Mediastinal lymphoma with cardiac involvement mimicking acute coronary syndrome: a case report

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BACKGROUND

Lymphomas are a heterogeneous group of cancers characterized by uncontrolled clonal proliferation of lymphoid cells [1]. The disease may arise in lymph nodes as well as in extra-nodal organs and tissues. Modern classification divides them into two main groups depending on cellular origin: Hodgkin lymphoma (Hodgkin disease) and non-Hodgkin lymphomas, each of which includes numerous subtypes with various morphological, immunophenotypic, and clinical features [1–3].

Primary mediastinal large B-cell lymphoma is a rare aggressive B-cell lymphoma subtype, accounting for 2–3% of all non-Hodgkin lymphomas cases [4]. The disease predominantly occurs in young women (median age 30–35 years) and is characterized by a massive tumor conglomerate in the anterior mediastinum with frequent spread to adjacent structures [5]. Cardiac lymphomas are observed in 8–28% of cases according to autopsy [6]. Secondary cardiac lymphomas are more frequent, approximately in 30–40 times [7]. Cardiac involvement as the initial lymphoma manifestation is extremely rare, for less than 1% of all extra-nodal lymphomas and is characterized by isolated involvement [8, 9].

This article presents a clinical case of primary mediastinal lymphoma with cardiac structures involvement. The clinical picture features were the onset of symptoms at a late stage of the disease (dyspnea on exertion, cardiac arrhythmias, prolonged oppressive pain behind the sternum unrelated to exertion) and rapid progression leading to death.

CASE DESCRIPTION

Anamnesis Morbi

Patient A., 66-year-old woman. At the age of 39, during pregnancy, she experienced a blood pressure (BP) increase to 145/90 mmHg, which subsequently normalized. Episodic increases in BP up to 150/90 mmHg were recorded over the last 5 years. In early July 2023, the patient noted oppressive pain behind the sternum; the electrocardiography (ECG) did not show ischemic changes. A total of 24-hour ECG monitoring on July 20, 2023, recorded an episode of ST-segment depression of up to 2.1 mm at a 134 beats per minute heart rate (HR), after which the patient was recommend to undergo coronary angiography, and she refused. A treadmill test showed a negative result.

From October 28, 2023, negative T waves began to appear on the ECG in leads V₄–V₆. In November, the patient underwent stress echocardiography (a stress test for ischemic heart disease) in an outpatient setting. The test result was negative — the maximum heart rate was 128 beats per minute (85% of the maximum predicted rate), and no signs of local myocardial contractility violation at rest, at peak exercise, or during the recovery period were detected. The patient's condition worsened a week later: fever and cough appeared, an increase in C-reactive protein (CRP) concentration to 110 mg/L and an increase in the erythrocyte sedimentation rate to 95 mm/h were recorded. The condition was assessed as tracheobronchitis.

Paroxysmal atrial fibrillation was first recorded in the patient on November 26 and 27, 2023, and terminated medically. She was prescribed metoprolol at 25 mg and rivaroxaban at 20 mg. Computed tomography (CT) on November 30, 2023, revealed subsegmentary atelectasis of the right lung middle lobe, hydrothorax, and hydropericardium. The ECG showed deep negative T-waves in leads V₄–V₆. The therapist consulted the patient and did not rule out a history of myocardium.

First Hospitalization

On December 11, 2023, the patient was admitted to the cardiology department of the National Medical Research Center for Cardiology named after academician Yevgeniy Chazov of the Ministry of Health of the Russian Federation with complaints of dry cough, dyspnea on minimal physical exertion, rapid and irregular heartbeat, oppressive pain behind the sternum and in the back, worsening in supine position.

Diagnostic assessment

Laboratory tests performed on admission showed:

• N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration — 1900 pg/mL (normal range up to 150);
• C-reactive protein (CRP) — 25.2 mg/mL (normal range up to 5).

Instrumental examination revealed:

• electrocardiography showed negative T waves in standard leads II and III, and in augmented lead aVF; biphasic T waves in leads V₂–V₃; ST-segment elevation in leads V₃–V₄ up to 2 mm;
• echocardiography (EchoCG) showed hydropericardium and a pericardial mass; left ventricular ejection fraction of 60%, with no pulmonary hypertension signs.

Magnetic resonance imaging (MRI) of the heart with contrast enhancement was performed to characterize the nature of the lesion.

MRI data showed multiple focal lesions in the pericardial cavity, isointense on T1-weighted images (WI) and hypertensive on T2-WI (Fig. 1, a, b). These foci extended to the apical part of the left ventricle and the apex, as well as to the great vessels, including the arch and ascending aorta, and the pulmonary trunk, without invasion signs into the walls. Post-contrast T1- and T2-WI observed heterogeneous accumulation of contrast agent by the tissues of the formations (see Fig. 1, c, d). In the delayed phase (Late Gadolinium Enhancement, LGE), we noted the contrast enhancement of the pericardium visceral and parietal layers (see Fig. 1, g).

 

Fig. 1. Cardiac magnetic resonance imaging results: a, T1-weighted images, the pathological mass shows isointense signal relative to the myocardium. Tumor masses are visible within in the pericardial cavity with extension to the left ventricular myocardium in the apex region, apical segments and the anterior and inferior walls (white arrows); b, T2-weighted images, hyperintense signal from the mass relative to the myocardium (white arrows); c, d, post-contrast T1- and T2-weighted images, heterogeneous contrast enhancement by the mass (white arrows); e, f, T1-mapping images (before and after contrast administration), a heterogeneous hyperintense signal from pathological foci (white arrows); g, late gadolinium enhancement (delayed phase), contrast enhancement of both the visceral and parietal layers of the pericardium (white arrows).

 

Treatment

Based on the clinical picture and the laboratory and instrumental diagnostics results, the patient was prescribed a complex therapy, including beta-blockers for heart rate control, anticoagulants, and diuretics. It was decided not to prescribe colchicine and non-steroidal anti-inflammatory drugs according to the idiopathic pericarditis.

Follow-Up and Outcomes

The patient was discharged from the clinic with a cardiac rhythm disturbances (paroxysmal atrial fibrillation). Multinodular soft-tissue pericardial masses. Myopericarditis, subacute stage. She was subsequently referred to a specialized oncological hospital for further examination to determine the mass etiology on cardiac MRI from December 12, 2023.

Repeat Hospitalization

The patient developed another paroxysmal atrial fibrillation with the development of severe hypotension one month after discharge, on January 18, 2024. She called an emergency medical services. By the time of their arrival, the hypotension had progressed, leading to the arrhythmic shock development. At the pre-hospital stage, electrical cardioversion was performed, restoring sinus rhythm and stabilizing hemodynamics. The patient was hospitalized again in the intensive care unit of the City Clinical Hospital No. 1 named after N. I. Pirogov on January 19, 2023.

On the admission the patient's condition was severe; however, she was oriented and her consciousness remained clear. Hemodynamic parameters were stable: blood pressure 110/70 mmHg, heart rate 77 beats per minute, sinus rhythm. ECG showed no remarkable changes compared to previous ones (Fig. 2).

 

Fig. 2. Electrocardiography: sinus rhythm, heart rate 81 beats per minute, normal electrical axis, ST-segment elevation in leads V₃–V₄ up to 2 mm, negative T-wave in leads II, III, and aVF, biphasic T-wave in V₂–V₃.

 

Diagnostic Assessment

Laboratory tests revealed an increase in troponin I concentration to 0.14 µg/L (normal range < 0.023), normal NT-ProBNP values of 187.7 pg/mL, a moderate decrease in renal function (glomerular filtration rate, calculated using the CKD-EPI formula, was 37 mL/min/1.73 × m², chronic kidney disease stage 3B), and lactate dehydrogenase activity of 2859 U/L.

Echocardiography revealed multiple hypoechoic masses with irregular borders localized in the pericardial cavity. In addition, an extrapericardial hypoechoic structure around the right ventricle and pulmonary artery was identified, which is likely a neoplastic mass. A moderate amount of fluid was present in the pericardial cavity. Calculated cardiac chamber volumes were reduced due to external compression:

• estimated end-diastolic volume approximately 45 mL (normal range 59–138 mL)
• ejection fraction 47% (normal range > 50%).

Regional contractility abnormalities were not detected; the pulmonary artery systolic pressure was 80 mmHg (normal range up to 20). A left atrium enlargement (size 3.6 × 7.0 cm, volume 70 mL, normal up to 4.0 × 4.9 cm and up to 65 mL, respectively) and the right atrium (size 3.4 × 6.2 cm, volume 61 mL, normal up to 3.8 × 4.6 cm and up to 55 mL, respectively) were recorded. A hypoechoic mass is visualized in the left atrial cavity on the interatrial septum side, filling more than 2/3 of its volume.

Given the myocardial injury signs, the patient underwent diagnostic coronary angiography. The results demonstrated (Fig. 3, a):

• Remarkable left main coronary artery stenosis, the stenosis of circumflex artery of > 90% and the left anterior descending artery up to 90% in the proximal segment, TIMI II antegrade flow [moderate (slow) flow, complete antegrade contrast passage, but slower than normal];
• Ramus intermedius artery in the proximal segment stenosis of > 99%, TIMI I antegrade flow (minimal flow, partial filling).

 

Fig. 3. Coronary angiography results: a, the left main coronary artery has an irregular contour, long stenosis up to 90% of the right interventricular artery in the proximal segment (yellow arrow), ramus intermedius stenosis of > 99% in the proximal segment (orange star), long stenosis of circumflex artery of > 90% in the proximal segment from the ostium, distal bed without hemodynamically significant stenoses (blue arrow); b, after administration of vasodilators, improvement in antegrade blood flow through the left coronary artery, remarkable increase in the proximal lumens of the right interventricular artery (yellow arrow) and the circumflex artery (blue arrow).

 

Positive changes were observed after following the vasodilators administration: nitroglycerin at a dose of 1 mg and papaverine solution at a dose of 40 mg (see Fig. 3, b) show the improvement in antegrade flow through the left coronary artery, remarkable proximal lumens increase of the left anterior descending artery and the circumflex artery, and final TIMI II flow in the left coronary artery. This condition was interpreted as coronary vasospasm; therefore, percutaneous coronary intervention was not performed.

Multispiral CT of the chest (Fig. 4) and peritoneal cavity (Fig. 5) with intravenous contrast was performed during follow-up examination on January 19, 2024. The study revealed a pericardial tumor invading the myocardium and compressing the aorta, pulmonary artery, pulmonary veins, superior vena cava, and coronary arteries, as well as extrathoracic metastases with diaphragm infiltration and involvement in subphrenic space of the left lobe of the liver.

 

Fig. 4. Chest computed tomography with intravenous contrast enhancement showed: a, diffuse solid tumor masses with irregular and ill-defined borders (white arrows) in the pericardial cavity, with a density of up to 50 HU and mild contrast enhancement in the delayed phase up to 75 HU, the structure of the masses is heterogeneous due to hypovascular areas; b, the above-describ from t ed pathological structures extend in a sleeve-like mannerhe walls of the ascending aorta to the diaphragmatic surface of the pericardium (white lines). RA — right atrium; RV — right ventricle; LA — left atrium; LV — left ventricle.

 

Fig. 5. Computed tomography of the peritoneal cavity organs with intravenous contrast enhancement showed spread of the tumor process to the diaphragm and into the subdiaphragmatic space above the liver left lobe (white arrows).

 

Compared with month earlier cardiac MRI results, negative progression in the substantial increase of the tumor process spread was marked.

Differential Diagnosis

Primary cardiac lymphoma with mediastinal involvement was considered as the primary diagnosis. Differential diagnosis was also performed between the following conditions: mediastinal lymphoma with cardiac involvement and cardiac angiosarcoma.

Treatment

The patient's condition continued to progressively deteriorate: respiratory failure and hemodynamic instability increased, necessitating transfer to mechanical ventilation and the initiation of inotropic support. Antibiotic therapy with meropenem at 4 g per day was administrated due to the nosocomial infection development during the underlying disease progression.

Follow-Up and Outcomes

Despite the intensive therapy provided, the patient's condition continued to progressively deteriorate, leading to circulatory arrest in the setting of increasing heart failure on the second day of hospitalization.

Postmortem diagnosis: Community-acquired left lower lobe pneumonia. The pericardial neoplasm with invasion into the ascending aorta walls, the pulmonary trunk and its main branches, the superior vena cava, the left main coronary artery and its branches (proximal segments of the left anterior descending artery and the circumflex artery are narrowed by 80%–90%), the right coronary artery trunk, as well as the great cardiac vein, which is fragmentarily indistinguishable amidst the aforementioned masses; with fragmentary spread to the myocardium, predominantly at the apex and atria level; with invasion into the mediastinal fat, the anterior wall of the distal trachea and the left main bronchus, as well as the diaphragm. Cardiac rhythm disorders (paroxysmal atrial fibrillation). Type 2 myocardial infarction.

We conducted a post-mortem examination. We noted a substantial enlargement of the heart (Fig. 6). In its cavities and within the myocardium of all sections, particularly in the atria and the interventricular septum, we identified multiple infiltrative foci of whitish tissue of dense consistency, merging with each other in places. The tumor masses borders were irregular and infiltrative. We found a massive tumor mass in the mediastinum, spreading to the surrounding tissues, including the pericardium and adjacent lung. Tissue samples were obtained for histological examination (Fig. 7). Subsequently, the final diagnosis by immunohistochemical methods was established: diffuse large B-cell lymphoma.

 

Fig. 6. Gross processing of the heart: on section, the tumor tissue is represented by grayish-white and yellowish areas with a soft, in places homogeneous and necrotic consistency; hemorrhage foci and necrosis are observed in some zones. The myocardium is thickened due to infiltration and has a heterogeneous structure in the affected areas, with foci of gray-white infiltration spreading along the vessels and intermuscular septa.

 

Fig. 7. Gross processing of the myocardium (a–c) and bronchus (d) (hematoxylin and eosin staining): a, a diffuse tumor lymphoid infiltrate with massive necrosis zones in the myocardial wall (magnification ×5); b, myocardium infiltration by tumor lymphoid cells (magnification ×10); c, at higher magnification, the lymphoid infiltrate consists of medium and large cells with round-to-oval nuclei and moderate cytoplasm (magnification ×40); d, lymphoid infiltrate ingrowth of similar structure into the bronchial wall (magnification ×5).

 

Final diagnosis: Community-acquired left lower lobe pneumonia. Diffuse large B-cell lymphoma of the mediastinum with extension along the ascending aorta walls, the pulmonary trunk and its main branches, the superior vena cava, the left main coronary artery and its branches (proximal anterior interventricular artery segments and the circumflex artery are narrowed by 80%–90%), the right main coronary artery (the great cardiac vein is fragmentarily not differentiated amidst the above-described masses), with fragmentary extension to the myocardium, most pronounced at the level of the apex and atria, with invasion into the mediastinal tissue, the anterior wall of the distal trachea and the left main bronchus, and the diaphragm. Cardiac rhythm disturbances: paroxysmal atrial fibrillation. Type 2 myocardial infarction.

DISCUSSION

Lymphoma is one of the most common mediastanum tumors, accounting for approximately 10%–15% of all neoplasms in this location [10].

The presented clinical case demonstrates a rare and aggressive primary mediastinal large B-cell lymphoma course with involvement of the heart and pericardium.

A case feature is the atypical clinical presentation in the early stages of the desease, mimicking the symptoms of acute coronary syndrome. The initial complaints were interpreted, such as oppressive pain behind the sternum, ECG changes, as ischemic heart disease, leading to a delay in establishing the correct diagnosis.

Primary cardiac lymphoma occurs extremely rare, for approximately 1% of extranodal lymphoma cases [11–14]. At the same time, secondary myocardium in the tumor process of varying severity is identified in 30% of patients with the disseminated systemic lymphoma according to autopsy data [15].

Lymphomas with cardiac involvement can present in various symptoms, including rhythm disturbances, heart failure, and pericardial effusion [16, 17]. In the presented clinical case, a rapid increase of symptoms was noted, indicating the aggressive disease nature.

Diagnosis of primary mediastinal large B-cell lymphoma with cardiac involvement presents substantial difficulties. Standard instrumental research methods, such as CT and echocardiography, allow tumor mass detection and the determination of its extent. However, biopsy followed by immunohistochemical study is necessary for final diagnosis verification [18].

When we suspect mediastinal lymphoma, CT and MRI are key methods of its visualization. In primary mediastinal large B-cell lymphoma, CT data reveal massive tumor conglomerates in the anterior mediastinum, which usually have a solid structure and variable heterogeneous density. Hypovascular areas with the presence of necrosis zones or fibrosis in the tumor tissue are often noted [19, 20].

MRI provides more detailed information on soft tissue structures and can be useful for assessing cardiac and pericardial involvements in primary mediastinal large B-cell lymphoma, particularly in suspected myocardial infiltration cases. In the clinical case, MRI visualized multiple focal lesions in the pericardium and myocardium, characterized by an isointense signal on T1-weighted imaging and a hyperintense signal on T2-weighted imaging, which is typical for lymphomas and consistent with data presented in the published sources [21, 22].

The diffuse large B-cell lymphoma diagnosis was confirmed after patient's death on the basis of post-mortem examination data with immunohistochemical methods.

Overall, the prognosis for primary mediastinal large B-cell lymphoma is considered relatively favorable, especially with timely diagnosis and adequate treatment [4]. However, cardiac involvement strongly worsens the prognosis and requires a personalized and multidisciplinary approach to treatment [16].

Rare cases of cardiac lymphoma are also described in Russian publications. For example, Abramenko et al. [23], Kondratyev et al. [24], and Blagova et al. [25] presented observations of primary and secondary myocardial involvements in non-Hodgkin lymphomas, accompanied by non-specific symptoms (dyspnea, arrhythmia, pericardial effusion, heart failure), which complicated their early diagnosis. Despite attempts at surgical treatment and chemotherapy, in all described cases, the disease resulted in death.

In the presented clinical case, despite intensive multicomponent therapy aimed at maintaining cardiovascular activity and managing complications, the disease also led to death in the shortest time.

CONCLUSION

This clinical case emphasizes the importance of early diagnosis of mediastinal lymphomas, especially in the atypical symptoms and cardiac signs. Primary mediastinal large B-cell lymphoma represents a complex clinical condition requiring a multidisciplinary approach for timely diagnosis and effective treatment.

ADDITIONAL INFORMATION

Author contributions: G.M. Shaginyan: data curation, writing — original draft, writing — review & editing, visualization; O.V. Stukalova: patient's medical history, data curation; A.V. Sherashov, A.S. Shilova: investigation, data curation; D.Yu. Shchekochikhin: data curation, writing — original draft; A.A. Oganesyan: patient's medical history, data curation; Z.M. Magomedova: data curation, writing — review & editing; E.S. Pershina: patient's medical history, data curation. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: Not applicable.

Consent for publication: No informed consent was obtained from the patient's legal representatives for publication of information on her health status during hospitalization. Reason: the patient's legal representatives were lost to follow-up (the telephone number in the medical record was blocked; the e-mail address was unknown; and contact information of the patient's family members was unavailable). All data presented are anonymized.

Funding sources: No funding.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: No previously published material (text, images, or data) was used in this study or article.

Data availability statement: The editorial policy regarding data sharing does not apply to this work.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer-review: This article was submitted unsolicited and reviewed following the standard procedure. The peer-review process involved two external reviewers and member of the Editorial Board.

About the authors

George M. Shaginyan

City Clinical Hospital No. 1 named after N.I. Pirogov

Author for correspondence.
Email: namegeorge1@gmail.com
ORCID iD: 0000-0001-9289-6104
SPIN-code: 4271-2309
Russian Federation, Moscow

Olga V. Stukalova

National Medical Research Center of Cardiology named after Academician E.I. Chazov

Email: olgastukalova@mail.ru
ORCID iD: 0000-0001-8377-2388
SPIN-code: 4261-0827

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow

Andrei V. Sherashov

Endocrinology Research Centre

Email: sherashovmd@yandex.ru
ORCID iD: 0000-0003-2220-5990
SPIN-code: 1477-3266
Russian Federation, Moscow

Alexandra S. Shilova

City Clinical Hospital No. 1 named after N.I. Pirogov

Email: a.s.shilova@gmail.com
ORCID iD: 0000-0002-4092-5222

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Dmitry Yu. Shchekochikhin

City Clinical Hospital No. 1 named after N.I. Pirogov; Sechenov First Moscow State Medical University (Sechenov University)

Email: agishm@list.ru
ORCID iD: 0000-0002-8209-2791
SPIN-code: 3753-6915

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow; Moscow

Anait A. Oganesyan

City Clinical Hospital No. 1 named after N.I. Pirogov

Email: talilen@mail.ru
ORCID iD: 0000-0003-1896-023X
SPIN-code: 6531-2957
Russian Federation, Moscow

Zainab M. Magomedova

City Clinical Hospital No. 1 named after N.I. Pirogov; Sechenov First Moscow State Medical University (Sechenov University)

Email: magomedova.zainab.97@mail.ru
ORCID iD: 0000-0001-6753-1525
SPIN-code: 5271-4915
Russian Federation, Moscow; Moscow

Ekaterina S. Pershina

City Clinical Hospital No. 1 named after N.I. Pirogov; Sechenov First Moscow State Medical University (Sechenov University)

Email: pershina86@mail.ru
ORCID iD: 0000-0002-3952-6865
SPIN-code: 7311-9276

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow; Moscow

References

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