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Prognostic significance of BLK expression in R-CHOP treated diffuse large B-cell lymphoma
Soyeon Choi, Yoo Jin Lee, Yunsuk Choi, Misung Kim, Hyun-Jung Kim, Ji Eun Kim, Sukjoong Oh, Seoung Wan Chae, Hee Jeong Cha, Jae-Cheol Jo
J Pathol Transl Med. 2022;56(5):281-288.   Published online September 13, 2022
DOI: https://doi.org/10.4132/jptm.2022.07.26
  • 2,368 View
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  • 2 Web of Science
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AbstractAbstract PDF
Background
The aim of the present study was to evaluate the prognostic significance of B-cell lymphocyte kinase (BLK) expression for survival outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP.
Methods
We retrospectively analyzed the medical records of 89 patients from two tertiary referral hospitals. The expression of BLK, SYK, and CDK1 were evaluated in a semiquantitative method using an H-score, and the proportions of BCL2 and C-MYC were evaluated.
Results
A total of 89 patients received R-CHOP chemotherapy as a first-line chemotherapy. The expression rates of BLK in tumor cells was 39.2% (n = 34). BLK expression status was not significantly associated with clinical variables; however, BLK expression in tumor cells was significantly associated with the expression of both C-MYC and BCL2 (p = .003). With a median follow-up of 60.4 months, patients with BLK expression had significantly lower 5-year progression-free survival (PFS) and overall survival rates (49.8% and 60.9%, respectively) than patients without BLK expression (77.3% and 86.7%, respectively). In multivariate analysis for PFS, BLK positivity was an independent poor prognostic factor (hazard ratio, 2.208; p = .040).
Conclusions
Here, we describe the clinicopathological features and survival outcome according to expression of BLK in DLBCL. Approximately 39% of DLBCL patients showed BLK positivity, which was associated as a predictive marker for poor prognosis in patients who received R-CHOP chemotherapy.

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  • Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies
    Philippe Decruyenaere, Edoardo Giuili, Kimberly Verniers, Jasper Anckaert, Katrien De Grove, Malaïka Van der Linden, Dries Deeren, Jo Van Dorpe, Fritz Offner, Jo Vandesompele
    Frontiers in Oncology.2023;[Epub]     CrossRef
The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma
Sun Ah Shin, Hee Young Na, Ji Young Choe, Doohyun Chung, Mira Park, Sohee Oh, Ji Eun Kim
J Pathol Transl Med. 2018;52(6):357-362.   Published online October 4, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.13
  • 5,112 View
  • 106 Download
  • 6 Web of Science
  • 5 Crossref
AbstractAbstract PDF
Background
The up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma.
Methods
Expression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed.
Results
A total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS.
Conclusions
Activated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type.

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Reviews
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
  • 18,213 View
  • 1,066 Download
  • 63 Web of Science
  • 61 Crossref
AbstractAbstract 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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Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives
Yoon Kyung Jeon, Sun Och Yoon, Jin Ho Paik, Young A Kim, Bong Kyung Shin, Hyun-Jung Kim, Hee Jeong Cha, Ji Eun Kim, Jooryung Huh, Young-Hyeh Ko
J Pathol Transl Med. 2017;51(3):224-241.   Published online May 10, 2017
DOI: https://doi.org/10.4132/jptm.2017.04.09
  • 16,475 View
  • 669 Download
  • 9 Web of Science
  • 11 Crossref
AbstractAbstract PDF
Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

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Brief Case Report
Inflammatory Pseudotumor-like Follicular Dendritic Cell Tumor of the Spleen with Extensive Histiocytic Granulomas and Necrosis: A Case Report and Literature Review
Hyun-Jung Kim, Ji Eun Kim, Gu-Hyun Kang, Jung Yeon Kim, Kyeongmee Park
Korean J Pathol. 2013;47(6):599-602.   Published online December 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.599
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PDF

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Original Articles
Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of EGFR Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosin
Hyun Ju Lee, Xianhua Xu, Hyojin Kim, Yan Jin, Pingli Sun, Ji Eun Kim, Jin-Haeng Chung
Korean J Pathol. 2013;47(1):52-60.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.52
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AbstractAbstract PDF
Background

The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (EGFR) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlate EGFR mutational status as determined by each method with the clinical response to EGFR tyrosine kinase inhibitors (TKIs).

Methods

Sixty-one NSCLC patients treated with EGFR TKIs were identified to investigate somatic mutations in the EGFR gene (exons 18-21).

Results

Mutations in the EGFR gene were detected in 38 of the 61 patients (62%) by DS, 35 (57%) by PNA clamping and 37 (61%) by pyrosequencing. A total of 44 mutations (72%) were found by at least one of the three methods, and the concordances among the results were relatively high (82-85%; kappa coefficient, 0.713 to 0.736). There were 15 discordant cases (25%) among the three different methods.

Conclusions

All three EGFR mutation tests had good concordance rates (over 82%) for FFPE samples. These results suggest that if the DNA quality and enrichment of tumor cells are assured, then DS, PNA clamping, and pyrosequencing are appropriate methods for the detection of EGFR mutations.

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Expression of c-Met Is Different along the Location and Associated with Lymph Node Metastasis of Head and Neck Carcinoma
Ji-Young Choe, Ji Yun Yun, Soo-Jeong Nam, Ji Eun Kim
Korean J Pathol. 2012;46(6):515-522.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.515
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AbstractAbstract PDF
Background

Activation of the c-Met pathway is involved in cancer progression and the prognosis. We aimed to identify any association of c-Met protein expression with a number of clinicopathologic variables including infection of human papillomavirus and Epstein-Barr virus (EBV) in head and neck carcinomas (HNCa).

Methods

Eighty-two cases were enrolled in this study. Expression of c-Met and p16 was investigated immunohistochemically. EBV was detected by in situ hybridization and amplification of the c-Met gene by fluorescence in situ hybridization.

Results

The c-Met protein was expressed in 41.5% (34/82), and gene amplification was found in 1.4% (1/71). High expression of c-Met was associated with the primary location of the tumor; the hypopharynx showed the highest expression, followed by the oral cavity, larynx, and nasal cavity. Squamous cell carcinoma expressed c-Met more frequently than undifferentiated carcinoma. Also, p16 immunoreactivity or EBV infection was associated with the tumor location and well-differentiated histologic type, but were not linked to c-Met expression. The patients with positive c-Met expression showed frequent lymph node metastasis.

Conclusions

Activation of the c-Met pathway might be involved in a subset of HNCa. Cases showing positive c-Met expression should be carefully monitored because of the high probability of lymph node metastasis.

Citations

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Detection of Survivin and COX-2 in Thyroid Carcinoma: Anaplastic Carcinoma Shows Overexpression of Nuclear Survivin and Low COX-2 Expression
Young A Kim, Meesoo Chang, Young Joo Park, Ji Eun Kim
Korean J Pathol. 2012;46(1):55-60.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.55
  • 7,959 View
  • 64 Download
  • 5 Crossref
AbstractAbstract PDF
Background

Overexpression of survivin, a member of the inhibitors of apoptosis protein, has been reported in various carcinomas, and its interaction with cyclooxygenase 2 (COX-2) results in accelerated tumor progression. The purpose of this study is to investigate the immunohistochemical expression of survivin and COX-2 in benign and malignant thyroid tissues and to define its association with pathologic and clinical features.

Methods

We examined expression of survivin and COX-2 by immunohistochemistry in 334 benign and malignant thyroid tissues and evaluated their clinical significance.

Results

Expression of survivin showed an increase along the spectrum of thyroid carcinoma progression; rarely positive in adenomatous goiter, moderately positive in papillary carcinoma, and strongly positive in anaplastic carcinoma (AC). Papillary microcarcinoma revealed the highest COX-2 positivity and AC demonstrated the lowest positivity among thyroid cancers. Node negative carcinomas showed higher COX-2 expression than node positive tumors. Survivin expression did not correlate with COX-2.

Conclusions

Our findings suggest that survivin overexpression may be related to the pathogenesis of AC and can be a predictor of disease progression. COX-2 may be involved in the early phase of thyroid carcinoma.

Citations

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  • Survivin as a diagnostic and therapeutic marker for thyroid cancer
    Mohammad-Reza Mahmoudian-Sani, Arash Alghasi, Ali Saeedi-Boroujeni, Akram Jalali, Mohammad Jamshidi, Ali Khodadadi
    Pathology - Research and Practice.2019; 215(4): 619.     CrossRef
  • TFAP2B overexpression contributes to tumor growth and progression of thyroid cancer through the COX-2 signaling pathway
    Xiaoyan Fu, Huayong Zhang, Zhipeng Chen, Zhongyuan Yang, Dingbo Shi, Tianrun Liu, Weichao Chen, Fan Yao, Xuan Su, Wuguo Deng, Miao Chen, Ankui Yang
    Cell Death & Disease.2019;[Epub]     CrossRef
  • Expression of nm23-H1 and COX-2 in thyroid papillary carcinoma and microcarcinoma
    Marija Milkovic Perisa, Bozena Sarcevic, Koraljka Gall Troselj, Kresimir Grsic, Sanda Sitic, Sven Seiwerth
    Oncology Letters.2017; 13(5): 3547.     CrossRef
  • The Diagnostic Usefulness of HMGA2, Survivin, CEACAM6, and SFN/14-3-3 δ in Follicular Thyroid Carcinoma
    Min Hye Jang, Kyeong Cheon Jung, Hye Sook Min
    Journal of Pathology and Translational Medicine.2015; 49(2): 112.     CrossRef
  • Evaluation of survivin expression and its prognostic value in papillary thyroid carcinoma
    Sonja Selemetjev, Tijana Isic Dencic, Ilona Marecko, Jelena Jankovic, Ivan Paunovic, Svetlana Savin, Dubravka Cvejic
    Pathology - Research and Practice.2014; 210(1): 30.     CrossRef
Expression of P-glycoprotein and Apoptosis in Diffuse Large B-cell Lymphoma.
Ji Eun Kim, Young A Kim, Mee Soo Chang, Yunkyeong Jeon, JinHo Paik, Seon Og Yoon
Korean J Pathol. 2009;43(4):317-320.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.317
  • 3,182 View
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AbstractAbstract PDF
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma which responds well to conventional chemotherapy. However, quite a few patients have a recurrence with more aggressive forms after completion of therapy. Multidrug resistance proteins (MRP) are related to this process in several ways such as cell cycle alteration and modulation of apoptosis. METHODS: We investigated the expression of P-glycoprotein (Gp), one of the well-known MRP, as well as apoptosis associated proteins in DLBCL. Immunohistochemical staining for Gp, p53, Bcl-2, Ki-67, active caspase 3 and FADD was done in forty DLBCL cases. The association between MRP and apoptosis associated proteins to clinical findings was also tested. RESULTS: Twenty-nine patients out of 40 (73%) with DLBCL were positive for Gp, and 26 cases (65%) had a strong positive for Gp. Gp expression was stronger in high-grade lesions than in low-grade lesions and was associated to Bcl-2 expression. However, we could not find an adverse impact of Gp expression on patients' overall survival or relapse free survival rate. CONCLUSIONS: Our study revealed a high frequency of expression for Gp in DLBCL with a possible relationship between the expressions of Gp to apoptosis associated proteins.
Detection of SV40 Large T Antigen in Malignant Lymphomas.
Young A Kim, MeeSoo Chang, Jinho Paik, Sun Och Yoon, Yoon Kyung Jeon, Chul Woo Kim, Ji Eun Kim
Korean J Pathol. 2009;43(4):312-316.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.312
  • 3,898 View
  • 67 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
The association of simian virus 40 (SV40) with certain types of human cancers, including malignant lymphomas, has been a topic of interest for some time. Although the virus is distributed worldwide, its incidences vary according to the specific types of tumors, and the epidemiological areas. The aim of this study was to investigate the frequency of SV40 in malignant lymphomas among Korean patients. METHODS: One hundred seventy three cases of malignant lymphomas were evaluated by immunohistochemical staining for SV40 large T antigen (TAg), using an extremely sensitive, tyramide based, catalyzed signal amplification method. RESULTS: From 158 non-Hodgkin's lymphomas, including 115 diffuse large B-cell lymphomas, and 15 Hodgkin's lymphomas, none of the cases were positive for SV40 TAg. CONCLUSIONS: SV40 does not appear to be related to the pathogenesis of malignant lymphomas among Koreans.

Citations

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  • No Detection of Simian Virus 40 in Malignant Mesothelioma in Korea
    Minseob Eom, Jamshid Abdul-Ghafar, Sun-Mi Park, Joung Ho Han, Soon Won Hong, Kun Young Kwon, Eun Suk Ko, Lucia Kim, Wan Seop Kim, Seung Yeon Ha, Kyo Young Lee, Chang Hun Lee, Hye Kyoung Yoon, Yoo Duk Choi, Myoung Ja Chung, Soon-Hee Jung
    Korean Journal of Pathology.2013; 47(2): 124.     CrossRef
Case Reports
Chromomycosis of the Nasolacrimal Duct: Report of a case.
So Dug Lim, Ji Eun Kim, Kyu Rae Kim
Korean J Pathol. 1996;30(4):358-360.
  • 1,550 View
  • 17 Download
AbstractAbstract PDF
Chromomycosis is a chronic cutaneous fungal infection characterized by the presence of dark brown parasitic forms of fungi in biopsied tissues. It is usually resulted from the entry of the causative organism through a minor trauma, and therefore, most lesions are found on the exposed part of the body, such as limbs or face, and occurrence on the nasolacrimal duct is extremely rare. We report a case of chromomycosis of the right nasolacrimal duct, which was presented with clinical symptoms of nasolacrimal duct obstruction. The patient was a 40 year-old male who had had minor injuries on his left eye twice by paper and branches of the tree two months prior to epiphora in right eye. On dacryocystorhinostomy, right nasolacrimal duct was obstructed by pinkish brown mucoid ball. Microscopically, the mucoid ball revealed eosinophilic, amorphous, necrotic materials admixed with brown pigmented fungi. The organism showed characteristic dark brown, round, thick-walled, often septated, sclerotic bodies and brown pigmented long bead-like hyphae. The adjacent mucosa shows marked chronic nonspecific inflammation with fibrosis.
Myofibroblastoma of the Male Breast: Report of a case.
Ji Eun Kim, Yeon Lim Suh, Howe Jung Ree
Korean J Pathol. 1996;30(7):623-629.
  • 1,654 View
  • 10 Download
AbstractAbstract
A case of myofibroblastoma of the breast in a 55-year-old man is described. Myofibroblastoma is a relatively recently recognized benign stromal tumor, and predominantly occurs in middle aged men. The pateint presented with a nontender firm mass in his right breast. Fine needle aspiration biopsy revealed bland looking stromal cell clusters without epithelial cells. Simple excision was done and the patient discharged uneventfully. The mass was well demarcated, lobulated and sligtly myxoid. Microscopically bipolar elongated spindle cell fascicles with interspersing broad collagen bands are so characteristic. Ultrastructurally the tumor cell show features of fibroblast as well as smooth muscle cell.
Well-Differentiated Papillary Mesothelioma of the Peritoneum: Report of a case.
Ji Eun Kim, So Duk Lim, Kyu Rae Kim, Han Young Choi
Korean J Pathol. 1996;30(7):646-648.
  • 1,656 View
  • 15 Download
AbstractAbstract PDF
We described a case of well differentiated papillary mesothelioma (WDPM) of the peritoneum in a 68-year-old man because of its rarity. It was incidentally found during operation for renal cell carcinoma. Grossly, the tumor appeared as multiple small granules or nodules on the entire peritoneal surface, including serosa of the intestine, omentum and mesentery. Microscopically, characteristic features are papillary, tubulopapillary or solid architecture lined by single layer of uniform, cytologically bland, cuboidal or polygonal mesothelial cells. The tumor cells were positive for EMA, cytokeratin and vimentin, but negative for CEA on immunohistochemical staining. Ultrastructural study showed characteristic long slender microvilli on the surface and intercellular junctions.
Intraductal Papillary-Mucinous Neoplasm of the Pancreas: A case report.
Ji Eun Kim, Young Hyeh Ko, Howe Jung Ree, Yong Il Kim, Poong Ryul Lee
Korean J Pathol. 1996;30(8):726-732.
  • 1,833 View
  • 22 Download
AbstractAbstract PDF
Intraductal papillary mucinous neoplasm (IPMN) is a recently recognized clinicopathologic entity characterized by dilatation of pancreatic duct filled with copious mucin and papillary ductal epithelial proliferation ranging from simple hyperplasia to invasive carcinoma. The exact clinicopathologic identification of this tumor is important because of favorable prognosis contrast to that of conventional ductal adenocarcinoma. Herein we report a case of surgically resected typical IPMN. A 59-year-old man had a long history of diabetes mellitus with epigastric pain of 4 months duration. Ultrasonography and computed tomographic examination revealed cystic dilatations of main pancreatic duct in the head. The patient underwent total pancreatectomy. The gross appearance showed diffuse dilatation of main pancreatic duct associated with cystic dilatation of subbranches in the uncinate process. Histologic examination revealed diffuse papillary proliferations lined by mucinous epithelium with mild atypism within ectatic ducts. No invasive carcinoma was noted. Histochemically, the papillary epithelium contained mostly neutral and acid sialomucin.
Original Article
The Value of Immunohistochemistry on Paraffin Embedded Tissue Sections in the Differentiation of Subgroups of Low Grade B-Cell Lymphomas.
Tae Sook Hwang, Seung Sook Lee, Ji Eun Kim, Hye Seung Han, Chul Woo Kim
Korean J Pathol. 1998;32(12):1066-1073.
  • 1,489 View
  • 10 Download
AbstractAbstract
There had been a continuous evolution of lymphoma classification and recently a Revised European-American Lymphoma Classification was proposed by the International Lymphoma Study Group. This new classification often requires information on immunophenotypic and molecular biologic markers in addition to the usual histologic findings. Recent advances in the production of commercially available monoclonal antibodies reactive on formalin-fixed paraffin-embedded tissues provide us a great help to classify the non-Hodgkin's lymphoma. We have analyzed 31 low grade B-cell lymphomas by the schemes proposed by the International Lymphoma Study Group using antibodies to CD3, CD5, CD20, CD23, CD43, cyclin D1, and bcl-2 protein, and have analyzed the immunophenotypic features. Among 31 low grade B-cell lymphomas, 8 small lymphocytic lymphomas, 5 mantle cell lymphomas, 7 follicle center lymphomas (2 grade I, 3 grade II, and 2 grade III), and 11 marginal zone B-cell lymphomas (all of which were extranodal) were identified. Among 8 small lymphocytic lymphomas, 5 cases were positive for CD5; 6 cases were positive for CD23; 7 cases were positive for CD43; all 8 cases were negative for cyclin D1; and 7 cases were positive for bcl-2. Among 5 mantle cell lymphomas, 4 cases were positive for CD5 and CD43; all five cases were negative for CD23; 4 cases were positive for cyclin D1 and bcl-2. All 7 follicle center lymphomas were negative for CD5, CD43 and cyclin D1 and 2 cases were positive for CD23; and 6 cases were positive for bcl-2. All marginal zone B-cell lymphomas were negative for CD5, CD23 and cyclin D1; 3 cases were positive for CD43 and 9 cases were positive for bcl-2. Diagnostic utility for CD5 antigen detection on paraffin embedded tissue has a limitation due to weak antigen expression in tumor cells of B-cell lymphomas; however, still be useful in differentiating small lymphocytic lymphoma and mantle cell lymphoma from other B-cell lymphomas when applied in conjunction with CD43. CD23, CD43, and cyclin D1 appear to be of great help in differentiating subgroups of low grade B-cell lymphomas. Bcl-2, as known, is found to be useful to rule out reactive follicular hyperplasia.

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