Journal of Pathology and Translational Medicine

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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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

Citations to this article as recorded by

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

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.

Citations

Citations to this article as recorded by

Warthin tumor concomitant with mantle cell lymphoma: a case report and review of literature
Hai-Chao Tong, Shuang Ma, Lan Chen, Xiangyun Meng, Ying-Chun Li, Le-Yao Li, Lingyun Dong, Wan-Lin Zhang, Tyler Wildes, Lian-He Yang, Endi Wang
Diagnostic Pathology.2024;[Epub] CrossRef
Warthin’s Tumor of the Parotid Gland With Degeneration to Diffuse Large B-cell Lymphoma: A Case Report and Review of Literature
Mauricio Gutierrez-Alvarez, Cynthia Martinez, Ana Priscila Campollo Lopez, Kevin Fuentes, Jorge Alberto Robles Aviña
Cureus.2023;[Epub] CrossRef
Pathogenesis Analysis of Salivary Gland Tumors Through the Expression of Programmed Death-Ligand 1 (PD-L1)
Aisyah Izzatul Muna, Maria Evata Krismawati Surya, Meiske Margaretha, Jane Kosasih, Mei Syafriadi
Indian Journal of Otolaryngology and Head & Neck Surgery.2023; 75(4): 3098. CrossRef
Role of cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in the pathogenesis of Warthin’s tumor growth
Alvionika Nadyah Qotrunnada, Tecky Indriana, Jane Kosasih, Meiske Margaretha, Mei Syafriadi
Dental Journal (Majalah Kedokteran Gigi).2022; 55(4): 194. CrossRef
Lymphoepithelial Carcinoma of Salivary Glands
Lester D.R. Thompson, Rumeal D. Whaley
Surgical Pathology Clinics.2021; 14(1): 75. CrossRef
Follicular Lymphoma Diagnosed in Warthin Tumor: A Case Report and Review of the Literature
Fnu Alnoor, Jatin S. Gandhi, Matthew K. Stein, Joel F. Gradowski
Head and Neck Pathology.2020; 14(2): 386. CrossRef
Prevalence of Lymphoid Neoplasia in a Retrospective Analysis of Warthin Tumor: A Single Institution Experience
F. N. U. Alnoor, Jatin S. Gandhi, Matthew K. Stein, Jorge Solares, Joel F. Gradowski
Head and Neck Pathology.2020; 14(4): 944. CrossRef
A Case of Diffuse Large B Cell Lymphoma in Submandibular Gland
Sang Hoo Park, Min Gyoung Pak, Dong Kun Lee
Journal of Clinical Otolaryngology Head and Neck Surgery.2020; 31(1): 111. CrossRef
Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours
Henrik Hellquist, António Paiva-Correia, Vincent Vander Poorten, Miquel Quer, Juan C. Hernandez-Prera, Simon Andreasen, Peter Zbären, Alena Skalova, Alessandra Rinaldo, Alfio Ferlito
Advances in Therapy.2019; 36(8): 1950. CrossRef
Diffuse large B-cell lymphoma arising from follicular lymphoma with warthin’s tumor of the parotid gland - immunophenotypic and genetic features: A case report
Chang-Song Wang, Xia Chu, Di Yang, Lei Ren, Nian-Long Meng, Xue-Xia Lv, Tian Yun, Yan-Sha Cao
World Journal of Clinical Cases.2019; 7(22): 3895. CrossRef
Presentation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in a Warthin Tumor: Case Report and Literature Review
Hadeel Jawad, Peter McCarthy, Gerard O’Leary, Cynthia C. Heffron
International Journal of Surgical Pathology.2018; 26(3): 256. CrossRef
Bilateral Warthin tumor in psoriatic patients in therapy with multiple immunosuppressive therapy
M Burlando, E Cozzani, C Chinazzo, M larosa, M Boggio, A Parodi
International Journal of Immunopathology and Pharmacology.2015; 28(1): 138. CrossRef
Nodular Lymphocyte-Predominant Hodgkin Lymphoma in a Warthin Tumor of the Parotid Gland
Arianna Di Napoli, Giuseppe Mallel, Armando Bartolazzi, Elena Cavalieri, Roberto Becelli, Claudia Cippitelli, Luigi Ruco
International Journal of Surgical Pathology.2015; 23(5): 419. CrossRef

Original Articles

Application of Gene Rearrangement Analysis for Diagnosis of Malignant Lymphoma.: Kyung Soo Kim, Chan Choi; Korean J Pathol. 1995;29(4):415-422.

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Abstract PDF: To evaluate the utility of gene rearrangement analysis, eight cases of malignant lymphoma, one case of Hodgkin's disease, two cases of angioiminunoblastic lymphadenopathy (AILD) and two cases of non-specific lymphadenitis were studied by immunohistochemical and genetic analysis. Southern blot analysis was perfon-ned by a using vacuum transfer system and a biotin labelled probe. This method was faster, safer, and more convenient than conventional methods. Gene rearrangement study showed rearranged novel bands in five of six cases of B cell lymphoma, in all cases of T cell lymphoma, and in all cases of AILD. No rearrangement of the B cell receptor(BCR) or of the T cell receptor(TCR) was seen in Hodgkin's disease or in nonspecific lymphadenitis. These results suggest that gene rearrangement analysis of BCR and TCR is a recommended method for the diagnosis of clonality in lymphoproliferative disorders. It would allow pathologists to differentiate lymphoma from polyclonal lymphoid proliferation and to provide information for cell lineage.

Characteristics of the Immortalized Human B-cells by Epstein-Barr Virus.: Ho Jong Jeon, Bong Nam Choi, Yoon Kyeong Oh; Korean J Pathol. 1997;31(9):832-846.

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Abstract PDF: Human lymphoblastoid B-cell lines immortalized by Epstein-Barr virus (EBV) were established from peripheral blood of patients with acute myeloblastic and chronic lymphocytic leukemia and chronic fatigue syndrome. The sera of patients with acute myeloblastic and chronic lymphocytic leukemia did not show antibodies to Epstein-Barr viral capsid antigen (VCA), but serum of a patient with chronic fatigue syndrome disclosed antibodies to VCA (IgG, IgM), and EBNA was demonstrated in peripheral blood mononuclear cells by polymerase chain reaction. The established cell lines were mature B-cell phenotypes with polyclonal proliferation in early passage and no evidence for commitment to other lineages. The immortalized cells by EBV were designated as CSUP-1 and CSUP-2 (from acute myeloblastic leukemia, FAB classification M2 and M1), CSUP-3 (from chronic lymphocytic leukemia) and CSUP-4 (from a patient with chronic fatigue syndrome). The CSUP-1, 2, 3, and 4 grew in suspension forming clumps with a doubling time of 38 to 49 hours. Colony formation was not recognized in plate. By light and electron microscopic examination, the immortalized cells showed features of lymphoblastoid to plasmacytoid lymphocytes, and multinucleated giant cells. The lymphoblastoid cells showed scanty cytoplasm with poorly developed organelles. Immunophenotypic analyses of CUSP-1, 2, 3, and 4 with monoclonal antibodies by flow cytometry showed B-cell phenotype with polyclonal proliferation in early passage. Epstein-Barr virus nuclear antigen was confirmed in the extracted DNAs from immortalized cells by polymerase chain reaction. DNA analysis showed a normodiploid stemline with a DNA index of 1.12. The established cells were strongly reactive for CD10, CD30 (Ki-1) in early passage, and bcl-2 and c-myc onco-protein in early and late passage. Karyotypic analysis of CSUP-1, 2, 3 and 4 showed 46, XY or 46, XX. No tumorigenesis in heterotransplanted SCID mouse was recognized. This immortalized cells by EBV should be a valuable cell lines to study the pathogenesis of EBV-related malignant lymphoma.

Identification of Zinc Finger Genes that are Differentially Expressed upon Apoptosis of Ramos B Cells.: Min Sun Shin, Su Young Kim, Seung Myung Dong, Eun Young Na, Sug Hyung Lee, Won Sang Park, Jung Young Lee, Nam Jin Yoo; Korean J Pathol. 1998;32(12):1043-1048.

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Abstract: Typical programmed cell death requires de novo macromolecular synthesis and shares common morphological changes referred to as apoptosis. To elucidate the molecular mechanism of apoptosis, we isolated 13 cDNA clones of zinc finger genes that are differentially expressed in calcium ionophore-induced apoptosis of Ramos human B cell by 'targeted RNA fingerprinting' protocol (Stone & Wharton, 1993). According to DNA sequence analysis of the 13 cDNA clones, three clones are identical with ZNF7, ZNF143 and MTB-Zf, respectively, and 8 out of the other 10 clones showed partial homology to known zinc finger genes. Differential expression was confirmed in the three known zinc finger genes by ribonuclease protection assay. ZNF7 and ZNF143 are up-regulated after induction of apoptosis, and, in contrast, MTB-Zf is down-regulated. According to the previous reports on these three genes, all of the three genes have been suspected to be tumor suppressor genes, but their functions have not been identified yet. Taken together, our results suggest that many of the novel and known zinc finger genes might play important roles in regulation of apoptosis and that these findings also provide clues as to the functions of the three putative tumor suppressor genes, ZNF7, ZNF143 and MTB-Zf in terms of apoptosis. In addition, the isolation of zinc finger genes by targeted RNA fingerprinting could be a straightforward approach for the identification of novel candidate genes associated with apoptosis.

Case Report

Fine Needle Aspiration Cytology of Extranodal Marginal Zone B cell Lymphoma with Abundant Plasma Cells and Eosinophilic Histiocytes in Parotid Gland.: Youngseok Lee, Jungsuk An, Yang Seok Chae, Bom Woo Yeom, Jong Sang Choi, Chul Hwan Kim; Korean J Cytopathol. 2007;18(2):165-169.

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Abstract PDF: The authors present the fine needle aspiration cytology (FNAC) cytologic findings of a case of extranodal marginal zone B cell lymphoma (MZBCL), which featured abundant plasma cells and eosinophilic histiocytes arising in both parotid glands. A 49-year-old female presented with palpable masses in both parotid glands. She had been suffering from systemic lupus erythematosus and rheumatoid arthritis. The lesions were evaluated by FNAC and smears showed a small number of clusters of oncocytic cells with abundant eosinophilic granular cytoplasm and small nuclei, intermixed with small to medium-sized lymphoid cells containing round to lobulated nuclei, which suggested Warthin's tumor. Some of lymphoid cells had a plasmacytoid appearance, and some scattered large cells contained a large amount of eosinophilic cytoplasm. Bilateral superficial parotidectomy was performed and a histopathologic study indicated MZBCL with abundant plasma cells, intermixed with eosinophilic histiocytes. The presence of oncocytic cells and a mixture of lymphoid and plasma cells indicates Warthin's tumor, but the cytologic features of a relatively monotonous small to medium-sized lymphoid infiltrate suggest the possibility of MZBCL in the clinical setting of an FNAC study performed on a patient suffering from a connective tissue disease.

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