Angioimmunoblastic T-cell lymphoma harboring a t(8;14)(q24;q11.2)/TCR::MYC translocation that presented with intestinal infiltration

Angioimmunoblastic T-cell lymphoma harboring a t(8;14)(q24;q11.2)/TCR::MYC translocation that presented with intestinal infiltration | 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 Angioimmunoblastic T-cell lymphoma harboring a t(8;14)(q24;q11.2)/TCR::MYC translocation that presented with intestinal infiltration Satoshi Ichikawa, Hiroki Kato, Naoya Morota, Hiroaki Abe, Akihisa Kawajiri, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4978464/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Dec, 2024 Read the published version in Annals of Hematology → Version 1 posted 9 You are reading this latest preprint version Abstract Although rearrangement of the MYC oncogene (MYC-R) is frequently observed in aggressive B-cell lymphomas, it is extremely rare in T-cell malignancies. A 64-year-old man who had been under observation for several years because of asymptomatic pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue(MALToma) was admitted to our hospital because of poor general condition and hypotension. Blood tests revealed thrombocytopenia and elevated serum lactate dehydrogenase levels, whereas computed tomography revealed systemic lymphadenopathy and splenomegaly. An inguinal lymph node biopsy precipitated a diagnosis of angioimmunoblastic T-cell lymphoma (AITL). Shortly after admission, the patient experienced spontaneous intestinal perforation and hemorrhage caused by multiple intestinal infiltrations of the AITL. Although chemotherapy was administered, the patient died several weeks after admission. A 46,XY,t(8;14)(q24;q11.2) karyotype was identified, and fluorescence in situ hybridization analyses showed split signals for the MYC and T-cell receptor (TCR) alpha genes, by which a TCR::MYC translocation was confirmed. Pathological autopsy analysis revealed systemic infiltration of the AITL and no MALToma lesions. Only a few cases of mature T-cell lymphoma harboring MYC-R have been reported in the literature thus far. To the best of our knowledge, this is the first reported case of AITL with TCR::MYC rearrangement. This condition could be associated with refractoriness to chemotherapy and aggressive clinical course with systemic infiltrationthat included the intestine. Figures Figure 1 Figure 2 Figure 3 Introduction The MYC oncogene (also known as c-MYC) is commonly activated in various human malignancies, as it can promote neoplastic growth through various mechanisms. MYC rearrangement (MYC-R) is frequently observed in aggressive B-cell lymphomas such as Burkitt lymphoma and diffuse large B-cell lymphoma, and is associated with aggressive clinical behavior and a poor prognosis. However, the clinicopathological significance of MYC activation in T-cell malignancies remains unclear. Thus far, MYC-R in mature T-cell neoplasms is considered extremely rare, and TCR::MYC translocation has only been reported in some cases of T-lymphoblastic leukemia or lymphoma [ 1 – 3 ]. To the best of our knowledge, this is the first reported case of angioimmunoblastic T-cell lymphoma (AITL) with MYC-R. Case Report A 64-year-old man who had been suffering from general fatigue and anorexia for one month was admitted to our hospital because of a poor general condition. He had been diagnosed with extranodal marginal zone lymphoma with mucosa-associated lymphoid tissue (MALToma) of the stomach 23 years prior, which resolved after Helicobacter pylori eradication and radiotherapy. MALToma had developed again in the patient’s lung 7 years prior, for which no therapeutic intervention was performed because the lesion had been asymptomatic and stable in size. On admission, he was alert and afebrile, but critically ill with hypotension. Complete blood testing revealed mild leukopenia (3,000/µL, with 82% neutrophil, 1% basophil, 12% lymphocyte, 4% monocyte, and 1% atypical lymphocyte) and thrombocytopenia (74,000/µL). Coagulation tests revealed elevated levels of fibrin degenerative product (18.4 µg/dL) and D-dimer (14.9 µg/dL), without decrease in fibrinogen level (204 mg/dL). Biochemical data showed elevated lactate dehydrogenase (LDH; 584 IU/L) and soluble interleukin-2 receptor (10,247 U/mL) levels, as well as mild liver dysfunction. Renal insufficiency (urea nitrogen 47 mg/dL and creatinine 2.03 mg/dL) and hypoalbuminemia (2.90 g/dL) were also observed, and considered likely to have been caused by dehydration and malnutrition since the patient could not eat or drink well immediately preceding his admission. The patient’s C-reactive protein (3.85 mg/dL) and ferritin (1,555 ng/mL) levels were mildly elevated. His plasma level of Epstein-Barr viral DNA was elevated (1.7 × 10 4 copies/µg DNA). Computed tomography (CT) showed systemic lymphadenopathy and splenomegaly. A biopsy of his inguinal lymph nodes was performed on the second day of his admission, which revealed the proliferation of abnormal pale and clear cells with irregularly shaped nuclei, under the background of infiltration of inflammatory cells and venules (Fig. 1 a). The abnormal cells were immunophenotypically CD2 + , CD3 + , CD4 + , CD5 + , CD7 – , CD8 – , ICOS + , and PD-1 + (Fig. 1 b–f). Tests for cytotoxic molecules such as TIA-1 and granzyme B were negative. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in only a few of the smaller lymphocytes (Fig. 1 g). The patient’s Ki-67 labeling index was ~ 70%. Rearrangement of the T-cell receptor gene at the Cβ1 locus was demonstrated via Southern blotting, whereas that of the immunoglobin heavy chain joining region (J H ) was negative. Based on these findings, a diagnosis of AITL was made. On the patient’s fourth day of admission, he suddenly experienced severe abdominal pain caused by a small intestinal perforation, which required emergency surgery. The resected intestinal specimen showed multiple infiltrations of abnormal T cells that were phenotypically identical to the lymphoma cells in the lymph nodes (Fig. 2 ). Bone marrow examination also revealed infiltration of the lymphoma cells (Fig. 3 a). One week after surgery, the patient experienced a massive intestinal hemorrhage, for which endoscopic procedures barely resulted in hemostasis. He received chemotherapy with an etoposide, prednisolone, cyclophosphamide, and doxorubicin (EP(O)CH regimen; omitting vincristine) beginning one week after the hemorrhage. Slight regression of the lymphadenopathies was observed via CT after three weeks of this treatment. However, over the next several days, rapid progression of the disease was observed, with severe coagulopathy resulting in intracranial hemorrhage. Shortly thereafter, the patient died. A pathological autopsy revealed infiltration of his AITL into the liver, spleen, kidneys, heart, right lung, small intestine, colon, and multiple lymph nodes (Supplementary Fig. 1). B-cell lymphoma lesions were not detected in any of the organs. G-banding analysis of the bone marrow showed a karyotype of t(8;14)(q24;q11.2) in 12 of the 16 analyzed cells (Fig. 3 b), which was also observed in an analysis of lymph nodes cell. Fluorescence in situ hybridization for the MYC (located on 8q24) and T-cell receptor alpha (TCRa; located on 14q11.2) genes revealed split signals for both (Fig. 3 c,d). These findings confirmed TCR::MYC translocation. Discussion The clinicopathological significance of MYC expression in peripheral T-cell lymphomas, including AITL, has yet to be established—although some investigations concerning this issue have been reported in the literature. Manso et al. analyzed C-MYC, GATA3, and Ki-67 expression in PTCLs (n=128, including 74 AITL cases and 54 cases of PTCL, not otherwise specified) using immunohistochemistry (IHC) and reported a significant correlation between positive C-MYC expression (>20% positivity) and high Ki-67 labeling index (>80%) [4]. C-MYC was positive in 13.3% of the cases, and its presence correlated with a poor prognosis among AITL cases. In another study, Peng et al. analyzed C-MYC statuses using IHC and FISH in 44 AITL cases. Those with positive C-MYC expression (defined as >5%; n=29) had lower survival rates than their negative counterparts, and monoclonal B-cell expansion was frequently observed in the C-MYC-positive population [5]. MYC amplification was detected in several cases, but its translocation was not observed. Considering these findings, positive MYC expression in AITL may be associated with an aggressive clinical course and poor prognosis, which should be confirmed in larger trials. MYC rearrangements in PTCL are extremely rare. Only a few PTCL cases harboring MYC rearrangements have been reported in the literature thus far. Their clinicopathological features, alongside those of the present case, are listed in Table 1 [6-11]. Among them, anaplastic large cell lymphoma (ALCL) is the most common histological type. Many of these appear to be accompanied by systemic lesions and B symptoms. Although ALCL, particularly if ALK-positive, typically has favorable chemosensitivity and a good prognosis, most ALCL cases with MYC rearrangement seem to be refractory to chemotherapy and result in early death. Consistent with these findings, our patient presented with systemic lesions, was refractory to chemotherapy, and experienced premature death. These aggressive clinical aspects may be associated with consistent activation of the MYC oncogene [12]. Although patients with AITL typically present with systemic extranodal lesions in regions such as the skin, liver, spleen, and bone marrow [13], intestinal AITL infiltration is considered extremely rare. Postmortem pathological investigations in previous cases of angioimmunoblastic lymphoid dysplasia (AILD), most of which would have been diagnosed as AITL using present-day criteria, did not reveal intestinal infiltration of lymphoma cells [14-17]. Some reported cases of AILD in which intestinal infiltration was pathologically demonstrated also showed disseminated lymphoma lesions [18, 19]. One patient presented with abdominal pain and diarrhea, was diagnosed via biopsies of the ileocecum and lymph nodes, and died 10 months after his diagnosis, without chemotherapeutic intervention [20]. That case was unique among a larger report of 27 cases of intestinal NK/T-cell lymphomas at a single institute. The present case is considered a unique case of AITL complicated by spontaneous intestinal perforation and fatal intestinal bleeding caused by AITL infiltration into the intestinal wall, accompanied by systemic infiltration into various other organs as well. These features may be associated with TCR::MYC translocation, considering the aggressive clinical behavior of MYC-associated lymphoma—irrespective of the histological subtype. In summary, we herein described a case of AITL harboring TCR::MYC that presented with intestinal infiltration. To the best of our knowledge, this is the first case report of AITL harboring a TCR::MYC translocation, which was clinically characterized by intestinal infiltration, refractoriness to chemotherapy, and an aggressive clinical course. Further experiences with this disease etiology are required to elucidate the clinicopathological features of AITL with MYC rearrangements. Declarations Funding No funding was provided for this study. Ethical approval Patient identifiers have been redacted. Written informed consent was obtained from the patient. Conflicts of interest The authors declare no conflicts of interest relevant to this study. References La Starza R, Borga C, Barba G et al. (2014) Genetic profile of T-cell acute lymphoblastic leukemias with MYC translocations. Blood 124:3577-3582. Parolini M, Mecucci C, Matteucci C et al. (2014) Highly aggressive T-cell acute lymphoblastic leukemia with t(8;14)(q24;q11): extensive genetic characterization and achievement of early molecular remission and long-term survival in an adult patient. Blood Cancer J 4:e176. Zhang X, Wang T, Zhang Y et al. (2023) Characteristics and therapeutic approaches for patients diagnosed with T-ALL/LBL exhibiting t(8;14)(q24;q11)/TCRA/D:MYC translocation. Leuk Lymphoma 64:2133-2139. Manso R, Bellas C, Martin-Acosta P et al. (2016) C-MYC is related to GATA3 expression and associated with poor prognosis in nodal peripheral T-cell lymphomas. Haematologica 101:e336-338. Peng Y, Yan H, Wang J, Zhang M, He J (2022) The clinicopathological characteristics of C-MYC protein in angioimmunoblastic T-cell lymphoma. Acta Biochim Pol 69:559-565. Monaco S, Tsao L, Murty VV et al. (2007) Pediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24) translocation and c-myc rearrangement terminating in a leukemic phase. Am J Hematol 82:59-64. Moritake H, Shimonodan H, Marutsuka K, Kamimura S, Kojima H, Nunoi H (2011) C-MYC rearrangement may induce an aggressive phenotype in anaplastic lymphoma kinase positive anaplastic large cell lymphoma: Identification of a novel fusion gene ALO17/C-MYC. Am J Hematol 86:75-78. Liang X, Branchford B, Greffe B et al. (2013) Dual ALK and MYC rearrangements leading to an aggressive variant of anaplastic large cell lymphoma. J Pediatr Hematol Oncol 35:e209-213. Luo DX, Li W, Ye MT, Yang Y, Tang G, You MJ (2020) "Double hit" anaplastic large cell lymphoma with concurrent ALK and MYC rearrangements. Am J Hematol 95:1625-1627. Khanlari M, Tang G, Hao S et al. (2021) Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma with MYC rearrangement. Br J Haematol 192:e17-e21. Okumura K, Ikebe M, Shimokama T et al. (2012) An unusual enteropathy-associated T-cell lymphoma with MYC translocation arising in a Japanese patient: a case report. World J Gastroenterol 18:2434-2437. Ott G, Rosenwald A, Campo E (2013) Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification. Blood 122:3884-3891. Swerdlow SH, Campo E, Harris NL et al. (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. International Agency for Research on Cancer, Lyon Frizzera G, Moran EM, Rappaport H (1974) Angio-immunoblastic lymphadenopathy with dysproteinaemia. Lancet 1:1070-1073. Lukes RJ, Tindle BH (1975) Immunoblastic lymphadenopathy. A hyperimmune entity resembling Hodgkin's disease. N Engl J Med 292:1-8. Cullen MH, Stansfeld AG, Oliver RT, Lister TA, Malpas JS (1979) Angio-immunoblastic lymphadenopathy: report of ten cases and review of the literature. Q J Med 48:151-177. Schauer PK, Straus DJ, Bagley CM, Jr. et al. (1981) Angioimmunoblastic lymphadenopathy: clinical spectrum of disease. Cancer 48:2493-2498. Rosenstein ED, Rickert RR, Gutkin M, Bacay A, Kramer N (1988) Colonic involvement in angioimmunoblastic lymphadenopathy resembling inflammatory bowel disease. Cancer 61:2244-2250. Turan I, Ozsan N, Doganavsargil B, Davulcu EA, Bulbul H (2020) The first report of colonic involvement of angioimmunoblastic T-cell lymphoma. Turk J Gastroenterol 31:413-414. Tang XF, Yang L, Duan S, Guo H, Guo QN (2018) Intestinal T-cell and NK/T-cell lymphomas: A clinicopathological study of 27 Chinese patients. Ann Diagn Pathol 37:107-117. Table Table 1. Reported peripheral T-cell lymphoma cases harboring MYC rearrangement Refer-ences Histological subtypes Age/sex Lesion sites B symp-toms Cytogenetic findings Therapy HSCT (donor) Outcome [6] ALCL, ALK(+) 13/M LN, peripheral blood NA NPM::ALK, MYC[R] CHOP-like, COPADM1 Yes (HLA-identical sibling) DOD (<6 months from presentation) [7] ALCL, ALK(+) 11/F LN, thyroid, skin Yes NPM::ALK, ALO17::MYC ALCL99 No DOD (7 months from diagnosis) [8] ALCL, ALK(+) 9/M Bone, intra-abdominal, adrenal, paratracheal, small intestine Yes NPM::ALK， MYC[R] ANHL0131, CCG-0894 Yes (cord blood) Alive without disease (>18 months from HSCT) [9] ALCL, ALK(+) 28/M LN No ALK[R], MYC[R] CHOP No Alive without disease (58 months from diagnosis) [10] ALCL, ALK(–) 58/F LN Yes MYC[R] CHOP, ESHAP No DOD (9 months from diagnosis) [10] ALCL, ALK(–) 63/M LN No MYC[R] , DUSP22[R] BV Yes (autologous) Died of unknown cause (53 months from diagnosis) [11] EATL 66/F Small intestine Yes MYC[R] NA* Yes (autologous) Alive without disease (6 months from operation) Present case AITL 64/M LN, intestine, bone marrow No TCR::MYC EPOCH No DOD (1.5 months from diagnosis) Abbreviations: ALCL, anaplastic large cell lymphoma; DOD, died of disease; EATL, enteropathy-associated T-cell lymphoma; F, female; HSCT, hematopoietic stem cell transplantation; LN, lymph node; M, male; NA, not available. Additional Declarations No competing interests reported. Supplementary Files TCRMYCAITLSupplFigs01.pptx Supplementary Figure 1: Pathological autopsy findings. Hematoxylin-Eosin staining of the liver (a, ×5; b, ×20), spleen (c, ×5; d, ×20), kidney (e, ×5; f, ×20), adrenal gland (g, ×5; h, ×20), small intestine (i, ×5; j, ×20), large intestine (k, ×5; l, ×20), heart (m, ×5; n, ×20), and lungs (o, ×5; p, ×20) showing lymphoma cell infiltration in all tissues. The abnormal cells in the pulmonary lesion were immunohistochemically CD3 + (q), CD4 + (r), and CD20 – (s), which suggests a T-cell lineage and excludes the possibility of MALT lymphoma. Cite Share Download PDF Status: Published Journal Publication published 18 Dec, 2024 Read the published version in Annals of Hematology → Version 1 posted Editorial decision: Revision requested 11 Nov, 2024 Reviews received at journal 29 Oct, 2024 Reviews received at journal 27 Oct, 2024 Reviewers agreed at journal 21 Oct, 2024 Reviewers agreed at journal 19 Oct, 2024 Reviewers invited by journal 10 Sep, 2024 Editor assigned by journal 30 Aug, 2024 Submission checks completed at journal 30 Aug, 2024 First submitted to journal 26 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4978464","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":357412760,"identity":"44c7b7a0-d8a5-45a7-b192-03659b99047b","order_by":0,"name":"Satoshi Ichikawa","email":"data:image/png;base64,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","orcid":"","institution":"Tohoku Medical and Pharmaceutical University","correspondingAuthor":true,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Ichikawa","suffix":""},{"id":357412761,"identity":"36a62cae-841e-494a-999b-41e95933ecbd","order_by":1,"name":"Hiroki Kato","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Kato","suffix":""},{"id":357412762,"identity":"068c83e1-45eb-40ec-8b7d-dd2250d12f9c","order_by":2,"name":"Naoya Morota","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Naoya","middleName":"","lastName":"Morota","suffix":""},{"id":357412763,"identity":"f232fc86-09c7-4ac3-b88c-9a2e43ea321c","order_by":3,"name":"Hiroaki Abe","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hiroaki","middleName":"","lastName":"Abe","suffix":""},{"id":357412764,"identity":"35bd2da6-84d1-4ff0-a362-7e3e103ef062","order_by":4,"name":"Akihisa Kawajiri","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Akihisa","middleName":"","lastName":"Kawajiri","suffix":""},{"id":357412765,"identity":"17ada4ce-ae76-4575-ba6a-76a6375b1fc5","order_by":5,"name":"Kyoko Inokura","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kyoko","middleName":"","lastName":"Inokura","suffix":""},{"id":357412766,"identity":"a7aa8bc3-7fbb-4658-b59f-6ce2c49e046d","order_by":6,"name":"Koichi Onodera","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Koichi","middleName":"","lastName":"Onodera","suffix":""},{"id":357412767,"identity":"bb51c090-cea2-4b9e-89fc-b3faa44e7220","order_by":7,"name":"Yasushi Onishi","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yasushi","middleName":"","lastName":"Onishi","suffix":""},{"id":357412768,"identity":"2afe4a71-817b-463c-ba22-35b062f17bf3","order_by":8,"name":"Noriko Fukuhara","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Noriko","middleName":"","lastName":"Fukuhara","suffix":""},{"id":357412769,"identity":"888f0064-bf4c-4f9f-b9d2-2e6e34c2b879","order_by":9,"name":"Satoko Sato","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Satoko","middleName":"","lastName":"Sato","suffix":""},{"id":357412770,"identity":"d5c084f8-3d9c-49ad-93b1-ecdfcbe1e84a","order_by":10,"name":"Fumiyoshi Fujishima","email":"","orcid":"","institution":"Tohoku Medical and Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Fumiyoshi","middleName":"","lastName":"Fujishima","suffix":""},{"id":357412771,"identity":"a53565d5-883c-4230-8bd9-79da13010c4a","order_by":11,"name":"Ryo Ichinohasama","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ryo","middleName":"","lastName":"Ichinohasama","suffix":""},{"id":357412772,"identity":"f81f0ae9-4859-4505-9d7c-ecb6a653813b","order_by":12,"name":"Hideo Harigae","email":"","orcid":"","institution":"Tohoku University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hideo","middleName":"","lastName":"Harigae","suffix":""}],"badges":[],"createdAt":"2024-08-26 13:52:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4978464/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4978464/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00277-024-06148-2","type":"published","date":"2024-12-18T15:58:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66939237,"identity":"9262484e-edad-4990-b03b-c7ccf8663b2e","added_by":"auto","created_at":"2024-10-18 08:39:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2190597,"visible":true,"origin":"","legend":"\u003cp\u003ePathological lymph node findings. \u003cstrong\u003e(a)\u003c/strong\u003e Hematoxylin-Eosin staining (×20; inlet, ×40). \u003cstrong\u003e(b–f)\u003c/strong\u003e Immunohistochemical staining for CD3 (b), CD4 (c), CD8 (d), PD-1 (e), and MYC (f). \u003cstrong\u003e(g)\u003c/strong\u003e \u003cem\u003eIn situ\u003c/em\u003ehybridization for EBER.\u003c/p\u003e","description":"","filename":"Slide1.png","url":"https://assets-eu.researchsquare.com/files/rs-4978464/v1/57f5838f53b116b2cec59d36.png"},{"id":66940102,"identity":"a8a62558-d987-498c-9218-a7715fb7aae9","added_by":"auto","created_at":"2024-10-18 08:47:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2200484,"visible":true,"origin":"","legend":"\u003cp\u003ePathological small intestine findings. \u003cstrong\u003e(a,b)\u003c/strong\u003e Hematoxylin-Eosin staining (a, ×4; b, ×40). \u003cstrong\u003e(c–f)\u003c/strong\u003e Immunohistochemical staining for CD3 (c), CD4 (d), PD-1 (e), and MYC (f). \u003cstrong\u003e(g)\u003c/strong\u003e In situ hybridization for EBER.\u003c/p\u003e","description":"","filename":"Slide2.png","url":"https://assets-eu.researchsquare.com/files/rs-4978464/v1/72e8d501a2fd0f47827676d6.png"},{"id":66939222,"identity":"feb17d43-a84e-4ea9-b74a-192f85d0f4c1","added_by":"auto","created_at":"2024-10-18 08:39:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":355013,"visible":true,"origin":"","legend":"\u003cp\u003eCytogenetical lymph node findings. \u003cstrong\u003e(a)\u003c/strong\u003e G-banding analysis. \u003cstrong\u003e(b)\u003c/strong\u003e FISH analysis of the MYC gene. \u003cstrong\u003e(c)\u003c/strong\u003e FISH analysis of the T-cell receptor alpha gene.\u003c/p\u003e","description":"","filename":"Slide3.png","url":"https://assets-eu.researchsquare.com/files/rs-4978464/v1/df74525d9e40d374b188a47d.png"},{"id":72201900,"identity":"969176c0-1462-4e02-942d-3694d86479bf","added_by":"auto","created_at":"2024-12-23 16:11:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5126633,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4978464/v1/ac5665ed-8c5f-42b5-8e82-da1947ef6e3a.pdf"},{"id":66939238,"identity":"5af6584d-5072-44ed-813d-579c9c07ad7e","added_by":"auto","created_at":"2024-10-18 08:39:07","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":10611492,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Figure 1:\u003c/strong\u003e Pathological autopsy findings. Hematoxylin-Eosin staining of the liver \u003cstrong\u003e(a\u003c/strong\u003e, ×5; \u003cstrong\u003eb\u003c/strong\u003e, ×20\u003cstrong\u003e)\u003c/strong\u003e, spleen \u003cstrong\u003e(c\u003c/strong\u003e, ×5; \u003cstrong\u003ed\u003c/strong\u003e, ×20\u003cstrong\u003e)\u003c/strong\u003e, kidney \u003cstrong\u003e(e\u003c/strong\u003e, ×5; \u003cstrong\u003ef\u003c/strong\u003e, ×20\u003cstrong\u003e)\u003c/strong\u003e, adrenal gland \u003cstrong\u003e(g\u003c/strong\u003e, ×5; \u003cstrong\u003eh\u003c/strong\u003e, ×20\u003cstrong\u003e)\u003c/strong\u003e, small intestine \u003cstrong\u003e(i\u003c/strong\u003e, ×5; \u003cstrong\u003ej\u003c/strong\u003e, ×20\u003cstrong\u003e)\u003c/strong\u003e, large intestine \u003cstrong\u003e(k\u003c/strong\u003e, ×5; \u003cstrong\u003el\u003c/strong\u003e, ×20\u003cstrong\u003e)\u003c/strong\u003e, heart \u003cstrong\u003e(m\u003c/strong\u003e, ×5; \u003cstrong\u003en\u003c/strong\u003e, ×20\u003cstrong\u003e)\u003c/strong\u003e, and lungs \u003cstrong\u003e(o\u003c/strong\u003e, ×5; \u003cstrong\u003ep\u003c/strong\u003e, ×20\u003cstrong\u003e)\u003c/strong\u003e showing lymphoma cell infiltration in all tissues. The abnormal cells in the pulmonary lesion were immunohistochemically CD3\u003csup\u003e+\u003c/sup\u003e \u003cstrong\u003e(q)\u003c/strong\u003e, CD4\u003csup\u003e+\u003c/sup\u003e \u003cstrong\u003e(r)\u003c/strong\u003e, and CD20\u003csup\u003e–\u003c/sup\u003e (\u003cstrong\u003es\u003c/strong\u003e), which suggests a T-cell lineage and excludes the possibility of MALT lymphoma.\u003c/p\u003e","description":"","filename":"TCRMYCAITLSupplFigs01.pptx","url":"https://assets-eu.researchsquare.com/files/rs-4978464/v1/9060e7f3f89f6d757e8d255c.pptx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Angioimmunoblastic T-cell lymphoma harboring a t(8;14)(q24;q11.2)/TCR::MYC translocation that presented with intestinal infiltration","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe MYC oncogene (also known as c-MYC) is commonly activated in various human malignancies, as it can promote neoplastic growth through various mechanisms. MYC rearrangement (MYC-R) is frequently observed in aggressive B-cell lymphomas such as Burkitt lymphoma and diffuse large B-cell lymphoma, and is associated with aggressive clinical behavior and a poor prognosis. However, the clinicopathological significance of MYC activation in T-cell malignancies remains unclear. Thus far, MYC-R in mature T-cell neoplasms is considered extremely rare, and TCR::MYC translocation has only been reported in some cases of T-lymphoblastic leukemia or lymphoma [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. To the best of our knowledge, this is the first reported case of angioimmunoblastic T-cell lymphoma (AITL) with MYC-R.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 64-year-old man who had been suffering from general fatigue and anorexia for one month was admitted to our hospital because of a poor general condition. He had been diagnosed with extranodal marginal zone lymphoma with mucosa-associated lymphoid tissue (MALToma) of the stomach 23 years prior, which resolved after \u003cem\u003eHelicobacter pylori\u003c/em\u003e eradication and radiotherapy. MALToma had developed again in the patient\u0026rsquo;s lung 7 years prior, for which no therapeutic intervention was performed because the lesion had been asymptomatic and stable in size. On admission, he was alert and afebrile, but critically ill with hypotension. Complete blood testing revealed mild leukopenia (3,000/\u0026micro;L, with 82% neutrophil, 1% basophil, 12% lymphocyte, 4% monocyte, and 1% atypical lymphocyte) and thrombocytopenia (74,000/\u0026micro;L). Coagulation tests revealed elevated levels of fibrin degenerative product (18.4 \u0026micro;g/dL) and D-dimer (14.9 \u0026micro;g/dL), without decrease in fibrinogen level (204 mg/dL). Biochemical data showed elevated lactate dehydrogenase (LDH; 584 IU/L) and soluble interleukin-2 receptor (10,247 U/mL) levels, as well as mild liver dysfunction. Renal insufficiency (urea nitrogen 47 mg/dL and creatinine 2.03 mg/dL) and hypoalbuminemia (2.90 g/dL) were also observed, and considered likely to have been caused by dehydration and malnutrition since the patient could not eat or drink well immediately preceding his admission. The patient\u0026rsquo;s C-reactive protein (3.85 mg/dL) and ferritin (1,555 ng/mL) levels were mildly elevated. His plasma level of Epstein-Barr viral DNA was elevated (1.7 \u0026times; 10\u003csup\u003e4\u003c/sup\u003ecopies/\u0026micro;g DNA). Computed tomography (CT) showed systemic lymphadenopathy and splenomegaly. A biopsy of his inguinal lymph nodes was performed on the second day of his admission, which revealed the proliferation of abnormal pale and clear cells with irregularly shaped nuclei, under the background of infiltration of inflammatory cells and venules (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). The abnormal cells were immunophenotypically CD2\u003csup\u003e+\u003c/sup\u003e, CD3\u003csup\u003e+\u003c/sup\u003e, CD4\u003csup\u003e+\u003c/sup\u003e, CD5\u003csup\u003e+\u003c/sup\u003e, CD7\u003csup\u003e\u0026ndash;\u003c/sup\u003e, CD8\u003csup\u003e\u0026ndash;\u003c/sup\u003e, ICOS\u003csup\u003e+\u003c/sup\u003e, and PD-1\u003csup\u003e+\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb\u0026ndash;f). Tests for cytotoxic molecules such as TIA-1 and granzyme B were negative. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in only a few of the smaller lymphocytes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eg). The patient\u0026rsquo;s Ki-67 labeling index was ~\u0026thinsp;70%. Rearrangement of the T-cell receptor gene at the Cβ1 locus was demonstrated via Southern blotting, whereas that of the immunoglobin heavy chain joining region (J\u003csub\u003eH\u003c/sub\u003e) was negative. Based on these findings, a diagnosis of AITL was made.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOn the patient\u0026rsquo;s fourth day of admission, he suddenly experienced severe abdominal pain caused by a small intestinal perforation, which required emergency surgery. The resected intestinal specimen showed multiple infiltrations of abnormal T cells that were phenotypically identical to the lymphoma cells in the lymph nodes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Bone marrow examination also revealed infiltration of the lymphoma cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). One week after surgery, the patient experienced a massive intestinal hemorrhage, for which endoscopic procedures barely resulted in hemostasis. He received chemotherapy with an etoposide, prednisolone, cyclophosphamide, and doxorubicin (EP(O)CH regimen; omitting vincristine) beginning one week after the hemorrhage. Slight regression of the lymphadenopathies was observed via CT after three weeks of this treatment. However, over the next several days, rapid progression of the disease was observed, with severe coagulopathy resulting in intracranial hemorrhage. Shortly thereafter, the patient died. A pathological autopsy revealed infiltration of his AITL into the liver, spleen, kidneys, heart, right lung, small intestine, colon, and multiple lymph nodes (Supplementary Fig.\u0026nbsp;1). B-cell lymphoma lesions were not detected in any of the organs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eG-banding analysis of the bone marrow showed a karyotype of t(8;14)(q24;q11.2) in 12 of the 16 analyzed cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb), which was also observed in an analysis of lymph nodes cell. Fluorescence in situ hybridization for the MYC (located on 8q24) and T-cell receptor alpha (TCRa; located on 14q11.2) genes revealed split signals for both (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec,d). These findings confirmed TCR::MYC translocation.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe clinicopathological significance of MYC expression in peripheral T-cell lymphomas, including AITL, has yet to be established—although some investigations concerning this issue have been reported in the literature. Manso et al. analyzed C-MYC, GATA3, and Ki-67 expression in PTCLs (n=128, including 74 AITL cases and 54 cases of PTCL, not otherwise specified) using immunohistochemistry (IHC) and reported a significant correlation between positive C-MYC expression (\u0026gt;20% positivity) and high Ki-67 labeling index (\u0026gt;80%) [4]. C-MYC was positive in 13.3% of the cases, and its presence correlated with a poor prognosis among AITL cases. In another study, Peng et al.\u0026nbsp;analyzed C-MYC statuses using IHC and FISH in 44 AITL cases. Those with positive C-MYC expression (defined as \u0026gt;5%; n=29) had\u0026nbsp;lower survival rates than their negative counterparts, and monoclonal B-cell expansion was frequently observed in the C-MYC-positive population [5]. MYC amplification was detected in several cases, but its translocation was not observed. Considering these findings, positive MYC expression in AITL may be associated with an\u0026nbsp;aggressive clinical course and poor prognosis, which should be confirmed in larger trials.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;MYC rearrangements in PTCL\u0026nbsp;are extremely rare. Only a few PTCL cases harboring MYC rearrangements have been reported in the literature thus far. Their clinicopathological features,\u0026nbsp;alongside those of the present case, are listed in Table 1 [6-11]. Among them, anaplastic large cell lymphoma (ALCL) is the most common histological type. Many of these appear to be accompanied by systemic lesions and B symptoms. Although ALCL, particularly if ALK-positive, typically has favorable chemosensitivity and a good prognosis,\u0026nbsp;most ALCL cases with MYC rearrangement seem to be refractory to chemotherapy and result in early death. Consistent with these\u0026nbsp;findings, our patient presented with systemic lesions, was refractory to chemotherapy, and experienced premature death. These aggressive clinical aspects may be associated with consistent activation of the MYC oncogene [12].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; Although patients with AITL typically present with systemic extranodal lesions\u0026nbsp;in regions such as the\u0026nbsp;skin, liver, spleen, and bone marrow [13], intestinal AITL infiltration is considered extremely rare. Postmortem pathological investigations in previous cases of angioimmunoblastic lymphoid dysplasia (AILD), most of which would have been\u0026nbsp;diagnosed as AITL using present-day criteria, did not reveal intestinal infiltration of lymphoma cells [14-17]. Some reported cases of AILD in which intestinal infiltration was pathologically demonstrated also showed disseminated lymphoma lesions [18, 19]. One patient presented with abdominal pain and diarrhea, was diagnosed via biopsies of the ileocecum and lymph nodes, and\u0026nbsp;died 10 months after his diagnosis, without chemotherapeutic intervention [20]. That case was unique among a larger report of\u0026nbsp;27 cases of intestinal\u0026nbsp;NK/T-cell lymphomas at a single institute. The present case is considered a unique case of AITL complicated by spontaneous intestinal perforation and fatal intestinal bleeding caused by AITL infiltration into the intestinal wall, accompanied by systemic infiltration into various other organs as well. These features may be associated with TCR::MYC translocation, considering the aggressive clinical behavior of MYC-associated lymphoma—irrespective of the histological subtype.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;In summary, we herein described a case of AITL harboring TCR::MYC that presented with intestinal infiltration. To the best of our knowledge, this is the first case report of AITL harboring a\u0026nbsp;TCR::MYC translocation, which was clinically characterized by intestinal infiltration, refractoriness to chemotherapy, and an aggressive\u0026nbsp;clinical course. Further experiences with this disease etiology are required to elucidate the clinicopathological features of AITL with MYC rearrangements.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was provided for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003cbr\u003e\u0026nbsp;\u003c/strong\u003ePatient identifiers have been redacted. Written informed consent was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest relevant to this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLa Starza R, Borga C, Barba G et al. (2014) Genetic profile of T-cell acute lymphoblastic leukemias with MYC translocations. Blood 124:3577-3582.\u003c/li\u003e\n\u003cli\u003eParolini M, Mecucci C, Matteucci C et al. (2014) Highly aggressive T-cell acute lymphoblastic leukemia with t(8;14)(q24;q11): extensive genetic characterization and achievement of early molecular remission and long-term survival in an adult patient. Blood Cancer J 4:e176.\u003c/li\u003e\n\u003cli\u003eZhang X, Wang T, Zhang Y et al. (2023) Characteristics and therapeutic approaches for patients diagnosed with T-ALL/LBL exhibiting t(8;14)(q24;q11)/TCRA/D:MYC translocation. Leuk Lymphoma 64:2133-2139.\u003c/li\u003e\n\u003cli\u003eManso R, Bellas C, Martin-Acosta P et al. (2016) C-MYC is related to GATA3 expression and associated with poor prognosis in nodal peripheral T-cell lymphomas. Haematologica 101:e336-338.\u003c/li\u003e\n\u003cli\u003ePeng Y, Yan H, Wang J, Zhang M, He J (2022) The clinicopathological characteristics of C-MYC protein in angioimmunoblastic T-cell lymphoma. Acta Biochim Pol 69:559-565.\u003c/li\u003e\n\u003cli\u003eMonaco S, Tsao L, Murty VV et al. (2007) Pediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24) translocation and c-myc rearrangement terminating in a leukemic phase. Am J Hematol 82:59-64.\u003c/li\u003e\n\u003cli\u003eMoritake H, Shimonodan H, Marutsuka K, Kamimura S, Kojima H, Nunoi H (2011) C-MYC rearrangement may induce an aggressive phenotype in anaplastic lymphoma kinase positive anaplastic large cell lymphoma: Identification of a novel fusion gene ALO17/C-MYC. Am J Hematol 86:75-78.\u003c/li\u003e\n\u003cli\u003eLiang X, Branchford B, Greffe B et al. (2013) Dual ALK and MYC rearrangements leading to an aggressive variant of anaplastic large cell lymphoma. J Pediatr Hematol Oncol 35:e209-213.\u003c/li\u003e\n\u003cli\u003eLuo DX, Li W, Ye MT, Yang Y, Tang G, You MJ (2020) \u0026quot;Double hit\u0026quot; anaplastic large cell lymphoma with concurrent ALK and MYC rearrangements. Am J Hematol 95:1625-1627.\u003c/li\u003e\n\u003cli\u003eKhanlari M, Tang G, Hao S et al. (2021) Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma with MYC rearrangement. Br J Haematol 192:e17-e21.\u003c/li\u003e\n\u003cli\u003eOkumura K, Ikebe M, Shimokama T et al. (2012) An unusual enteropathy-associated T-cell lymphoma with MYC translocation arising in a Japanese patient: a case report. World J Gastroenterol 18:2434-2437.\u003c/li\u003e\n\u003cli\u003eOtt G, Rosenwald A, Campo E (2013) Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification. Blood 122:3884-3891.\u003c/li\u003e\n\u003cli\u003eSwerdlow SH, Campo E, Harris NL et al. (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. International Agency for Research on Cancer, Lyon\u003c/li\u003e\n\u003cli\u003eFrizzera G, Moran EM, Rappaport H (1974) Angio-immunoblastic lymphadenopathy with dysproteinaemia. Lancet 1:1070-1073.\u003c/li\u003e\n\u003cli\u003eLukes RJ, Tindle BH (1975) Immunoblastic lymphadenopathy. A hyperimmune entity resembling Hodgkin\u0026apos;s disease. N Engl J Med 292:1-8.\u003c/li\u003e\n\u003cli\u003eCullen MH, Stansfeld AG, Oliver RT, Lister TA, Malpas JS (1979) Angio-immunoblastic lymphadenopathy: report of ten cases and review of the literature. Q J Med 48:151-177.\u003c/li\u003e\n\u003cli\u003eSchauer PK, Straus DJ, Bagley CM, Jr. et al. (1981) Angioimmunoblastic lymphadenopathy: clinical spectrum of disease. Cancer 48:2493-2498.\u003c/li\u003e\n\u003cli\u003eRosenstein ED, Rickert RR, Gutkin M, Bacay A, Kramer N (1988) Colonic involvement in angioimmunoblastic lymphadenopathy resembling inflammatory bowel disease. Cancer 61:2244-2250.\u003c/li\u003e\n\u003cli\u003eTuran I, Ozsan N, Doganavsargil B, Davulcu EA, Bulbul H (2020) The first report of colonic involvement of angioimmunoblastic T-cell lymphoma. Turk J Gastroenterol 31:413-414.\u003c/li\u003e\n\u003cli\u003eTang XF, Yang L, Duan S, Guo H, Guo QN (2018) Intestinal T-cell and NK/T-cell lymphomas: A clinicopathological study of 27 Chinese patients. Ann Diagn Pathol 37:107-117.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1. Reported peripheral T-cell lymphoma cases harboring MYC rearrangement\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"973\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.825462012320329%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRefer-ences\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8028747433264884%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistological subtypes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge/sex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.480492813141684%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLesion sites\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eB symp-toms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.453798767967147%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCytogenetic findings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.650924024640657%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.677618069815194%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHSCT (donor)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.404517453798768%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.825462012320329%\" valign=\"top\"\u003e\n \u003cp\u003e[6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8028747433264884%\" valign=\"top\"\u003e\n \u003cp\u003eALCL, ALK(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e13/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.480492813141684%\" valign=\"top\"\u003e\n \u003cp\u003eLN, peripheral blood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.453798767967147%\" valign=\"top\"\u003e\n \u003cp\u003eNPM::ALK, \u003cstrong\u003eMYC[R]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.650924024640657%\" valign=\"top\"\u003e\n \u003cp\u003eCHOP-like, COPADM1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.677618069815194%\" valign=\"top\"\u003e\n \u003cp\u003eYes (HLA-identical sibling)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.404517453798768%\" valign=\"top\"\u003e\n \u003cp\u003eDOD (\u0026lt;6 months from presentation)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.825462012320329%\" valign=\"top\"\u003e\n \u003cp\u003e[7]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8028747433264884%\" valign=\"top\"\u003e\n \u003cp\u003eALCL, ALK(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e11/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.480492813141684%\" valign=\"top\"\u003e\n \u003cp\u003eLN, thyroid, skin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.453798767967147%\" valign=\"top\"\u003e\n \u003cp\u003eNPM::ALK, \u003cstrong\u003eALO17::MYC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.650924024640657%\" valign=\"top\"\u003e\n \u003cp\u003eALCL99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.677618069815194%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.404517453798768%\" valign=\"top\"\u003e\n \u003cp\u003eDOD (7 months from diagnosis)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.825462012320329%\" valign=\"top\"\u003e\n \u003cp\u003e[8]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8028747433264884%\" valign=\"top\"\u003e\n \u003cp\u003eALCL, ALK(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e9/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.480492813141684%\" valign=\"top\"\u003e\n \u003cp\u003eBone, intra-abdominal, adrenal, paratracheal, small intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.453798767967147%\" valign=\"top\"\u003e\n \u003cp\u003eNPM::ALK，\u003cstrong\u003eMYC[R]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.650924024640657%\" valign=\"top\"\u003e\n \u003cp\u003eANHL0131, CCG-0894\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.677618069815194%\" valign=\"top\"\u003e\n \u003cp\u003eYes (cord blood)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.404517453798768%\" valign=\"top\"\u003e\n \u003cp\u003eAlive without disease (\u0026gt;18 months from HSCT)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.825462012320329%\" valign=\"top\"\u003e\n \u003cp\u003e[9]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8028747433264884%\" valign=\"top\"\u003e\n \u003cp\u003eALCL, ALK(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e28/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.480492813141684%\" valign=\"top\"\u003e\n \u003cp\u003eLN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.453798767967147%\" valign=\"top\"\u003e\n \u003cp\u003eALK[R], \u003cstrong\u003eMYC[R]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.650924024640657%\" valign=\"top\"\u003e\n \u003cp\u003eCHOP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.677618069815194%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.404517453798768%\" valign=\"top\"\u003e\n \u003cp\u003eAlive without disease (58 months from diagnosis)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.825462012320329%\" valign=\"top\"\u003e\n \u003cp\u003e[10]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8028747433264884%\" valign=\"top\"\u003e\n \u003cp\u003eALCL, ALK(\u0026ndash;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e58/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.480492813141684%\" valign=\"top\"\u003e\n \u003cp\u003eLN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.453798767967147%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMYC[R]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.650924024640657%\" valign=\"top\"\u003e\n \u003cp\u003eCHOP, ESHAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.677618069815194%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.404517453798768%\" valign=\"top\"\u003e\n \u003cp\u003eDOD (9 months from diagnosis)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.825462012320329%\" valign=\"top\"\u003e\n \u003cp\u003e[10]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8028747433264884%\" valign=\"top\"\u003e\n \u003cp\u003eALCL, ALK(\u0026ndash;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e63/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.480492813141684%\" valign=\"top\"\u003e\n \u003cp\u003eLN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.453798767967147%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMYC[R]\u003c/strong\u003e, DUSP22[R]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.650924024640657%\" valign=\"top\"\u003e\n \u003cp\u003eBV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.677618069815194%\" valign=\"top\"\u003e\n \u003cp\u003eYes (autologous)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.404517453798768%\" valign=\"top\"\u003e\n \u003cp\u003eDied of unknown cause\u003cbr\u003e\u0026nbsp;(53 months from diagnosis)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.825462012320329%\" valign=\"top\"\u003e\n \u003cp\u003e[11]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8028747433264884%\" valign=\"top\"\u003e\n \u003cp\u003eEATL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e66/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.480492813141684%\" valign=\"top\"\u003e\n \u003cp\u003eSmall intestine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.453798767967147%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMYC[R]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.650924024640657%\" valign=\"top\"\u003e\n \u003cp\u003eNA*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.677618069815194%\" valign=\"top\"\u003e\n \u003cp\u003eYes (autologous)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.404517453798768%\" valign=\"top\"\u003e\n \u003cp\u003eAlive without disease\u003cbr\u003e\u0026nbsp;(6 months from operation)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.825462012320329%\" valign=\"top\"\u003e\n \u003cp\u003ePresent case\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8028747433264884%\" valign=\"top\"\u003e\n \u003cp\u003eAITL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003e64/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.480492813141684%\" valign=\"top\"\u003e\n \u003cp\u003eLN, intestine, bone marrow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.852156057494867%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.453798767967147%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTCR::MYC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.650924024640657%\" valign=\"top\"\u003e\n \u003cp\u003eEPOCH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.677618069815194%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.404517453798768%\" valign=\"top\"\u003e\n \u003cp\u003eDOD (1.5 months from diagnosis)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: ALCL, anaplastic large cell lymphoma; DOD, died of disease; EATL, enteropathy-associated T-cell lymphoma; F, female; HSCT, hematopoietic stem cell transplantation; LN, lymph node; M, male; NA, not available.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4978464/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4978464/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAlthough rearrangement of the MYC oncogene (MYC-R) is frequently observed in aggressive B-cell lymphomas, it is extremely rare in T-cell malignancies. A 64-year-old man who had been under observation for several years because of asymptomatic pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue(MALToma) was admitted to our hospital because of poor general condition and hypotension. Blood tests revealed thrombocytopenia and elevated serum lactate dehydrogenase levels, whereas computed tomography revealed systemic lymphadenopathy and splenomegaly. An inguinal lymph node biopsy precipitated a diagnosis of angioimmunoblastic T-cell lymphoma (AITL). Shortly after admission, the patient experienced spontaneous intestinal perforation and hemorrhage caused by multiple intestinal infiltrations of the AITL. Although chemotherapy was administered, the patient died several weeks after admission. A 46,XY,t(8;14)(q24;q11.2) karyotype was identified, and fluorescence in situ hybridization analyses showed split signals for the MYC and T-cell receptor (TCR) alpha genes, by which a TCR::MYC translocation was confirmed. Pathological autopsy analysis revealed systemic infiltration of the AITL and no MALToma lesions. Only a few cases of mature T-cell lymphoma harboring MYC-R have been reported in the literature thus far. To the best of our knowledge, this is the first reported case of AITL with TCR::MYC rearrangement. This condition could be associated with refractoriness to chemotherapy and aggressive clinical course with systemic infiltrationthat included the intestine.\u003c/p\u003e","manuscriptTitle":"Angioimmunoblastic T-cell lymphoma harboring a t(8;14)(q24;q11.2)/TCR::MYC translocation that presented with intestinal infiltration","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-18 08:38:59","doi":"10.21203/rs.3.rs-4978464/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-11T18:42:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-29T14:49:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-28T02:40:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331027426767575848261570190383499248792","date":"2024-10-21T11:15:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"217221184731625614023144564411839675682","date":"2024-10-20T02:00:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-10T16:03:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-30T12:13:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-30T12:13:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2024-08-26T13:50:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a2b7e258-b371-4cba-bc59-d86abb125262","owner":[],"postedDate":"October 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-23T16:03:44+00:00","versionOfRecord":{"articleIdentity":"rs-4978464","link":"https://doi.org/10.1007/s00277-024-06148-2","journal":{"identity":"annals-of-hematology","isVorOnly":false,"title":"Annals of Hematology"},"publishedOn":"2024-12-18 15:58:01","publishedOnDateReadable":"December 18th, 2024"},"versionCreatedAt":"2024-10-18 08:38:59","video":"","vorDoi":"10.1007/s00277-024-06148-2","vorDoiUrl":"https://doi.org/10.1007/s00277-024-06148-2","workflowStages":[]},"version":"v1","identity":"rs-4978464","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4978464","identity":"rs-4978464","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}