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

doi:10.21203/rs.3.rs-2506827/v1

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Case Report

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

https://doi.org/10.21203/rs.3.rs-2506827/v1

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Journal Publication

published 31 May, 2023

Read the published version in Cardio-Oncology →

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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

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.

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. O₂ 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.

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).

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.

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

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.

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 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*10⁶ cells/µL
Pericardial Fluid WBC	2499 cells/µL (Neut:75% Lymph:25%)
ADA fluid	22
Pericardial Fluid culture	Negative

No competing interests reported.

Download PDF

Journal Publication

published 31 May, 2023

Read the published version in Cardio-Oncology →

Submission checks completed at journal
24 Jan, 2023
First submitted to journal
23 Jan, 2023

You are reading this latest preprint version

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

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Journal Publication

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Abstract

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Background

Case Presentation

Discussion

Conclusions

Abbreviations

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References

Table

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Journal Publication

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