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Hiratsuka T, Ito S, Sakai R, Yokose T, Endo T, Daigo Y, Miyagi Y, Tsuruyama T. Proteome analysis of CD5-positive diffuse large B cell lymphoma FFPE tissue reveals downregulation of DDX3X, DNAJB1, and B cell receptor signaling pathway proteins including BTK and Immunoglobulins. Clin Proteomics 2023; 20:36. [PMID: 37705009 PMCID: PMC10498596 DOI: 10.1186/s12014-023-09422-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 07/25/2023] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND The molecular pathology of diffuse large B cell lymphoma (DLBCL) has been extensively studied. Among DLBCL subtypes, the prognosis of CD5-positive DLBCL is worse than that of CD5-negative DLBCL, considering the central nervous system relapse and poor response to R-CHOP therapy. However, the molecular mechanisms underlying the tumorigenesis and progression of CD5-positive DLBCL remain unknown. METHODS To identify molecular markers that can be targeted for treating DLBCL, a proteomic study was performed using liquid chromatography-mass spectrometry with chemically pretreated formalin-fixed paraffin-embedded specimens from CD5-positive (n = 5) and CD5-negative DLBCL patients (n = 6). RESULTS Twenty-one proteins showed significant downregulation in CD5-positive DLBCL compared to CD5-negative DLBCL. Principal component analysis of protein expression profiling in CD5-positive and CD5-negative DLBCL revealed that DNAJB1, DDX3X, and BTK, which is one of the B cell phenotypic proteins, were the most significantly downregulated proteins and served as biomarkers that distinguished both groups. Additionally, a set of immunoglobulins, including IgG4, exhibited significant downregulation. Immunohistochemistry analysis for BTK demonstrated reduced staining in CD5-positive DLBCL compared to CD5-negative DLBCL. CONCLUSIONS In conclusion, DNAJB1 and DDX3X, BTK, and a set of immunoglobulins are promising biomarkers. Probably, the suppression of BCR signaling is the unique phenotype of CD5-positive DLBCL. This formalin-fixed paraffin-embedded (FFPE)-based profiling may help to develop novel therapeutic molecularly targeted drugs for treating DLBCL.
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Affiliation(s)
- Takuya Hiratsuka
- Department of Drug Discovery Medicine, Pathology Division, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Shinji Ito
- Medical Research Support Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Rika Sakai
- Department of Oncology, Kanagawa Cancer Center Research Institute, Yokohama, Japan
| | - Tomoyuki Yokose
- Department of Pathology, Kanagawa Cancer Center Research Institute, Yokohama, Japan
| | - Tatsuya Endo
- Department of Physics, Graduate School of Science, Tohoku University, Sendai, Japan
| | - Yataro Daigo
- Department of Medical Oncology, Cancer Center, and Center for Advanced Medicine Against Cancer, Shiga University of Medical Science, Otsu, Japan
- Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Yohei Miyagi
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan
| | - Tatsuaki Tsuruyama
- Department of Drug Discovery Medicine, Pathology Division, Kyoto University Graduate School of Medicine, Kyoto, Japan.
- Department of Physics, Graduate School of Science, Tohoku University, Sendai, Japan.
- Tazuke-Kofukai Medical Institute Kitano Hospital, Ogimachi, Osaka, Japan.
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Zhou QL, Li ZK, Xu F, Liang XG, Wang XB, Su J, Tang YF. Guillain-Barré syndrome and hemophagocytic syndrome heralding the diagnosis of diffuse large B cell lymphoma: A case report. World J Clin Cases 2022; 10:9502-9509. [PMID: 36159426 PMCID: PMC9477672 DOI: 10.12998/wjcc.v10.i26.9502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/26/2022] [Accepted: 08/05/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Central nervous system (CNS) lesions and peripheral neuropathy are rare among patients with non-Hodgkin's lymphoma (NHL). Lymphomatous infiltration or local oppression usually accounts for CNS or peripheral nerve lesions. The incidence of peripheral neuropathy was 5%. Guillain-Barré syndrome (GBS) is rare and may occur in less than 0.3% of patients with NHL. Hemophagocytic syndrome (HPS) is a rare complication of NHL. It has been reported that 1% of patients with hematological malignancies develop HPS. Diffuse large B-cell lymphoma (DLBCL) combined with GBS has been reported in 10 cases.
CASE SUMMARY We report the case of a 53-year-old man who was initially hospitalized because of abnormal feelings in the lower limbs and urinary incontinence. He was finally diagnosed with DLBCL combined with GBS and HPS after 16 d, which was earlier than previously reported. Immunoglobulin pulse therapy, dexamethasone, and etoposide were immediately administered. The neurological symptoms did not improve, but cytopenia was relieved. However, GBS-related clinical symptoms were relieved partially after one cycle of rituximab - cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) chemotherapy and disappeared after six cycles of R-CHOP.
CONCLUSION GBS and HPS heralding the diagnosis of Epstein-Barr virus DLBCL are rare. Herein, we report a rare case of DLBCL combined with GBS and HPS, and share our clinical experience. Traditional therapies may be effective if GBS occurs before lymphoma is diagnosed. Rapid diagnosis and treatment of DLBCL are crucial.
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Affiliation(s)
- Qiao-Lin Zhou
- Department of Hematology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Zhao-Kun Li
- Department of Neurology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Fang Xu
- Department of Hematology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Xiao-Gong Liang
- Department of Hematology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Xing-Biao Wang
- Department of General Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Jing Su
- Department of Hematology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
| | - Yu-Feng Tang
- Department of Neurology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, Sichuan Province, China
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Magy L. Neuropathies périphériques : démarche diagnostique. Rev Med Interne 2018; 39:27-33. [DOI: 10.1016/j.revmed.2017.01.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 01/23/2017] [Indexed: 01/09/2023]
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Ma YY, Zhang L, Zhang DAL, Liu WS. Guillain-Barré syndrome and severe infection following chemotherapy for peripheral T-cell lymphoma: A case report. Oncol Lett 2014; 8:2695-2698. [PMID: 25360176 PMCID: PMC4214403 DOI: 10.3892/ol.2014.2541] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Accepted: 08/28/2014] [Indexed: 02/02/2023] Open
Abstract
Guillain-Barré syndrome (GBS) is a rare complication of malignant lymphoma. The current study describes a case of GBS in a patient with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). A 47-year-old male was admitted to the First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) with systemic multiple subcutaneous nodules and was diagnosed with stage IV high-grade PTCL-NOS (according to the Revised European American Lymphoma Classification). During chemotherapy, severe infection and progressive flaccid quadriparesis appeared, which eventually developed to respiratory muscles paralysis. The clinical course and neurological examination were consistent with GBS. Following mechanical ventilation and intravenous immunoglobulin administration, the neurological symptoms were in remission after one month. Three months later, the patient achieved complete remission without any treatment during this period. We hypothesized that immune reconstruction may have a significant role in this phenomenon.
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Affiliation(s)
- Yang-Yang Ma
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
| | - Lei Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
| | - DA-Liang Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
| | - Wen-Shuo Liu
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
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Kiyat Atamer A, Okutur K, Tüzün E, Hasbal B, Boyaciyan A, Krespi Y, Demir G. Guillain-Barre Syndrome in a Patient with Primary Extranodal Intestinal Non-Hodgkin's Lymphoma: Paraneoplastic, Drug Induced or Coincidental? Noro Psikiyatr Ars 2014; 51:288-292. [PMID: 28360641 DOI: 10.4274/npa.y7059] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Accepted: 04/03/2013] [Indexed: 12/26/2022] Open
Abstract
Neurological involvement is observed in 5%-25% of patients with lymphoma being either the first presentation of the disease or emerging during its course. However, Guillain-Barré syndrome is rarely reported. In this article, we present a case with intestinal lymphoma developing Guillain-Barré syndrome during the course of the disease. A 66-year-old male patient with primary extranodal intestinal lymphoma developed quadriparesis, sensory deficits and autonomic dysfunction while receiving chemotherapy. The findings of clinical, electrophysiological and laboratory examinations were consistent with Guillain-Barré syndrome. Guillain-Barré syndrome can potentially be fatal and mimic chemotherapy-induced neurotoxicity, especially in patients with lymphoma, and therefore, must be considered in the differential diagnosis.
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Affiliation(s)
- Aslı Kiyat Atamer
- İstanbul Bilim University Faculty of Medicine, Department of Neurology, İstanbul, Turkey
| | - Kerem Okutur
- İstanbul Bilim University Faculty of Medicine, Department of Medical Oncology, İstanbul, Turkey
| | - Erdem Tüzün
- İstanbul University İstanbul Faculty of Medicine, Institute of Experimental Medicine, İstanbul, Turkey
| | - Barış Hasbal
- İstanbul Bilim University Faculty of Medicine, Department of Internal Medicine, İstanbul, Turkey
| | - Ari Boyaciyan
- Vehbi Koç Foundation American Hospital, Department of Neurology, İstanbul, Turkey
| | - Yakup Krespi
- İstanbul Bilim University Faculty of Medicine, Department of Neurology, İstanbul, Turkey
| | - Gökhan Demir
- İstanbul Bilim University Faculty of Medicine, Department of Medical Oncology, İstanbul, Turkey
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