimized due to impact on tissue quality), additional baking/ deparaffinization not needed, and reduced dilution ratio and increased reaction time for primary antibody compared with single immunostaining. Furthermore, shorter second CC1 treatment time yielded better results. Multiple staining was the best quality in another immunostainer and for different types of EBV-associated malignancies when it was performed in the same manner as for the Ventana BenchMark XT as determined for AITL.
Conclusions
EBER-ISH and double IHC could be easily used in clinical practice with currently available automated immunostainers and adjustment of reagent treatment time, dilution ratio, and antibody reaction time.

Citations

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Yuuki Yamamoto, Akira Satou, Taishi Takahara, Daisuke Yamashita, Masafumi Seki, Akari Iwakoshi, Yusuke Ueda, Yasufumi Masaki, Kanae Yoshikawa, Hideki Murakami, Seiichi Kato, Kennosuke Karube, Shigeo Nakamura, Toyonori Tsuzuki
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Case Study

An Autopsy Case of Epstein-Barr Virus–Associated Diffuse Large B-Cell Lymphoma of the Central Nervous System in an Immunocompromised Host: Sun-Young Park, Seong Ik Kim, Hannah Kim, Yoojin Lee, Sung-Hye Park; J Pathol Transl Med. 2018;52(1):51-55. Published online August 4, 2017; DOI: https://doi.org/10.4132/jptm.2017.01.23

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Abstract PDF

Lymphomas arising in the central nervous system (CNS) of immunocompromised hosts are most commonly non-Hodgkin’s lymphomas and are highly associated with Epstein-Barr virus (EBV). Here we report an autopsy case of EBV-associated CNS diffuse large B-cell lymphoma (DLBCL) in a host suffering from systemic lupus erythematosus who underwent immunosuppressive therapy. After autopsy, EBV-associated CNS DLBCL as well as pulmonary mixed aspergillosis and Pneumocystis jirovecii pneumonia were added to the cause of clinical manifestations of complicated pneumonia and cerebral hemorrhage in this immunocompromised patient. In conclusion, complex disease processes were revealed by autopsy in this case, indicating that the clinicopathological correlations observed through autopsy can improve our understanding of disease progression and contribute to the management of similar patients in the future.

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Primary central nervous system lymphoma in neuropsychiatric systemic lupus erythematosus: case-based review
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Review

Epstein-Barr Virus–Associated Lymphoproliferative Disorders: Review and Update on 2016 WHO Classification: Hyun-Jung Kim, Young Hyeh Ko, Ji Eun Kim, Seung-Sook Lee, Hyekyung Lee, Gyeongsin Park, Jin Ho Paik, Hee Jeong Cha, Yoo-Duk Choi, Jae Ho Han, Jooryung Huh; J Pathol Transl Med. 2017;51(4):352-358. Published online June 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.15

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Abstract PDF

Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.

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N. G. Chernova, D. S. Tihomirov, N. P. Soboleva, S. A. Mariina, Y. V. Sidorova, M. N. Sinitsyna, V. N. Dvirnyk, S. M. Kulikov, T. A. Tupoleva, E. E. Zvonkov
Problems of Virology.2018; 63(4): 171. CrossRef

Case Studies

CD30-Positive T-Cell Lymphoproliferative Disease of the Oral Mucosa in Children: A Manifestation of Epstein-Barr Virus-Associated T-Lymphoproliferative Disorder: Mineui Hong, Young Hyeh Ko; J Pathol Transl Med. 2015;49(6):525-530. Published online September 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.13

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Abstract PDF

Eosinophilic ulcer of the oral mucosa (EUOM) is a very rare, benign, self-limiting ulcerative lesion of the oral cavity of unknown pathogenesis, and belongs to the same spectrum of CD30⁺ T-cell lymphoproliferative disease (LPD) of the oral mucosa. The etiology and pathogenesis of the disease are unknown. We report two cases in children who were initially diagnosed with EUOM and CD30⁺ T-cell LPD, respectively. However, retrospective analysis revealed that a majority of infiltrated atypical T cells were positive for Epstein-Barr virus (EBV). The present cases suggest that the pathogenesis and etiology of EUOM or CD30⁺ T-cell LPD occurring in children are different from those in adults. EUOM or CD30⁺ T-cell LPD in children is a manifestation of EBV-positive T-cell LPD, and should therefore be distinguished from the disease in adults.

Citations

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Pediatric oral Epstein-Barr virus associated self-remitting CD30+ lymphoproliferative disorder: A distinct entity
Ziv Schwartz, Robert B. Bowe, Morton Coleman, Cynthia M. Magro
Annals of Diagnostic Pathology.2018; 37: 57. CrossRef

Human Herpesvirus 8-Negative and Epstein-Barr Virus-Positive Effusion-Based Lymphoma in a Patient with Human Immunodeficiency Virus: Jung-Woo Choi, Younghye Kim, Ju-Han Lee, Young-Sik Kim; J Pathol Transl Med. 2015;49(5):409-412. Published online June 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.06.03

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Abstract PDF

A 39-year-old man infected with human immunodeficiency virus (HIV) was admitted to our hospital because of sudden onset of chest pain. Chest radiography revealed pneumothorax of the right lung. Computed tomographic scans disclosed a 5.8-cm-sized emphysematous bulla in the right middle lobe of the lung. Histologically, the wedge-resected lung showed medium to large atypical cells within the bullous cavity of the Pneumocystis jirovecii pneumonia, without solid mass formation. These atypical cells were confirmed to be large B-cell lymphoma, Epstein-Barr virus–positive and human herpesvirus 8–negative. Therefore, this case was not diagnosed as primary effusion lymphoma, but effusion-based lymphoma arising in an emphysematous cavity of an HIV-infected patient. This type of effusion-based lymphoma has never been reported, and, although rare, it should be noted in order to clinically diagnose this lymphoma.

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Chih-Yi Liu, Bo-Jung Chen, Shih-Sung Chuang
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Savanah D. Gisriel, Ji Yuan, Ryan C. Braunberger, Danielle L.V. Maracaja, Xueyan Chen, Xiaojun Wu, Jenna McCracken, Mingyi Chen, Yi Xie, Laura E. Brown, Peng Li, Yi Zhou, Tarsheen Sethi, Austin McHenry, Ronald G. Hauser, Nathan Paulson, Haiming Tang, Eric
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Age and CD20 Expression Are Significant Prognostic Factors in Human Herpes Virus-8-negative Effusion-based Lymphoma
Tomomi Kubota, Yosuke Sasaki, Eisuke Shiozawa, Masafumi Takimoto, Tsunekazu Hishima, Ja-Mun Chong
American Journal of Surgical Pathology.2018; 42(12): 1607. CrossRef

Follicular Dendritic Cell Sarcoma of the Inflammatory Pseudotumor-like Variant Presenting as a Colonic Polyp: Shien-Tung Pan, Chih-Yuan Cheng, Nie-Sue Lee, Peir-In Liang, Shih-Sung Chuang; Korean J Pathol. 2014;48(2):140-145. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.140

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Abstract PDF

Follicular dendritic cell (FDC) sarcoma is rare and is classified either as conventional type or inflammatory pseudotumor (IPT)-like variant. Extranodal presentation is uncommon and nearly all gastrointestinal FDC tumors are of the conventional type. IPT-like variant tumors occur almost exclusively in the liver and spleen and are consistently associated with Epstein-Barr virus (EBV). Here we report the case of a 78-year-old woman with an IPT-like FDC sarcoma presenting as a pedunculated colonic polyp. Histologically, scanty atypical ovoid to spindle cells were mixed with a background of florid lymphoplasmacytic infiltrate, which led to an initial misdiagnosis of pseudolymphoma. These atypical cells expressed CD21, CD23, CD35, and D2-40, and were positive for EBV by in situ hybridization, confirming the diagnosis. The patient was free of disease five months after polypectomy without adjuvant therapy. Although extremely rare, the differential diagnosis for colonic polyp should include FDC sarcoma to avoid an erroneous diagnosis. A review of the 24 cases of IPT-like FDC sarcoma reported in the literature reveal that this tumor occurs predominantly in females with a predilection for liver and spleen, and has a strong association with EBV.

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Original Articles

EBV-Positive T/NK-Cell Lymphoproliferative Disease of Childhood: Mineui Hong, Young Hyeh Ko, Keon Hee Yoo, Hong Hoe Koo, Seok Jin Kim, Won Seog Kim, Heejung Park; Korean J Pathol. 2013;47(2):137-147. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.137

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Abstract PDF

Background

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality.

Methods

Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed.

Results

STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis.

Conclusions

EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment.

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Genetic Analysis of Epstein-Barr Virus Latent Membrane Protein 1 and Immunohistochemical Expression of Transforming Growth Factor (TGF)-beta1, TGF-betaRII, p21, p16, E2F1, Thymidylate Synthase, and NF-kappaB in Epstein-Barr Virus Encoded RNA-positive Gastric Adenocarcinoma: Mee Yon Cho, Minseob Eom, Kwang Hwa Park, Mee Dong Kim, Seung Hoon Sung, Myoung Soo Kim, Dae Sung Kim, Sun Ju Choi; Korean J Pathol. 2006;40(3):176-184.

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Abstract PDF: BACKGROUND
:Although clinicopathologic differences have been described between Epstein-Barr virus (EBV)-positive and negative gastric adenocarcinomas, the pathogenetic basis for these differences remains unclear. In this study, efforts were made to confirm that expression of EBV-latent membrane protein (LMP1) and immunohistochemical characteristics of EBVpositive gastric adenocarcinomas.
METHODS
We investigated genomic deletion, and RNA & protein expression of the EBV-LMP1, as well as immunohistochemical protein expression of transforming growth factor (TGF)-beta1, TGF-bata RII, p21, p16, E2F1, thymidylate synthase, and NF-kappaB in relation to EBV positive gastric adenocarcinoma.
RESULTS
A total of 38 Epstein-Barr Virus Encoded RNA-positive and 80 negative gastric carcinomas were examined. A 30 bp DNA deletion in the EBV-LMP1 gene, initiating at codon 342, was detected in 94.4% of EBVpositive cases. By RT-PCR and western blotting, EBV-LMP1 mRNA and protein expressions were absent in all cases, re-gardless of DNA deletion. No significant differences in TGF-bata1, TGF-betaRII, p21, NF-kappaB, E2F1, or thymidylate synthase expression were identified. However, the decreased expression of p16 was found in 84.2% of EBV-positive carcinomas, relative to only 57.5% of EBV-negative tumors (p=0.024).
CONCLUSION
EBV-LMP1 DNA deletion, mRNA and protein losses are highly prevalent in EBV-positive gastric adenocarcinoma among Korean patients, along with decreased p16 expression.

Case Reports

Extranodal NK/T Cell Lymphoma Accompanied by Heavy Eosinophilic Infiltration and Peripheral Blood Eosinophilia, Involving Skeletal Muscles.: Jin Ho Paik, Yoon Kyung Jeon, Heounjeong Go, Chul Woo Kim; Korean J Pathol. 2011;45:S70-S74.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S70

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Abstract PDF

The patient was a 52-year-old female with swelling in both lower legs and peripheral blood eosinophilia. Biopsy specimen revealed the heavy infiltration of eosinophils with sparse small lymphocytes showing mild atypia. The diagnosis was Kimura disease. The symptoms including eosinophilia were relieved by steroid treatment. At 17 months from initial biopsy, the patient developed swelling of the buttock. At 25 months, fever and dyspnea with multiple lung nodules developed. Wedge resection revealed multiple aggregates of CD3(+), CD56(+), Epstein-Barr virus(+) large atypical lymphocytes with necrosis. The patient was finally diagnosed with extranodal NK/T cell lymphoma (NKTL). Epstein-Barr virus in situ hybridization retrospectively performed on the previous biopsies demonstrated Epstein-Barr virus infection in small CD3(+) lymphocytes. The patient expired after 26 months despite chemotherapy. Blood eosinophilia correlated well with disease activity during the clinical course. This case shows not only unusual histologic features, which hampered the correct diagnosis, but also a unique clinical manifestation of NKTL.

Citations

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Muscular involvement of extranodal natural killer/T cell lymphoma misdiagnosed as polymyositis: A case report and review of literature
Li-Hui Liu, Qing Huang, Yun-Hai Liu, Jie Yang, Han Fu, Lin Jin
World Journal of Clinical Cases.2020; 8(5): 963. CrossRef
Extranodal natural killer/T-cell lymphoma with paraneoplastic eosinophilic myositis
Jayati Mallick, Jasmine Zain, Dennis D. Weisenburger
Human Pathology: Case Reports.2020; 21: 200391. CrossRef
Extranodal NK/T-cell Lymphoma Mimicking Granulomatous Myositis
Norihiko Kawaguchi, Rumiko Izumi, Masahiro Kobayashi, Maki Tateyama, Naoki Suzuki, Fumiyoshi Fujishima, Juichi Fujimori, Masashi Aoki, Ichiro Nakashima
Internal Medicine.2019; 58(2): 277. CrossRef
Uveitis and Myositis as Immune Complications in Chemorefractory NK/T-Cell Nasal-Type Lymphoma Successfully Treated with Allogeneic Stem-Cell Transplant
Maria José Gómez-Crespo, Aránzazu García-Raso, Jose Luis López-Lorenzo, Teresa Villaescusa, María Rodríguez-Pinilla, José Fortes, Cristina Serrano, Salma Machan, Pilar Llamas, Raúl Córdoba
Case Reports in Hematology.2016; 2016: 1. CrossRef
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Wook Youn Kim, Soo Jeong Nam, Sehui Kim, Tae Min Kim, Dae Seog Heo, Chul-Woo Kim, Yoon Kyung Jeon
Leukemia & Lymphoma.2015; 56(6): 1778. CrossRef
Unusual case of metachronous EBV‐associated B‐cell and NK/T‐cell lymphoma mimicking polymyositis‐diagnostic challenges and pitfalls
Esther H.L. Chan, Suat‐Jin Lu, Fredrik Petersson, Kong‐Bing Tan, Wee‐Joo Chng, Siok‐Bian Ng
American Journal of Hematology.2014; 89(1): 110. CrossRef
CD30+ extranodal natural killer/T-cell lymphoma mimicking phlegmonous myositis: A case report
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Oncology Letters.2014; 7(5): 1419. CrossRef

Diffuse Large B-Cell Lymphoma Associated with Chronic Inflammation Manifested as a Soft Tissue Mass: Incidental Discovery on Histological Examination.: Sang Yun Ha, Yoon La Choi, Sung Joo Kim, Young Hye Ko; Korean J Pathol. 2011;45(4):417-422.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.417

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Abstract PDF

We report an extraordinary case of diffuse large B-cell lymphoma arising in a cystic necrotic mass in a 35-year-old man who presented with a soft tissue mass at the site of previous surgery. A benign mass was surgically removed 17 years ago, after which a cystic lesion gradually developed at the same site. The resected mass appeared as a thick-walled cyst filled with brown necrotic and hemorrhagic material. On microscopic examination, the cyst wall was primarily necrotic tissue with some aggregates of large atypical lymphoid cells. These atypical cells were diffusely positive for CD20 and showed a high proliferation index, Epstein-Barr virus positivity, and clonal rearrangement of the immunoglobulin gene. His present condition was diagnosed as Epstein-Barr virus-associated diffuse large B-cell lymphoma arising from chronic inflammation. It is important to be aware of the clinical manifestations and histological features of this rare disease in light of diagnosis and treatment.

Citations

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American Journal of Surgical Pathology.2017; 41(3): 299. CrossRef
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Korean Journal of Pathology.2014; 48(2): 81. CrossRef

Epstein-Barr virus-associated Inflammatory Pseudotumor-like Follicular Dendritic Cell Tumor in the Spleen of a Patient with Diffuse Large B Cell Lymphoma: A Case Report and Review of the Literature.: Sun Och Yoon, Hyoungsuk Ko, Baek hui Kim, Ghee Young Kwon, Yoon Kyung Jeon, Chul Woo Kim; Korean J Pathol. 2007;41(3):198-202.

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Abstract PDF: We report a case of an Epstein-Barr virus (EBV)-associated inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-like FDC tumor). The tumor occurred in the spleen of a 64-year-old woman with a history of a diffuse large B-cell lymphoma (DLBCL) of neck nodes that presented four years ago. The splenectomy specimen revealed a 5 cm-sized, tan-colored and well-circumscribed mass. Histologically, spindle or ovoid cells with large vesicular nuclei were admixed with abundant inflammatory cells. Immunohistochemically, spindle cells were positive for FDC marker CD35, but negative for CD20, CD30 and ALK. EBV was detected almost exclusively in spindle cells by EBER in situ hybridization. IPT-like FDC tumors are rare, and are recognized as a distinctive clinicopathologic variant of FDC tumors. Among only 18 similar cases reported in the English language literature, the present case is the first case of a patient with a history of DLBCL.

Original Articles

Expression of Cancer-Related Genes in Epstein Barr Virus-Infected Burkitt's Lymphoma Cell Line Treated with Mitomycin C.: Woo Bom Yeom, Seol Hee Park, Min Kyung Kim, Chul Hwan Kim, In Sun Kim, Dale Lee; Korean J Pathol. 2001;35(4):271-277.

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Abstract PDF: BACKGROUND
Infection of Epstein Barr virus (EBV) into B cells drives the infected cells into the cell cycle and frequently results in lymphoblastoid cells. Mitomycin C inhibits DNA synthesis of epithelial cells as well as lymphoid cells by cross-linking with DNA. Many of the cancer cells have various pathways for escaping the responsiveness to the negative growth-regulatory effects of mitomycin C and gaining the immortalized property. The auther performed a cell culture of an EBV infected Jijoye lymphoma cell line, and compared the cell cycle and cancer related genes between the mitomycin treated- and non-treated group.
METHODS
DNA and RNA were extracted from the Jijoye cells; and EBV nuclear antigen (EBNA)-1, 2 and latent membrane protein (LMP) of EBV and p53 and p21 mRNA analyse was performed.
RESULTS
Mitomycin C blocked G2/M phase, however, mitomycin did not affect the expression of EBNA-1, 2 and LMP. Mitomycin C also increased the p21 mRNA expression without p53 mRNA increase.
CONCLUSIONS
Mitomycin C induces B cell apoptosis by blocking the G2/M phase and by increasing p21 mRNA independent to p53, which reveals the presence of an alternative pathway of p21 induction by mitomycin C in EBV positive lymphoma cells

Detection of Epstein-Barr virus in the inflammatory and neoplastic uterine cervical lesions.: Hye Jin Jeong, Eung Seok Lee, Zhen Hua Lin, Seol Hee Park, In Sun Kim, Jae Sung Kang; J Pathol Transl Med. 2001;12(2):73-80.

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Abstract PDF: The prevalence of Epstein-Barr virus(EBV) in the uterine cervix was investigated to define the possible etiologic role in cervical carcinogenesis. The viral genotyping and LMP-1 30bp deletion were also studied. The materials included 169 uterine cervical swabs(152 within normal limits, 12 atypical squamous cells of uncertain significance, 3 low grade intraepithelial lesions, and 2 high grade squamous intraepithelial lesion) and 104 uterine cervical tissues obtained from hysterectomy specimens(32 carcinoma in situ, 9 microinvasive squamous cell carcinomas, 37 invasive squamous cell carcinomas, 7 adenocarcinomas, 7 adenosquamous carcinomas, and 12 cervicitis). EBV detected by PCR for EBNA-1 was positive in 52(56.5%) of 92 invasive and noninvasive cervical carcinomas, and 80(48.8%) of 164 inflammatory or normal cervices. The viruses detected in carcinomas were all type A, and LMP-1 30bp deletion form was more frequent in premalignant and malignant cervical lesions than in nonneoplastic cervices. From the above results, it may be concluded that EBV is one of common viruses detected in uterine cervix of Korean women, and type A virus and LMP-1 30bp deletion form may have a role in cervical carcinogenesis.

Predictive Factors of Epstein-Barr Virus Association in Gastric Adenocarcinoma.: Young Su Kim, Sang Chul Nam, Man Hoon Han, Ji Yun Jeong, Sun Kyun Park, In Soo Suh, Han Ik Bae; Korean J Pathol. 2008;42(4):193-197.

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Abstract PDF: BACKGROUND
It is important to detect Epstein-Barr virus (EBV) in the setting of gastric cancer so that early viral targeted therapy and prevention can be undertaken. The aim of this study was to investigate the predictive clinicopathologic factors for EBV-related gastric cancer.
METHODS
The archival tumor tissues from 335 patients with gastric cancer were examined using tissue microarray. The detection of EBV was performed using EBV mRNA in situ hybridization (EBV-ISH), and the results were compared against clinicopathologic factors.
RESULTS
EBV-related gastric cancers were identified in 21 of 335 investigated cases (6.27%). The anatomical predisposition of EBV-related cancers to manifest in the upper stomach was statistically significant (p<0.001). EBV-related cancers were almost always (20/21) accompanied by lymphoid stroma. No differences in age, sex, histologic differentiation, or T or N stage were noted between EBV-positive and EBV-negative gastric carcinomas.
CONCLUSIONS
The association of EBV with gastric adenocarcinomas could be predicted when tumors with lymphoid stroma occurred in the upper stomach.

Characteristics of the Immortalized Human B-cells by Epstein-Barr Virus.: Ho Jong Jeon, Bong Nam Choi, Yoon Kyeong Oh; Korean J Pathol. 1997;31(9):832-846.

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Abstract PDF: Human lymphoblastoid B-cell lines immortalized by Epstein-Barr virus (EBV) were established from peripheral blood of patients with acute myeloblastic and chronic lymphocytic leukemia and chronic fatigue syndrome. The sera of patients with acute myeloblastic and chronic lymphocytic leukemia did not show antibodies to Epstein-Barr viral capsid antigen (VCA), but serum of a patient with chronic fatigue syndrome disclosed antibodies to VCA (IgG, IgM), and EBNA was demonstrated in peripheral blood mononuclear cells by polymerase chain reaction. The established cell lines were mature B-cell phenotypes with polyclonal proliferation in early passage and no evidence for commitment to other lineages. The immortalized cells by EBV were designated as CSUP-1 and CSUP-2 (from acute myeloblastic leukemia, FAB classification M2 and M1), CSUP-3 (from chronic lymphocytic leukemia) and CSUP-4 (from a patient with chronic fatigue syndrome). The CSUP-1, 2, 3, and 4 grew in suspension forming clumps with a doubling time of 38 to 49 hours. Colony formation was not recognized in plate. By light and electron microscopic examination, the immortalized cells showed features of lymphoblastoid to plasmacytoid lymphocytes, and multinucleated giant cells. The lymphoblastoid cells showed scanty cytoplasm with poorly developed organelles. Immunophenotypic analyses of CUSP-1, 2, 3, and 4 with monoclonal antibodies by flow cytometry showed B-cell phenotype with polyclonal proliferation in early passage. Epstein-Barr virus nuclear antigen was confirmed in the extracted DNAs from immortalized cells by polymerase chain reaction. DNA analysis showed a normodiploid stemline with a DNA index of 1.12. The established cells were strongly reactive for CD10, CD30 (Ki-1) in early passage, and bcl-2 and c-myc onco-protein in early and late passage. Karyotypic analysis of CSUP-1, 2, 3 and 4 showed 46, XY or 46, XX. No tumorigenesis in heterotransplanted SCID mouse was recognized. This immortalized cells by EBV should be a valuable cell lines to study the pathogenesis of EBV-related malignant lymphoma.

Detection and Subtyping of Epstein-Barr Virus in Gastrointestinal Adenocarcinomas and Malignant Lymphomas.: Young Sik Kim, Seol Hee Park, In sun Kim; Korean J Pathol. 1997;31(9):847-861.

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Abstract PDF: Epstein-Barr virus (EBV) has been linked to a spectrum of neoplastic conditions, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, lymphoepithelioma-like carcinomas and malignant lymphomas in immunocompromised state. To determine the prevalence and the subtype of EBV in gatrointestinal malignancies, fifty cases of adenocarcinomas and seventeen cases of malignant lymphomas were analyzed by EBERs in situ hybridization and polymerase chain reaction using primers for EBNA-1, EBNA-2A and EBNA-2B, on the paraffin sections. In addition, immunohistochemical stain for p53 protein was performed to investigate the potential role of EBV infection on tumor suppressor gene, p53, during tumorigenesis. EBER was detected in 6 of 26 gastric adenocarcinomas, 2 of 24 colon adenocarcinomas, and 8 of 17 malignant lymphomas. EBER was more prevalent in malignant lymphoma arising in the intestine (6/6) than in the stomach (2/11), and was detected in both B and T cell phenotypes. EBNA-1 was positive in 11 of 16 EBER positive cases and the subtyping was possible in 8; both type 1 and 2 were detected in gastric cancers, whereas only type 2 was found in intestinal neoplasms. In adenocarcinomas the high rate of p53 protein overexpression was found in both EBER positive (8/8) and negative cases (32/42), whereas the positive rate was higher in EBER positive cases (7/8) than in EBER negative cases (4/9) of malignant lymphomas. From the results, it can be concluded that EBV infection and the p53 tumor suppressor gene are independently associated in a significant portion of the gastrointestinal malignancies, but the mechanism of action remains to be elucidated.

The Studies of bcl-2 Oncoprotein and Epstein-Barr Virus Expression in Malignant Lymphomas: Immunohistochemical and in situ hybridization analysis on 66 cases.: Hye Jae Cho, Yeon Mee Kim, Hyun Ju Yoo, Jong Eun Joo; Korean J Pathol. 1996;30(2):121-131.

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Abstract PDF: Bcl-2 oncoprotein is being localized to mitochondria and interfering with programmed cell death (apoptosis) independent of promoting cell division in the lymphoid and nonlymphoid cells. The bcl-2 oncoprotein expression has been reported in follicular lymphomas as well as in diffuse non-Hodgkin's lymphoma, leukemia and a variable propotion of Hodgkin's lymphoma cases. Recent evidence suggests that some lymphomas protected from apoptosis is conferred through expression of Epstein-Barr virus(EBV) latent membrane protein which turn to cause upregulation of bcl-2. To define the role of the bcl-2 oncoprotein and EBV in lymphoid malignancy, we tried immunohistochemical studies with anti-bcl-2 antibody and In situ hybridization (ISH) with EBV-encoded small nuclear RNAs(EBER) in the paraffin embedded sections of 46 non-Hodgkin's lymphoma (NHL) cases and 20 Hodgkin's lymphoma (HL) cases. Bcl-2 oncoprotein expression was found in 37 of 46 cases (80%) of NHL with relatively strong cytoplasmic staining, and in 14 of 20 cases (70%) of HL with weak cytoplasmic staining in limited small numbers of RS, Hodgkin and lacunar cells. The widespread presence of bcl-2 oncogene in many different types of both NHL and HL supports that the extended cell survival through overexpression of bcl-2 gene protein may be a growth advantage of neoplastic lymphoid cells. In the ISH analysis for EBV, the presence of EBV was detected in 17 of 20 cases (85%) of HL, compared to 6 of 44 cases(13.6%) of NHL. It appears to be no direct correlation between overexpression of bcl-2 oncoprotein by neoplastic lymphoid cells and the presence of EBV in NHL but it seems to be a definite association between EBV and HL.

Histopathologic Analysis of Malignant Lymphoma Involving the Skin and Its Relationship with the Epstein-Barr Virus.: Yun Hee Jin, Seong Ho Kim, Chan Kum Park; Korean J Pathol. 2000;34(1):20-28.

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Abstract PDF: The author classified 38 cases of malignant lymphoma involving the skin primarily or secondarily by the new WHO classification with minor modifications and carried out RNA in situ hybridization and/or polymerase chain reaction (PCR) to investigate the role of Epstein-Barr virus (EBV). A case was follicular lymphoma of B cell origin and 37 cases were malignant lymphomas of T cell origin, including 15 cases of Mycosis fungoides/Sezary syndrome, five cases of subcutaneous panniculitis-like T cell lymphomas, a case of anaplastic large cell lymphoma, and four cases of primary cutaneous CD30 T cell lymphoproliferative disorders. There were eight cases of unspecified peripheral T cell lymphomas, in which four cases were composed of medium-sized cells, three cases of large cells, and a case of lymphoepithelioid cells. Four cases of nasal and nasal type NK/T cell lymphomas and three cases of unspecified peripheral T cell lymphomas showed EBV genome. The nasal and nasal type NK/T cell lymphomas, especially those involving the nasal cavity, showed close association with the EBV infection.

Case Report

Epstein-Barr Virus Associated Lymphoepithelial Carcinoma of the Parotid Gland: A case report.: Kwang Il Kim, Young Sik Kim, In Sun Kim; Korean J Pathol. 1998;32(2):150-152.

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Abstract PDF: Lymphoepithelial carcinoma is a rare subtype of undifferentiated carcinoma in the salivary gland. The incidence of lymphoepithelial carcinoma is about 0.4% among the patients with major salivary gland tumors. It has a racial preference; about 75% of the patients are of Mongolian ancestry. We report a case of lymphoepithelial carcinoma arising in the left parotid gland of a 52-year-old man. Grossly, the tumor was relatively well demarcated, gray-white, and solid. Microscopically, the irregular shaped syncytial tumor cell islands were evident within lymphoplasma cell-rich and desmoplastic stroma. The carcinoma cells had large vesicular nuclei and prominent nucleoli. The tumor invaded the surrounding salivary gland tissue. Epstein-Barr virus (EBV) was demonstrated by in situ hybridization for EBV-encoded RNA-1 (EBER-1) and polymerase chain reaction for EBV nuclear antigen-1 (EBNA-1).

Original Articles

Application of Epstein-Barr Virus Cell Lines (CCL85 EB-3) in Performing the EBER mRNA In Situ Hybridization as a Positive Control.: Sung Sook Kim, Woon Sup Han, Joo Young Suh, Joo Ryung Huh; J Pathol Transl Med. 1996;7(1):38-43.

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Abstract PDF: Epstein-Barr virus(EBV) is associated with a wide spectrum of benign and malignant disorders including leukoplakia, Hodgkin's lymphoma, central nervous system lymphoma, peripheral T cell lymphoma and nasopharyngeal undifferentiated carcinoma. There are several distinctive aspects of biology of the virus that are important in investigation of virus in clinical specimens. The abundant expression of the EBER mRNA transcripts makes possible the sensitive detection of latent expression in EBV-associated tumors. Although there has been a dramatic increased interest in the direct characterization of EBV in clinical specimens, there have been few studies about the effective and reliable positive controls in performing in situ hybridization technique for EBV, especially on paraffin-embedded tissue. We applied Burkitts lymphoma cell line as positive control in EBV in hydridization using Oncor Kit. The cell block of Burkitt lymphoma cell line(CCL85 EB-3) showed strong and specific positivity for EBER in situ in nuclei of EBV infected cells.

EBV in Situ Hybridization Study for Cutaneous T-Cell Lymphomas.: Chan Kum Park, Chang Woo Lee, Jung Dal Lee; Korean J Pathol. 1996;30(8):699-705.

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Abstract PDF: We studied 24 cases of cutaneous T-cell lymphomas and six cases of benign lymphoproliferative diseases of the skin (2 Jessner's lymphocytic infiltration, 2 pseudolymphoma, 2 lymphomatoid papulosis) for the presence of Epstein-Barr Virus(EBV) RNA, using the in situ hybridization(ISH) method. Among the 24 cases of cutaneous T-cell lymphomas (CTCL), 18 cases including 12 cases of mycosis fungoides(MF) were primary CTCL, and the other 6 cases were secondary CTCL. The ISH study demonstrated a positive reaction for EBER probe in 6 out of the 24 cases(25%) of CTCL, and a negative reaction for BHLF nuclear RNA probe in all the cases studied. Double-labelling immunohistochemistry/ISH studies revealed that the EBV positive cells were CD45RO positive and CD20 negative. EBV genome was not demonstrated in any benign lymphoproliferative diseases of the skin. Among the EBER positive cases, none of the 12 cases of MF demonstrated EBER signals, and 6 out of the 12(50%) cases of CTCL were positive for EBER probe. In conclusion, latent infection of EBV may play a role in the development of non-mycosis fungoides T-cell lymphomas involving the skin.

Establishment and Characterization of an Epstein-Barr Virus-negative B-cell Line from a Patient with Dissemination of Peripheral Blood and Bone Marrow by Malignant Lymphoid Cell.: Ho Jong Jeon, Mi Ja Lee, Yu Kyung Jeong, Yoo Hwan Park, Choon Hae Chung, Yoon Kyung Oh, Chul Heel Choi, Sang Woo Cheong; Korean J Pathol. 1996;30(9):792-809.

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Abstract PDF: A human malignant lymphoid cell line(JeKo-1) was established from a Korean patient with retroperitoneal tumor presenting peripheral blood and bone marrow involvement by malignant lymphoid cells. This cell line was established from peripheral blood, and the cell line had the identical immunophenotypic features as malignant cells from the peripheral blood. The established cell line had features of a mature B-cell phenotype with no evidence for commitment to other lineages. The JeKo-1 grows in suspension with a doubling time of 33 hours. By light and electron microscopic examination, the established cells had a follicular center showing, a small, cleaved, lymphoid appearance, and had a large amount of cytoplasm containing few vacuoles and an irregular cytoplasmic membrane. Immunophenotypic analyses with monoclonal antibodies using flow cytometry showed a monoclonal IgM kappa and CD5- B-cell phenotype. The cells were non-reactive for T-cells and myeloid/monocyte antigens, and no evidence of Epstein-Barr virus nuclear antigen by polymerase chain reaction. DNA analysis showed a hypodiploid stemline with a DNA index of 0.83. The established cells were strongly reactive for bcl-2 and c-myc onco-protein, but lacked expression of multidrug resistance gene protein, p-glycoprotein by Western blot analysis. Karyotypic analysis of JeKo-1 showed 40-41 chromosomes. This cell line should be a valuable tool to study the dissemination of malignant lymphoma into the peripheral blood and bone marrow.

Deletion within LMP-1 Oncogene in Hodgkin's Disease in Korea.: Ghee Young Kwon, Woo Sung Ahn, Bo Young Lee, Seung Sook Lee, Jooryung Huh, Chul Woo Kim; Korean J Pathol. 1998;32(9):638-646.

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Abstract: LMP (latent membrane protein)-1 protein is one of the Epstein-Barr viral proteins and it is the most crucial one for the transforming activity. It is known to show considerable variation in its nucleic acid sequence and some biologic difference is reported to be associated with the variation. Twenty four cases of the EBV-associated Hodgkin's disease cases were searched for the 30-bp deletion within the C terminal intracytoplasmic domain of LMP-1 oncogene, one of the well-known genetic variation, by PCR and Southern blot using selected sets of primers and probes. The strain of the virus was also determined with PCR. Each case was positive both on LMP-1 immunostaining and in situ hybridization for EBER (Epstein-Barr encoded RNA). Deletion within LMP-1 oncogene was identified in 22 cases (92%), of which 5 cases showed wild form as well as a deleted form of LMP-1 at the same specimens. In seven cases showing the non-deleted form, pure or mixed with a deleted form, the distribution of sex and age was similar to that of the deleted form-only-group, but there was a slight tendency for a higher stage at presentation (4 of the 7 cases presented with stage IV). Those seven cases comprised of 4 cases of nodular sclerosis (NS), 2 cases of mixed cellularity (MC) and a case of lymphocyte depletion subtype while there were 9 and 12 cases of NS and MC among all the examined cases, respectively. Two cases with both a deleted form and the non-deleted form of LMP-1 showed type I and II strain of the virus while all the others contained only type of the. In conclusion, the rate of deletion in LMP-1 oncogene in our series was higher than that reported in western countries and there was a slight tendency for higher stages in cases detecting mixed deleted and non-deleted forms of LMP-1 than in cases a of deleted from of LMP-1.

Case Report

Lymphoepithelioma-like Carcinomas of the Stomach Report of 4 cases associated with Epstein-Barr virus.: Eun Sook Nam, Duck Hwan Kim, Hye Kyung Ahn, Hyung Sik Shin, Young Sik Kim, Han Kyum Kim, Insun Kim; Korean J Pathol. 1998;32(9):680-686.

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Abstract: Lymphoepithelioma-like carcinoma (LELC) that histologically resembles nasopharyngeal lymphoepithelioma has been reported in various sites including the stomach, salivary gland, lung, skin, thymus, tonsil and uterine cervix. LELC of the stomach was rarely reported after the first report by Burke et al. in 1990. More than 60% of them were associated with Epstein-Barr virus (EBV). Most commonly affecting elderly Asians with slight male predominance (M/F ; 1.2/1), it usually is located in the proximal portion of the stomach and distinguished from lymphoid-rich adenocarcinoma by the absence of definitive glandular differentiation in the LELC. We recently experienced 4 cases of LELC of the stomach associated with EBV. Patients consisted of two Korean females and two Korean males with one in 3rd decade, one in 5th decade and two in 6th decade. The tumors of all cases were located in the proximal portion of the stomach. Gross types were 1 Borrman type I, 2 Borrman type II and 1 early gastric carcinoma type IIc. The size of the tumors varied from 0.8 cm to 7 cm. Microscopic findings were similar in all 4 tumors.; The tumors were composed of syncytial nests of undifferentiated cells having vesicular nuclei with prominent nucleoli, admixed with abundant lymphoplasma cell infiltration in the stroma. Immunohistochemical staining revealed that the tumor cells were reactive for cytokeratin and the stromal lymphocytes were mostly T cells. There were dark hybridization signals in the nuclei of most of the tumor cells but no signals in the stromal lymphocytes in three cases on in situ PCR hybridization and on all cases PCR amplification for EBNA-1. It is concluded that LELCs of the stomach have distinctive histologic characteristics and the usual association with EBV. Further accumulation of these cases will define the prognosis.

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