- Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies
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Jiwon Koh, Sun Ah Shin, Ji Ae Lee, Yoon Kyung Jeon
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J Pathol Transl Med. 2022;56(4):173-186. Published online July 4, 2022
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DOI: https://doi.org/10.4132/jptm.2022.05.16
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- 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.
- An unusual case of microsatellite instability–high/deficient mismatch repair (MSI-H/dMMR) diffuse large B-cell lymphoma revealed by targeted gene sequencing
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Bogyeong Han, Sehui Kim, Jiwon Koh, Jeong Mo Bae, Hongseok Yun, Yoon Kyung Jeon
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J Pathol Transl Med. 2022;56(2):92-96. Published online November 16, 2021
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DOI: https://doi.org/10.4132/jptm.2021.10.15
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- 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.
- Clinicopathologic implication of PD-L1 gene alteration in primary adrenal diffuse large B cell lymphoma
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Ki Rim Lee, Jiwon Koh, Yoon Kyung Jeon, Hyun Jung Kwon, Jeong-Ok Lee, Jin Ho Paik
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J Pathol Transl Med. 2022;56(1):32-39. Published online November 16, 2021
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DOI: https://doi.org/10.4132/jptm.2021.10.05
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- 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.
- A case of concomitant EGFR/ALK alteration against a mutated EGFR background in early-stage lung adenocarcinoma
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Ki-Chang Lee, Jiwon Koh, Doo Hyun Chung, Yoon Kyung Jeon
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J Pathol Transl Med. 2021;55(2):139-144. Published online January 22, 2021
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DOI: https://doi.org/10.4132/jptm.2020.12.16
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- 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.
- Morphologic variant of follicular lymphoma reminiscent of hyaline-vascular Castleman disease
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Jiwon Koh, Yoon Kyung Jeon
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J Pathol Transl Med. 2020;54(3):253-257. Published online February 5, 2020
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DOI: https://doi.org/10.4132/jptm.2019.12.17
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- 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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In‐situ
follicular neoplasia: a clinicopathological spectrum
Gurdip S Tamber, Myriam Chévarie‐Davis, Margaret Warner, Chantal Séguin, Carole Caron, René P Michel Histopathology.2021; 79(6): 1072. CrossRef
- 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
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Jeemin Yim, Seung Geun Song, Sehui Kim, Jae Won Choi, Kyu-Chong Lee, Jeong Mo Bae, Yoon Kyung Jeon
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J Pathol Transl Med. 2019;53(1):57-61. Published online October 1, 2018
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DOI: https://doi.org/10.4132/jptm.2018.08.21
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4,338
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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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- Clinicopathologic and Genetic Features of Primary T-cell Lymphomas of the Central Nervous System
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 American Journal of Surgical Pathology.2022; 46(4): 486. CrossRef - Peripheral T-Cell Lymphomas Involving the Central Nervous System: A Report From the Czech Lymphoma Study Group Registry
Heidi Mocikova, Robert Pytlík, Katerina Benesova, Andrea Janikova, Juraj Duras, Alice Sykorova, Katerina Steinerova, Vit Prochazka, Vit Campr, David Belada, Marek Trneny Frontiers in Oncology.2022;[Epub] CrossRef
- Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives
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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
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J Pathol Transl Med. 2017;51(3):224-241. Published online May 10, 2017
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DOI: https://doi.org/10.4132/jptm.2017.04.09
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14,429
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- 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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- Thymus and lung mucosa-associated lymphoid tissue lymphoma with adenocarcinoma of the lung: a case report and literature review
Yu Pang, Daosheng Li, Yiqian Chen, Qinqin Liu, Yuheng Wu, Qingliang Teng, Yuyu Liu World Journal of Surgical Oncology.2023;[Epub] CrossRef - A comparison of capillary electrophoresis and next-generation sequencing in the detection of immunoglobulin heavy chain H and light chain κ gene rearrangements in the diagnosis of classic hodgkin’s lymphoma
Juan-Juan Zhang, Yu-Xin Xie, Li-Lin Luo, Xuan-Tao Yang, Yi-Xing Wang, Yue Cao, Zheng-Bo Long, Wan-Pu Wang Bioengineered.2022; 13(3): 5868. CrossRef - Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies
Jiwon Koh, Sun Ah Shin, Ji Ae Lee, Yoon Kyung Jeon Journal of Pathology and Translational Medicine.2022; 56(4): 173. CrossRef - Diagnostic Workup of Primary Cutaneous B Cell Lymphomas: A Clinician's Approach
Giulia Tadiotto Cicogna, Martina Ferranti, Mauro Alaibac Frontiers in Oncology.2020;[Epub] CrossRef - Kappa and lambda immunohistochemistry and in situ hybridization in the evaluation of atypical cutaneous lymphoid infiltrates
Alexandra C. Hristov, Nneka I. Comfere, Claudia I. Vidal, Uma Sundram Journal of Cutaneous Pathology.2020; 47(11): 1103. CrossRef - Primary lung mucosa-associated lymphoid tissue lymphoma accompanied by multiple sclerosis
Ke-Ke Yu, Lei Zhu, Ji-Kai Zhao, Rui-Ying Zhao, Yu-Chen Han Chinese Medical Journal.2019; 132(13): 1625. CrossRef - Diagnostic accuracy of SOX11 immunohistochemistry in mantle cell lymphoma: A meta-analysis
Woojoo Lee, Eun Shin, Bo-Hyung Kim, Hyunchul Kim, Riccardo Dolcetti PLOS ONE.2019; 14(11): e0225096. CrossRef - Views of dermatopathologists about clonality assays in the diagnosis of cutaneous T-cell and B-cell lymphoproliferative disorders
Nneka Comfere, Uma Sundram, Maria Yadira Hurley, Brian Swick Journal of Cutaneous Pathology.2018; 45(1): 39. CrossRef - A Next-Generation Sequencing Primer—How Does It Work and What Can It Do?
Yuriy O. Alekseyev, Roghayeh Fazeli, Shi Yang, Raveen Basran, Thomas Maher, Nancy S. Miller, Daniel Remick Academic Pathology.2018; 5: 2374289518766521. CrossRef
- Characteristics of Cutaneous Lymphomas in Korea According to the New WHO-EORTC Classification: Report of a Nationwide Study
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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
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Korean J Pathol. 2014;48(2):126-132. Published online April 28, 2014
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DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.126
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- 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. MethodsA 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. ResultsThe 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. ConclusionsIn 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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- Benign Indolent CD56-Positive NK-Cell Lymphoproliferative Lesion Involving Gastrointestinal Tract in an Adolescent
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Jaemoon Koh, Heounjeong Go, Won Ae Lee, Yoon Kyung Jeon
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Korean J Pathol. 2014;48(1):73-76. Published online February 25, 2014
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DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.73
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6,710
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50
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