Aggressive Primary Pericardial Mesothelioma: A Case Report and Review of the Literature

doi:10.21203/rs.3.rs-3340134/v1

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Case Report

Aggressive Primary Pericardial Mesothelioma: A Case Report and Review of the Literature

https://doi.org/10.21203/rs.3.rs-3340134/v1

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Pericardial mesothelioma is a rare malignant tumor with atypical and nonspecific clinical manifestations. Therefore, the diagnosis of pericardial tumors is usually made in advanced stages, and there is currently no satisfactory treatment method, resulting in a low average survival period. In this case analysis, we report a case of a giant primary pericardial mesothelioma, describe its diagnosis and treatment, and discuss treatment methods for pericardial mesothelioma through a literature review.

Pericardial Mesothelioma

Cardiac Surgical Procedures

bevacizumab

Malignant mesothelioma is a rare malignant tumor that originates from the pleura, peritoneum, pericardium, testicular vaginal membrane, and ovarian epithelium. It is commonly detected in the pleura, with rare occurrences in the pericardium, as pericardial mesothelioma (PM). PM can occur across all age groups and has the potential to metastasize to the spine, neighboring soft tissues, and the brain. It exhibits a higher prevalence in men compared to women. Like numerous cardiac and pericardial conditions, the clinical manifestations of this disease are not specific and may manifest as pericardial effusion and constrictive pericarditis [1]. The diagnosis of pericardial tumors is usually made when the disease is in the terminal stage, resulting in a low survival outcome. In the present case, we report a patient with a large primary pericardial mesothelioma, describe the diagnosis and treatment, and discuss the treatments for PM patients based on a literature review.

History and examinations:

The patient is a 28-year-old young male who was treated in November 2022. He presented with shoulder and back pain for over three years, and was suspected of suffering from cervical spondylosis. One months before, he had been diagnosed as having pericardial effusion of unknown aetiology. The patient denied paroxysmal nocturnal dyspnea, chest pain, fever, and cough. Results of electrocardiogram examination did not reveal any abnormalities, and laboratory tests showed elevated D-dimer level (2.04 mg/L), high-sensitivity C-reactive protein (71.5 mg/L), CA125 (78.9 U/ml), and squamous cell carcinoma antigen (2.1 ng/ml). Cardiac ultrasound suggested a large lesion in the pericardial wall (Fig. 1). Further, a cardiac MRI revealed a lesion in the left ventricular lateral wall within the pericardial cavity, accompanied by slight calcification and necrotic foci (Fig. 2). There were no metastases to distant organ or lymph nodes as detected by PET-CT (data not show).

The patient underwent a pericardial tumor resection to completely excise the pericardial tumor. The tumor with a specimen volume of 12cm*8cm*5cm, which, according to published literature, represents the largest volume of pericardial tumor ever removed surgically (Fig. 3). Pathological examination confirmed sarcomatoid malignant mesothelioma, malignant fibrous/myofibroblastic tumor (Fig. 4). Based on these results, a diagnosis of mesothelioma was made.

A follow-up chest enhanced CT scan uncovered enlargement and central necrosis of lymph nodes in the 2R and 4L mediastinal regions, with the possibility of metastasis. Other examinations revealed CDKN2A positivity, suggesting that the use of platinum-based chemotherapy with pemetrexed as first-line treatment may be effective. However, considering the unique nature of the pericardial tumor and the surgical resection site, a combination cisplatin therapy, pemetrexed, and bevacizumab was applied. Following three cycles of consistent treatment, the patient underwent combined radiotherapy for mediastinal lymph nodes (PGTV: 66Gy/30F, PVT: 54Gy/30F). It has now been more than 9 months since the removal of the pericardial tumor, and the patient's condition remains stable. Bevacizumab is a recombinant humanized monoclonal antibody of immunoglobulin G1 (IgG1) that can bind to VEGF-A and inhibit its binding to VEGF receptor-2 (VEGFR-2), which suppresses the biological effects of VEGF. It affects vascular permeability, proliferation, endothelial cell migration, and survival, to inhibit tumor angiogenesis, growth, and metastasis. In a study of mesothelioma[2], vacizumab was shown to effectively prevent tumor progression and pleural effusion in a mouse model overexpressing VEGF. In addition, the combination with pemetrexed enhanced the efficacy. Among the 29 cases analyzed, 34.7% exhibited imaging evidence of pericardial effusion, which was also commonly detected during treatment and at the end of survival. Therefore, we collected blood samples from the patient before and after treatment, and VEGF level of serum were measured using ELISA (Fig. 5). The results showed that VEGF was overexpressed before treatment, and decreased significantly after bevacizumab treatment.

Malignant mesothelioma is a rare tumor that predominantly affects the pleura, and is often associated with asbestos exposure. Pericardial mesothelioma is a rare subtype of malignant mesothelioma. To gain a better understanding of this disease, we conducted a review of 29 cases (including the present case) from 2001 to the present. The current condition of three patients remains uncertain, two are still alive, while the disease has claimed the lives of the remaining 24 cases. Table 1 indicates that among these 29 cases, the male-to-female ratio was 7:1. A broad spectrum of ages was observed, and the initial symptoms were non-specific; however, respiratory distress, lower limb edema, and chest tightness were the prevalent symptoms. With the advancement of imaging technology, the detected proportion of cardiac involvement in these tumors has increased, which improves patient diagnosis. Compared to common mesotheliomas, pericardial mesothelioma is weakly associated with asbestos exposure, and the role of asbestos in the development of pericardial mesothelioma remains unclear. In this retrospective analysis, only one case had a confirmed history of asbestos exposure, indicating that asbestos is not a causative factor in this disease [3]. Out of the 29 cases, 6 patients did not receive any treatment (with a survival period of less than 2 months), excluding cases of intraoperative death, post-mortem diagnosis, and one case with an unusually long survival period. The average survival period for treated patients was 6 months.

Table 1

characteritic of previous and the present case.
male n(%)	20(68.9%)
Age Mean(Range)	54(19–85)
Dyspnea n(%)	22(75.8%)
Lower limb edema n(%)	10(34.4%)
Chest pain n(%)	8 (27.5%)
Average life expectancy	Results available22
	Untreated (About two months)
	Treatment (About six months)

In this case, we report a young patient with aggressive primary pericardial mesothelioma. To our knowledge, this is the largest pericardial mesothelioma resected so far. The anti-VEGF antibody bevacizumab was applied as a combination therapy for the disease and its effectiveness in the disease was confirmed.

VEGF has dual roles in the development of malignant mesothelioma. Firstly, VEGF can stimulate angiogenesis as a mitogen for endothelial cells, thereby promoting tumor growth. Previous reports have shown a negative correlation between tumor micro-vessel density and the survival rate of various malignant tumors [4]. Secondly, it increases vascular permeability to promote the production of pleural effusion [5]. This case suggests that inhibiting VEGF-mediated signaling pathways with bevacizumab may also be beneficial in slowing down the advancement of pericardial mesothelioma. Malignant pericardial mesothelioma is a rare disease, and its diagnosis and treatment are challenging. Currently, surgical resection, chemotherapy, and radiotherapy are the main treatments for the disease. Although advances in imaging technology have improved its diagnosis, it is often diagnosed at an advanced stage, and complete tumor resection is often not feasible. For this reason, most patients undergo partial resection followed by chemotherapy and radiotherapy, resulting in an average survival period of six months [6–32]. In this article, we presented a case in which a total resection of the pericardial tumor was successfully accomplished through surgery. We also incorporated bevacizumab into the initial treatment plan, extending the patient's survival well beyond the typical duration. Our intention is that this study can offer valuable insights and evidence for future approaches to treating pericardial mesothelioma.

pericardial mesothelioma (PM)

Ethics approval and consent to participate

All informed consent was obtained from the subject.

Consent for publication

All informed consent was obtained from the subject.

Availability of data and materials

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Competing interests

The authors have no conflict of interest.

Funding（Not applicable）

Author information

Authors and Affiliations：

Liyuan Hospital,Tongji Medical College, Huazhong University of Science and Technology Department of Cardiology

Yibo Yan ，Yinsong Ye

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Xiangguang Li, Lizhi Hu

Contributions：

All authors read and approved the final manuscript

Acknowledgements（Not applicable）

Corresponding author：

Correspondence to Fengxiao Zhang

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No competing interests reported.

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Aggressive Primary Pericardial Mesothelioma: A Case Report and Review of the Literature

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Introduction

Case report

History and examinations:

Literature Review

Discussion

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