Journal of Pathology and Translational Medicine

Original Articles

Diagnostic yield of fine needle aspiration with simultaneous core needle biopsy for thyroid nodules: Mohammad Ali Hasannia, Ramin Pourghorban, Hoda Asefi, Amir Aria, Elham Nazar, Hojat Ebrahiminik, Alireza Mohamadian; J Pathol Transl Med. 2025;59(3):180-187. Published online April 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.03.04

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Abstract PDF: Background
Fine needle aspiration (FNA) is a widely utilized technique for assessing thyroid nodules; however, its inherent non-diagnostic rate poses diagnostic challenges. The present study aimed to evaluate and compare the diagnostic efficacy of FNA, core needle biopsy (CNB), and their combined application in the assessment of thyroid nodules.
Methods
A total of 56 nodules from 50 patients was analyzed using both FNA and simultaneous CNB. The ultrasound characteristics were categorized according to the American College of Radiology Thyroid Imaging Reporting and Data Systems classification system. The study compared the sensitivity, specificity, and accuracy of FNA, CNB, and the combination of the two techniques.
Results
The concordance between FNA and CNB was notably high, with a kappa coefficient of 0.837. The sensitivity for detecting thyroid malignancy was found to be 25.0% for FNA, 66.7% for CNB, and 83.3% for the combined FNA/CNB approach, with corresponding specificities of 84.6%, 97.4%, and 97.4%. The accuracy of the FNA/CNB combination was the highest at 94.1%.
Conclusions
The findings of this study indicate that both CNB and the FNA/CNB combination offer greater diagnostic accuracy for thyroid malignancy compared to FNA alone, with no significant complications reported. Integrating CNB with FNA findings may enhance management strategies and treatment outcomes for patients with thyroid nodules.

Educational exchange in thyroid core needle biopsy diagnosis: enhancing pathological interpretation through guideline integration and peer learning: Agnes Stephanie Harahap, Chan Kwon Jung; J Pathol Transl Med. 2024;58(5):205-213. Published online July 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.06.24

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Background
While fine needle aspiration cytology (FNAC) plays an essential role in the screening of thyroid nodules, core needle biopsy (CNB) acts as an alternative method to address FNAC limitations. However, diagnosing thyroid CNB samples can be challenging due to variations in background and levels of experience. Effective training is indispensable to mitigate this challenge. We aim to evaluate the impact of an educational program on improving the accuracy of CNB diagnostics.
Methods
The 2-week observational program included a host mentor pathologist with extensive experience and a visiting pathologist. The CNB classification by The Practice Guidelines Committee of the Korean Thyroid Association was used for the report. Two rounds of reviewing the case were carried out, and the level of agreement between the reviewers was analyzed.
Results
The first-round assessment showed a concordance between two pathologists for 247 thyroid CNB specimens by 84.2%, with a kappa coefficient of 0.74 (indicating substantial agreement). This finding was attributed to the discordance in the use of categories III and V. After peer learning, the two pathologists evaluated 30 new cases, which showed an overall improvement in the level of agreement. The percentage of agreement between pathologists on thyroid CNB diagnosis was 86.7%, as measured by kappa coefficient of 0.80.
Conclusions
This educational program, consisting of guided mentorship and peer learning, can substantially enhance the diagnostic accuracy of thyroid CNB. It is useful in promoting consistent diagnostic standards and contributes to the ongoing development of global pathology practices.

Citations

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Lessons learned from the first 2 years of experience with thyroid core needle biopsy at an Indonesian national referral hospital
Agnes Stephanie Harahap, Maria Francisca Ham, Retno Asti Werdhani, Erwin Danil Julian, Rafi Ilmansyah, Chloe Indira Arfelita Mangunkusumso, Tri Juli Edi Tarigan
Journal of Pathology and Translational Medicine.2025; 59(3): 149. CrossRef

Case Studies

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.

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 Article

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.

Citations

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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
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 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.

Citations

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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

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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Abstract PDF

Background
The aim of the present study was to evaluate the prognostic significance of B-cell lymphocyte kinase (BLK) expression for survival outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP.
Methods
We retrospectively analyzed the medical records of 89 patients from two tertiary referral hospitals. The expression of BLK, SYK, and CDK1 were evaluated in a semiquantitative method using an H-score, and the proportions of BCL2 and C-MYC were evaluated.
Results
A total of 89 patients received R-CHOP chemotherapy as a first-line chemotherapy. The expression rates of BLK in tumor cells was 39.2% (n = 34). BLK expression status was not significantly associated with clinical variables; however, BLK expression in tumor cells was significantly associated with the expression of both C-MYC and BCL2 (p = .003). With a median follow-up of 60.4 months, patients with BLK expression had significantly lower 5-year progression-free survival (PFS) and overall survival rates (49.8% and 60.9%, respectively) than patients without BLK expression (77.3% and 86.7%, respectively). In multivariate analysis for PFS, BLK positivity was an independent poor prognostic factor (hazard ratio, 2.208; p = .040).
Conclusions
Here, we describe the clinicopathological features and survival outcome according to expression of BLK in DLBCL. Approximately 39% of DLBCL patients showed BLK positivity, which was associated as a predictive marker for poor prognosis in patients who received R-CHOP chemotherapy.

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

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.

Citations

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Chimeric and mutant CARD9 constructs enable analyses of conserved and diverged autoinhibition mechanisms in the CARD‐CC protein family
Jens Staal, Yasmine Driege, Femke Van Gaever, Jill Steels, Rudi Beyaert
The FEBS Journal.2024; 291(6): 1220. CrossRef
PD-L1+diffuse large B-cell lymphoma with extremely high mutational burden and microsatellite instability due to acquiredPMS2mutation
Andrew W. Allbee, James Gerson, Guang Yang, Adam Bagg
Molecular Case Studies.2023; 9(4): a006318. CrossRef

Original Article

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.

Case Studies

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.

Citations

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Intravascular large B-cell lymphoma of the central nervous system with renal involvement: a case report and literature review
Jun Li, Zhaojiao Li, Yifeng Shi, Jiajie Chen, Heng Zhao, Xueye Mao, Shan Li, Huiying Wang, Qiang Meng, Lingchun Liu
Frontiers in Oncology.2025;[Epub] CrossRef
EBV-Positive Intravascular Large B-Cell Lymphoma of the Small Intestine: A Case Report and Literature Review
Chenglong Pan, Xiaoling Ma, Yanfei Yao, Chunyan Wang
International Journal of Surgical Pathology.2024; 32(3): 586. CrossRef
Intravascular large B‐cell lymphoma in renal cell carcinoma incidentally detected by robot‐assisted partial nephrectomy
Michio Noda, Yutaka Enomoto, Yukari Shirasugi, Sumiyo Ando, Yukimasa Matsuzawa, Haruki Kume
IJU Case Reports.2022; 5(3): 191. CrossRef
Case Report: Intravascular Large B-Cell Lymphoma: A Clinicopathologic Study of Four Cases With Review of Additional 331 Cases in the Literature
Yingying Han, Qingjiao Li, Dan Wang, Lushan Peng, Tao Huang, Chunlin Ou, Keda Yang, Junpu Wang
Frontiers in Oncology.2022;[Epub] CrossRef
Renal Involvement of CD20-Negative Intravascular Large B Cell Lymphoma with Neurological Manifestations
Faten Aqeel, Serena M. Bagnasco, Duvuru Geetha, Yoshihide Fujigaki
Case Reports in Nephrology.2022; 2022: 1. CrossRef

Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder: Jiyoon Jung, Yang-Seok Chae, Chul Hwan Kim, Youngseok Lee, Jeong Hyeon Lee, Dong-Sik Kim, Young-Dong Yu, Joo Young Kim; J Pathol Transl Med. 2018;52(2):121-125. Published online October 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.20

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Abstract PDF

Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

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Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?
Ya-Fei Hu, Jun-Ke Wang, Wen-Jie Ma, Hai-Jie Hu, Han-Fei Gu, Fei Liu, Tian-Run Lv, Si-Qi Yang, Yu-Shi Dai, Rui-Qi Zou, Yan-Wen Jin, Fu-Yu Li
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Az epehólyag adenosquamosus daganata
Fanni Hegedűs, Anita Sejben
Orvosi Hetilap.2024; 165(49): 1945. CrossRef
Comparison of Metastatic Patterns Among Neuroendocrine Tumors, Neuroendocrine Carcinomas, and Nonneuroendocrine Carcinomas of Various Primary Organs
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Clinical features and outcomes analysis of Gallbladder neuroendocrine carcinoma
Man Jiang, Yijing Zhang
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Xu Ren, Hong Jiang, Kan Sun, Xufu Qin, Yongping Qu, Tian Xia, Yan Chen
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Neuroendocrine Neoplasms of the Gallbladder: A Clinicopathological Analysis of 13 Patients and a Review of the Literature
Pengyan Wang, Jingci Chen, Ying Jiang, Congwei Jia, Junyi Pang, Shan Wang, Xiaoyan Chang, Oronzo Brunetti
Gastroenterology Research and Practice.2021; 2021: 1. CrossRef
Gallbladder Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN) Arising in Intracholecystic Papillary Neoplasm: Clinicopathologic and Molecular Analysis of a Case and Review of the Literature
Amedeo Sciarra, Edoardo Missiaglia, Mounir Trimech, Emmanuel Melloul, Jean-Philippe Brouland, Christine Sempoux, Stefano La Rosa
Endocrine Pathology.2020; 31(1): 84. CrossRef
Mixed neuroendocrine-non-neuroendocrine carcinoma of gallbladder: case report
Adam Skalický, Lucie Vištejnová, Magdaléna Dubová, Tomáš Malkus, Tomáš Skalický, Ondřej Troup
World Journal of Surgical Oncology.2019;[Epub] CrossRef

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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Clinical manifestations and outcomes of patients with intravascular large B-cell lymphoma with neurological involvement: highlighting longitudinally extensive myelopathy as a distinct feature
Ekdanai Uawithya, Palakorn Lertsakworakul, Weerapat Owatthanapanich, Jiraporn Jitprapaikulsan
BMJ Neurology Open.2025; 7(1): e000915. CrossRef
Intravascular large B-cell lymphoma of the central nervous system with renal involvement: a case report and literature review
Jun Li, Zhaojiao Li, Yifeng Shi, Jiajie Chen, Heng Zhao, Xueye Mao, Shan Li, Huiying Wang, Qiang Meng, Lingchun Liu
Frontiers in Oncology.2025;[Epub] CrossRef
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Jiafei Zeng, Jin Li, Shuai Luo, Jinjing Wang
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A case report and literature review of cutaneous intravascular large B-cell lymphoma presenting clinically as panniculitis: a difficult diagnosis, but a good prognosis
Deniz Bayçelebi, Levent Yıldız, Nilgün Şentürk
Anais Brasileiros de Dermatologia.2021; 96(1): 72. CrossRef
Diffuse large B-cell lymphoma (DLBCL) with significant intravascular invasion. Close resemblance of its clinicopathological features to intravascular large B-cell lymphoma, but not to DLBCL-not otherwise specified
Hiroe Itami, Hirokazu Nakamine, Masayuki Kubo, Kohei Ogawa, Rina Tani, Shinji Nakamura, Maiko Takeda, Yuji Nitta, Tomoko Uchiyama, Tomomi Fujii, Kinta Hatakeyama, Chiho Ohbayashi
Journal of Clinical and Experimental Hematopathology.2021; 61(3): 152. CrossRef
Unusual and Fatal Case of an Undiagnosed Intravascular Large B‐cell Lymphoma: The Oncologist’s Great Imitator†
Rosario Barranco, Fiorella Caputo, Davide Bedocchi, Francesca Maria Elena Frigiolini, Lara Castelletti, Giulio Fraternali Orcioni, Francesco Ventura
Journal of Forensic Sciences.2020; 65(1): 314. CrossRef
Pituitary Gland and Neurological Involvement in a Case of Hemophagocytic Syndrome Revealing an Intravascular Large B-Cell Lymphoma
Sylvain Raoul Simeni Njonnou, Bruno Couturier, Yannick Gombeir, Sylvain Verbanck, France Devuyst, Georges El Hachem, Ivan Theate, Anne-Laure Trepant, Virginie De Wilde, Frédéric-Alain Vandergheynst
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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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133 Download
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Abstract PDF

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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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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Abstract PDF

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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