Mediastinal gray zone lymphoma in a pregnant woman presenting with cardiac tamponade

Mediastinal gray zone lymphoma in a pregnant woman presenting with cardiac tamponade | 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 Mediastinal gray zone lymphoma in a pregnant woman presenting with cardiac tamponade Azin Alizadeasl, Kamran Roudini, Mahshid Hesami, Farid kosari, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2506827/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 May, 2023 Read the published version in Cardio-Oncology → Version 1 posted 2 You are reading this latest preprint version Abstract Background: Mediastinal gray zone lymphoma is a newly recognized rare B cell neoplasm, which is challenging in diagnosis and treatment. Case presentation: In the current study, we aimed to report a 25-year-old pregnant woman at 25 weeks of gestation who presented with chronic cough and progressive shortness of breath, hypotension, tachycardia, and tachypnea. A large circumferential pericardial effusion with compressive effect on the right atrium and right ventricle and a large extracardiac mass with external pressure to mediastinal structures was seen on trans thoracic echocardiography. The emergency pericardiocentesis was performed with the diagnosis of cardiac tamponade. Also, CMR revealed a huge heterogeneous anterior mediastinal mass, and the pathology and the immunohistochemistry of the mass biopsy revealed gray zone lymphoma with positive CD3, CD20, CD30, CD45, PAX5, and negative CD15 expression. Three courses of chemotherapy with the CHOP regimen were performed with an acceptable response every three weeks before delivery. An elective caesarian section was performed at 37 weeks without any problem for the patient and fetus. She had an appropriate health status, and chemotherapy will start three weeks after delivery. Conclusion : Cardiac tamponade as an emergency condition occurred in this pregnant patient by malignant pericardial effusion and mediastinal mass pressure. Accurate diagnosis and on time interventions caused a significant improvement and a successful delivery. Gray zone lymphoma Pericardial effusion Cardiac tamponade pregnancy chemotherapy Figures Figure 1 Figure 2 Background Mediastinal gray zone lymphoma was described as a “missing link” with intermediate features between the classic Hodgkin lymphoma and mediastinal large B cell lymphoma in 2005. Overlap in immunophenotype, histopathology, and clinical features complicates definitive diagnosis and treatment (1). The fourth most frequent malignancy in pregnancy is lymphoma, with a 1:6000 occurrence in deliveries. Limitations in the usage of imaging modalities in staging the tumor and choosing the appropriate treatment options during pregnancy have always been a challenge for physicians (2). Here we introduce a pregnant patient presenting to the hospital with cardiac tamponade due to an anterior mediastinal mass with morphologic and IHC staining of gray zone lymphoma. Case Presentation A 25-year-old primigravida female was admitted at 25 weeks of gestation with severe dyspnea that progressed in the last month; also, she noticed a progressive, productive cough from six months ago. At presentation, she had a regular pulse rate of 140 beats per minute, a Blood Pressure of 90/50 mmHg, and a respiratory rate of 30 breaths/min. O 2 saturation was 94% in the room air, and she was afebrile. Cardiac examinations revealed muffled heart sounds, pulsus paradoxus, and elevated jugular venous pressure. Other examinations and past medical history were unremarkable, and she denied any constitutional sign. Her electrocardiogram demonstrated sinus tachycardia. On echocardiography, the size and the systolic function of the right and left ventricles were normal. There was evidence of large pericardial effusion with significant right atrial invagination and RVOT diastolic collapse. There were significant respiratory variations of TV and MV inflow velocities, and IVC was plethoric. A large extra-cardiac mass at the pulmonary valve site adjacent to distal RVOT was seen, resulting in turbulency in pulmonic outflow without significant gradient and stenosis. The blood tests showed neutrophilic leukocytosis with a white blood cell count of 16410 cells/mm3, a hemoglobin level of 9.2 g/dl, a platelet count of 403*103 /mm3, and an ESR level of 95 mm/h, an LDH level of 300 IU/L, and CRP>90 with standard coagulation test. The results of the pericardial fluid analysis are mentioned in the table. (Table 1- Pericardial Fluid analysis) Cardiac magnetic resonance determined a 146*126*136 mm heterogeneous mass in the anterior mediastinum attached to the pericardium with a compressive effect on RVOT. (Figure 1- Cardiac magnetic resonance- (A) Short axis T1-W sequence view shows iso-signal tumor. (B-C) Short axis and axial SSFP sequence views reveal heterogeneous high signal tumor. (D) Short axis STIR sequence view demonstrates high signal tumor. (E) Coronal Late Gadolinium Enhancement (LGE) shows heterogeneous enhancement and necrosis (arrow) SSFP= steady-state free precession, STIR= Short tau inversion recovery) A mass biopsy was performed, and the pathology revealed diffuse and nodular infiltration of lymphocytes, neutrophils, eosinophils, and atypical cells with enlarged hyperchromatic nuclei with irregular contours and prominent nucleoli in the fibrotic stroma. The immunohistochemistry showed negative CD15 and positive CD3, CD20, CD30, CD45, PAX5 expression. According to the clinical and paraclinical findings, the diagnosis of gray zone lymphoma was confirmed. (Figure 2- Mediastinal mass pathology- (A-B) Microscopic examination (H&E staining) shows diffuse and nodular infiltration of lymphocytes, neutrophils, eosinophils and some large atypical cells with enlarged hyperchromatic nuclei with irregular contour and prominent nucleoli in fibrotic stroma. (C) All lymphoid cells including some large atypical cells are positive for CD45. (D) Many large atypical cells are positive for CD20. (E) Many small lymphocytes are positive for CD3. (F) Large atypical cells are negative for CD15. (G) Large atypical cells are positive for CD30. (H) Large atypical cells are strongly positive for PAX5) Subcutaneous Pericardiocentesis under fluoroscopy with a subxiphoid approach was performed, and after drainage of 200CC serous fluid, the pigtail catheter was fixed under negative pressure. The hemodynamic status improved but did not recover completely until receiving the high dose of dexamethasone. An oncology consultation was requested, and dexamethasone was started at 40 mg daily for four days . Three courses of chemotherapy with the CHOP regimen (Cyclophosphamide, Hydroxydaunorubicin, vincristine sulfate, and Prednisone) started at twenty-one days of intervals and stopped three weeks before delivery. The clinical manifestation of the patient improved significantly. All the fetal ultra-sonographies done during chemotherapy were normal. An elective cesarean section was performed at 37 weeks of gestation. The mother's health status during and after delivery was good, and her son was in perfect health with no observable abnormality. Her chemotherapy will start three weeks after delivery. Discussion Cardiac involvement, secondary to malignancies, due to chemotherapy agents or radiation therapy is a significant complication among cancers. The pericardium is affected in the form of pericarditis or pericardial effusion by local invasion, obstruction of lymphatic and venous drainage, and hematogenous or lymphatic spread during malignancies. Lung, breast, leukemia, and lymphoma are the most common neoplasms with malignant pericardial effusion (3). Cardiac tamponade is a life-threatening medical emergency that requires immediate intervention. The compression of heart chambers through tamponade is caused by fluid, gas, or extracardiac mass effect and leads to decreased cardiac output and shock (4). The term "Gray zone lymphoma" was first used to delineate the border cases between classic Hodgkin's and non-Hodgkin's lymphoma in 1998; then, in 2008, included in the WHO classification of lymphoid neoplasm as an "unclassifiable B-cell lymphoma, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma" and finally in 2022 WHO named this entity as Mediastinal Gray Zone lymphoma (MGZL) (5-7). Overlap in immunophenotype, histopathology, and clinical features complicates definitive diagnosis and treatment. CD45, CD20, PAX5, BOB1, CD79a, OCT2 expression, and the absence of CD15 expression are common immunohistochemical findings in MGZL. Strong expression of CD20 and PAX5 as B cell associated markers, frequently not seen in CHL. CD45 expression is highly specific for DLBCL and reported in 100% of non-Hodgkin's lymphoma. CD15 expression is positive in 75-90% of CHL cases, and CD30 is more expressed in CHL than DLBCL. Differences in therapeutic regimen and lower survival rate compared to CHL and DLBCL demonstrate the importance of identifying MGZL to find a treatment appropriate for neoplasm (8). Physiologic changes in pregnancy can imitate or hide the cancer symptoms and lead to a delay in diagnosis. Cancer staging and treatment are also challenging in pregnancy because of the risk that threatens the mother and fetus (9). Currently, the R-CHOP regimen is the treatment of choice for gray zone lymphoma (10). chemotherapy without Rituximab was started for the patient because the evidence showed CHOP regimen is safe beyond the first trimester (11). Conclusions Cardiac tamponade is an emergency condition that needs immediate pericardiocentesis. Tamponade occurred in this patient by mediastinal mass pressure and malignant pericardial effusion. The simultaneous occurrence of cardiac tamponade and mediastinal gray zone lymphoma as a rare neoplasm in pregnancy creates a complex condition for patient and physicians. Abbreviations RVOT= Right ventricular outflow tract TV= Tricuspid valve MV= Mitral valve IVC= Inferior vena cava CMR= Cardiac magnetic resonance R-CHOP= Rituximab+ (Cyclophosphamide, Hydroxydaunorubicin, vincristine sulfate, and Prednisone) CHL= Classic Hodgkin’s lymphoma DLBCL= Diffuse large B cell lymphoma Declarations Ethical approval and consent to participate: This study protocol was approved by Rajaie Cardiovascular, Medical and Research Center ethics committee. Consent for publication : Consent for publication obtained from the patient. Availability of data and materials: The authors can confirm that all relevant data are included in the article. Competing interests: The authors declare that they have no competing interests. Funding : Non to report. Author’s contributions AA and ND : critical revision and major contributor in writing the manuscript. KR: acquisition of data by performing the oncologic treatment. MH and FK: acquisition of data by performing the histological examinations. HP: acquisition of data by performing the radiologic examinations. MM : acquisition of data by performing the echocardiographic examinations. Acknowledgements : Non to report. References Traverse-Glehen A, Pittaluga S, Gaulard P, Sorbara L, Alonso MA, Raffeld M, et al. Mediastinal gray zone lymphoma: the missing link between classic Hodgkin's lymphoma and mediastinal large B-cell lymphoma. The American journal of surgical pathology. 2005;29(11):1411-21. Pereg D, Koren G, Lishner M. The treatment of Hodgkin’s and non-Hodgkin’s lymphoma in pregnancy. Haematologica. 2007;92(9):1230-7. Adler AC, Cestero C. Symptomatic pericardial effusion in Hodgkin's lymphoma: a rare occurrence. Case report and review of the literature. Tumori. 2012;98(2):50e-2e. Spodick DH. Acute cardiac tamponade. New England Journal of Medicine. 2003;349(7):684-90. Rüdiger T, Jaffe E, Delsol G, deWolf-Peeters C, Gascoyne R, Georgii A, et al. Workshop report on Hodgkin’s disease and related diseases (‘grey zone’lymphoma). Annals of oncology. 1998;9:s31-s8. Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBdO, Berti E, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022;36(7):1720-48. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood, The Journal of the American Society of Hematology. 2011;117(19):5019-32. Bhargava R, Dabbs D. Diagnostic Immunohistochemistry. Theranostic and Genomic Applications. 2019:Elsevier. Botha MH, Rajaram S, Karunaratne K. Cancer in pregnancy. International Journal of Gynecology & Obstetrics. 2018;143:137-42. Simon Z, Virga B, Pinczés L, Méhes G, Miltényi Z, Barna S, et al. Transition Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma–Our Histopathological and Clinical Experience With Patients With Intermediate Lymphoma. Pathology and Oncology Research. 2021:47. Lishner M, Avivi I, Apperley JF, Dierickx D, Evens AM, Fumagalli M, et al., editors. Hematologic malignancies in pregnancy: management guidelines from an international consensus meeting2016: American Society of Clinical Oncology. Table Table 1- Pericardial Fluid analysis Pericardial Fluid analysis Pericardial Fluid Glucose 107 ml/dl Pericardial Fluid Protein 7 g/dl Pericardial Fluid LDH 4380 IU/L Pericardial Fluid Alkaline Phosphatase 128 U/L Pericardial Fluid Cholesterol 89 ml/dl Pericardial Fluid Triglyceride 44 ml/dl Pericardial Fluid RBC 0.3*10 6 cells/µL Pericardial Fluid WBC 2499 cells/µL (Neut:75% Lymph:25%) ADA fluid 22 Pericardial Fluid culture Negative Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 31 May, 2023 Read the published version in Cardio-Oncology → Version 1 posted Submission checks completed at journal 24 Jan, 2023 First submitted to journal 23 Jan, 2023 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-2506827","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":170300284,"identity":"589b1ef6-b418-45ae-86c6-2f864353c059","order_by":0,"name":"Azin Alizadeasl","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Azin","middleName":"","lastName":"Alizadeasl","suffix":""},{"id":170300285,"identity":"561e0a97-b720-4c3e-b41f-d08dbcfbd444","order_by":1,"name":"Kamran Roudini","email":"","orcid":"","institution":"Imam Khomeini hospital complex, Tehran University of medical sciences","correspondingAuthor":false,"prefix":"","firstName":"Kamran","middleName":"","lastName":"Roudini","suffix":""},{"id":170300286,"identity":"fbc9f018-37b3-4995-ad9c-820fdc0e48a4","order_by":2,"name":"Mahshid Hesami","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mahshid","middleName":"","lastName":"Hesami","suffix":""},{"id":170300287,"identity":"1440e5fc-323b-4d9b-aa14-1959ef50d30f","order_by":3,"name":"Farid kosari","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Farid","middleName":"","lastName":"kosari","suffix":""},{"id":170300288,"identity":"e255f756-d226-494e-b8ed-f88cb4c64786","order_by":4,"name":"Hamid Reza Pouraliakbar","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hamid","middleName":"Reza","lastName":"Pouraliakbar","suffix":""},{"id":170300289,"identity":"c740fffe-42c1-4ce5-9638-4af8c1300bfa","order_by":5,"name":"Mina Mohseni","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mina","middleName":"","lastName":"Mohseni","suffix":""},{"id":170300290,"identity":"70f75560-343e-4a6f-912f-8a11d50959cf","order_by":6,"name":"Negar Dokhani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYBACfh4eIGlgw8AgQawWyR6wljQStBicAWlhOEyCFoYzZw9+Lig4n9g/u/ngA4Yam2iCOhh7+5KlZxjcTpxx51iyAcOxtNwGQlqY+XkMpHmAWhpu5JhJMDYcJqyFjZ/H+DePwbnE+URr4eHtMQPaciBxA9FaJHjOmFnzGCQbb7yRlmyQQIxf7M/kGN/m+WMnO+9G8sEHH2psCGuBAUewygRilYNtI0XxKBgFo2AUjDAAAEPVPLuIMcNHAAAAAElFTkSuQmCC","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Negar","middleName":"","lastName":"Dokhani","suffix":""}],"badges":[],"createdAt":"2023-01-23 12:29:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2506827/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2506827/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40959-023-00173-2","type":"published","date":"2023-05-31T21:00:41+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":32139828,"identity":"d48e053c-2562-4a5b-86f9-7ec2c1d0084d","added_by":"auto","created_at":"2023-01-27 22:18:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":385886,"visible":true,"origin":"","legend":"\u003cp\u003eCardiac magnetic resonance- (A) Short axis T1-W sequence view shows iso-signal tumor. (B-C) Short axis and axial SSFP sequence views reveal heterogeneous high signal tumor. (D) Short axis STIR sequence view demonstrates high signal tumor. (E) Coronal Late Gadolinium Enhancement (LGE) shows heterogeneous enhancement and necrosis (arrow)\u003c/p\u003e\n\u003cp\u003eSSFP= steady-state free precession, STIR= Short tau inversion recovery\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2506827/v1/debbf7f1a0f835addbe7758a.png"},{"id":32139829,"identity":"8a4fc0ef-ff77-4cf5-bf95-341ba06ac062","added_by":"auto","created_at":"2023-01-27 22:18:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1974637,"visible":true,"origin":"","legend":"\u003cp\u003eMediastinal mass pathology- (A-B) Microscopic examination (H\u0026amp;E staining) shows diffuse and nodular infiltration of lymphocytes, neutrophils, eosinophils and some large atypical cells with enlarged hyperchromatic nuclei with irregular contour and prominent nucleoli in fibrotic stroma. (C) All lymphoid cells including some large atypical cells are positive for CD45. (D) Many large atypical cells are positive for CD20. (E) Many small lymphocytes are positive for CD3. (F) Large atypical cells are negative for CD15. (G) Large atypical cells are positive for CD30. (H) Large atypical cells are strongly positive for PAX5\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-2506827/v1/a864c7cb8f311ae3e0ed032d.png"},{"id":44730030,"identity":"681c3d82-7e2f-4559-a732-40e204206090","added_by":"auto","created_at":"2023-10-16 21:25:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2661538,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2506827/v1/96ecee45-04b4-40bf-857a-aa933436c450.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mediastinal gray zone lymphoma in a pregnant woman presenting with cardiac tamponade","fulltext":[{"header":"Background","content":"\u003cp\u003eMediastinal gray zone lymphoma was described as a \u0026ldquo;missing link\u0026rdquo; with intermediate features between the classic Hodgkin lymphoma and mediastinal large B cell lymphoma in 2005. Overlap in immunophenotype, histopathology, and clinical features complicates definitive diagnosis and treatment (1). The fourth most frequent malignancy in pregnancy is lymphoma, with a 1:6000 occurrence in deliveries. Limitations in the usage of imaging modalities in staging the tumor and choosing the appropriate treatment options during pregnancy have always been a challenge for physicians (2). Here we introduce a pregnant patient presenting to the hospital with cardiac tamponade due to an anterior mediastinal mass with morphologic and IHC staining of gray zone lymphoma.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 25-year-old primigravida female was admitted at 25 weeks of gestation with severe dyspnea that progressed in the last month; also, she noticed a progressive, productive cough from six months ago. At presentation, she had a regular pulse rate of 140 beats per minute, a Blood Pressure of 90/50 mmHg,\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eand a respiratory rate of 30 breaths/min. O\u003csub\u003e2\u003c/sub\u003e saturation was 94% in the room air, and she was afebrile. Cardiac examinations revealed muffled heart sounds, pulsus paradoxus, and elevated jugular venous pressure. Other examinations and past medical history were unremarkable, and she denied any constitutional sign. Her electrocardiogram demonstrated sinus tachycardia. On echocardiography, the size and the systolic function of the right and left ventricles were normal. There was evidence of large pericardial effusion with significant right atrial invagination and RVOT diastolic collapse. There were significant respiratory variations of TV and MV inflow velocities, and IVC was plethoric. A large extra-cardiac mass at the pulmonary valve site adjacent to distal RVOT was seen, resulting in turbulency in pulmonic outflow without significant gradient and stenosis.\u003c/p\u003e\n\u003cp\u003eThe blood tests showed neutrophilic leukocytosis with a white blood cell count of 16410 cells/mm3, a hemoglobin level of 9.2 g/dl, a platelet count of 403*103 /mm3, and an ESR level of 95 mm/h, an LDH level of 300 IU/L, and CRP\u0026gt;90 with standard coagulation test.\u0026nbsp;The results of the pericardial fluid analysis are mentioned in the table. (Table\u0026nbsp;1- Pericardial Fluid analysis)\u003c/p\u003e\n\u003cp\u003eCardiac magnetic resonance determined a 146*126*136\u003csup\u003emm\u003c/sup\u003e heterogeneous mass in the anterior mediastinum attached to the pericardium with a compressive effect on RVOT. (Figure 1- Cardiac magnetic resonance- (A) Short axis T1-W sequence view shows iso-signal tumor. (B-C) Short axis and axial SSFP sequence views reveal heterogeneous high signal tumor. (D) Short axis STIR sequence view demonstrates high signal tumor. (E) Coronal Late Gadolinium Enhancement (LGE) shows heterogeneous enhancement and necrosis (arrow)\u0026nbsp;\u003cspan style=\"text-align: inherit;\"\u003eSSFP= steady-state free precession,\u0026nbsp;STIR= Short tau inversion recovery)\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eA mass biopsy was performed, and the pathology revealed diffuse and nodular infiltration of lymphocytes, neutrophils, eosinophils, and atypical cells with enlarged hyperchromatic nuclei with irregular contours and prominent nucleoli in the fibrotic stroma. The immunohistochemistry showed negative CD15 and positive CD3, CD20, CD30, CD45, PAX5 expression. According to the clinical and paraclinical findings, the diagnosis of gray zone lymphoma was confirmed. (Figure 2- Mediastinal mass pathology- (A-B) Microscopic examination (H\u0026amp;E staining) shows diffuse and nodular infiltration of lymphocytes, neutrophils, eosinophils and some large atypical cells with enlarged hyperchromatic nuclei with irregular contour and prominent nucleoli in fibrotic stroma. (C) All lymphoid cells including some large atypical cells are positive for CD45. (D) Many large atypical cells are positive for CD20. (E) Many small lymphocytes are positive for CD3. (F) Large atypical cells are negative for CD15. (G) Large atypical cells are positive for CD30. (H) Large atypical cells are strongly positive for PAX5)\u003c/p\u003e\n\u003cp\u003eSubcutaneous Pericardiocentesis under fluoroscopy with a subxiphoid approach was performed, and after drainage of 200CC serous fluid, the pigtail catheter was fixed under negative pressure. The hemodynamic status improved but did not recover completely until receiving the high dose of dexamethasone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAn oncology consultation was requested, and dexamethasone was started at 40 mg daily for four days\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e Three courses of chemotherapy with the CHOP regimen (Cyclophosphamide, Hydroxydaunorubicin, vincristine sulfate, and Prednisone) started at twenty-one days of intervals and stopped three weeks before delivery. The clinical manifestation of the patient improved significantly. All the fetal ultra-sonographies done during chemotherapy were normal. An elective cesarean section was performed at 37 weeks of gestation. The mother\u0026apos;s health status during and after delivery was good, and her son was in perfect health with no observable abnormality. Her chemotherapy will start three weeks after delivery.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCardiac involvement, secondary to malignancies, due to chemotherapy agents or radiation therapy is a significant complication among cancers. The pericardium is affected in the form of pericarditis or pericardial effusion by local invasion, obstruction of lymphatic and venous drainage, and hematogenous or lymphatic spread during malignancies. Lung, breast, leukemia, and lymphoma are the most common neoplasms with malignant pericardial effusion (3). Cardiac tamponade is a life-threatening medical emergency that requires immediate intervention. The compression of heart chambers through tamponade is caused by fluid, gas, or extracardiac mass effect and leads to decreased cardiac output and shock (4). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe term \u0026quot;Gray zone lymphoma\u0026quot; was first used to delineate the border cases between classic Hodgkin\u0026apos;s and non-Hodgkin\u0026apos;s lymphoma in 1998; then, in 2008, included in the WHO classification of lymphoid neoplasm as an \u0026quot;unclassifiable B-cell lymphoma, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma\u0026quot; and finally in 2022 WHO named this entity as Mediastinal Gray Zone lymphoma (MGZL) (5-7). Overlap in immunophenotype, histopathology, and clinical features complicates definitive diagnosis and treatment. CD45, CD20, PAX5, BOB1, CD79a, OCT2 expression, and the absence of CD15 expression are common immunohistochemical findings in MGZL. Strong expression of CD20 and PAX5 as B cell associated markers, frequently not seen in CHL. CD45 expression is highly specific for DLBCL and reported in 100% of non-Hodgkin\u0026apos;s lymphoma.\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eCD15 expression is positive in 75-90% of CHL cases, and CD30 is more expressed in CHL than DLBCL. Differences in therapeutic regimen and lower survival rate compared to CHL and DLBCL demonstrate the importance of identifying MGZL to find a treatment appropriate for neoplasm (8).\u003c/p\u003e\n\u003cp\u003ePhysiologic changes in pregnancy can imitate or hide the cancer symptoms and lead to a delay in diagnosis. Cancer staging and treatment are also challenging in pregnancy because of the risk that threatens the mother and fetus (9). Currently, the R-CHOP regimen is the treatment of choice for gray zone lymphoma (10). chemotherapy without Rituximab was started for the patient because the evidence showed CHOP regimen is safe beyond the first trimester (11).\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCardiac tamponade is an emergency condition that needs immediate pericardiocentesis. Tamponade occurred in this patient by mediastinal mass pressure and malignant pericardial effusion. The simultaneous occurrence of cardiac tamponade and mediastinal gray zone lymphoma as a rare neoplasm in pregnancy creates a complex condition for patient and physicians.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRVOT= Right ventricular outflow tract\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTV= Tricuspid valve\u003c/p\u003e\n\u003cp\u003eMV= Mitral valve\u003c/p\u003e\n\u003cp\u003eIVC= Inferior vena cava\u003c/p\u003e\n\u003cp\u003eCMR= Cardiac magnetic resonance\u003c/p\u003e\n\u003cp\u003eR-CHOP= Rituximab+ (Cyclophosphamide, Hydroxydaunorubicin, vincristine sulfate, and Prednisone)\u003c/p\u003e\n\u003cp\u003eCHL= Classic Hodgkin\u0026rsquo;s lymphoma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDLBCL= Diffuse large B cell lymphoma\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThis study protocol was approved by Rajaie Cardiovascular, Medical and Research Center ethics committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Consent for publication obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The authors can confirm that all relevant data are included in the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e:\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNon to report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAA and ND\u003c/strong\u003e: critical revision and major contributor in writing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKR:\u0026nbsp;\u003c/strong\u003eacquisition of data by performing the oncologic treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMH and FK:\u0026nbsp;\u003c/strong\u003eacquisition of data by performing the histological examinations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHP:\u0026nbsp;\u003c/strong\u003eacquisition of data by performing the radiologic examinations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMM\u003c/strong\u003e: acquisition of data by performing the echocardiographic examinations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: Non to report.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTraverse-Glehen A, Pittaluga S, Gaulard P, Sorbara L, Alonso MA, Raffeld M, et al. Mediastinal gray zone lymphoma: the missing link between classic Hodgkin\u0026apos;s lymphoma and mediastinal large B-cell lymphoma. The American journal of surgical pathology. 2005;29(11):1411-21.\u003c/li\u003e\n\u003cli\u003ePereg D, Koren G, Lishner M. The treatment of Hodgkin\u0026rsquo;s and non-Hodgkin\u0026rsquo;s lymphoma in pregnancy. Haematologica. 2007;92(9):1230-7.\u003c/li\u003e\n\u003cli\u003eAdler AC, Cestero C. Symptomatic pericardial effusion in Hodgkin\u0026apos;s lymphoma: a rare occurrence. Case report and review of the literature. Tumori. 2012;98(2):50e-2e.\u003c/li\u003e\n\u003cli\u003eSpodick DH. Acute cardiac tamponade. New England Journal of Medicine. 2003;349(7):684-90.\u003c/li\u003e\n\u003cli\u003eR\u0026uuml;diger T, Jaffe E, Delsol G, deWolf-Peeters C, Gascoyne R, Georgii A, et al. Workshop report on Hodgkin\u0026rsquo;s disease and related diseases (\u0026lsquo;grey zone\u0026rsquo;lymphoma). Annals of oncology. 1998;9:s31-s8.\u003c/li\u003e\n\u003cli\u003eAlaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBdO, Berti E, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022;36(7):1720-48.\u003c/li\u003e\n\u003cli\u003eCampo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood, The Journal of the American Society of Hematology. 2011;117(19):5019-32.\u003c/li\u003e\n\u003cli\u003eBhargava R, Dabbs D. Diagnostic Immunohistochemistry. Theranostic and Genomic Applications. 2019:Elsevier.\u003c/li\u003e\n\u003cli\u003eBotha MH, Rajaram S, Karunaratne K. Cancer in pregnancy. International Journal of Gynecology \u0026amp; Obstetrics. 2018;143:137-42.\u003c/li\u003e\n\u003cli\u003eSimon Z, Virga B, Pincz\u0026eacute;s L, M\u0026eacute;hes G, Milt\u0026eacute;nyi Z, Barna S, et al. Transition Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma\u0026ndash;Our Histopathological and Clinical Experience With Patients With Intermediate Lymphoma. Pathology and Oncology Research. 2021:47.\u003c/li\u003e\n\u003cli\u003eLishner M, Avivi I, Apperley JF, Dierickx D, Evens AM, Fumagalli M, et al., editors. Hematologic malignancies in pregnancy: management guidelines from an international consensus meeting2016: American Society of Clinical Oncology.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1- Pericardial Fluid analysis\u003c/p\u003e\n\u003ctable width=\"432\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePericardial Fluid analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003ePericardial Fluid Glucose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003e107 ml/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003ePericardial Fluid Protein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003e7 g/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003ePericardial Fluid LDH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003e4380 IU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003ePericardial Fluid Alkaline Phosphatase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003e128 U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003ePericardial Fluid Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003e89 ml/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003ePericardial Fluid Triglyceride\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003e44 ml/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003ePericardial Fluid RBC\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003e0.3*10\u003csup\u003e6\u003c/sup\u003e cells/\u0026micro;L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003ePericardial Fluid WBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003e2499 cells/\u0026micro;L (Neut:75% Lymph:25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003eADA fluid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"56.25%\"\u003e\n \u003cp\u003ePericardial Fluid culture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"43.75%\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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":"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":"Gray zone lymphoma, Pericardial effusion, Cardiac tamponade, pregnancy, chemotherapy","lastPublishedDoi":"10.21203/rs.3.rs-2506827/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2506827/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Mediastinal gray zone lymphoma is a newly recognized rare B cell neoplasm, which is challenging in diagnosis and treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e In the current study, we aimed to report a 25-year-old pregnant woman at 25 weeks of gestation who presented with chronic cough and progressive shortness of breath, hypotension, tachycardia, and tachypnea. A large circumferential pericardial effusion with compressive effect on the right atrium and right ventricle and a large extracardiac mass with external pressure to mediastinal structures was seen on trans thoracic echocardiography. The emergency pericardiocentesis was performed with the diagnosis of cardiac tamponade. Also, CMR revealed a huge heterogeneous anterior mediastinal mass, and the pathology and the immunohistochemistry of the mass biopsy revealed gray zone lymphoma with positive CD3, CD20, CD30, CD45, PAX5, and negative CD15 expression. Three courses of chemotherapy with the CHOP regimen were performed with an acceptable response every three weeks before delivery. An elective caesarian section was performed at 37 weeks without any problem for the patient and fetus. She had an appropriate health status, and chemotherapy will start three weeks after delivery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Cardiac tamponade as an emergency condition occurred in this pregnant patient by malignant pericardial effusion and mediastinal mass pressure. Accurate diagnosis and on time interventions caused a significant improvement and a successful delivery.\u003c/p\u003e","manuscriptTitle":"Mediastinal gray zone lymphoma in a pregnant woman presenting with cardiac tamponade","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-01-27 22:18:49","doi":"10.21203/rs.3.rs-2506827/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"checksComplete","content":"","date":"2023-01-24T10:48:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cardio-Oncology","date":"2023-01-23T12:19:29+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":"5c5d33e5-d676-43cd-833e-de87d26bcc49","owner":[],"postedDate":"January 27th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T21:10:05+00:00","versionOfRecord":{"articleIdentity":"rs-2506827","link":"https://doi.org/10.1186/s40959-023-00173-2","journal":{"identity":"cardio-oncology","isVorOnly":false,"title":"Cardio-Oncology"},"publishedOn":"2023-05-31 21:00:41","publishedOnDateReadable":"May 31st, 2023"},"versionCreatedAt":"2023-01-27 22:18:49","video":"","vorDoi":"10.1186/s40959-023-00173-2","vorDoiUrl":"https://doi.org/10.1186/s40959-023-00173-2","workflowStages":[]},"version":"v1","identity":"rs-2506827","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2506827","identity":"rs-2506827","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}