Pulmonary arterial hypertension as an unusual presentation of angioimmunoblastic T-cell lymphoma: a case report

Pulmonary arterial hypertension as an unusual presentation of angioimmunoblastic T-cell lymphoma: 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 Pulmonary arterial hypertension as an unusual presentation of angioimmunoblastic T-cell lymphoma: a case report Ji Yoon Jung This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4686831/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 3 You are reading this latest preprint version Abstract Background: Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkin lymphoma with diverse clinical presentations. This report describes a unique case of AITL presenting with pulmonary arterial hypertension (PAH), a rarely associated complication. Case presentation: An 84-year-old male with a history of gastric cancer presented with dyspnea. Initial investigations revealed lymphadenopathy, pleural effusion, and severe PAH. Diagnostic workup, including histopathological and immunohistochemical analysis of an excisional lymph node biopsy and advanced imaging techniques, confirmed the diagnosis of AITL. The patient was treated with a mini-CHOP (comprising adriamycin, cyclophosphamide, mesna, vincristine, and prednisolone) chemotherapy regimen, leading to significant improvement in PAH and other symptoms, and achieving complete remission as confirmed by torso positron emission tomography-computed tomography scans. This case highlights the diagnostic challenge posed by atypical manifestations of AITL, such as PAH. The effective response to chemotherapy in this patient emphasizes the potential for conventional treatment regimens in managing rare presentations of AITL. Conclusions: This report contributes to the limited literature on AITL with PAH and underscores the importance of considering AITL in differential diagnoses for patients presenting with PAH. Angioimmunoblastic T-cell lymphoma AITL Pulmonary artery hypertension Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of mature peripheral T-cell lymphoma (PTCL) originating from follicular T helper cells [ 1 ]. Diagnosing AITL presents a challenge due to its diverse symptomatic presentation, which may include lymphadenopathy, B-symptoms (fever, weight loss, and night sweats), skin rash, pleural effusion, hepatosplenomegaly, and immune dysregulation. A comprehensive diagnostic approach is required, involving excisional lymph node biopsy, imaging and laboratory tests, and morphologic, immunophenotypic, molecular, and cytogenetic analyses [ 2 ]. Histologically, AITL exhibits lymph node structural effacement, enhanced proliferation of follicular dendritic cells, and high endothelial venules [ 3 – 5 ]. Recent advancements in next-generation sequencing (NGS) have identified mutations in genes such as Tet methyl cytosine dioxygenase 2 (TET2), DNA-methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 2 (IDH2)-R172, and Ras homolog family member A (RHOA), significantly aiding AITL diagnosis [ 6 – 12 ]. The prognosis of AITL depends on various factors, including age, Eastern Cooperative Oncology Group (ECOG) performance status, presence of B symptoms, extra nodal involvement, and platelet count [ 2 , 13 ]. This case report documents an 84-year-old male patient with AITL, who presented with an atypical manifestation of pulmonary arterial hypertension (PAH) and transudative pleural effusion. This case underscores the diagnostic complexity of AITL with non-classical presentations and highlights the necessity of including AITL in differential diagnoses for patients with PAH. Notably, this patient exhibited clinical improvement with targeted treatment, marking the first documented case of PAH resolution following AITL treatment [ 14 ] . Case presentation An 84-year-old male with a history of early gastric cancer (treated in 2016) presented to the Department of Respiratory Medicine in May 2022 with dyspnea. Initial chest radiography revealed cardiomegaly and bilateral moderate pleural effusion (Fig. 1 ). Pleural fluid analysis indicated a transudative effusion, with fluid protein at 3.16 g/dL, serum protein at 6.87 g/dL, fluid lactate dehydrogenase (LDH) at 259 IU/L, and serum LDH at 740 IU/L. Transthoracic echocardiography (TTE) showed markedly increased right ventricular systolic pressure (RVSP) at 114 mmHg, indicative of pulmonary hypertension. Computed tomography (CT) of the chest identified multiple mediastinal lymph node enlargements (Fig. 2 ). The patient was subsequently referred to the Department of Hematology and Oncology. Laboratory findings included an elevated LDH level of 824 U/L and NT-proBNP at 1,090 pg/mL. A positron emission tomography-computed tomography (PET-CT) scan was performed to evaluate for hematologic malignancy, revealing hypermetabolic lymph nodes and moderate splenomegaly (Fig. 3 ). An excisional biopsy of a right axillary lymph node confirmed the diagnosis of AITL. Immunohistochemical analysis showed positive staining for CD4, CD10, CD21, BCL6, and CXCL13 in the follicular dendritic cells (FDCs) (Fig. 4 , Table 1 ). In situ hybridization detected positive Epstein-Barr encoding region (EBER) signals. NGS identified mutations in two tier-1 genes and four tier-3 genes (Table 2 ). Table 1 Immunohistochemical stain Marker Target cells CD3 Positive CD20 Negative CD4:CD8 CD4 > CD8 CD21 Expanded FDC meshworks CD10 Positive, some BCL6 Positive, weak PD1 Positive CXCL13 Positive CD30 Positive, mainly immunoblasts ALK1 Negative Ki-67 30–40% Table 2 Next generation sequencing (NGS) lymphoma panel Tier1 Tier3 Gene TET2 RHOA KLHL6 SPEN TET2 UBR5 DNA c.1648C > T c.50G > T c.1103T > C c.7796C > T c.4138C > T c.5759A > G Protein p.Arg550* p.Gly17Val p.Val368Ala p.Ser2599Leu p.His1380Tyr p.Tyr1920Cys VAF (%) 12 6 40 48 12 14 Depth 768 610 655 300 382 503 COSMIC ID COSM41644 COSM78415 - - COSM87161 - Table 3 Swan-Ganz catheterization PCWP (s/d/mean) 5 mmHg/5 mmHg/4 mmHg PA pressure (s/d/mean) 24 mmHg/18 mmHg/19mmHg PA saturation 62.4% RV pressure (s/d/mean) 16 mmHg/0 mmHg/1 mmHg RV saturation 62.2% RA pressure (s/d/mean) -5 mmHg/-6 mmHg/-5 mmHg RA saturation 59.7% SVC pressure (mean) -5 mmHg SVC saturation 52.4% LA saturation 100% Aorta saturation 100% *PCWP; pulmonary capillary wedge pressure, PA; pulmonary artery, RV; right ventricle, RA; right atrium. SVC; superior vena cava, LA; left atrium Treatment with a mini-CHOP chemotherapy regimen (comprising adriamycin, cyclophosphamide, mesna, vincristine, and prednisolone) was initiated, planned for 6 cycles. Post the second chemotherapy cycle, a significant reduction in RVSP to 36 mmHg was observed on TTE, a notable improvement from 114 mmHg in May. A follow-up PET scan after the third cycle showed complete remission (Fig. 5 ). Laboratory tests reported an LDH level of 171 U/L 1 week after the final cycle. The patient was then transferred to a local medical center for rehabilitation following a spine fracture incurred between the 5th and 6th chemotherapy cycles. One weak post-transfer, the patient was readmitted with dyspnea and fever. Chest radiography indicated increased right-sided pleural effusion. Intravenous antibiotic therapy was initiated for pneumonia. TTE showed severe pulmonary hypertension (RVSP 75 mmHg). A repeat torso PET scan confirmed maintenance of complete lymphoma remission. Pleural fluid analysis now suggested exudative effusion, with fluid protein at 1.7 g/dL, serum protein at 4.66 g/dL, fluid LDH at 215 IU/L, and serum LDH at 207 IU/L. Cardiac catheterization revealed a pulmonary artery wedge pressure (PAWP) of 19 mmHg and confirmed pulmonary embolism (Fig. 6 , Table 2 ). Anticoagulant therapy was commenced following confirmation of pulmonary embolism by chest CT. Subsequent pleural effusion analysis indicated exudate with fluid protein at 3 g/dL, serum protein at 5.33 g/dL, and serum LDH at 200 IU/L. A pleural biopsy, conducted to exclude recurrent lymphoma or pleural metastasis, showed chronic inflammation suggestive of anthracosis without evidence of metastasis. The patient was subsequently transferred back to the local medical center for continued rehabilitation. Discussion In this case, an 84-year-old patient diagnosed with AITL exhibited lymphadenopathy and pleural effusion, commonly associated with AITL. However, the patient's primary presenting symptom was dyspnea attributed to PAH, a notably rare manifestation in AITL, complicating the diagnostic process. AITL lacks a universally accepted gold-standard treatment. Typically, therapeutic strategies range from single-agent oral therapies to intensive chemotherapy regimens, often incorporating the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), and may include autologous hematopoietic stem cell transplantation in certain cases, depending on prognostic risk classification [ 14 – 18 ]. In this instance, the patient was treated with a mini-CHOP regimen, demonstrating a favorable response. PAH is characterized by remodeling of the pulmonary vasculature, leading to increased pulmonary arterial pressure and vascular resistance, potentially progressing to right ventricular failure if left untreated [ 19 ]. Pathological hallmarks of PAH include the uncontrolled proliferation of endothelial cells, smooth muscle cells, fibroblasts, and inflammatory cell infiltration, resulting in luminal narrowing of pulmonary vessels [ 20 ]. Triggers for these changes may include factors such as shear stress, hypoxia, autoimmune phenomena, viral infections, drugs, toxins, or genetic alterations [ 21 ]. Inflammatory involvement in PAH pathogenesis is further supported by the presence of organized lymphoid follicles, T and B lymphocyte infiltration near lesions, and circulating inflammatory markers [ 22 , 23 ]. In this patient, TTE performed before chemotherapy initiation confirmed PAH. Remarkably, during chemotherapy, symptoms of PAH, along with pleural effusion and dyspnea, showed significant improvement, particularly after the second cycle. Post the sixth chemotherapy cycle, complete remission was evidenced by PET-CT scans. This improvement trajectory suggests that PAH in this patient was secondary to AITL. The absence of other underlying diseases commonly associated with PAH reinforces this correlation. Conclusion However, the occurrence of AITL concomitant with PAH is exceedingly rare, and the pathophysiological mechanisms linking the two conditions remain unclear. The atypical presentation in cases of AITL with PAH can lead to diagnostic delays. Therefore, this case report not only contributes to the medical literature by documenting a rare instance of AITL with PAH but also underscores the need for further research to elucidate the potential interplay between these conditions. Declarations Ethics approval This case report was based on standard care procedures, and no special ethical approval was required. Patient information has been anonymized to ensure privacy. Patient Consent Written informed consent for submitting this case report was provide by the patient. Funding None. Conflicts of Interest The authors declare that they have no conflicts of interest. Author Contribution Jiyoon Jung wrote the entire manuscript, prepared all figures and tables, and reviewed the manuscript. References Swerdlow SH, Campo E, Harris NL, Jaffe ES, Piler SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon : International Agency for Research on Cancer; 2017. Federico M, Rudiger T, Bellei M, Nathwani BN, Luminari S, Coiffier B, et al. Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol. 2013;31:240-6. https://dx.doi.org/10.1200/JCO.2011.37.3647. Willenbrock K, Brauninger A, Hansmann ML. Frequent occurrence of B-cell lymphomas in angioimmunoblastic T-cell lymphoma and proliferation of Epstein-Barr virus-infected cells in early cases. Br J Haematol. 2007;138:733-9. https://dx.doi.org/10.1111/j.1365-2141.2007.06725.x. de Leval L, Parrens M, Le Bras F, Jais JP, Fataccioli V, Martin A, et al. Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets. Haematologica. 2015;100:e361-4. https://dx.doi.org/10.3324/haematol.2015.126300. Merchant SH, Amin MB, Viswanatha DS. Morphologic and immunophenotypic analysis of angioimmunoblastic T-cell lymphoma: Emphasis on phenotypic aberrancies for early diagnosis. Am J Clin Pathol. 2006;126:29-38. https://dx.doi.org/10.1309/28YP-0DEL-GKEJ-GRXG. Yoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S, et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46:371-5. https://dx.doi.org/10.1038/ng.2916. Vallois D, Dobay MP, Morin RD, Lemonnier F, Missiaglia E, Juilland M, et al. Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas. Blood. 2016;128:1490-502. https://dx.doi.org/10.1182/blood-2016-02-698977. Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46:171-5. https://dx.doi.org/10.1038/ng.2872. Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014;46:166-70. https://dx.doi.org/10.1038/ng.2873. Odejide O, Weigert O, Lane AA, Toscano D, Lunning MA, Kopp N, et al. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood. 2014;123:1293-6. https://dx.doi.org/10.1182/blood-2013-10-531509. Lemonnier F, Couronne L, Parrens M, Jais JP, Travert M, Lamant L, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012;120:1466-9. https://dx.doi.org/10.1182/blood-2012-02-408542. Cairns RA, Iqbal J, Lemonnier F, Kucuk C, de Leval L, Jais JP, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012;119:1901-3. https://dx.doi.org/10.1182/blood-2011-11-391748. Vose J, Armitage J, Weisenburger D, International TCLP. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124-30. https://dx.doi.org/10.1200/JCO.2008.16.4558. Lunning MA, Vose JM. Angioimmunoblastic T-cell lymphoma: the many-faced lymphoma. Blood. 2017;129:1095-102. https://dx.doi.org/10.1182/blood-2016-09-692541. Mosalpuria K, Bociek RG, Vose JM. Angioimmunoblastic T-cell lymphoma management. Semin Hematol. 2014;51:52-8. https://dx.doi.org/10.1053/j.seminhematol.2013.11.008. Schmitz N, Trumper L, Ziepert M, Nickelsen M, Ho AD, Metzner B, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. Blood. 2010;116:3418-25. https://dx.doi.org/10.1182/blood-2010-02-270785. Chiba S, Sakata-Yanagimoto M. Advances in understanding of angioimmunoblastic T-cell lymphoma. Leukemia. 2020;34:2592-606. https://dx.doi.org/10.1038/s41375-020-0990-y. Moskowitz AJ. Practical Treatment Approach for Angioimmunoblastic T-Cell Lymphoma. J Oncol Pract. 2019;15:137-43. https://dx.doi.org/10.1200/JOP.18.00511. Hassoun PM. Pulmonary Arterial Hypertension. N Engl J Med. 2021;385:2361-76. https://dx.doi.org/10.1056/NEJMra2000348. Price LC, Wort SJ, Perros F, Dorfmuller P, Huertas A, Montani D, et al. Inflammation in pulmonary arterial hypertension. Chest. 2012;141:210-21. https://dx.doi.org/10.1378/chest.11-0793. Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004;109:159-65. https://dx.doi.org/10.1161/01.CIR.0000102381.57477.50. Soon E, Holmes AM, Treacy CM, Doughty NJ, Southgate L, Machado RD, et al. Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation. 2010;122:920-7. https://dx.doi.org/10.1161/CIRCULATIONAHA.109.933762. Perros F, Dorfmuller P, Montani D, Hammad H, Waelput W, Girerd B, et al. Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012;185:311-21. https://dx.doi.org/10.1164/rccm.201105-0927OC Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editor assigned by journal 10 Jul, 2024 Submission checks completed at journal 04 Jul, 2024 First submitted to journal 04 Jul, 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-4686831","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":325294166,"identity":"7f79f19c-4457-44e3-9f0b-5427d2201194","order_by":0,"name":"Ji Yoon Jung","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYDCCAwkG0kBKzgDMM7AgXosxVIsEkGAmTkviBgiXCC18x5M33i6ouZO+nf3s0Q0/CiQYzNn7D+DVInnmWbH1jGPPcnf25KXd7AE6zLLnMH5bDG7kmEnzsB3O3XAgx+wGD1CLwY1kYrT8O5xucP6N2c0/IC33HxOhhbftcAKIcRtiCwHvg/3C23fYcMONN2a3ZQwkeAzOJBvg1QIOMZ5vh+UNzueY3Xzzx0bO4PjBB/itQQc8pCkfBaNgFIyCUYAVAAD3XUsW89HxmgAAAABJRU5ErkJggg==","orcid":"","institution":"Yeungnam University College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Ji","middleName":"Yoon","lastName":"Jung","suffix":""}],"badges":[],"createdAt":"2024-07-04 13:17:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4686831/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4686831/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62188814,"identity":"d6eba50b-5b3d-4d22-9e4d-5271b21a83bf","added_by":"auto","created_at":"2024-08-10 12:18:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":986100,"visible":true,"origin":"","legend":"\u003cp\u003eChest radiography shows increased cardiothoracic ratio and both lung field consolidation and pleural effusion.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4686831/v1/cf63a6b71e442ae267990c49.png"},{"id":62188819,"identity":"8a6f2c47-9eeb-4bae-83f2-97d976831ac6","added_by":"auto","created_at":"2024-08-10 12:18:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2472569,"visible":true,"origin":"","legend":"\u003cp\u003eChest computed tomography shows moderate amount of pleural effusion and multiple enlarged lymph nodes in cervical, axilla, mediastinum, and upper abdomen.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4686831/v1/4b4b4cea71accb210d39dc3a.png"},{"id":62188815,"identity":"01e23e14-5817-4282-a419-8236e9774d37","added_by":"auto","created_at":"2024-08-10 12:18:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1245342,"visible":true,"origin":"","legend":"\u003cp\u003eTorso positron emission tomography shows splenomegaly with moderate fluorodeoxyglucose (FDG) uptake and numerous lymph nodes and lymphatic tissues with avid FDG uptake distributed in multiple nodal regions of both sides of diaphragm involving tonsils, bilateral neck, supraclavicular, axillar, parasternal, mediastinal, cardio-phrenic, celiac trunk, gastro-hepatic, hepatoduodenal, retrocrural, mesentric, aortocaval, paraaortic, both iliac, inguinal and presacral regions.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4686831/v1/385b8a9ce821c8f96200888d.png"},{"id":62188817,"identity":"9f61e415-d9aa-44c1-9bb4-60ee259d7f44","added_by":"auto","created_at":"2024-08-10 12:18:28","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":7583040,"visible":true,"origin":"","legend":"\u003cp\u003eH\u0026amp;E sections show a complete effacement of the lymph node architecture by a diffuse and polymorphic infiltrate (A). Paracortical areas show increased vascularity with an arborizing pattern and the endothelial cells are prominent. The polymorphic infiltrate is composed of small to intermediate size atypical cells with slight nuclear irregular contours admixed with plasma cells, Reed-Sternberg-like cells, neutrophils and reactive small lymphocytes (B–D).\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-4686831/v1/795961195ea8d122ee213734.png"},{"id":62190243,"identity":"d16e1d08-eae8-490b-b0f9-e1c52f91ab68","added_by":"auto","created_at":"2024-08-10 12:26:28","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":652342,"visible":true,"origin":"","legend":"\u003cp\u003eTorso positron emission tomography shows normalized fluorodeoxyglucose (FDG) uptake of spleen and markedly decreased numbers, size, and metabolic intensity of previous numerous FDG-avid lymph nodes.\u003c/p\u003e","description":"","filename":"Fig5.png","url":"https://assets-eu.researchsquare.com/files/rs-4686831/v1/6002715687fb3c63ea2be50f.png"},{"id":62188818,"identity":"886915cc-4c3c-4eab-a164-404a5422d6ec","added_by":"auto","created_at":"2024-08-10 12:18:28","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1640184,"visible":true,"origin":"","legend":"\u003cp\u003eThis image depicts a scene during Swan-Ganz catheterization, showing a pulmonary embolism in the left lower lobe pulmonary artery (arrow).\u003c/p\u003e","description":"","filename":"Fig6.png","url":"https://assets-eu.researchsquare.com/files/rs-4686831/v1/4f3108d29980333d852d4f8c.png"},{"id":62190271,"identity":"00c4b744-186e-4003-a6bb-66554f49d07d","added_by":"auto","created_at":"2024-08-10 12:26:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":282745,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4686831/v1/f0a29234-e5c3-4f7c-9734-a685b36226e2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pulmonary arterial hypertension as an unusual presentation of angioimmunoblastic T-cell lymphoma: a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAngioimmunoblastic T-cell lymphoma (AITL) is a subtype of mature peripheral T-cell lymphoma (PTCL) originating from follicular T helper cells [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Diagnosing AITL presents a challenge due to its diverse symptomatic presentation, which may include lymphadenopathy, B-symptoms (fever, weight loss, and night sweats), skin rash, pleural effusion, hepatosplenomegaly, and immune dysregulation.\u003c/p\u003e \u003cp\u003eA comprehensive diagnostic approach is required, involving excisional lymph node biopsy, imaging and laboratory tests, and morphologic, immunophenotypic, molecular, and cytogenetic analyses [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Histologically, AITL exhibits lymph node structural effacement, enhanced proliferation of follicular dendritic cells, and high endothelial venules [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Recent advancements in next-generation sequencing (NGS) have identified mutations in genes such as Tet methyl cytosine dioxygenase 2 (TET2), DNA-methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 2 (IDH2)-R172, and Ras homolog family member A (RHOA), significantly aiding AITL diagnosis [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The prognosis of AITL depends on various factors, including age, Eastern Cooperative Oncology Group (ECOG) performance status, presence of B symptoms, extra nodal involvement, and platelet count [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis case report documents an 84-year-old male patient with AITL, who presented with an atypical manifestation of pulmonary arterial hypertension (PAH) and transudative pleural effusion. This case underscores the diagnostic complexity of AITL with non-classical presentations and highlights the necessity of including AITL in differential diagnoses for patients with PAH. Notably, this patient exhibited clinical improvement with targeted treatment, marking the first documented case of PAH resolution following AITL treatment [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] .\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eAn 84-year-old male with a history of early gastric cancer (treated in 2016) presented to the Department of Respiratory Medicine in May 2022 with dyspnea. Initial chest radiography revealed cardiomegaly and bilateral moderate pleural effusion (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Pleural fluid analysis indicated a transudative effusion, with fluid protein at 3.16 g/dL, serum protein at 6.87 g/dL, fluid lactate dehydrogenase (LDH) at 259 IU/L, and serum LDH at 740 IU/L. Transthoracic echocardiography (TTE) showed markedly increased right ventricular systolic pressure (RVSP) at 114 mmHg, indicative of pulmonary hypertension. Computed tomography (CT) of the chest identified multiple mediastinal lymph node enlargements (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient was subsequently referred to the Department of Hematology and Oncology. Laboratory findings included an elevated LDH level of 824 U/L and NT-proBNP at 1,090 pg/mL. A positron emission tomography-computed tomography (PET-CT) scan was performed to evaluate for hematologic malignancy, revealing hypermetabolic lymph nodes and moderate splenomegaly (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). An excisional biopsy of a right axillary lymph node confirmed the diagnosis of AITL. Immunohistochemical analysis showed positive staining for CD4, CD10, CD21, BCL6, and CXCL13 in the follicular dendritic cells (FDCs) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In situ hybridization detected positive Epstein-Barr encoding region (EBER) signals. NGS identified mutations in two tier-1 genes and four tier-3 genes (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eImmunohistochemical stain\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarker\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTarget cells\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD4:CD8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCD4\u0026thinsp;\u0026gt;\u0026thinsp;CD8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExpanded FDC meshworks\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive, some\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCL6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive, weak\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePD1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCXCL13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive, mainly immunoblasts\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALK1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKi-67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u0026ndash;40%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNext generation sequencing (NGS) lymphoma panel\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTier1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c8\" namest=\"c5\"\u003e \u003cp\u003eTier3\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTET2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eRHOA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eKLHL6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSPEN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTET2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUBR5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ec.1648C\u0026thinsp;\u0026gt;\u0026thinsp;T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003ec.50G\u0026thinsp;\u0026gt;\u0026thinsp;T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ec.1103T\u0026thinsp;\u0026gt;\u0026thinsp;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ec.7796C\u0026thinsp;\u0026gt;\u0026thinsp;T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ec.4138C\u0026thinsp;\u0026gt;\u0026thinsp;T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ec.5759A\u0026thinsp;\u0026gt;\u0026thinsp;G\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProtein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep.Arg550*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003ep.Gly17Val\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep.Val368Ala\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep.Ser2599Leu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep.His1380Tyr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep.Tyr1920Cys\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVAF (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e768\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e655\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e382\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e503\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOSMIC ID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOSM41644\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eCOSM78415\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCOSM87161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSwan-Ganz catheterization\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCWP (s/d/mean)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 mmHg/5 mmHg/4 mmHg\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA pressure (s/d/mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 mmHg/18 mmHg/19mmHg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA saturation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV pressure (s/d/mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 mmHg/0 mmHg/1 mmHg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV saturation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRA pressure (s/d/mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-5 mmHg/-6 mmHg/-5 mmHg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRA saturation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSVC pressure (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-5 mmHg\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSVC saturation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLA saturation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAorta saturation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e*PCWP; pulmonary capillary wedge pressure, PA; pulmonary artery, RV; right ventricle, RA; right atrium. SVC; superior vena cava, LA; left atrium\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTreatment with a mini-CHOP chemotherapy regimen (comprising adriamycin, cyclophosphamide, mesna, vincristine, and prednisolone) was initiated, planned for 6 cycles. Post the second chemotherapy cycle, a significant reduction in RVSP to 36 mmHg was observed on TTE, a notable improvement from 114 mmHg in May. A follow-up PET scan after the third cycle showed complete remission (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Laboratory tests reported an LDH level of 171 U/L 1 week after the final cycle. The patient was then transferred to a local medical center for rehabilitation following a spine fracture incurred between the 5th and 6th chemotherapy cycles.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOne weak post-transfer, the patient was readmitted with dyspnea and fever. Chest radiography indicated increased right-sided pleural effusion. Intravenous antibiotic therapy was initiated for pneumonia. TTE showed severe pulmonary hypertension (RVSP 75 mmHg). A repeat torso PET scan confirmed maintenance of complete lymphoma remission. Pleural fluid analysis now suggested exudative effusion, with fluid protein at 1.7 g/dL, serum protein at 4.66 g/dL, fluid LDH at 215 IU/L, and serum LDH at 207 IU/L. Cardiac catheterization revealed a pulmonary artery wedge pressure (PAWP) of 19 mmHg and confirmed pulmonary embolism (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Anticoagulant therapy was commenced following confirmation of pulmonary embolism by chest CT. Subsequent pleural effusion analysis indicated exudate with fluid protein at 3 g/dL, serum protein at 5.33 g/dL, and serum LDH at 200 IU/L. A pleural biopsy, conducted to exclude recurrent lymphoma or pleural metastasis, showed chronic inflammation suggestive of anthracosis without evidence of metastasis. The patient was subsequently transferred back to the local medical center for continued rehabilitation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this case, an 84-year-old patient diagnosed with AITL exhibited lymphadenopathy and pleural effusion, commonly associated with AITL. However, the patient's primary presenting symptom was dyspnea attributed to PAH, a notably rare manifestation in AITL, complicating the diagnostic process.\u003c/p\u003e \u003cp\u003eAITL lacks a universally accepted gold-standard treatment. Typically, therapeutic strategies range from single-agent oral therapies to intensive chemotherapy regimens, often incorporating the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), and may include autologous hematopoietic stem cell transplantation in certain cases, depending on prognostic risk classification [\u003cspan additionalcitationids=\"CR15 CR16 CR17\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In this instance, the patient was treated with a mini-CHOP regimen, demonstrating a favorable response.\u003c/p\u003e \u003cp\u003ePAH is characterized by remodeling of the pulmonary vasculature, leading to increased pulmonary arterial pressure and vascular resistance, potentially progressing to right ventricular failure if left untreated [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Pathological hallmarks of PAH include the uncontrolled proliferation of endothelial cells, smooth muscle cells, fibroblasts, and inflammatory cell infiltration, resulting in luminal narrowing of pulmonary vessels [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Triggers for these changes may include factors such as shear stress, hypoxia, autoimmune phenomena, viral infections, drugs, toxins, or genetic alterations [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Inflammatory involvement in PAH pathogenesis is further supported by the presence of organized lymphoid follicles, T and B lymphocyte infiltration near lesions, and circulating inflammatory markers [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this patient, TTE performed before chemotherapy initiation confirmed PAH. Remarkably, during chemotherapy, symptoms of PAH, along with pleural effusion and dyspnea, showed significant improvement, particularly after the second cycle. Post the sixth chemotherapy cycle, complete remission was evidenced by PET-CT scans. This improvement trajectory suggests that PAH in this patient was secondary to AITL. The absence of other underlying diseases commonly associated with PAH reinforces this correlation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eHowever, the occurrence of AITL concomitant with PAH is exceedingly rare, and the pathophysiological mechanisms linking the two conditions remain unclear. The atypical presentation in cases of AITL with PAH can lead to diagnostic delays. Therefore, this case report not only contributes to the medical literature by documenting a rare instance of AITL with PAH but also underscores the need for further research to elucidate the potential interplay between these conditions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report was based on standard care procedures, and no special ethical approval was required. Patient information has been anonymized to ensure privacy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for submitting this case report was provide by the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJiyoon Jung wrote the entire manuscript, prepared all figures and tables, and reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSwerdlow SH, Campo E, Harris NL, Jaffe ES, Piler SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon : International Agency for Research on Cancer; 2017.\u003c/li\u003e\n \u003cli\u003eFederico M, Rudiger T, Bellei M, Nathwani BN, Luminari S, Coiffier B, et al. Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol. 2013;31:240-6. https://dx.doi.org/10.1200/JCO.2011.37.3647.\u003c/li\u003e\n \u003cli\u003eWillenbrock K, Brauninger A, Hansmann ML. Frequent occurrence of B-cell lymphomas in angioimmunoblastic T-cell lymphoma and proliferation of Epstein-Barr virus-infected cells in early cases. Br J Haematol. 2007;138:733-9. https://dx.doi.org/10.1111/j.1365-2141.2007.06725.x.\u003c/li\u003e\n \u003cli\u003ede Leval L, Parrens M, Le Bras F, Jais JP, Fataccioli V, Martin A, et al. Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets. Haematologica. 2015;100:e361-4. https://dx.doi.org/10.3324/haematol.2015.126300.\u003c/li\u003e\n \u003cli\u003eMerchant SH, Amin MB, Viswanatha DS. Morphologic and immunophenotypic analysis of angioimmunoblastic T-cell lymphoma: Emphasis on phenotypic aberrancies for early diagnosis. Am J Clin Pathol. 2006;126:29-38. https://dx.doi.org/10.1309/28YP-0DEL-GKEJ-GRXG.\u003c/li\u003e\n \u003cli\u003eYoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S, et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46:371-5. https://dx.doi.org/10.1038/ng.2916.\u003c/li\u003e\n \u003cli\u003eVallois D, Dobay MP, Morin RD, Lemonnier F, Missiaglia E, Juilland M, et al. Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas. Blood. 2016;128:1490-502. https://dx.doi.org/10.1182/blood-2016-02-698977.\u003c/li\u003e\n \u003cli\u003eSakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46:171-5. https://dx.doi.org/10.1038/ng.2872.\u003c/li\u003e\n \u003cli\u003ePalomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014;46:166-70. https://dx.doi.org/10.1038/ng.2873.\u003c/li\u003e\n \u003cli\u003eOdejide O, Weigert O, Lane AA, Toscano D, Lunning MA, Kopp N, et al. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood. 2014;123:1293-6. https://dx.doi.org/10.1182/blood-2013-10-531509.\u003c/li\u003e\n \u003cli\u003eLemonnier F, Couronne L, Parrens M, Jais JP, Travert M, Lamant L, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012;120:1466-9. https://dx.doi.org/10.1182/blood-2012-02-408542.\u003c/li\u003e\n \u003cli\u003eCairns RA, Iqbal J, Lemonnier F, Kucuk C, de Leval L, Jais JP, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012;119:1901-3. https://dx.doi.org/10.1182/blood-2011-11-391748.\u003c/li\u003e\n \u003cli\u003eVose J, Armitage J, Weisenburger D, International TCLP. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124-30. https://dx.doi.org/10.1200/JCO.2008.16.4558.\u003c/li\u003e\n \u003cli\u003eLunning MA, Vose JM. Angioimmunoblastic T-cell lymphoma: the many-faced lymphoma. Blood. 2017;129:1095-102. https://dx.doi.org/10.1182/blood-2016-09-692541.\u003c/li\u003e\n \u003cli\u003eMosalpuria K, Bociek RG, Vose JM. 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N Engl J Med. 2021;385:2361-76. https://dx.doi.org/10.1056/NEJMra2000348.\u003c/li\u003e\n \u003cli\u003ePrice LC, Wort SJ, Perros F, Dorfmuller P, Huertas A, Montani D, et al. Inflammation in pulmonary arterial hypertension. Chest. 2012;141:210-21. https://dx.doi.org/10.1378/chest.11-0793.\u003c/li\u003e\n \u003cli\u003eBudhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004;109:159-65. https://dx.doi.org/10.1161/01.CIR.0000102381.57477.50.\u003c/li\u003e\n \u003cli\u003eSoon E, Holmes AM, Treacy CM, Doughty NJ, Southgate L, Machado RD, et al. Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation. 2010;122:920-7. https://dx.doi.org/10.1161/CIRCULATIONAHA.109.933762.\u003c/li\u003e\n \u003cli\u003ePerros F, Dorfmuller P, Montani D, Hammad H, Waelput W, Girerd B, et al. Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012;185:311-21. https://dx.doi.org/10.1164/rccm.201105-0927OC\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"cardio-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caon","sideBox":"Learn more about [Cardio-Oncology](http://cardiooncologyjournal.biomedcentral.com)","snPcode":"40959","submissionUrl":"https://submission.nature.com/new-submission/40959/3","title":"Cardio-Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Angioimmunoblastic T-cell lymphoma, AITL, Pulmonary artery hypertension","lastPublishedDoi":"10.21203/rs.3.rs-4686831/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4686831/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eAngioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkin lymphoma with diverse clinical presentations. This report describes a unique case of AITL presenting with pulmonary arterial hypertension (PAH), a rarely associated complication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e \u0026nbsp;An 84-year-old male with a history of gastric cancer presented with dyspnea. Initial investigations revealed lymphadenopathy, pleural effusion, and severe PAH. Diagnostic workup, including histopathological and immunohistochemical analysis of an excisional lymph node biopsy and advanced imaging techniques, confirmed the diagnosis of AITL. The patient was treated with a mini-CHOP (comprising adriamycin, cyclophosphamide, mesna, vincristine, and prednisolone) chemotherapy regimen, leading to significant improvement in PAH and other symptoms, and achieving complete remission as confirmed by torso positron emission tomography-computed tomography scans. This case highlights the diagnostic challenge posed by atypical manifestations of AITL, such as PAH. The effective response to chemotherapy in this patient emphasizes the potential for conventional treatment regimens in managing rare presentations of AITL.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e This report contributes to the limited literature on AITL with PAH and underscores the importance of considering AITL in differential diagnoses for patients presenting with PAH.\u003c/p\u003e","manuscriptTitle":"Pulmonary arterial hypertension as an unusual presentation of angioimmunoblastic T-cell lymphoma: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-10 12:18:23","doi":"10.21203/rs.3.rs-4686831/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2024-07-10T16:17:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-05T02:15:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cardio-Oncology","date":"2024-07-04T13:16:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cardio-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caon","sideBox":"Learn more about [Cardio-Oncology](http://cardiooncologyjournal.biomedcentral.com)","snPcode":"40959","submissionUrl":"https://submission.nature.com/new-submission/40959/3","title":"Cardio-Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d56720fd-aedc-4242-91b0-a22221e9ed13","owner":[],"postedDate":"August 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-08-10T12:18:23+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-10 12:18:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4686831","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4686831","identity":"rs-4686831","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}