Classical Hodgkin Lymphoma progressing to Nodal T follicular helper cell lymphomas with aberrant CD20 expression and monoclonal TCR, IG rearrangements: A case report

Classical Hodgkin Lymphoma progressing to Nodal T follicular helper cell lymphomas with aberrant CD20 expression and monoclonal TCR, IG rearrangements: A case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Classical Hodgkin Lymphoma progressing to Nodal T follicular helper cell lymphomas with aberrant CD20 expression and monoclonal TCR, IG rearrangements: A case report Ning Zhu, Li Zhang, Liling Song, Na Li, Xiaolong Sui, Ping Yang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4251775/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background CHL is a rare malignant neoplasm of the lymphatic system. While CHL typically responds well to conventional treatments, some cases may experience relapse or progression to other subtypes, with the development of secondary PTCL being relatively uncommon. Herein, we report a rare case of nTFHL-NOS arising from CHL, accompanied by aberrant CD20 expression and clonal rearrangements of TCR and IG. Case presentation: A 74-year-old male, was diagnosed with CHL, leaning towards the mixed cell type, six years ago. He received six cycles of the ABVD regimen, achieving complete clinical remission. The patient was admitted to our hospital due to the appearance of multiple skin nodules 66 months later. Physical examination showed a palpable mass measuring 3cm × 2cm in its largest dimension on the skin of the right shoulder blade, characterized by firm consistency and limited mobility. A subcutaneous tissue biopsy of the right shoulder blade was performed. Histopathological analysis revealed nTFHL-NOS, with aberrant CD20 expression and clonal rearrangements of TCR and IG. The patient underwent two cycles of chemotherapy with brentuximab vedotin and the G-mox regimen, resulting in a reduction of the skin lesions to 2cm × 1cm. Conclusion EBV infection, complex tumor microenvironment, and genetic susceptibility may all contribute to the occurrence of CHL progressing to PTCL. Addressing the stability of the tumor microenvironment during CHL treatment to mitigate the risk of secondary PTCL development poses a significant challenge that warrants investigation. Figures Figure 1 Figure 2 Background Cases of CHL progressing to PTCL are particularly rare [ 1 , 2 ]. This study reports a case of a CHL patient who developed PTCL after receiving ABVD therapy, highlighting the clinical complexity of CHL with concurrent PTCL. We conducted a thorough analysis of its pathological features and discussed its pathogenesis. Through this study, we aim to provide new insights into similar complications, offer guidance for clinical decision-making, and facilitate further research in the field of CHL and its secondary PTCL. Case report Summary of case. A 74-year-old male was admitted to our hematology department with a one-year history of swelling in the right upper limb and three months of generalized weakness six years ago. A left cervical lymph node biopsy was performed. Microscopically, the tumor cell showed disrupted lymph node architecture with scattered mono- or binucleated cells of large size, abundant cytoplasm, coarse chromatin, and prominent nucleoli, amidst small lymphocytes, histiocytes, plasma cells, and eosinophils (Fig. 1 C). Immunohistochemical staining revealed positivity for large cell markers CD30 (Fig. 1 D), weakly positive for PAX-5 (Fig. 1 F), positive for Ki67 and MUM1 (Fig. 1 G), and negative for CD15, ALK, EMA, LCA (Fig. 1 E), CD3, CD20, CD21, and Bcl-2. In situ hybridization for EBV-EBER showed positivity in large cells (Fig. 1 H). The lesion was consistent with CHL, with a tendency towards mixed cellularity. The patient was treated with six cycles of the ABVD regimen, achieving clinical complete remission. He was readmitted to our hematology department with swelling on the right shoulder, back, and upper arm 66 months later. Physical examination revealed palpable enlarged nodules on the skin of the right shoulder and back, measuring approximately 4cm×3cm, with erythema and swelling but no ulceration, slightly elevated skin temperature, firm consistency, mild tenderness, no fluctuation, and no oozing or bleeding. Multiple nodules were palpable on the outer side of the right upper arm, with the largest one measuring about 1.0cm×0.8cm, firm consistency, and no tenderness. Bilateral lung auscultation revealed coarse breath sounds without crackles or wheezes; cardiac rhythm was regular, and no significant abnormalities were detected in the auscultation areas of each valve. There was no edema in the lower limbs. Laboratory examination showed that white blood cell count was 7.81×10 9 /L, lymphocyte count was 1.31×10 9 /L, hemoglobin 138g/L, platelet count was 178×10 9 /L. β2-microglobulin was elevated at a level of 2.63mg/L and the lactate dehydrogenase level was 223U/L. PET-CT upon admission in July 2018 revealed multiple lymph node enlargements in the left parapharyngeal, bilateral cervical, bilateral supraclavicular, mediastinal, and retroperitoneal regions, as well as nodules in the right parotid gland area, subcutaneous nodules on the chest wall, and small nodules on the right forearm, all showing FDG hypermetabolism, suggesting a high possibility of malignant lymphoma (Fig. 1 A). Upon re-examination during hospitalization in October 2018, PET-CT showed a regular soft tissue density shadow in the right parotid gland area with clear borders and increased FDG metabolism. When compared with the imaging from July 2018, there were no significant changes in the volume or metabolism of the lesion, suggesting a possibility of benign pathology in the right parotid gland and then no abnormal FDG metabolism lesions were observed in other parts of the body on the whole-body PET-CT scan (Fig. 1 B). Prior to admission in January 2024, PET-CT identified showed multiple subcutaneous soft tissue nodules throughout the body with increased FDG metabolism, multiple lymph nodes of varying sizes throughout the body with increased FDG metabolism, bilateral thickening of the nasal turbinates and enlargement of the bilateral pharyngeal tonsils, with increased FDG metabolism observed in these lesions,and increased FDG uptake in the posterior wall of the nasopharynx. These findings suggested recurrence of lymphoma (Fig. 2 A). Pathological findings. The patient underwent a right shoulder-back subcutaneous tissue biopsy. Gross examination revealed two tissue samples, measuring 1.5cm and 1cm in length, respectively, with a diameter of 0.1cm. Microscopic examination showed disrupted lymph node architecture, diffuse proliferation of lymphocytes with varying cell sizes, abundant cytoplasm, stained or translucent cytoplasm, round or irregular nuclei, fine chromatin, inconspicuous nucleoli, and visible mitotic figures (Fig. 2 B, 2 C). Immunohistochemical staining revealed proliferation of lymphocytes positive for CD3 (Fig. 2 E), CD4, CD5 (Fig. 2 F), PD-1 (Fig. 2 J), CXCL13, partial CD20 (Fig. 2 H), Bcl-6, CD30 (30%), and Ki67 (60%) (Fig. 2 K), negative for CD2 (Fig. 2 D), CD7 (Fig. 2 G), CD8, CD56, TIA, GraB, PAX-5, CD79a, MUM1, CD21, CD10 (Fig. 2 I), and Bcl-2, and scattered positive for EBV-EBER in situ hybridization (Fig. 2 L). Lymphocyte gene rearrangement testing showed positive results for TCRβ (Vβ + Jβ1/2), TCRγ (Vγ1–11), IGk (Vk-Jk), and IGk (Vk-Kde + intron-Kde). Taken together, the above results suggest that this case may be the nTFHL-NOS with aberrant CD20 expression and monoclonal TCR, IG rearrangements. Treatment and outcome. The patient underwent 2 cycles of chemotherapy with bendamustine and G-mox regimen.After two cycles of treatment, the skin lesions reduced to 2cm × 1cm in size. We will continue to follow up with the patient. Discussion CL refers to the simultaneous or sequential occurrence of two or more different types of lymphomas in the same anatomical structure [ 3 ]. CL is a rare condition, accounting for 1-4.7% of new lymphoma cases each year. The pathogenesis of CL may be related to immune defects, such as immunosuppression caused by EBV infection in patients or immune dysregulation due to autoimmune diseases like rheumatoid arthritis. Mutations in DNA methylation genes such as IDH2 may also contribute to CL [ 1 , 2 ]. In this case, the development of nTFHL-NOS following treatment for CHL may be attributed to several mechanisms. EBV may induce the transformation of lymphocytes, stimulating T cell proliferation and leading to the development of T cell lymphoma [ 4 ]. Additionally, EBV-positive CHL patients have been found to exhibit increased secretion of interleukin-10 by Tr1 cells, enhancing immunosuppression in the lymphoma microenvironment and promoting unrestricted lymphocyte proliferation, thereby facilitating the development of a second lymphoma [ 5 , 6 ]. HRS cells can secrete factors such as interferons and interleukins, which can suppress the immune response mediated by cytotoxic T lymphocytes. Furthermore, regulatory T cells interacting with HRS cells may inhibit the function of cytotoxic T lymphocytes, resulting in immune deficiency and increased susceptibility to T cell lymphomas [ 7 ]. Both CHL and nTFHL-NOS are EBV-related lymphomas with complex microenvironments, and chemotherapy for Hodgkin lymphoma may create conditions conducive to the transformation of a second lymphoma [ 8 ]. In this case, the patient was diagnosed with CHL and underwent ABVD chemotherapy. After 66 months, they developed nTFHL-NOS, with tumor cells showing abnormal expression of CD20 and monoclonal rearrangements of TCR and IG. While CD20 is typically expressed on B cells at various developmental stages, including tumor B cells, it is lost before terminal B cell differentiation into plasma cells. Although CD20-positive T cell lymphomas are rare, when analyzing abnormal lymphocytes expressing CD20, it's important to consider both B lymphocytes expressing CD5 and T lymphocytes expressing CD20, hence co-analysis with CD3 and CD20 is recommended to distinguish CD20-positive T cell lymphoma [ 9 ]. Clinically, CD20-positive T cell lymphomas predominantly affect elderly males, primarily manifesting as lymph node lesions and often presenting at stage III/IV, with a generally poor prognosis possibly associated with CD20 expression. Among 101 CD20-positive T cell lymphoma patients treated with rituximab, 5 achieved complete remission, 3 had stable disease, 15 had partial remission or stable disease followed by relapse, and 4 showed no response [ 10 – 12 ]. Rituximab may be effective in treating CD20-positive T cell lymphomas, but its efficacy may vary depending on the intensity of CD20 expression. Approximately 85,000 CHL cases are reported globally each year, with a higher incidence in individuals aged 15–35 and over 55. As CHL has a high cure rate, the development of secondary tumors becomes a significant factor influencing patient survival. Therefore, preventing the occurrence of secondary tumors in CHL is crucial [ 13 ]. The tumor microenvironment is considered a critical factor in tumor prevention and progression. To inhibit tumor growth in the tumor microenvironment, the role of immune cells and molecules cannot be overlooked [ 14 ]. Abbreviations CHL Classical Hodgkin Lymphoma PTCL Peripheral T-cell Lymphoma nTFHL-NOS Nodal T follicular helper cell lymphomas,nos TCR T cell reception IG immunoglobulin ABVD Adriamycin, Bleomycin, Vinblastine, Dacarbazine G-mox Gemcitabine, Oxaliplatin PET-CT Positron emission tomography-computed tomography CL Composite lymphoma Declarations Acknowledgments The authors are grateful for Shandong Natural Science Foundation and Yantai Science and Technology Plan for their support of this project. Authors’ contributions Ning Zhu wrote the manuscript; Li Zhang performed immunohistochemial staining; Liling Song reviewed the cases and edited the manuscript; Xiaolong Sui provided the pathological pictures and contributed to the diagnosis; Na Li, Xiaoqian Liu and Ping Yang was in charge of the physical examination and follow-up; Guohua Yu designed the study; All authors issued final approval for the version to be submitted; All authors approved the manuscript for publication. Funding This study was supported by the fund of Shandong Natural Science Foundation [NO.ZR2022MH297], and Yantai Science and Technology Plan [NO.2021MSGY043]. Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of Yuhuangding Hospital in Yantai, Shandong, China, and was exempted from signing a written informed consent form by the Medical Ethics Committee. Consent for publication Written informed consent was obtained from the patient to publish this manuscript and any accompanying images. Competing interests The authors declare that they have no any conflict of interests. References Gui W, Wang J, Ma L, Wang Y, Su Lp. Clinicopathological analysis of composite lymphoma: A two-case report and literature review. Open Med (Wars). 2020; 15(1): 654-8. http://dx.doi.org/10.1515/med-2020-0191. Jin X, Liu H, Li J, Xiao X, Yuan X, Chen P, et al. Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review. J Zhejiang Univ Sci B. 2023; 24(8): 711-22. http://dx.doi.org/10.1631/jzus.B2300181. Wang H, Yang L, Li Q, Song H, Ji H. Case report: Composite mantle cell lymphoma and classical Hodgkin lymphoma. Pathol Oncol Res. 2023; 29: 1611051. http://dx.doi.org/10.3389/pore.2023.1611051. Abraham L, Paul M, Varghese D, D'souza Co. A Rare Case of Metachronous Peripheral T-cell Non-Hodgkin Lymphoma Following Epstein-barr Virus-positive Diffuse Large B-cell Lymphoma, Not Otherwise Specified. Oman Med J. 2023; 38(2): e487. http://dx.doi.org/10.5001/omj.2023.13. Küppers R, Dührsen U, Hansmann Ml. Pathogenesis, diagnosis, and treatment of composite lymphomas. Lancet Oncol. 2014; 15(10): e435-46. http://dx.doi.org/10.1016/s1470-2045(14)70153-6. Morales O, Mrizak D, François V, Mustapha R, Miroux C, Depil S, et al. Epstein-Barr virus infection induces an increase of T regulatory type 1 cells in Hodgkin lymphoma patients. Br J Haematol. 2014; 166(6): 875-90. http://dx.doi.org/10.1111/bjh.12980. Ichikawa A, Miyoshi H, Yamauchi T, Arakawa F, Kawano R, Muta H, et al. Composite lymphoma of peripheral T-cell lymphoma and Hodgkin lymphoma, mixed cellularity type; pathological and molecular analysis. Pathol Int. 2017; 67(4): 194-201. http://dx.doi.org/10.1111/pin.12515. Zhu X, Wu H, Yin W, Sun W. EBV positive classic Hodgkin's lymphoma secondary to peripheral T-cell lymphoma: a case report and literature review. Chin J Cancer Prev Treat. 2016; 23(001): 56-9. http://dx.doi.org/10.16073/j.cnki.cjcpt.2016.01.013. Kakinoki Y, Hashiguchi J, Ishio T, Chiba K, Niino D, Ohshima K. CD20-positive primary gastric T-cell lymphoma poorly responding to initial treatment with rituximab plus CHOP, and a literature review. Int J Hematol. 2015; 102(6): 702-8. http://dx.doi.org/10.1007/s12185-015-1841-x. Teshima K, Ohyagi H, Kume M, Takahashi S, Saito M, Takahashi N. Refractory CD20-positive peripheral T-cell lymphoma showing loss of CD20 expression after rituximab therapy and gain of CD20 expression after administration of vorinostat and gemcitabine. Rinsho Ketsueki. 2017; 58(11): 2227-31. http://dx.doi.org/10.11406/rinketsu.58.2227. Li D, Kang H, Zhang L, Xu Z, Wang X, Wang L, et al. CD20 or CD79 α Clinicopathological features of mature T/NK cell lymphoma with abnormal expression. Chin J Pathol. 2022; 51(5): 413-8. http://dx.doi.org/10.3760/cma.j.cn112151-20211219-00913. Shao S, Wang Y, Dai X, Xiao Y, Guan J, Lin D, et al. Clinical and pathological characteristics of CD20 positive T-cell lymphoma in five cases. Chin J Pathol. 2020; 49(10): 1021-6. http://dx.doi.org/10.3760/cma.j.cn112151-20200212-00081. Munir F, Hardit V, Sheikh I. N, Alqahtani S, He J, Cuglievan B, et al. Classical Hodgkin Lymphoma: From Past to Future-A Comprehensive Review of Pathophysiology and Therapeutic Advances. Int J Mol Sci. 2023; 24(12). http://dx.doi.org/10.3390/ijms241210095. Dogan A. The real risk of secondary non-Hodgkin lymphoma following classical Hodgkin lymphoma. Haematologica. 2023; 108(5): 1220-1. http://dx.doi.org/10.3324/haematol.2022.281700. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4251775","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":290331228,"identity":"6e4b4b73-493b-41f3-8c95-879791fd6ecb","order_by":0,"name":"Ning Zhu","email":"","orcid":"","institution":"Department of Pathology, Binzhou Medical University, College of Basic Medical Sciences, China","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Zhu","suffix":""},{"id":290331232,"identity":"296489d2-9e49-4d66-a2b2-343c1063d434","order_by":1,"name":"Li Zhang","email":"","orcid":"","institution":"Department of Pathology, Yantai Yuhuangding Hospital, China","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Zhang","suffix":""},{"id":290331235,"identity":"27c18e97-7c03-450c-a93e-26e88f5d9cfb","order_by":2,"name":"Liling Song","email":"","orcid":"","institution":"The Second Medical College of Binzhou Medical University, China","correspondingAuthor":false,"prefix":"","firstName":"Liling","middleName":"","lastName":"Song","suffix":""},{"id":290331239,"identity":"9218c65e-6dc5-4633-847d-903d37837d8a","order_by":3,"name":"Na Li","email":"","orcid":"","institution":"The Second Medical College of Binzhou Medical University, China","correspondingAuthor":false,"prefix":"","firstName":"Na","middleName":"","lastName":"Li","suffix":""},{"id":290331243,"identity":"8530f584-ee9c-4f64-933a-c4006f4d57c9","order_by":4,"name":"Xiaolong Sui","email":"","orcid":"","institution":"Department of Pathology, Yantai Yuhuangding Hospital, China","correspondingAuthor":false,"prefix":"","firstName":"Xiaolong","middleName":"","lastName":"Sui","suffix":""},{"id":290331246,"identity":"4eecd4bc-b415-43b4-985e-f4c96d5fd825","order_by":5,"name":"Ping Yang","email":"","orcid":"","institution":"Department of Pathology, Yantai Yuhuangding Hospital, China","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Yang","suffix":""},{"id":290331249,"identity":"b41ece23-0628-474b-84d9-3a78563c3418","order_by":6,"name":"Xiaoqian Liu","email":"","orcid":"","institution":"Department of Hematology, Yantai Yuhuangding Hospital, China","correspondingAuthor":false,"prefix":"","firstName":"Xiaoqian","middleName":"","lastName":"Liu","suffix":""},{"id":290331251,"identity":"3c6e934f-dfb1-4aa2-93e6-2908da67c562","order_by":7,"name":"Guohua Yu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYHACNjDJLwHhMTYQrUVyBslaDG4Qq0U+IvnYY56aw4mbb7c/3fCDwUZ2wwHmZw/waTG8kZZuzHPscOK2OwfSbvYwpBlvOMBmboBXy4wcM2keNqCWGwnHbjMwHE7ccICHTYKwln9Ah81IbANq+U9Yi7wEUAtvG9BwiWQ2oJYDhLUY8DxLk5zbl248484xtps9BsnGMw+zmeG3pT35mMSbb9ay/bPbn934UWEn23e8+Rl+Ww6AqWYYF4iZ8akH2dIApuoIKBsFo2AUjIIRDQAHgU0W/pzysgAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Pathology, Yantai Yuhuangding Hospital, China","correspondingAuthor":true,"prefix":"","firstName":"Guohua","middleName":"","lastName":"Yu","suffix":""}],"badges":[],"createdAt":"2024-04-11 10:17:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4251775/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4251775/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55002510,"identity":"40c38d6b-b13d-49de-98b3-c9160ca021a8","added_by":"auto","created_at":"2024-04-19 18:40:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3913659,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e A whole-body PET-CT revealed intense FDG uptake in the left parapharyngeal, bilateral cervical, bilateral supraclavicular, mediastinal, and retroperitoneal regions, etc. \u003cstrong\u003eB \u003c/strong\u003ePET-CT showed a regular soft tissue density shadow in the right parotid gland area with increased FDG metabolism, and then no abnormal FDG metabolism lesions were observed in other parts of the body.\u003cstrong\u003e C \u003c/strong\u003eMicroscopic findings (Haematoxylin and eosin [HE] staining) showed disrupted lymph node architecture with scattered mono- or binucleated cells of large size, abundant cytoplasm, coarse chromatin, and prominent nucleoli, amidst small lymphocytes, histiocytes, plasma cells, and eosinophils. Immunohistochemical analysis of the breast showed tumor cells were positive for CD30 (\u003cstrong\u003eD\u003c/strong\u003e), weak PAX-5 (\u003cstrong\u003eF\u003c/strong\u003e) and MUM1 (\u003cstrong\u003eG\u003c/strong\u003e), but negative for LCA (\u003cstrong\u003eE\u003c/strong\u003e). \u003cstrong\u003eH\u003c/strong\u003e Tumor cells were also positive for Epstein-Barr virus small-encoded RNA by in situ hybridization. (\u003cstrong\u003eC 55.5×; D CD30, 92.0×; E LCA, 63.0×; F PAX-5, 58.2×; G MUU1, 1.0×; H EBER-ISH, 55.5×\u003c/strong\u003e)\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-4251775/v1/b78537a8e600626c645f535e.png"},{"id":55002512,"identity":"8e2a412a-f088-4568-aa8a-8091d6de69b1","added_by":"auto","created_at":"2024-04-19 18:40:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":6395320,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA \u003c/strong\u003ePET-CT identified showed multiple subcutaneous soft tissue nodules throughout the body with increased FDG metabolism, multiple lymph nodes of varying sizes throughout the body with increased FDG metabolism. \u003cstrong\u003eB,C\u003c/strong\u003eHE showed disrupted lymph node architecture, diffuse proliferation of lymphocytes with varying cell sizes, abundant cytoplasm, stained or translucent cytoplasm, round or irregular nuclei, fine chromatin, inconspicuous nucleoli, and visible mitotic figures. Immunohistochemical analysis of the breast showed tumor cells were positive for CD3 (\u003cstrong\u003eE\u003c/strong\u003e), CD5 (\u003cstrong\u003eF\u003c/strong\u003e), CD20 (\u003cstrong\u003eH\u003c/strong\u003e), PD1(\u003cstrong\u003eJ\u003c/strong\u003e), and Ki67(60%) (\u003cstrong\u003eK\u003c/strong\u003e), but negative for CD2 (\u003cstrong\u003eD\u003c/strong\u003e), CD7 (\u003cstrong\u003eG\u003c/strong\u003e) and CD10 (\u003cstrong\u003eI\u003c/strong\u003e). \u003cstrong\u003eL\u003c/strong\u003e Tumor cells were also positive for Epstein-Barr virus small-encoded RNA by in situ hybridization. (\u003cstrong\u003eB HE, 5.0×; C HE, 55.5×; D-K,55.5×; L EBER-ISH, 55.5×\u003c/strong\u003e)\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-4251775/v1/1fbb2c5b2f67bb4e2343c646.png"},{"id":55015201,"identity":"fe0bdfea-33b1-4071-b855-6a2648f25110","added_by":"auto","created_at":"2024-04-19 22:52:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3421338,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4251775/v1/a429d5a0-c6c1-4af0-96d7-39607f3126df.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Classical Hodgkin Lymphoma progressing to Nodal T follicular helper cell lymphomas with aberrant CD20 expression and monoclonal TCR, IG rearrangements: A case report","fulltext":[{"header":"Background","content":"\u003cp\u003eCases of CHL progressing to PTCL are particularly rare [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This study reports a case of a CHL patient who developed PTCL after receiving ABVD therapy, highlighting the clinical complexity of CHL with concurrent PTCL. We conducted a thorough analysis of its pathological features and discussed its pathogenesis. Through this study, we aim to provide new insights into similar complications, offer guidance for clinical decision-making, and facilitate further research in the field of CHL and its secondary PTCL.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003e \u003cem\u003eSummary of case.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eA 74-year-old male was admitted to our hematology department with a one-year history of swelling in the right upper limb and three months of generalized weakness six years ago. A left cervical lymph node biopsy was performed. Microscopically, the tumor cell showed disrupted lymph node architecture with scattered mono- or binucleated cells of large size, abundant cytoplasm, coarse chromatin, and prominent nucleoli, amidst small lymphocytes, histiocytes, plasma cells, and eosinophils (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Immunohistochemical staining revealed positivity for large cell markers CD30 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD), weakly positive for PAX-5 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF), positive for Ki67 and MUM1 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eG), and negative for CD15, ALK, EMA, LCA (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE), CD3, CD20, CD21, and Bcl-2. In situ hybridization for EBV-EBER showed positivity in large cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eH). The lesion was consistent with CHL, with a tendency towards mixed cellularity. The patient was treated with six cycles of the ABVD regimen, achieving clinical complete remission. He was readmitted to our hematology department with swelling on the right shoulder, back, and upper arm 66 months later.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePhysical examination revealed palpable enlarged nodules on the skin of the right shoulder and back, measuring approximately 4cm\u0026times;3cm, with erythema and swelling but no ulceration, slightly elevated skin temperature, firm consistency, mild tenderness, no fluctuation, and no oozing or bleeding. Multiple nodules were palpable on the outer side of the right upper arm, with the largest one measuring about 1.0cm\u0026times;0.8cm, firm consistency, and no tenderness. Bilateral lung auscultation revealed coarse breath sounds without crackles or wheezes; cardiac rhythm was regular, and no significant abnormalities were detected in the auscultation areas of each valve. There was no edema in the lower limbs.\u003c/p\u003e \u003cp\u003eLaboratory examination showed that white blood cell count was 7.81\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, lymphocyte count was 1.31\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, hemoglobin 138g/L, platelet count was 178\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L. β2-microglobulin was elevated at a level of 2.63mg/L and the lactate dehydrogenase level was 223U/L.\u003c/p\u003e \u003cp\u003ePET-CT upon admission in July 2018 revealed multiple lymph node enlargements in the left parapharyngeal, bilateral cervical, bilateral supraclavicular, mediastinal, and retroperitoneal regions, as well as nodules in the right parotid gland area, subcutaneous nodules on the chest wall, and small nodules on the right forearm, all showing FDG hypermetabolism, suggesting a high possibility of malignant lymphoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Upon re-examination during hospitalization in October 2018, PET-CT showed a regular soft tissue density shadow in the right parotid gland area with clear borders and increased FDG metabolism. When compared with the imaging from July 2018, there were no significant changes in the volume or metabolism of the lesion, suggesting a possibility of benign pathology in the right parotid gland and then no abnormal FDG metabolism lesions were observed in other parts of the body on the whole-body PET-CT scan (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Prior to admission in January 2024, PET-CT identified showed multiple subcutaneous soft tissue nodules throughout the body with increased FDG metabolism, multiple lymph nodes of varying sizes throughout the body with increased FDG metabolism, bilateral thickening of the nasal turbinates and enlargement of the bilateral pharyngeal tonsils, with increased FDG metabolism observed in these lesions,and increased FDG uptake in the posterior wall of the nasopharynx. These findings suggested recurrence of lymphoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003ePathological findings.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe patient underwent a right shoulder-back subcutaneous tissue biopsy. Gross examination revealed two tissue samples, measuring 1.5cm and 1cm in length, respectively, with a diameter of 0.1cm. Microscopic examination showed disrupted lymph node architecture, diffuse proliferation of lymphocytes with varying cell sizes, abundant cytoplasm, stained or translucent cytoplasm, round or irregular nuclei, fine chromatin, inconspicuous nucleoli, and visible mitotic figures (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB,\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Immunohistochemical staining revealed proliferation of lymphocytes positive for CD3 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE), CD4, CD5 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF), PD-1 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eJ), CXCL13, partial CD20 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eH), Bcl-6, CD30 (30%), and Ki67 (60%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eK), negative for CD2 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD), CD7 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eG), CD8, CD56, TIA, GraB, PAX-5, CD79a, MUM1, CD21, CD10 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eI), and Bcl-2, and scattered positive for EBV-EBER in situ hybridization (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eL). Lymphocyte gene rearrangement testing showed positive results for TCRβ (Vβ\u0026thinsp;+\u0026thinsp;Jβ1/2), TCRγ (Vγ1\u0026ndash;11), IGk (Vk-Jk), and IGk (Vk-Kde\u0026thinsp;+\u0026thinsp;intron-Kde). Taken together, the above results suggest that this case may be the nTFHL-NOS with aberrant CD20 expression and monoclonal TCR, IG rearrangements.\u003c/p\u003e \u003cp\u003e \u003cem\u003eTreatment and outcome.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe patient underwent 2 cycles of chemotherapy with bendamustine and G-mox regimen.After two cycles of treatment, the skin lesions reduced to 2cm \u0026times; 1cm in size. We will continue to follow up with the patient.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCL refers to the simultaneous or sequential occurrence of two or more different types of lymphomas in the same anatomical structure [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. CL is a rare condition, accounting for 1-4.7% of new lymphoma cases each year. The pathogenesis of CL may be related to immune defects, such as immunosuppression caused by EBV infection in patients or immune dysregulation due to autoimmune diseases like rheumatoid arthritis. Mutations in DNA methylation genes such as IDH2 may also contribute to CL [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In this case, the development of nTFHL-NOS following treatment for CHL may be attributed to several mechanisms. EBV may induce the transformation of lymphocytes, stimulating T cell proliferation and leading to the development of T cell lymphoma [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Additionally, EBV-positive CHL patients have been found to exhibit increased secretion of interleukin-10 by Tr1 cells, enhancing immunosuppression in the lymphoma microenvironment and promoting unrestricted lymphocyte proliferation, thereby facilitating the development of a second lymphoma [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. HRS cells can secrete factors such as interferons and interleukins, which can suppress the immune response mediated by cytotoxic T lymphocytes. Furthermore, regulatory T cells interacting with HRS cells may inhibit the function of cytotoxic T lymphocytes, resulting in immune deficiency and increased susceptibility to T cell lymphomas [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Both CHL and nTFHL-NOS are EBV-related lymphomas with complex microenvironments, and chemotherapy for Hodgkin lymphoma may create conditions conducive to the transformation of a second lymphoma [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this case, the patient was diagnosed with CHL and underwent ABVD chemotherapy. After 66 months, they developed nTFHL-NOS, with tumor cells showing abnormal expression of CD20 and monoclonal rearrangements of TCR and IG. While CD20 is typically expressed on B cells at various developmental stages, including tumor B cells, it is lost before terminal B cell differentiation into plasma cells. Although CD20-positive T cell lymphomas are rare, when analyzing abnormal lymphocytes expressing CD20, it's important to consider both B lymphocytes expressing CD5 and T lymphocytes expressing CD20, hence co-analysis with CD3 and CD20 is recommended to distinguish CD20-positive T cell lymphoma [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Clinically, CD20-positive T cell lymphomas predominantly affect elderly males, primarily manifesting as lymph node lesions and often presenting at stage III/IV, with a generally poor prognosis possibly associated with CD20 expression. Among 101 CD20-positive T cell lymphoma patients treated with rituximab, 5 achieved complete remission, 3 had stable disease, 15 had partial remission or stable disease followed by relapse, and 4 showed no response [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Rituximab may be effective in treating CD20-positive T cell lymphomas, but its efficacy may vary depending on the intensity of CD20 expression.\u003c/p\u003e \u003cp\u003eApproximately 85,000 CHL cases are reported globally each year, with a higher incidence in individuals aged 15\u0026ndash;35 and over 55. As CHL has a high cure rate, the development of secondary tumors becomes a significant factor influencing patient survival. Therefore, preventing the occurrence of secondary tumors in CHL is crucial [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The tumor microenvironment is considered a critical factor in tumor prevention and progression. To inhibit tumor growth in the tumor microenvironment, the role of immune cells and molecules cannot be overlooked [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCHL \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Classical Hodgkin Lymphoma\u003c/p\u003e\n\u003cp\u003ePTCL \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Peripheral T-cell Lymphoma\u003c/p\u003e\n\u003cp\u003enTFHL-NOS \u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Nodal T follicular helper cell lymphomas,nos\u003c/p\u003e\n\u003cp\u003eTCR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;T cell reception\u003c/p\u003e\n\u003cp\u003eIG \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;immunoglobulin\u003c/p\u003e\n\u003cp\u003eABVD \u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Adriamycin, Bleomycin, Vinblastine, Dacarbazine\u003c/p\u003e\n\u003cp\u003eG-mox \u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Gemcitabine, Oxaliplatin\u003c/p\u003e\n\u003cp\u003ePET-CT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Positron emission tomography-computed tomography\u003c/p\u003e\n\u003cp\u003eCL \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Composite lymphoma\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are grateful for Shandong Natural Science Foundation and Yantai Science and Technology Plan for their support of this project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNing Zhu wrote the manuscript; Li Zhang performed immunohistochemial staining; Liling Song reviewed the cases and edited the manuscript; Xiaolong Sui provided the pathological pictures and contributed to the diagnosis; Na Li, Xiaoqian Liu and Ping Yang was in charge of the physical examination\u0026nbsp;and follow-up; Guohua Yu designed the study; All authors issued final approval for the version to be submitted; All authors approved the manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the fund of Shandong Natural Science Foundation [NO.ZR2022MH297], and Yantai Science and Technology Plan [NO.2021MSGY043].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Medical Ethics Committee of Yuhuangding Hospital in Yantai, Shandong, China, and was exempted from signing a written informed consent form by the Medical Ethics Committee.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient to publish this manuscript and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no any conflict of interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGui W, Wang J, Ma L, Wang Y, Su Lp. Clinicopathological analysis of composite lymphoma: A two-case report and literature review. Open Med (Wars). 2020; 15(1): 654-8. http://dx.doi.org/10.1515/med-2020-0191.\u003c/li\u003e\n\u003cli\u003eJin X, Liu H, Li J, Xiao X, Yuan X, Chen P, et al. Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review. J Zhejiang Univ Sci B. 2023; 24(8): 711-22. http://dx.doi.org/10.1631/jzus.B2300181.\u003c/li\u003e\n\u003cli\u003eWang H, Yang L, Li Q, Song H, Ji H. Case report: Composite mantle cell lymphoma and classical Hodgkin lymphoma. Pathol Oncol Res. 2023; 29: 1611051. http://dx.doi.org/10.3389/pore.2023.1611051.\u003c/li\u003e\n\u003cli\u003eAbraham L, Paul M, Varghese D, D\u0026apos;souza Co. A Rare Case of Metachronous Peripheral T-cell Non-Hodgkin Lymphoma Following Epstein-barr Virus-positive Diffuse Large B-cell Lymphoma, Not Otherwise Specified. Oman Med J. 2023; 38(2): e487. http://dx.doi.org/10.5001/omj.2023.13.\u003c/li\u003e\n\u003cli\u003eK\u0026uuml;ppers R, D\u0026uuml;hrsen U, Hansmann Ml. Pathogenesis, diagnosis, and treatment of composite lymphomas. Lancet Oncol. 2014; 15(10): e435-46. http://dx.doi.org/10.1016/s1470-2045(14)70153-6.\u003c/li\u003e\n\u003cli\u003eMorales O, Mrizak D, Fran\u0026ccedil;ois V, Mustapha R, Miroux C, Depil S, et al. Epstein-Barr virus infection induces an increase of T regulatory type 1 cells in Hodgkin lymphoma patients. Br J Haematol. 2014; 166(6): 875-90. http://dx.doi.org/10.1111/bjh.12980.\u003c/li\u003e\n\u003cli\u003eIchikawa A, Miyoshi H, Yamauchi T, Arakawa F, Kawano R, Muta H, et al. Composite lymphoma of peripheral T-cell lymphoma and Hodgkin lymphoma, mixed cellularity type; pathological and molecular analysis. Pathol Int. 2017; 67(4): 194-201. http://dx.doi.org/10.1111/pin.12515.\u003c/li\u003e\n\u003cli\u003eZhu X, Wu H, Yin W, Sun W. EBV positive classic Hodgkin\u0026apos;s lymphoma secondary to peripheral T-cell lymphoma: a case report and literature review. Chin J Cancer Prev Treat. 2016; 23(001): 56-9. http://dx.doi.org/10.16073/j.cnki.cjcpt.2016.01.013.\u003c/li\u003e\n\u003cli\u003eKakinoki Y, Hashiguchi J, Ishio T, Chiba K, Niino D, Ohshima K. CD20-positive primary gastric T-cell lymphoma poorly responding to initial treatment with rituximab plus CHOP, and a literature review. Int J Hematol. 2015; 102(6): 702-8. http://dx.doi.org/10.1007/s12185-015-1841-x.\u003c/li\u003e\n\u003cli\u003eTeshima K, Ohyagi H, Kume M, Takahashi S, Saito M, Takahashi N. Refractory CD20-positive peripheral T-cell lymphoma showing loss of CD20 expression after rituximab therapy and gain of CD20 expression after administration of vorinostat and gemcitabine. Rinsho Ketsueki. 2017; 58(11): 2227-31. http://dx.doi.org/10.11406/rinketsu.58.2227.\u003c/li\u003e\n\u003cli\u003eLi D, Kang H, Zhang L, Xu Z, Wang X, Wang L, et al. CD20 or CD79 \u0026alpha; Clinicopathological features of mature T/NK cell lymphoma with abnormal expression. Chin J Pathol. 2022; 51(5): 413-8. http://dx.doi.org/10.3760/cma.j.cn112151-20211219-00913.\u003c/li\u003e\n\u003cli\u003eShao S, Wang Y, Dai X, Xiao Y, Guan J, Lin D, et al. Clinical and pathological characteristics of CD20 positive T-cell lymphoma in five cases. Chin J Pathol. 2020; 49(10): 1021-6. http://dx.doi.org/10.3760/cma.j.cn112151-20200212-00081.\u003c/li\u003e\n\u003cli\u003eMunir F, Hardit V, Sheikh I. N, Alqahtani S, He J, Cuglievan B, et al. Classical Hodgkin Lymphoma: From Past to Future-A Comprehensive Review of Pathophysiology and Therapeutic Advances. Int J Mol Sci. 2023; 24(12). http://dx.doi.org/10.3390/ijms241210095.\u003c/li\u003e\n\u003cli\u003eDogan A. The real risk of secondary non-Hodgkin lymphoma following classical Hodgkin lymphoma. Haematologica. 2023; 108(5): 1220-1. http://dx.doi.org/10.3324/haematol.2022.281700.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4251775/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4251775/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCHL is a rare malignant neoplasm of the lymphatic system. While CHL typically responds well to conventional treatments, some cases may experience relapse or progression to other subtypes, with the development of secondary PTCL being relatively uncommon. Herein, we report a rare case of nTFHL-NOS arising from CHL, accompanied by aberrant CD20 expression and clonal rearrangements of TCR and IG.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eA 74-year-old male, was diagnosed with CHL, leaning towards the mixed cell type, six years ago. He received six cycles of the ABVD regimen, achieving complete clinical remission. The patient was admitted to our hospital due to the appearance of multiple skin nodules 66 months later. Physical examination showed a palpable mass measuring 3cm \u0026times; 2cm in its largest dimension on the skin of the right shoulder blade, characterized by firm consistency and limited mobility. A subcutaneous tissue biopsy of the right shoulder blade was performed. Histopathological analysis revealed nTFHL-NOS, with aberrant CD20 expression and clonal rearrangements of TCR and IG. The patient underwent two cycles of chemotherapy with brentuximab vedotin and the G-mox regimen, resulting in a reduction of the skin lesions to 2cm \u0026times; 1cm.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eEBV infection, complex tumor microenvironment, and genetic susceptibility may all contribute to the occurrence of CHL progressing to PTCL. Addressing the stability of the tumor microenvironment during CHL treatment to mitigate the risk of secondary PTCL development poses a significant challenge that warrants investigation.\u003c/p\u003e","manuscriptTitle":"Classical Hodgkin Lymphoma progressing to Nodal T follicular helper cell lymphomas with aberrant CD20 expression and monoclonal TCR, IG rearrangements: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-19 18:40:02","doi":"10.21203/rs.3.rs-4251775/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"aa2cf14d-aee2-401a-a0b4-97eb0d7a9377","owner":[],"postedDate":"April 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-19T22:44:20+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-19 18:40:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4251775","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4251775","identity":"rs-4251775","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}