Journal of Pathology and Translational Medicine

Case Study

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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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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Cutaneous Intravascular Hematolymphoid Entities: A Review
Emily Hatheway Marshall, Bethany Brumbaugh, Allison Holt, Steven T. Chen, Mai P. Hoang
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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.

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.

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.

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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.

Citations

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Primary central nervous system lymphoma in neuropsychiatric systemic lupus erythematosus: case-based review
Takanori Ichikawa, Yasuhiro Shimojima, Dai Kishida, Tomoki Kaneko, Yoshiki Sekijima
Rheumatology International.2021; 41(5): 1009. CrossRef

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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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

Citations to this article as recorded by

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.

Citations

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Primary Effusion Lymphoma: A Timely Review on the Association with HIV, HHV8, and EBV
Chih-Yi Liu, Bo-Jung Chen, Shih-Sung Chuang
Diagnostics.2022; 12(3): 713. CrossRef
Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics
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.

Citations

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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.

Citations

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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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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.

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Original Article

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.

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