Journal of Pathology and Translational Medicine

Case Studies

Diagnostic challenge in Burkitt lymphoma of the mandible initially misdiagnosed as osteomyelitis: a case report: Jiwon Do, Jin-Young Choi; J Pathol Transl Med. 2025;59(6):460-466. Published online November 14, 2025; DOI: https://doi.org/10.4132/jptm.2025.09.18

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Abstract PDF: Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm that rarely involves the mandible in elderly without apparent immunodeficiency. We report a case of a 72-year-old male who presented with persistent mandibular pain following extraction of tooth #46. Initial imaging findings were consistent with incipient osteomyelitis, and the patient was treated with antibiotics. Despite treatment, pain persisted, and follow-up imaging revealed swelling and diffusion restriction in the lateral pterygoid muscle without evidence of a distinct mass. Biopsy revealed BL confirmed by immunohistochemistry: CD10+, BCL6+, c-MYC+, Ki-67 >95%, and negative for BCL2, MUM-1, and Epstein-Barr virus. Although c-MYC immunopositivity was demonstrated, fluorescence in situ hybridization for MYC rearrangement could not be performed due to limited tissue, representing a diagnostic limitation. Notably, the patient had no trismus despite deep muscle involvement, but complained of facial paresthesia and showed remote swelling in the scapular area during hospitalization. Systemic staging with imaging, cerebrospinal fluid cytology, and imaging revealed disseminated nodal and extranodal involvement including the central nervous system, corresponding to stage IV disease by Lugano classification. This case highlights the diagnostic challenge of distinguishing lymphoma from osteomyelitis and underscores the importance of considering malignancy in cases of refractory mandibular inflammation with atypical features.

Concurrent intestinal plasmablastic lymphoma and diffuse large B-cell lymphoma with a clonal relationship: a case report and literature review: Nao Imuta, Kosuke Miyai, Motohiro Tsuchiya, Mariko Saito, Takehiro Sone, Shinichi Kobayashi, Sho Ogata, Fumihiko Kimura, Susumu Matsukuma; J Pathol Transl Med. 2024;58(4):191-197. Published online June 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.05.14

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Abstract PDF: Herein, we report a case of plasmablastic lymphoma (PBL) and diffuse large B-cell lymphoma (DLBCL) that occurred concurrently in the large intestine. An 84-year-old female presented with a palpable rectal tumor and ileocecal tumor observed on imaging analyses. Endoscopic biopsy of both lesions revealed lymphomatous round cells. Hartmann’s operation and ileocecal resection were performed for regional control. The ileocecal lesion consisted of a proliferation of CD20/CD79a-positive lymphoid cells, indicative of DLBCL. In contrast, the rectal tumor showed proliferation of atypical cells with pleomorphic nuclei and abundant amphophilic cytoplasm, with immunohistochemical findings of CD38/CD79a/MUM1/MYC (+) and CD20/CD3/CD138/PAX5 (–). Tumor cells were positive for Epstein-Barr virus– encoded RNA based on in situ hybridization and MYC rearrangement in fluorescence in situ hybridization analysis. These findings indicated the rectal tumor was most likely a PBL. Sequencing analysis for immunoglobulin heavy variable genes indicated a common B-cell origin of the two sets of lymphoma cells. This case report and literature review provide new insights into PBL tumorigenesis.

Primary epithelioid inflammatory myofibroblastic sarcoma of the brain with EML4::ALK fusion mimicking intra-axial glioma: a case report and brief literature review: Eric Eunshik Kim, Chul-Kee Park, Koung Mi Kang, Yoonjin Kwak, Sung-Hye Park, Jae-Kyung Won; J Pathol Transl Med. 2024;58(3):141-145. Published online May 14, 2024; DOI: https://doi.org/10.4132/jptm.2024.04.12

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Abstract PDF

An aggressive subtype of inflammatory myofibroblastic tumor, epithelioid inflammatory myofibroblastic sarcoma occurs primarily inside the abdominal cavity, followed by a pulmonary localization. Most harbor anaplastic lymphoma kinase (ALK) gene rearrangements, with RANBP2 and RRBP1 among the well-documented fusion partners. We report the second case of primary epithelioid inflammatory myofibroblastic sarcoma of the brain, with a well-known EML4::ALK fusion. The case is notable for its intra-axial presentation that clinico-radiologically mimicked glioma.

Citations

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Inflammatory Myofibroblastic Tumor: An Updated Review
Joon Hyuk Choi
Cancers.2025; 17(8): 1327. CrossRef
Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review)
Ho Huang, Jia Ouyang
Oncology Letters.2025; 31(1): 1. CrossRef

Fibrin-associated large B-cell lymphoma arising in an endovascular graft: first case report in Korea: Min Gyoung Pak, Mee Sook Roh; J Pathol Transl Med. 2024;58(2):87-90. Published online January 24, 2024; DOI: https://doi.org/10.4132/jptm.2023.12.28

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Abstract PDF: Fibrin-associated large B-cell lymphoma (FA-LBCL) is an extremely rare subtype of LBCL that consists of microscopic aggregates of atypical large B cells in the background of fibrin. Here, we report the first case of FA-LBCL in Korea. A 57-year-old male presented with a large amount of thrombus in the thoracic aorta during follow-up for graft replacement of the thoracoabdominal aorta 8 years prior. The removed thrombus, measuring 4.3 × 3.1 cm, histologically exhibited eosinophilic fibrinous material with several small clusters of atypical lymphoid cells at the periphery. The atypical cells were positive for CD20 by immunohistochemistry and for Epstein-Barr virus by in situ hybridization. The Ki-67 proliferation rate was 85%. The patient was still alive with no recurrence at the 7-year follow-up after thrombectomy. Although the diagnosis can be very difficult and challenging due to its paucicellular features, pathologists should be aware of FALBCL, which has likely been underestimated in routine evaluations of thrombi.

Original Articles

Clinicopathological implications of immunohistochemical expression of TBX21, CXCR3, GATA3, CCR4, and TCF1 in nodal follicular helper T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified: Bogyeong Han, Sojung Lim, Jeemin Yim, Young Keun Song, Jiwon Koh, Sehui Kim, Cheol Lee, Young A Kim, Yoon Kyung Jeon; J Pathol Transl Med. 2024;58(2):59-71. Published online January 22, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.04

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Abstract PDF Supplementary Material

Background
The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1- and Th2-like molecules in nodal PTCL is unclear.
Methods
Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)/nodal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-Tfh/nTFHL–not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed.
Results
TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/ nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-Tfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054).
Conclusions
The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

Citations

Citations to this article as recorded by

T-bet: biological functions, molecular mechanisms, and therapeutic applications: a systematic review
Xiaowen Yang, Min Sun, Xinyi Tang, Xiaoyuan Zhang, Wenzhi Shen
Frontiers in Immunology.2026;[Epub] CrossRef
CXCR Family and Hematologic Malignancies in the Bone Marrow Microenvironment
Yanquan Liu, Huanwen Tang
Biomolecules.2025; 15(5): 716. CrossRef
Diagnostic and therapeutic pathways for lymphoma patients: expert consensus through Nominal Group Technique and Delphi methodology
Attilio Guarini, Valentina Bozzoli, Sabino Ciavarella, Michele Cimminiello, Francesca Donatelli, Angelo Fama, Vincenza Fernanda Fesce, Vincenzo Fraticelli, Francesco Gaudio, Giuseppina Greco, Augusto Martellini, Francesca Merchionne, Rosanna Maria Miccoli
Frontiers in Oncology.2025;[Epub] CrossRef
Prognostic Significance of TBX21 and GATA3 Subtype Classification in Indolent Adult T‐Cell Leukemia‐Lymphoma With Cutaneous Lesions
Kazuhiro Kawai, Youhei Uchida, Takuro Kanekura
The Journal of Dermatology.2025; 52(11): 1674. CrossRef

Immunohistochemical expression of anaplastic lymphoma kinase in neuroblastoma and its relations with some clinical and histopathological features: Thu Dang Anh Phan, Thao Quyen Nguyen, Nhi Thuy To, Thien Ly Thanh, Dat Quoc Ngo; J Pathol Transl Med. 2024;58(1):29-34. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.12.07

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Abstract PDF

Background
Anaplastic lymphoma kinase (ALK) mutations have been identified as a prominent cause of some familial and sporadic neuroblastoma (NB). ALK expression in NB and its relationship with clinical and histopathological features remains controversial. This study investigated ALK expression and its potential relations with these features in NB.
Methods
Ninety cases of NB at the Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam from 01/01/2018 to 12/31/2021, were immunohistochemically stained with ALK (D5F3) antibody. The ALK expression and its relations with some clinical and histopathological features were investigated.
Results
The rate of ALK expression in NB was 91.1%. High ALK expression (over 50% of tumor cells were positive with moderate-strong intensity) accounted for 65.6%, and low ALK expression accounted for 34.4%. All the MYCN-amplified NB patients had ALK immunohistochemistry positivity, most cases had high ALK protein expression. The undifferentiated subtype of NB had a lower ALK-positive rate than the poorly differentiated and differentiated subtype. The percentages of ALK positivity were significantly higher in more differentiated histological types of NB (p = .024). There was no relation between ALK expression and: age group, sex, primary tumor location, tumor stage, MYCN status, clinical risk, Mitotic-Karyorrhectic Index, prognostic group, necrosis, and calcification.
Conclusions
ALK was highly expressed in NB. ALK expression was not related to several clinical and histopathological features. More studies are needed to elucidate the association between ALK expression and ALK gene status and to investigate disease progression, especially the oncogenesis of ALK-positive NB.

Citations

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A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers
Alberto D. Guerra, Smita Matkar, Christina Acholla, Colleen Casey, Grant Li, Martina Mazzeschi, Khushbu Patel, Kateryna Krytska, Chuan Chen, Skye Balyasny, Joshua Kalna, Paul Kamitsuka, Mark Gerelus, Grace Polkosnik, David Groff, Apratim Mukherje, Cynthia
Nature Communications.2025;[Epub] CrossRef
Integration of ALK gene mutations and targeted therapies in pediatric high-risk neuroblastoma: advancements in precision oncology
Bhumika Bheemavarapu, Mohammad Khalil, Aseef Rehman, Saman Javid, FNU Cyrus, Sardar Noman Qayyum, Aasvi Gohil, Siraj Ul Muneer, Samim Noori
Annals of Medicine & Surgery.2025; 87(10): 6470. CrossRef

Tumor-infiltrating T lymphocytes evaluated using digital image analysis predict the prognosis of patients with diffuse large B-cell lymphoma: Yunjoo Cho, Jiyeon Lee, Bogyeong Han, Sang Eun Yoon, Seok Jin Kim, Won Seog Kim, Junhun Cho; J Pathol Transl Med. 2024;58(1):12-21. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.02

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Abstract PDF

Background
The implication of the presence of tumor-infiltrating T lymphocytes (TIL-T) in diffuse large B-cell lymphoma (DLBCL) is yet to be elucidated. We aimed to investigate the effect of TIL-T levels on the prognosis of patients with DLBCL.
Methods
Ninety-six patients with DLBCL were enrolled in the study. The TIL-T ratio was measured using QuPath, a digital pathology software package. The TIL-T ratio was investigated in three foci (highest, intermediate, and lowest) for each case, resulting in TIL-T–Max, TIL-T–Intermediate, and TIL-T–Min. The relationship between the TIL-T ratios and prognosis was investigated.
Results
When 19% was used as the cutoff value for TIL-T–Max, 72 (75.0%) and 24 (25.0%) patients had high and low TIL-T–Max, respectively. A high TIL-T–Max was significantly associated with lower serum lactate dehydrogenase levels (p < .001), with patient group who achieved complete remission after RCHOP therapy (p < .001), and a low-risk revised International Prognostic Index score (p < .001). Univariate analysis showed that patients with a low TIL-T–Max had a significantly worse prognosis in overall survival compared to those with a high TIL-T–Max (p < .001); this difference remained significant in a multivariate analysis with Cox proportional hazards (hazard ratio, 7.55; 95% confidence interval, 2.54 to 22.42; p < .001).
Conclusions
Patients with DLBCL with a high TIL-T–Max showed significantly better prognosis than those with a low TIL-T–Max, and the TIL-T–Max was an independent indicator of overall survival. These results suggest that evaluating TIL-T ratios using a digital pathology system is useful in predicting the prognosis of patients with DLBCL.

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Do Pre‐Treatment Biopsy Characteristics Predict Early Tumour Progression in Feline Diffuse Large B Cell Nasal Lymphoma Treated With Radiotherapy?
Valerie J. Poirier, Valeria Meier, Michelle Turek, Neil Christensen, Jacqueline Bowal, Matthew D. Ponzini, Stefan M. Keller
Veterinary and Comparative Oncology.2025; 23(1): 82. CrossRef
Comprehensive Analysis of Tumor Microenvironment and PD-L1 Expression Associations with Clinicopathological Features and Prognosis in Diffuse Large B-Cell Lymphoma
Yun-Li Xie, Long-Feng Ke, Wen-Wen Zhang, Fu Kang, Shu-Yi Lu, Chen-Yu Wu, Huan-Huan Zhu, Jian-Chao Wang, Gang Chen, Yan-Ping Chen
Blood and Lymphatic Cancer: Targets and Therapy.2025; Volume 15: 167. CrossRef
Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL
Chengqian Chen, Wei Guo, Haotian Wang, Luming Cao, Ou Bai
Frontiers in Immunology.2025;[Epub] CrossRef
Integrative analysis of a novel immunogenic PANoptosis‑related gene signature in diffuse large B-cell lymphoma for prognostication and therapeutic decision-making
Ming Xu, Ming Ruan, Wenhua Zhu, Jiayue Xu, Ling Lin, Weili Li, Weirong Zhu
Scientific Reports.2024;[Epub] CrossRef

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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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
Diagnostics.2024; 14(7): 679. CrossRef
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
Journal of Clinical and Experimental Hematopathology.2024; 64(4): 328. CrossRef

Case Report

Metallic implant-associated lymphoma: ALK-negative anaplastic large cell lymphoma associated with total knee replacement arthroplasty: Jai-Hyang Go; J Pathol Transl Med. 2023;57(1):75-78. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.10.30

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Abstract PDF

Metallic implant-associated lymphomas are extremely rare. Only seven cases have been reported in association with knee joint arthroplasty, and all tumors were large B-cell lymphomas. This report is the first case of anaplastic large cell lymphoma occurring after total knee replacement arthroplasty. An 80‑year‑old female patient was admitted because of right knee pain for 2 years. She had undergone total knee replacement arthroplasty 10 years prior. Computed tomography showed an irregular osteolytic lesion in the right lateral femoral condyle, adjacent to the metallic prosthesis. Histologic findings reveal sheets of anaplastic tumor cells that were positive for CD2, CD4, CD5, CD43, and CD30 but negative for CD3, CD20, CD15, and anaplastic lymphoma kinase. Epstein-Barr encoding region in situ hybridization was negative. Analysis of T-cell receptor γ gene rearrangement studies using BIOMED-2–based multiplex polymerase chain reaction confirmed monoclonal T cell proliferation. The woman was finally diagnosed with ALK-negative anaplastic large cell lymphoma.

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Clinical and microscopic evidence of biofilm formation on titanium miniplates applied in maxillofacial surgery: a case series analysis
Bramasto Purbo Sejati, Ahmad Kusumaatmaja, Maria Goreti Widiastuti, Tetiana Haniastuti
Case Reports in Plastic Surgery and Hand Surgery.2025;[Epub] CrossRef
Granulomatous Mycosis Fungoides Associated with Knee Prostheses: A Case Report and Literature Review
Belloso Rosa Izu, Rodriguez Blandon Jurvist Stee, Peña Nekane Martinez, Colunga Barbara Lada, Izaguirre Ane Lobato, Apraiz Isabel Gainza, Ponsa Carla Valenti
International Journal of Dermatology and Clinical Research.2025; 11(1): 022. CrossRef
Primary bone diffuse large B‐cell lymphoma (PB‐DLBCL): a distinct extranodal lymphoma of germinal centre origin, with a common EZB‐like mutational profile and good prognosis
Vanesa‐Sindi Ivanova, John Davies, Thomas Menter, Damian Wild, Anne Müller, Fatime Krasniqi, Frank Stenner, Alexandros Papachristofilou, Stefan Dirnhofer, Alexandar Tzankov
Histopathology.2024; 84(3): 525. CrossRef
Osteosarcoma After Total Knee Arthroplasty
Pablo Martínez-Collado, Oriol Pujol, Andrés Bustos, Martí Plomer, María G. Carrasco, Tulio Silva, Roberto Vélez, Joan Minguell
JBJS Case Connector.2024;[Epub] CrossRef

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

Original Article

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

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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.

Citations

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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

Case Study

Primary pulmonary epithelioid inflammatory myofibroblastic sarcoma: a rare entity and a literature review: Priyanka Singh, Aruna Nambirajan, Manish Kumar Gaur, Rahul Raj, Sunil Kumar, Prabhat Singh Malik, Deepali Jain; J Pathol Transl Med. 2022;56(4):231-237. Published online July 7, 2022; DOI: https://doi.org/10.4132/jptm.2022.05.08

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Abstract PDF

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

Citations

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Inflammatory Myofibroblastic Tumor: An Updated Review
Joon Hyuk Choi
Cancers.2025; 17(8): 1327. CrossRef
Epithelioid Inflammatory Myofibroblastic Sarcoma: Case Series With a First Report of CLTC::ALK Fusion in an Aggressive Disease
Daisy Maharjan, Carina Dehner, Ali Alani, Robert Bell, Sheila Segura
Genes, Chromosomes and Cancer.2025;[Epub] CrossRef
ALK rearranged malignant mesenchymal neoplasms of thorax: therapeutically targetable ‘ALKomas’ beyond the spectrum of non-small cell lung carcinomas and thoracic inflammatory myofibroblastic tumors
Shreya Sadhu, Adarsh Barwad, Asit Ranjan Mridha, Prabhat Singh Malik, Aruna Nambirajan, Deepali Jain
Virchows Archiv.2025; 487(5): 1003. CrossRef
Mediastinal epithelioid inflammatory myofibroblastic sarcoma with the EML4‐ALK fusion: A case report and literature review
Tingyu Pan, Xinyu Sun, Xiao Wu, Futing Tang, Xianmei Zhou, Qian Wang, Shi Chen
Respirology Case Reports.2024;[Epub] CrossRef
Primary epithelioid inflammatory myofibroblastic sarcoma of the brain with EML4::ALK fusion mimicking intra-axial glioma: a case report and brief literature review
Eric Eunshik Kim, Chul-Kee Park, Koung Mi Kang, Yoonjin Kwak, Sung-Hye Park, Jae-Kyung Won
Journal of Pathology and Translational Medicine.2024; 58(3): 141. CrossRef
Epithelioid Inflammatory Myofibroblastic Sarcoma: A Report of a Rare Case
Varun Ronanki, Vaddatti Tejeswini, Inuganti Venkata Renuka, Shaik Raheema, Bakkamanthala S K Kanth
Cureus.2024;[Epub] CrossRef
Thoracic epithelioid inflammatory myofibroblastic sarcoma: a rare and aggressive disease with case report and literature review
Linke Yang, Pei Li, Runze Liu, Baomin Feng, Huiqing Mao, Xiaoyong Tang, Guangjian Yang
Discover Oncology.2024;[Epub] CrossRef
Epithelioid inflammatory myofibroblastic sarcoma with exceptionally long response to lorlatinib—a case report
Rafał Becht, Kajetan Kiełbowski, Justyna Żychowska, Wojciech Poncyljusz, Aleksandra Łanocha, Katarzyna Kozak, Ewa Gabrysz-Trybek, Paweł Domagała
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Rare giant epithelioid inflammatory myofibroblastic sarcoma of the abdominal cavity in a child: a case report and review of the literature
Jinzhou Li, Haixing Su, Sheng Zhang, Xianyun Chen, Chongzhi Hou, Tao Cheng
Frontiers in Oncology.2024;[Epub] CrossRef
Case report: Epithelioid inflammatory myofibroblastic sarcoma treated with an ALK TKI ensartinib
Mengmeng Li, Ruyue Xing, Jiuyan Huang, Chao Shi, Chunhua Wei, Huijuan Wang
Frontiers in Oncology.2023;[Epub] CrossRef
Epithelioid Inflammatory Myofibroblastic Sarcoma With Poor Response to Crizotinib: A Case Report
Soheila Aminimoghaddam, Roghayeh Pourali
Clinical Medicine Insights: Case Reports.2023;[Epub] CrossRef
Epithelioid inflammatory myofibroblastic sarcoma: a case report and brief literature review
Weidong Dou, Yu Guan, Tao Liu, Hang Zheng, Shuo Feng, Yingchao Wu, Xin Wang, Zhanbing Liu
Frontiers in Oncology.2023;[Epub] CrossRef

Reviews

Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies: Jiwon Koh, Sun Ah Shin, Ji Ae Lee, Yoon Kyung Jeon; J Pathol Transl Med. 2022;56(4):173-186. Published online July 4, 2022; DOI: https://doi.org/10.4132/jptm.2022.05.16

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Abstract PDF

Lymphocyte-rich effusions represent benign reactive process or neoplastic condition. Involvement of lymphoproliferative disease in body cavity is not uncommon, and it often causes diagnostic challenge. In this review, we suggest a practical diagnostic approach toward lymphocyte-rich effusions, share representative cases, and discuss the utility of ancillary tests. Cytomorphologic features favoring neoplastic condition include high cellularity, cellular atypia/pleomorphism, monomorphic cell population, and frequent apoptosis, whereas lack of atypia, polymorphic cell population, and predominance of small T cells usually represent benign reactive process. Involvement of non-hematolymphoid malignant cells in body fluid should be ruled out first, followed by categorization of the samples into either small/medium-sized cell dominant or large-sized cell dominant fluid. Small/medium-sized cell dominant effusions require ancillary tests when either cellular atypia or history/clinical suspicion of lymphoproliferative disease is present. Large-sized cell dominant effusions usually suggest neoplastic condition, however, in the settings of initial presentation or low overall cellularity, ancillary studies are helpful for more clarification. Ancillary tests including immunocytochemistry, in situ hybridization, clonality test, and next-generation sequencing can be performed using cytologic preparations. Throughout the diagnostic process, proper review of clinical history, cytomorphologic examination, and application of adequate ancillary tests are key elements for successful diagnosis.

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Follicular lymphoma: updates for pathologists: Mahsa Khanlari, Jennifer R. Chapman; J Pathol Transl Med. 2022;56(1):1-15. Published online December 27, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.29

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Abstract PDF

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and originates from germinal center B-cells (centrocytes and centroblasts) of the lymphoid follicle. Tumorigenesis is believed to initiate early in precursor B-cells in the bone marrow (BM) that acquire the t(14;18)(q32;q21). These cells later migrate to lymph nodes to continue their maturation through the germinal center reaction, at which time they acquire additional genetic and epigeneticabnormalities that promote lymphomagenesis. FLs are heterogeneous in terms of their clinicopathologic features. Most FLs are indolent and clinically characterized by peripheral lymphadenopathy with involvement of the spleen, BM, and peripheral blood in a substantial subset of patients, sometimes accompanied by constitutional symptoms and laboratory abnormalities. Diagnosis is established by the histopathologic identification of a B-cell proliferation usually distributed in an at least partially follicular pattern, typically, but not always, in a lymph node biopsy. The B-cell proliferation is biologically of germinal center cell origin, thus shows an expression of germinal center-associated antigens as detected by immunophenotyping. Although many cases of FLs are typical and histopathologic features are straightforward, the biologic and histopathologic variability of FL is wide, and an accurate diagnosis of FL over this disease spectrum requires knowledge of morphologic variants that can mimic other lymphomas, and rarely non-hematologic malignancies, clinically unique variants, and pitfalls in the interpretation of ancillary studies. The overall survival for most patients is prolonged, but relapses are frequent. The treatment landscape in FL now includes the application of immunotherapy and targeted therapy in addition to chemotherapy.

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Case Studies

An unusual case of microsatellite instability–high/deficient mismatch repair (MSI-H/dMMR) diffuse large B-cell lymphoma revealed by targeted gene sequencing: Bogyeong Han, Sehui Kim, Jiwon Koh, Jeong Mo Bae, Hongseok Yun, Yoon Kyung Jeon; J Pathol Transl Med. 2022;56(2):92-96. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.15

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Abstract PDF

Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status has been approved as a tissue-agnostic biomarker for immune checkpoint inhibitor therapy in patients with solid tumors. We report the case of an MSI-H/dMMR diffuse large B-cell lymphoma (DLBCL) identified by targeted gene sequencing (TGS). A 90-year-old female who presented with vaginal bleeding and a large mass in the upper vagina was diagnosed with germinal center-B-cell-like DLBCL, which recurred at the uterine cervix at 9 months after chemotherapy. Based on TGS of 121 lymphoma-related genes and the LymphGen algorithm, the tumor was classified genetically as DLBCL of EZB subtype. Mutations in multiple genes, including frequent frameshift mutations, were detected by TGS and further suggested MSI. The MSI-H/dMMR and loss of MLH1 and PMS2 expression were determined in MSI-fragment analysis, MSI real-time polymerase chain reaction, and immunohistochemical tests. This case demonstrates the potential diagnostic and therapeutic utility of lymphoma panel sequencing for DLBCL with MSI-H/dMMR.

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Jens Staal, Yasmine Driege, Femke Van Gaever, Jill Steels, Rudi Beyaert
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Andrew W. Allbee, James Gerson, Guang Yang, Adam Bagg
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Composite follicular lymphoma and classic Hodgkin lymphoma: Han-Na Kim, Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Chul-Won Choi, Young Hyeh Ko; J Pathol Transl Med. 2022;56(1):57-60. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.09

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Abstract PDF

Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

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Original Articles

Clinicopathologic implication of PD-L1 gene alteration in primary adrenal diffuse large B cell lymphoma: Ki Rim Lee, Jiwon Koh, Yoon Kyung Jeon, Hyun Jung Kwon, Jeong-Ok Lee, Jin Ho Paik; J Pathol Transl Med. 2022;56(1):32-39. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.05

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Abstract PDF: Background
Primary adrenal (PA) diffuse large B cell lymphoma (DLBCL) was previously reported as an aggressive subset of DLBCL, but its genetic features were not sufficiently characterized. From our previous study of DLBCL with programmed death-ligand 1 (PD-L1) gene alterations, we focused on PD-L1 gene alterations in PA-DLBCL with clinicopathologic implications.
Methods
We performed fluorescence in situ hybridization for PD-L1 gene translocation and amplification in PA-DLBCL (n = 18) and comparatively analyzed clinicopathologic characteristics with systemic non-adrenal (NA)-DLBCL (n = 90).
Results
PA-DLBCL harbored distinctive features (vs. NADLBCL), including high international prognostic index score (3–5) (72% [13/18] vs. 38% [34/90], p = .007), poor Eastern Cooperative Oncology Group performance score (≥ 2) (47% [7/15] vs. 11% [10/90], p = .003), elevated serum lactate dehydrogenase (LDH) (78% [14/18] vs. 51% [44/87], p = .035) and MUM1 expression (87% [13/15] vs. 60% [54/90], p = .047). Moreover, PA-DLBCL showed frequent PD-L1 gene alterations (vs. NA-DLBCL) (39% [7/18] vs. 6% [5/86], p = .001), including translocation (22% [4/18] vs. 3% [3/87], p = .016) and amplification (17% [3/18] vs. 2% [2/87], p = .034). Within the PA-DLBCL group, PD-L1 gene–altered cases (vs. non-altered cases) tended to have B symptoms (p = .145) and elevated LDH (p = .119) but less frequent bulky disease (≥ 10 cm) (p = .119). In the survival analysis, PA-DLBCL had a poor prognosis for overall survival (OS) and progression-free survival (PFS) (vs. NA-DLBCL; p = .014 and p = .004). Within the PA-DLBCL group, PD-L1 translocation was associated with shorter OS and PFS (p < .001 and p = .012).
Conclusions
PA-DLBCL is a clinically aggressive and distinct subset of DLBCL with frequent PD-L1 gene alterations. PD-L1 gene translocation was associated with poor prognosis in PA-DLBCL.

Upward trend in follicular lymphoma among the Korean population: 10-year experience at a large tertiary institution: Meejeong Kim, Hee Sang Hwang, Hyungwoo Cho, Dok Hyun Yoon, Cheolwon Suh, Chan Sik Park, Heounjeong Go, Jooryung Huh; J Pathol Transl Med. 2021;55(5):330-337. Published online September 2, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.25

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Abstract PDF Supplementary Material

Background
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) in Western countries. However, it is relatively rare in Asia. This study examined epidemiologic characteristics of FL in South Korea, with an emphasis on recent trends of increase in cases.
Methods
We retrospectively examined 239 cases of newly diagnosed FL at a large tertiary institution in Korea (Asan Medical Center, Seoul, Republic of Korea) between 2008 and 2017. Age-adjusted incidence rates and clinicopathological variables were analyzed, and joinpoint regression analysis was used to identify the changes.
Results
The age-adjusted incidence of FL significantly increased during the study period (p = .034), and the ratio of (relative incidence) patients with FL to patients with NHL increased from 4.28% to 9.35% in the same period. Over the 10-year study assessment duration, the proportion of patients with stage III/IV FL (p = .035) and expression of BCL2 (p = .022) or BCL6 (p = .039) significantly increased. From 2013–2017, the proportion of patients with highrisk Follicular Lymphoma International Prognostic Index (FLIPI) score increased (21.5% to 28.7%), whereas that of low-risk FLIPI decreased (55.4% to 38.6%), although those results were not statistically significant (p = .066).
Conclusions
We found an increasing incidence of FL, with a disproportionate increase in the incidence of high-stage disease and recent changes in the clinicopathologic features of the Korean patient population.

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Liang-Chun Chiu, Chih-Wen Lin, Hung-Ju Li, Jian-Han Chen, Fu-Cheng Chuang, Sheng-Fung Lin, Yu Chang, Yu-Chieh Su
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Case Studies

A case of concomitant EGFR/ALK alteration against a mutated EGFR background in early-stage lung adenocarcinoma: Ki-Chang Lee, Jiwon Koh, Doo Hyun Chung, Yoon Kyung Jeon; J Pathol Transl Med. 2021;55(2):139-144. Published online January 22, 2021; DOI: https://doi.org/10.4132/jptm.2020.12.16

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Abstract PDF

Rare cases of lung adenocarcinoma (LUAD) with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation have been reported. However, their clonal and evolutional relationship remains unclear. We report a case of early-stage EGFR-mutated LUAD with a focal concomitant EGFR/ALK alteration. A 63-year-old male underwent lobectomy to remove a 1.9-cm-sized lung nodule, which was diagnosed with EGFR-mutated LUAD. ALK immunohistochemistry (IHC) showed focal positivity within the part of the tumor characterized by lepidic pattern, also confirmed by fluorescence in-situ hybridization (FISH). Targeted next-generation sequencing was performed separately on the ALK IHC/FISH-positive and -negative areas. EGFR L833V/L858R mutations were detected in both areas, whereas EML4 (echinoderm microtubule-associated protein-like 4)-ALK translocations was confirmed only in the ALK IHC/FISH-positive area, suggesting the divergence of an EGFR/ALK co-altered subclone from the original EGFR-mutant clone. Our study suggests that concurrent alterations of EGFR and ALK can arise via divergent tumor evolution, even in the relatively early phases of tumorigenesis.

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Renal intravascular large B cell lymphoma: the first case report in Korea and a review of the literature: Moonsik Kim, Haerim Chung, Woo Ick Yang, Hyeon Joo Jeong; J Pathol Transl Med. 2020;54(5):426-431. Published online August 13, 2020; DOI: https://doi.org/10.4132/jptm.2020.06.18

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Abstract PDF Supplementary Material

Herein, we describe the first case of renal intravascular large B cell lymphoma in Korea occurring in a 66-year-old female. She presented with mild fever and dyspnea. On physical and laboratory evaluations, hemophagocytic lymphohistiocytosis was suspected, but the bone marrow biopsy results were unremarkable. During the work-up, massive proteinuria developed, which led to a renal biopsy. The renal architecture was relatively well-preserved, but the glomeruli were hypercellular with the infiltration of atypical, large lymphoid cells with increased nucleus-cytoplasm ratio and clumped chromatin. Similar cells were also present in the peritubular capillaries. The tumor cells exhibited membranous staining for CD20 and CD79a. After the diagnosis of intravascular large B cell lymphoma, the patient received rituximab-based chemotherapy under close follow-up.

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Gastric crystal-storing histiocytosis with concomitant mucosa-associated lymphoid tissue lymphoma: Mee Joo, Nam-Hoon Kim; J Pathol Transl Med. 2020;54(4):332-335. Published online May 22, 2020; DOI: https://doi.org/10.4132/jptm.2020.04.20

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Abstract PDF

Crystal-storing histiocytosis (CSH) is a rare entity that is characterized by intrahistiocytic accumulation of crystallized immunoglobulins. CSH is not a malignant process per se, but the majority of CSH cases are associated with underlying lymphoproliferative disorder. Although CSH can occur in a variety of organs, gastric CSH is very rare. We present a localized gastric CSH with concomitant mucosaassociated lymphoid tissue (MALT) lymphoma, manifesting as an ulcer bleeding in a 56-year-old man. Histologically, the biopsied gastric mucosa demonstrated expansion of the lamina propria by prominent collections of large eosinophilic mononuclear cells containing fibrillary crystalloid inclusions. Immunohistochemical studies revealed that the crystal-storing cells were histiocytes harboring kappa light chain-restricted immunoglobulin crystals. Within the lesion, atypical centrocyte-like cells forming lymphoepithelial lesions were seen, consistent with MALT lymphoma. Since this entity is rare and unfamiliar, difficulties in diagnosis may arise. Particularly, in this case, the lymphomatous area was obscured by florid CSH, making the diagnosis more challenging.

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Primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: Soyeon Choi, Ji Hye Kim, Kyungbin Kim, Misung Kim, Hye Jeong Choi, Young Min Kim, Jae Hee Suh, Min Jung Seo, Hee Jeong Cha; J Pathol Transl Med. 2020;54(4):340-345. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.18

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Abstract PDF

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), is one of the specific type of low-grade B-cell lymphoma not infrequently found worldwide. It typically involves mucosal sites such as stomach and conjunctiva; however, primary hepatic MALT lymphoma has been extremely rarely reported. We describe a case of hepatic MALT lymphoma in a 70-year-old male patient who underwent left hepatectomy due to the incidentally detected liver masses at a medical checkup. The resected specimen revealed multinodular masses consisting of small-to-intermediate-sized lymphoid cells with serpentine pattern and focal lymphoepithelial lesions. The tumor cells were diffusely positive for CD20 and Bcl-2 but negative for CD3, CD10, CD5, CD23, CD43, and cyclinD1. The Ki-67 labeling index was 10% and immunoglobulin heavy chain gene rearrangement study confirmed monoclonal proliferation. In this paper, we discuss several unique clinicopathologic characteristics which will be helpful to the differential diagnosis of hepatic MALT lymphoma.

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Morphologic variant of follicular lymphoma reminiscent of hyaline-vascular Castleman disease: Jiwon Koh, Yoon Kyung Jeon; J Pathol Transl Med. 2020;54(3):253-257. Published online February 5, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.17

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Abstract PDF

Follicular lymphoma (FL) with hyaline-vascular Castleman disease (FL-HVCD)-like features is a rare morphologic variant, with fewer than 20 cases in the literature. Herein, we report a case of FL-HVCD in a 37-year-old female who presented with isolated neck lymph node enlargement. The excised lymph node showed features reminiscent of HVCD, including regressed germinal centers (GCs) surrounded by onion skin-like mantle zones, lollipop lesions composed of hyalinized blood vessels penetrating into regressed GCs, and hyalinized interfollicular stroma. In addition, focal areas of abnormally conglomerated GCs composed of homogeneous, small centrocytes with strong BCL2, CD10, and BCL6 expression were observed, indicating partial involvement of the FL. Several other lymphoid follicles showed features of in situ follicular neoplasia. Based on the observations, a diagnosis of FL-HVCD was made. Although FLHVCD is very rare, the possibility of this variant should be considered in cases resembling CD. Identification of abnormal, neoplastic follicles and ancillary immunostaining are helpful for proper diagnosis.

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Unicentric Castleman Disease: Illustration of Its Morphologic Spectrum and Review of the Differential Diagnosis
Siba El Hussein, Andrew G. Evans, Hong Fang, Wei Wang, L. Jeffrey Medeiros
Archives of Pathology & Laboratory Medicine.2024; 148(1): 99. CrossRef
Finding a Needle in the Haystack
Hung-Yu Lin, Yi-Jen Peng, Yi-Ying Wu, Ping-Ying Chang
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Analysis of immunophenotypic features in hyaline vascular type Castleman disease
Yu Chang, Yu Ma, Chen Chang, Wensheng Li
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In‐situ follicular neoplasia: a clinicopathological spectrum
Gurdip S Tamber, Myriam Chévarie‐Davis, Margaret Warner, Chantal Séguin, Carole Caron, René P Michel
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Diffuse Involvement of Primary Colorectal Lymphoma Simulating Ulcerative Colitis: Ji-Ye Kim, Sun Hee Chang, Han Seong Kim, Mee Joo; J Pathol Transl Med. 2019;53(5):332-336. Published online August 2, 2019; DOI: https://doi.org/10.4132/jptm.2019.07.12

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93 Download

Abstract PDF: Diffuse involvement of colorectal lymphoma masquerading as colitis is a very rare presentation of primary colorectal lymphoma. Detecting occult lymphoma is difficult in the setting of diffuse colonic involvement with no definite mass and inflammatory mucosal changes. We encountered a case of diffuse-type primary colorectal lymphoma simulating ulcerative colitis in a previously healthy 31-year-old woman. Despite multiple mucosal biopsies, the biopsy diagnosis was not made due to unawareness of atypical lymphocytes admixed with dense lymphoplasmacytic infiltration. The present case emphasizes the importance of being aware of this rare presentation of primary colorectal lymphoma in order to avoid misdiagnosis.

Primary Peripheral Gamma Delta T-Cell Lymphoma of the Central Nervous System: Report of a Case Involving the Intramedullary Spinal Cord and Presenting with Myelopathy: Jeemin Yim, Seung Geun Song, Sehui Kim, Jae Won Choi, Kyu-Chong Lee, Jeong Mo Bae, Yoon Kyung Jeon; J Pathol Transl Med. 2019;53(1):57-61. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.08.21

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Primary central nervous system lymphoma of T-cell origin (T-PCNSL) is rare, and its clinicopathological features remain unclear. Peripheral T-cell lymphoma of γδ T-cell origin is an aggressive lymphoma mainly involving extranodal sites. Here, we report a case of γδ T-PCNSL involving the intramedullary spinal cord and presenting with paraplegia. A 75-year-old Korean woman visited the hospital complaining of back pain and lower extremity weakness. Magnetic resonance imaging revealed multifocal enhancing intramedullary nodular lesions in the thoracic and lumbar spinal cord. An enhancing nodular lesion was observed in the periventricular white matter of the lateral ventricle in the brain. There were no other abnormalities in systemic organs or skin. Laminectomy and tumor removal were performed. The tumor consisted of monomorphic, medium-to-large atypical lymphocytes with pale-to-eosinophilic cytoplasm. Immunohistochemically, the tumor cells were CD3(+), TCRβF1(-), TCRγ(+), CD30(-), CD4(-), CD8(-), CD56(+), TIA1(+), granzyme B(+), and CD103(+). Epstein-Barr virus in situ was negative. This case represents a unique T-PCNSL of γδ T-cell origin involving the spinal cord.

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Daniel Gregório Gonsalves, Paulo Eduardo Albuquerque Zito Raffa, Gabriela Gerenutti de Sousa, Melissa Esposito Gomes Rigueiral, Iracema Araújo Estevão, Cesar Cozar Pacheco, Roger Thomaz Rotta Medeiros, Paulo Roberto Franceschini, Paulo Henrique Pires de A
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Jeemin Yim, Jiwon Koh, Sehui Kim, Seung Geun Song, Jeong Mo Bae, Hongseok Yun, Ji-Youn Sung, Tae Min Kim, Sung-Hye Park, Yoon Kyung Jeon
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Original Article

Pulmonary Nodular Lymphoid Hyperplasia with Mass-Formation: Clinicopathologic Characteristics of Nine Cases and Review of the Literature: Jongmin Sim, Hyun Hee Koh, Sangjoon Choi, Jinah Chu, Tae Sung Kim, Hojoong Kim, Joungho Han; J Pathol Transl Med. 2018;52(4):211-218. Published online June 15, 2018; DOI: https://doi.org/10.4132/jptm.2018.04.27

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Abstract PDF

Background
Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features.
Methods
We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients.
Results
Two of the nine patients had experienced tuberculosis 40 and 30 years prior, respectively. Interestingly, none were current smokers, although two were ex-smokers. Three patients complaining of persistent cough underwent computed tomography of the chest. PNLH was incidentally discovered in five patients during examination for other reasons. The remaining patient was diagnosed with the disease following treatment for pneumonia. Imaging studies revealed consolidation or a mass-like lesion in eight patients. First impressions included invasive adenocarcinoma and mucosal-associated lymphoid tissue‒type lymphoma. Aspergillosis was suspected in the remaining patient based on radiological images. Resection was performed in all patients. Microscopically, the lesions consisted of nodular proliferation of reactive germinal centers accompanied by infiltration of neutrophils and macrophages in various degrees and surrounding fibrosis. Ultimately, all nine patients were diagnosed with PNLH and showed no evidence of recurrence on follow-up.
Conclusions
PNLH is an uncommon but distinct entity with a benign nature, and understanding the radiological and clinicopathological characteristics of PNLH is important.

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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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Review

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

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Abstract 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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Original Articles

A Small Case Series of Intravascular Large B-Cell Lymphoma with Unexpected Findings: Subset of Cases with Concomitant Extravascular Central Nervous System (CNS) Involvement Mimicking Primary CNS Lymphoma: Kate Poropatich, Dave Dittmann, Yi-Hua Chen, Kirtee Raparia, Kristy Wolniak, Juehua Gao; J Pathol Transl Med. 2017;51(3):284-291. Published online April 17, 2017; DOI: https://doi.org/10.4132/jptm.2017.02.16

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Abstract PDF

Background
Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal lymphoma with growth mainly in the lumina of vessels. We studied a small series of IVLBCL and focused on its central nervous system (CNS) involvement.
Methods
Searching the medical records of Northwestern Memorial Hospital, we identified five cases of IVLBCL from January 2007 to January 2015. Clinical information, hematoxylin and eosin stained histologic slides and immunohistochemistry studies were reviewed for all cases. Polymerase chain reaction (PCR) analysis for the immunoglobulin (Ig) heavy and light chain gene rearrangement was performed on all five cases.
Results
Three of the five cases of IVLBCL were autopsies. Patients’ age ranged from 56 to 84. CNS involvement was present in two cases—in both patients, the CNS involvement showed an extravascular pattern with confluent sheet-like formation. PCR analysis confirmed that in one case the systemic intravascular and CNS extravascular components were clonally identical.
Conclusions
In a small case series of IVLBCL, we observed that CNS involvement by IVLBCL often has an extravascular morphology, but is clonally identical to the intravascular counterpart by PCR analysis. As IVLBCL can have a rapidly progressing poor outcome, it should be kept in the differential diagnoses for patients presenting with lymphoma of the CNS. The presence of extravascular growth patterns in the CNS should not exclude IVLBCL as a diagnosis.

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Jun Li, Zhaojiao Li, Yifeng Shi, Jiajie Chen, Heng Zhao, Xueye Mao, Shan Li, Huiying Wang, Qiang Meng, Lingchun Liu
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GLUT1 as a Prognostic Factor for Classical Hodgkin’s Lymphoma: Correlation with PD-L1 and PD-L2 Expression: Young Wha Koh, Jae-Ho Han, Seong Yong Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh; J Pathol Transl Med. 2017;51(2):152-158. Published online February 21, 2017; DOI: https://doi.org/10.4132/jptm.2016.11.03

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Abstract PDF

Background
Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin’s lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL. Methods: Diagnostic tissues from 125 patients with cHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine were evaluated retrospectively via immunohistochemical analysis of GLUT1, PD-L1, PD-L2, and PD-1 expression. Results: The median follow-up time was 4.83 years (range, 0.08 to 17.33 years). GLUT1, PD-L1, PD-L2, and PD-1 were expressed in 44.8%, 63.2%, 9.6%, and 13.6% of the specimens, respectively. Positive correlations were found between GLUT1 and PD-L1 expression (p = .004) and between GLUT1 and PD-L2 expression (p = .031). GLUT1 expression in Hodgkin/Reed-Sternberg (HRS) cells was not associated with overall survival or event-free survival (EFS) in the entire cohort (p = .299 and p = .143, respectively). A subgroup analysis according to the Ann Arbor stage illustrated that GLUT1 expression in HRS cells was associated with better EFS in advanced-stage disease (p = .029). A multivariate analysis identified GLUT1 as a marginally significant prognostic factor for EFS (p = .068). Conclusions: This study suggests that GLUT1 expression is associated with better clinical outcomes in advanced-stage cHL and is significantly associated with PD-L1 and PD-L2 expressions.

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Long Non-coding RNA HOTAIR Expression in Diffuse Large B-Cell Lymphoma: In Relation to Polycomb Repressive Complex Pathway Proteins and H3K27 Trimethylation: Eun Ji Oh, Soo Hee Kim, Woo Ick Yang, Young Hyeh Ko, Sun Och Yoon; J Pathol Transl Med. 2016;50(5):369-376. Published online August 22, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.06

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Abstract PDF

Background
A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs).
Methods
The expression status of PRC2 (EZH2, SUZ12, and EED), H3K27me3, c-MYC, and BCL2 was analyzed using immunohistochemistry (n = 231), and HOTAIR was investigated by a quantification real-time polymerase chain reaction method (n = 164) in DLBCLs.
Results
The present study confirmed the positive correlation among PRC2 proteins, H3K27me3, and c-MYC in DLBCLs. Expression level of HOTAIR was also positively correlated to EZH2 (p < .05, respectively). Between c-MYC and HOTAIR, and between c- MYC/BCL2 co-expression and HOTAIR, however, negative correlation was observed in DLBCLs (p < .05, respectively). High level of H3K27me3 was determined as an independent prognostic marker in poor overall survival (hazard ratio, 2.0; p = .023) of DLBCL patients. High expression of HOTAIR, however, was associated with favorable overall survival (p = .004) in the univariate analysis, but the impact was not significant in the multivariate analysis. The favorable outcome of DLBCL with HOTAIR high expression levels may be related to the negative correlation with c- MYC expression or c-MYC/BCL2 co-expression.
Conclusions
HOTAIR expression could be one of possible mechanisms for inducing H3K27me3 via EZH2-related PRC2 activation, and induced H3K27me3 may be strongly related to aggressive DLBCLs which show poor patient outcome.

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Biomedical impact of the expression of HOX locus-associated LncRNAs HOTAIR and HOTTIP in diffuse large B cell lymphoma
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Mechanism of LncHOTAIR Regulating Proliferation, Apoptosis, and Autophagy of Lymphoma Cells through hsa-miR-6511b-5p/ATG7 Axis
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Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases: Taebum Lee, Boram Lee, Yoon-La Choi, Joungho Han, Myung-Ju Ahn, Sang-Won Um; J Pathol Transl Med. 2016;50(3):197-203. Published online April 18, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.09

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Abstract PDF

Background
Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy.
Methods
In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features.
Results
All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had ALK mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation.
Conclusions
EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

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Upregulated Neuro-oncological Ventral Antigen 1 (NOVA1) Expression Is Specific to Mature and Immature T- and NK-Cell Lymphomas: Eun Kyung Kim, Sun Och Yoon, Soo Hee Kim, Woo Ick Yang, Yoon Ah Cho, Soo Jeong Kim; J Pathol Transl Med. 2016;50(2):104-112. Published online February 29, 2016; DOI: https://doi.org/10.4132/jptm.2016.02.08

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Background
Recent studies have revealed that the splicing factor neuro-oncological ventral antigen 1 (NOVA1) is enriched in fibroblasts and accumulated T cells of tertiary lymphoid structures. In the present study, we investigated NOVA1 expression in various subtypes of mature and immature T- and natural killer (NK)-cell lymphomas as well as in various B-cell lymphoma subtypes. Methods: NOVA1 immunoexpression was evaluated in hyperplastic palatine tonsils (n = 20), T- and NK-cell lymphomas (n = 177), diffuse large B-cell lymphomas (n = 151), and other types of B cell lymphomas (n = 31). Nuclear staining intensity and percentage of positive tumor cells were graded. NOVA1 mRNA expression was analyzed in various lymphoma cell lines. Results: Tumor cells of T- and NK-cell lymphomas showed higher expression levels of NOVA1 than did normal paracortical T cells, and 56.5% of T- and NK-cell lymphoma cases showed diffuse and strong expression. The NOVA1 expression level varied according to the subtype; it was higher in angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), and T lymphoblastic leukemia/lymphoma (T-LBL), but it was lower in ALK-positive ALCL. In almost all B-cell lymphomas, NOVA1 expression was very low or negative. NOVA1 mRNA was also expressed in Jurkat, a T-LBL cell line. Conclusions: The present findings suggest that NOVA1 upregulation may be involved in certain subtypes of T- and NK-cell lymphomas, but not in B-cell lymphomas. Upregulated NOVA1 expression seems to be a specific biological feature of activated T cells such as T- and NK-cell lymphomas.

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Intraoperative pathologic diagnosis of central nervous system lymphomas: A comparison of frozen and permanent section diagnoses, and the significance of preoperative imaging
Aslı Kahraman, Fikret Dirilenoğlu, İsmail Güzeliş, Kenan Çetinoğlu
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NOVA1 acts on Impact to regulate hypothalamic function and translation in inhibitory neurons
Yoko Tajima, Keiichi Ito, Yuan Yuan, Mayu O. Frank, Yuhki Saito, Robert B. Darnell
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MicroRNA miR-27a-3p accelerates cardiac hypertrophy by targeting neuro-oncological ventral antigen 1
Dongyun Li, Mingzhi Shen, Xinxin Deng, Yongyi Bai
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NOVA1 promotes NSCLC proliferation and invasion by activating Wnt/β-catenin signaling
Lianyue Qu, Yulong Tian, Fan Wang, Zixuan Li
BMC Cancer.2022;[Epub] CrossRef
Identification of the Functions and Prognostic Values of RNA Binding Proteins in Bladder Cancer
Yue Wu, Zheng Liu, Xian Wei, Huan Feng, Bintao Hu, Bo Liu, Yang Luan, Yajun Ruan, Xiaming Liu, Zhuo Liu, Shaogang Wang, Jihong Liu, Tao Wang
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Nervous system and gastric cancer
Ke Wang, Xin-hui Zhao, Jun Liu, Rui Zhang, Ji-peng Li
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The RNA-binding protein RBM47 inhibits non-small cell lung carcinoma metastasis through modulation of AXIN1 mRNA stability and Wnt/β-catentin signaling
Di-jian Shen, You-hua Jiang, Jian-qiang Li, Li-wei Xu, Kai-yi Tao
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Genome-Wide Profiling of Cervical RNA-Binding Proteins Identifies Human Papillomavirus Regulation of RNASEH2A Expression by Viral E7 and E2F1
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NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma
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The RNA binding protein neuro‐oncological ventral antigen 1 (NOVA1) regulates IL-6 mRNA stability to enhance JAK2-STAT3 signaling in CRC
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NOVA1 acts as an oncogene in melanoma via regulating FOXO3a expression
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Prognostic Implication of Semi-quantitative Immunohistochemical Assessment of CD20 Expression in Diffuse Large B-Cell Lymphoma: Chang Hwan Choi, Young Hoon Park, Joo Han Lim, Suk Jin Choi, Lucia Kim, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu; J Pathol Transl Med. 2016;50(2):96-103. Published online February 15, 2016; DOI: https://doi.org/10.4132/jptm.2016.01.12

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Background
Immunohistochemical demonstration of CD20 in diffuse large B-cell lymphoma (DLBCL) is prerequisite not only for the diagnosis but also for assigning patients to rituximab-containing chemotherapy. However, little is known about the impact of abundance of CD20 expression assessed by immunohistochemistry on the clinical outcome of DLBCL. We performed a semi-quantitative immunohistochemical analysis of CD20 expression in DLBCL to examine the prognostic implication of the level of CD20 expression. Methods: Pre-treatment diagnostic tissue samples from 48 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen were represented in a tissue microarray and immunostained for CD20. The relative abundance of CD20 expression was semi-quantitatively scored using a web-based ImmunoMembrane plug-in. Receiver operating characteristic curve analysis was used to determine a prognostically relevant cut-off score in order to dichotomize the patients into CD20-high versus CD20-low groups. Results: The levels of CD20 expression were heterogeneous among the patients, with a wide and linear distribution of scores. Patients in CD20-low group showed significantly poor clinical outcome. Conclusions: The levels of CD20 expression in DLBCL are heterogeneous among the patients with DLBCL. A subgroup of the patients with CD20 expression levels below the cut-off score showed poor clinical outcome.

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Kravee Chaipoca, Theerapol Sirinarumitr, Supreeya Srisampan, Charuwan Wongsali, Attawit Kovitvadhi, Tassanee Jaroensong
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Prognostic molecular biomarkers in diffuse large B-cell lymphoma in the rituximab era and their therapeutic implications
Sotirios G. Papageorgiou, Thomas P. Thomopoulos, Ioannis Katagas, Anthi Bouchla, Vassiliki Pappa
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Novel tumour–infiltrating lymphocyte-related risk stratification based by flow cytometry for patients with de novo angioimmunoblastic T cell lymphoma
Qiqi Zhu, Xueqin Deng, Wenqing Yao, Zihang Chen, Yunxia Ye, Limin Gao, Wenyan Zhang, Weiping Liu, Sha Zhao
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Induced CD20 Expression on B-Cell Malignant Cells Heightened the Cytotoxic Activity of Chimeric Antigen Receptor Engineered T Cells
Yingxi Xu, Saisai Li, Ying Wang, Jia Liu, Xinhe Mao, Haiyan Xing, Zheng Tian, Kejing Tang, Xiaolong Liao, Qing Rao, Dongsheng Xiong, Min Wang, Jianxiang Wang
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Characterization of head and neck squamous cell carcinoma arising in young patients: Particular focus on molecular alteration and tumor immunity
Hyang Joo Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
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Immunoglobulin D (IgD) and IgD receptor expression in diffuse large B-cell lymphoma
Xing Dai, Yu-Jing Wu, Xiao-Yi Jia, Yan Chang, Hua-Xun Wu, Chun Wang, Wei Wei
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Hyang Joo Ryu, Yoon Woo Koh, Sun Och Yoon
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Implications of infiltrating immune cells within bone marrow of patients with diffuse large B-cell lymphoma
Juhyeon Jeong, Eun Ji Oh, Woo Ick Yang, Soo Jeong Kim, Sun Och Yoon
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Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma
Hyang Joo Ryu, Eun Kyung Kim, Su Jin Heo, Byoung Chul Cho, Hye Ryun Kim, Sun Och Yoon
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New developments in the pathology of malignant lymphoma. A review of the literature published from January–April 2016
J. Han van Krieken
Journal of Hematopathology.2016; 9(2): 73. CrossRef
Diffuse large B-cell lymphoma: R-CHOP failure—what to do?
Bertrand Coiffier, Clémentine Sarkozy
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Analysis of Histologic Features Suspecting Anaplastic Lymphoma Kinase (ALK)-Expressing Pulmonary Adenocarcinoma: In Ho Choi, Dong Won Kim, Sang Yun Ha, Yoon-La Choi, Hee Jeong Lee, Joungho Han; J Pathol Transl Med. 2015;49(4):310-317. Published online June 22, 2015; DOI: https://doi.org/10.4132/jptm.2015.05.13

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Background
Since 2007 when anaplastic lymphoma kinase (ALK) rearrangements were discovered in non-small cell lung cancer, the ALK gene has received attention due to ALK-targeted therapy, and a notable treatment advantage has been observed in patients harboring the EML4/ALK translocation. However, using ALK-fluorescence in situ hybridization (FISH) as the standard method has demerits such as high cost, a time-consuming process, dependency on interpretation skill, and tissue preparation. We analyzed the histologic findings which could complement the limitation of ALK-FISH test for pulmonary adenocarcinoma. Methods: Two hundred five cases of ALK-positive and 101 of ALK-negative pulmonary adenocarcinoma from January 2007 to May 2013 were enrolled in this study. The histologic findings and ALK immunohistochemistry results were reviewed and compared with the results of ALK-FISH and EGFR/KRAS mutation status. Results: Acinar, cribriform, and solid growth patterns, extracellular and intracellular mucin production, and presence of signet-ring-cell element, and psammoma body were significantly more often present in ALK-positive cancer. In addition, the presence of goblet cell-like cells and presence of nuclear inclusion and groove resembling papillary thyroid carcinoma were common in the ALK-positive group. Conclusions: The above histologic parameters can be helpful in predicting ALK rearranged pulmonary adenocarcinoma, leading to rapid FISH analysis and timely treatment.

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Case Study

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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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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Original Article

Smad1 Expression in Follicular Lymphoma: Jai Hyang Go; J Pathol Transl Med. 2015;49(3):243-248. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.03.30

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Abstract PDF: Background
Follicular lymphomas present with various immunohistologic patterns. The immunohistochemical markers used in the diagnosis of follicular lymphoma show variable degrees of sensitivity and specificity, and thus, additional germinal center markers are required. Smad1 has been reported to be overexpressed in follicular lymphoma, but little is known regarding the expression patterns of Smad proteins in human lymphoid tissue. Methods: In the present study, we performed immunohistochemistry for traditional germinal center markers and for Smad1 in human reactive lymphoid and follicular lymphoma tissues to investigate Smad1’s usefulness in the diagnosis of follicular lymphoma. Results: In the reactive germinal centers, most cells were positive for Smad1. Among the 27 follicular lymphoma cases, 17 of 21 (80%) were Smad1 positive, 17 of 27 (63%) were positive for CD10, and 23 of 27 (85%) were positive for Bcl6. Notably, three cases expressed CD10 only, and one only expressed Bcl6. All these cases were grade 3 tumors and showed follicular and diffuse growth patterns. Conclusions: These results indicate that Smad1 is a candidate as a germinal center marker. Furthermore, they suggest that the Smad signaling pathway might be involved in follicular lymphoma.

Review

Current Concepts in Primary Effusion Lymphoma and Other Effusion-Based Lymphomas: Yoonjung Kim, Chan Jeong Park, Jin Roh, Jooryung Huh; Korean J Pathol. 2014;48(2):81-90. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.81

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Abstract PDF

Primary effusion lymphoma (PEL) is a human herpes virus 8 (HHV8)-positive large B-cell neoplasm that presents as an effusion with no detectable tumor in individuals with human immunodeficiency virus infection or other immune deficiencies. PEL is an aggressive neoplasm with a poor prognosis. PEL cells show diverse morphologies, ranging from immunoblastic or plasmablastic to anaplastic. The immunophenotype of PEL is distinct, but its lineage can be misdiagnosed if not assessed thoroughly. PEL cells usually express CD45, lack B- and T-cell-associated antigens, and characteristically express lymphocyte activation antigens and plasma cell-associated antigens. Diagnosis of PEL often requires the demonstration of a B-cell genotype. HHV8 must be detected in cells to diagnose PEL. In most cases, PEL cells also harbor the Epstein-Barr virus (EBV) genome. Similar conditions associated with HHV8 but not effusion-based are called "extracavitary PELs." PELs should be differentiated from HHV8-negative, EBV-positive, body cavity-based lymphomas in patients with long-standing chronic inflammation; the latter can occur in tuberculous pleuritis, artificial pneumothorax, chronic liver disease and various other conditions. Despite their morphological similarity, these various lymphomas require different therapeutic strategies and have different prognostic implications. Correct diagnosis is essential to manage and predict the outcome of patients with PEL and related disorders.

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Original Article

Characteristics of Cutaneous Lymphomas in Korea According to the New WHO-EORTC Classification: Report of a Nationwide Study: Jae Ho Han, Young-Hyeh Ko, Yun Kyung Kang, Wan-Seop Kim, Yoon Jung Kim, Insun Kim, Hyun-Jung Kim, Soo Kee Min, Chan-Kum Park, Chan-Sik Park, Bong-Kyung Shin, Woo Ick Yang, Young-Ha Oh, Jong Sil Lee, Juhie Lee, Tae Hui Lee, Hyekyung Lee, Ho Jung Lee, Yoon Kyung Jeon, Hee Jeong Cha, Yoo-Duk Choi, Chul Woo Kim; Korean J Pathol. 2014;48(2):126-132. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.126

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Abstract PDF

Background

Previously, cutaneous lymphomas were classified according to either the European Organization for the Research and Treatment of Cancer (EORTC) or the World Health Organization (WHO) classification paradigms. The aim of this study was to determine the relative frequency of Korean cutaneous lymphoma according to the new WHO-EORTC classification system.

Methods

A total of 517 patients were recruited during a recent 5 year-period (2006-2010) from 21 institutes and classified according to the WHO-EORTC criteria.

Results

The patients included 298 males and 219 females, and the mean age at diagnosis was 49 years. The lesions preferentially affected the trunk area (40.2%). The most frequent subtypes in order of decreasing prevalence were mycosis fungoides (22.2%), peripheral T-cell lymphoma (17.2%), CD30+ T-cell lymphoproliferative disorder (13.7%), and extranodal natural killer/T (NK/T) cell lymphoma, nasal type (12.0%). Diffuse large B-cell lymphoma accounted for 11.2% of cases, half of which were secondary cutaneous involvement; other types of B-cell lymphoma accounted for less than 1% of cases.

Conclusions

In comparison with data from Western countries, this study revealed relatively lower rates of mycosis fungoides and B-cell lymphoma in Korean patients, as well as higher rates of subcutaneous panniculitis-like T-cell lymphoma and NK/T cell lymphoma.

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Review

Guideline Recommendations for Testing of ALK Gene Rearrangement in Lung Cancer: A Proposal of the Korean Cardiopulmonary Pathology Study Group: Hyojin Kim, Hyo Sup Shim, Lucia Kim, Tae-Jung Kim, Kun Young Kwon, Geon Kook Lee, Jin-Haeng Chung; Korean J Pathol. 2014;48(1):1-9. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.1

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Abstract PDF

Rearrangement of anaplastic lymphoma kinase (ALK) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor. However, the prevalence of the ALK fusion is low, so accurate patient identification is crucial for successful treatment using ALK inhibitors. Furthermore, most patients with lung cancer present with advanced-stage disease at the time of diagnosis, so it is important for pathologists to detect ALK-rearranged patients while effectively maximizing small biopsy or cytology specimens. In this review, we propose a guideline recommendation for ALK testing approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

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Case Study

Diffuse Large B-Cell Lymphoma Arising in Warthin's Tumor: Case Study and Review of the Literature: Güliz Özkök, Funda Taşlı, Nazan Özsan, Rafet Öztürk, Hakan Postacı; Korean J Pathol. 2013;47(6):579-582. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.579

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Abstract PDF

Warthin's tumor is the second most common type of salivary gland tumor. Microscopically, Warthin's tumor displays a proliferative epithelial component and lymphoid stroma. Carcinomas arising from the epithelial component are well known, but malignant transformations of the lymphoid stroma are rare. When they do occur, they are most commonly B-cell type non-Hodgkin lymphomas. A 60-year-old male patient underwent surgical resection of a parotid mass. After superficial parotidectomy, microscopic examination indicated that the tumor was of epithelial components with basaloid and oncocytic columns of cells neighboring lymphoid components. In addition to the lymphoid follicles with distinct germinal centers, there were large, bizarre and extremely atypical neoplastic cells seen in the lymphoid component. Large neoplastic cells were diffusely CD20 and CD30 positive. The patient was diagnosed with "Warthin's tumor and diffuse large B-cell lymphoma with expression of CD30." The histopathologic and clinical features are discussed along with a review of the literature.

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Original Articles

Diagnostic Utility of a Clonality Test for Lymphoproliferative Diseases in Koreans Using the BIOMED-2 PCR Assay: Young Kim, Yoo Duk Choi, Chan Choi, Jong-Hee Nam; Korean J Pathol. 2013;47(5):458-465. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.458

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Abstract PDF

Background

A clonality test for immunoglobulin (IG) and T cell receptor (TCR) is a useful adjunctive method for the diagnosis of lymphoproliferative diseases (LPDs). Recently, the BIOMED-2 multiplex polymerase chain reaction (PCR) assay has been established as a standard method for assessing the clonality of LPDs. We tested clonality in LPDs in Koreans using the BIOMED-2 multiplex PCR and compared the results with those obtained in European, Taiwanese, and Thai participants. We also evaluated the usefulness of the test as an ancillary method for diagnosing LPDs.

Methods

Two hundred and nineteen specimens embedded in paraffin, including 78 B cell lymphomas, 80 T cell lymphomas and 61 cases of reactive lymphadenitis, were used for the clonality test.

Results

Mature B cell malignancies showed 95.7% clonality for IG, 2.9% co-existing clonality, and 4.3% polyclonality. Mature T cell malignancies exhibited 83.8% clonality for TCR, 8.1% co-existing clonality, and 16.2% polyclonality. Reactive lymphadenitis showed 93.4% polyclonality for IG and TCR. The majority of our results were similar to those obtained in Europeans. However, the clonality for IGK of B cell malignancies and TCRG of T cell malignancies was lower in Koreans than Europeans.

Conclusions

The BIOMED-2 multiplex PCR assay was a useful adjunctive method for diagnosing LPDs.

Citations

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Enhancing diagnosis of T-cell lymphoma using non-recombined T-cell receptor sequences
Yi-Lin Chen, Chung-Liang Ho, Chen-Yan Hung, Wan-Li Chen, Chen Chang, Yi-Hsin Hou, Jian-Rong Chen, Pin-Jun Chen, Nan-Haw Chow, Wenya Huang, Ya-Ting Hsu, Tsai-Yun Chen, Tsunglin Liu
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Combined detection of lymphocyte clonality and MALT1 translocations in bronchoalveolar lavage fluid for diagnosing pulmonary lymphomas
Takashi Kido, Hiroshi Ishimoto, Hiroshi Ishii, Kanako Hara, Mutsumi Ozasa, Hiroki Kawabata, Toshinori Kawanami, Yu Suzuki, Hiroki Yoshikawa, Atsuko Hara, Noriho Sakamoto, Nobuhiro Matsumoto, Chiharu Yoshii, Junya Fukuoka, Masaki Fujita, Masamitsu Nakazato
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Cytologic Features of ALK-Positive Pulmonary Adenocarcinoma: Seung Yeon Ha, Jungsuk Ahn, Mee Sook Roh, Joungho Han, Jae Jun Lee, Boin Lee, Jun Yim; Korean J Pathol. 2013;47(3):252-257. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.252

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Abstract PDF

Background

The aim of this study was to determine the cytologic features of anaplastic lymphoma kinase (ALK) expressing pulmonary adenocarcinoma.

Methods

We analyzed the cytopathological findings of 15 cases of endobronchial ultrasound guided aspiration and a case of bronchial washing. These cases were selected based on the histomorphology of ALK-rearranged lung adenocarcinoma.

Results

Cytology showed mucinous (81.3%) and hemorrhagic (50%) backgrounds. The cells were arranged in tubulopapillary or tubulocribriform patterns (93.8%), and clusters (56.3%) admixed with signet ring cell features (87.5%). The tumor cells were monotonous and uniform with vesicular nuclei and a small nucleolus.

Conclusions

The characteristic findings were sheets showing a tubulopapillary or tubulocribriform appearance, with vesicular nuclei and a bland chromatin pattern (p<0.001). Scattered signet ring cells were helpful in suggesting ALK-positive adenocarcinoma (p<0.001).

Citations

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Cytomorphological and histomorphological features of lung adenocarcinoma with epidermal growth factor receptor mutation and anaplastic lymphoma kinase gene rearrangement
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Yoon Jin Cha, Joungho Han, Soo Hyun Hwang, Tae Bum Lee, Hojoong Kim, Jea Ill Zo
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Dae Hyun Song, Boram Lee, Yooju Shin, In Ho Choi, Sang Yun Ha, Jae Jun Lee, Min Eui Hong, Yoon‐La Choi, Joungho Han, Sang‐Won Um
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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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Case Report

Cervical Lymphadenopathy Mimicking Angioimmunoblastic T-Cell Lymphoma after Dapsone-Induced Hypersensitivity Syndrome: Min Young Rim, Junshik Hong, Inku Yo, Hyeonsu Park, Dong Hae Chung, Jeong Yeal Ahn, Sanghui Park, Jinny Park, Yun Soo Kim, Jae Hoon Lee; Korean J Pathol. 2012;46(6):606-610. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.606

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Abstract PDF

A 36-year-old woman presented with erythematous confluent macules on her whole body with fever and chills associated with jaundice after 8 months of dapsone therapy. Her symptoms had developed progressively, and a physical examination revealed bilateral cervical lymphadenopathy and splenomegaly. Excisional biopsy of a cervical lymph node showed effacement of the normal architecture with atypical lymphoid hyperplasia and proliferation of high endothelial venules compatible with angioimmunoblastic T-cell lymphoma. However, it was assumed that the cervical lymphadenopathy was a clinical manifestation of a systemic hypersensitivity reaction because her clinical course was reminiscent of dapsone-induced hypersensitivity syndrome. A liver biopsy revealed drug-induced hepatitis with no evidence of lymphomatous involvement. Intravenous glucocorticoid was immediately initiated and her symptoms and clinical disease dramatically improved. The authors present an unusual case of cervical lymphadenopathy mimicking angioimmunoblastic T-cell lymphoma as an adverse reaction to dapsone.

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Original Article

Expression of HAT1 and HDAC1, 2, 3 in Diffuse Large B-Cell Lymphomas, Peripheral T-Cell Lymphomas, and NK/T-Cell Lymphomas: Soo Kee Min, Young Ho Koh, Yunwoong Park, Hyo Jung Kim, Jinwon Seo, Hye-Rim Park, Seong Jin Cho, In Sun Kim; Korean J Pathol. 2012;46(2):142-150. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.142

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Abstract PDF

Background

It has generally been proven that histone acetylation and deacetylation are involved in the malignant transformation. To date, however, this has rarely been studied in cases of malignant lymphoma.

Methods

We studied nine cases of reactive lymphoid hyperplasia, 78 cases of diffuse large B-cell lymphoma (DLBCL), 13 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and 13 cases of extranodal NK/T-cell lymphoma, nasal type (NKTCL). Thus, we attempted to elucidate the associations of the degree of the expression of histone acetyltransferase 1 (HAT1), histone deacetylase (HDAC) 1, HDAC2, and HDAC3 with the clinical behaviors of above malignant lymphomas using the immunohistochemistry and a western blot analysis.

Results

The degree of the expression of HAT1 was higher in cases of DLBCL, PTCL-NOS or NKTCL as compared with reactive lymphoid hyperplasia (p<0.05). The degree of the expression of HAT1 was correlated with that of HDAC1 in cases of DLBCL or NKTCL (p<0.05). The degree of the expression of HAT1 and HDAC1 was correlated with a poor survival in cases of DLBCL or PTCL-NOS (p>0.05).

Conclusions

HAT1, HDAC1, and HDAC2 play a critical role in the development of malignant lymphomas. Both HAT1 and HDAC1 might be indicators for a poor prognosis in cases of DLBCL as cooperating factors.

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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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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
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Prognostic implications of CD30 expression in extranodal natural killer/T-cell lymphoma according to treatment modalities
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
YAN-JIA YANG, YA-XIN LI, YAN-BIN LIU, MEI YANG, KAI LIU
Oncology Letters.2014; 7(5): 1419. CrossRef

In Situ Follicular Lymphoma Developed after Hodgkin Lymphoma.: Ho Sung Park, Sang Jae Noh, Jae Yong Kwak, Eun Kee Song, Myung Hee Sohn, Ho Lee, Woo Sung Moon, Kyu Yun Jang; Korean J Pathol. 2011;45:S53-S57.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S53

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Abstract PDF: In situ follicular lymphoma is a newly defined entity among the lymphoid neoplasms and is defined as architecturally normal-appearing lymph nodes and other lymphoid tissues that have one or more follicles that demonstrate bcl-2 overexpressing centrocytes and centroblasts, with or without a monomorphic cytologic appearance suggestive of follicular lymphoma. Here we present a case of in situ follicular lymphoma diagnosed during the follow-up after a complete response to the treatment of lymphocyte-rich classical Hodgkin's lymphoma. In our case, because only a few germinal centers contained bcl-2 overexpressing cells, we missed the diagnosis of in situ follicular lymphoma in the initial histological examination. We could establish the diagnosis only after performing bcl-2 immunostaining in the sequential biopsy. Therefore, we recommend that careful histological examination along with bcl-2 immunostaining is needed in patients with suspicious clinical findings.

Original Articles

CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas.: Kyueng Whan Min, Young Ha Oh, Chan Kum Park, So Dug Lim, Wan Seop Kim; Korean J Pathol. 2011;45(6):589-595.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.589

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Abstract PDF: BACKGROUND
CD44 protein is known as a homing cellular adhesion molecule that is linked to diverse cellular functions such as adhesion, migration and invasion, which are all important in cancer progression and metastasis. The expression of CD44 standard and variant isoforms (CD44 standard isoform [CD44s] and CD44 splice variants containing exon v6 [CD44v6], respectively) is associated with an unfavorable clinical outcome in various neoplasms.
METHODS
Forty patients who were diagnosed with diffuse large B-cell lymphoma (DLBCL) through biopsy at Hanyang University Hospital between 1996 and 2003 were included in this study. CD44 proteins expression was analyzed by immunohistochemical staining on a tissue microarray and the correlation of CD44 with the types of DLBCL and clinical parameters, including the factors defined by the International Prognostic Index, was evaluated.
RESULTS
A high CD44s and intermediate to strong CD44v6 expression, including cytoplasmic membranous staining patterns, was present in 35% (14/40) and 25% (10/40) of DLBCL patients, respectively. High CD44s expression was correlated significantly with non-germinal center B-cell-like types (non-GCB, p=0.004) and patients with old age (p=0.041).
CONCLUSIONS
High CD44s expression may be significantly associated with the non-GCB type compared to the GCB type and may be essential to the prediction of disease outcome in tumor stage III in DLBCL patients.

Prognostic Implication of Programmed Death-1-Positive Tumor-infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma.: Young Sin Ko, Young Ha Oh, Chan Kum Park, Wook Youn Kim, Hye Seung Han, So Dug Lim, Tae Sook Hwang, Wan Seop Kim; Korean J Pathol. 2011;45(6):573-581.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.573

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Abstract PDF

BACKGROUND
Programmed death-1 (PD-1) is physiologically expressed by germinal center-associated helper T-cells and has an inhibitory effect on T-cell activity.
METHODS
We examined 63 cases of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal antibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400x).
RESULTS
Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (< or =20/HPF, n=30). The former group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score.
CONCLUSIONS
The high number of PD-1-positive cells might be associated with an unfavorable outcome in DLBCL patients.

Citations

Citations to this article as recorded by

Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: a summary of immunohistochemical studies
Pauline Gravelle, Barbara Burroni, Sarah Péricart, Cédric Rossi, Christine Bezombes, Marie Tosolini, Diane Damotte, Pierre Brousset, Jean-Jacques Fournié, Camille Laurent
Oncotarget.2017; 8(27): 44960. CrossRef
Expression of programmed cell death ligand 1 (PD-L1) in advanced stage EBV-associated extranodal NK/T cell lymphoma is associated with better prognosis
Wook Youn Kim, Ho Young Jung, Soo Jeong Nam, Tae Min Kim, Dae Seog Heo, Chul-Woo Kim, Yoon Kyung Jeon
Virchows Archiv.2016; 469(5): 581. CrossRef

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