A 47-year-old woman initially presented to an outside institution with dyspnea and hypotension. Transthoracic echocardiography demonstrated a large pericardial effusion with evidence of hemodynamic compromise, prompting urgent pericardiocentesis. The pericardial fluid was hemorrhagic, and cytological analysis showed no atypical cells. Laboratory studies revealed markedly elevated inflammatory markers, including an erythrocyte sedimentation rate (ESR) of 80 mm/h and a C-reactive protein (CRP) level of 100 mg/L. Despite initial improvement following drainage, the effusion rapidly recurred within 72 hours, again leading to signs of cardiac tamponade.

Question 1

In a patient with a rapidly recurrent pericardial effusion within 72 hours of drainage, again presenting with signs of cardiac tamponade, which of the following is the most appropriate next management step?

• A.

  Repeat pericardiocentesis, leave an indwelling pericardial drainage catheter, and continue anti-inflammatory therapy.

• B.

  Surgical creation of a pericardial window to allow continuous drainage and prevent tamponade recurrence.

• C.

  Establish an aggressive anti-inflammatory regimen and initially await resolution without repeat pericardial drainage.

Due to rapid reaccumulating of the effusion, a pericardia-peritoneal window was subsequently performed. A pericardial biopsy obtained during the procedure showed nonspecific chronic inflammation without evidence of malignancy. Cardiac magnetic resonance (CMR) imaging demonstrated mild pericardial thickening, with no evidence of myocardial infiltration or late gadolinium enhancement. The patient was discharged with a presumptive diagnosis of recurrent pericarditis and was treated with colchicine 0.5 mg twice and ibuprofen 500 mg every 8 hours, daily.

Approximately 1 month later, she was referred to our center with progressive exertional dyspnea, orthopnea, chest tightness suggestive of a new episode of hemodynamic decompensation. On admission, she was normotensive (BP 110/70), with sinus tachycardia (HR 110 bpm) without paradoxical pulse, and with preserved peripheral perfusion. Physical examination revealed jugular venous distention and muffled heart sounds. Electrocardiogram showed sinus tachycardia and T-wave inversions in the inferolateral leads. TTE confirmed a severe pericardial effusion (maximum posterior pericardial separation 40 mm) with right atrial collapse and significant respiratory variation in transvalvular flow ( Figure 1 ).

Admission echocardiogram demonstrating severe pericardial effusion.

Question 2

In a patient with a large recurrent pericardial effusion 1 month after creation of a pericardioperitoneal window, despite initial improvement and ongoing anti-inflammatory therapy, which of the following is the most likely explanation for her clinical deterioration?

• A.

  Progression of inflammatory pericarditis despite optimal medical therapy.

• B.

  Obstruction or malfunction of the pericardioperitoneal window leading to recurrent fluid accumulation.

• C.

  Development of constrictive pericarditis following prior pericardial intervention

A repeat pericardiocentesis was performed, again yielding hemorrhagic fluid. Cytology revealed reactive mesothelial cell hyperplasia without atypia or invasion. A thoracic, abdominal, and pelvic CT scan was performed, showing no evidence of adenopathy or suspicious tumoral lesions. However, demonstrated that the previously constructed pericardio-peritoneal window was no longer functional due to mechanical obstruction by the liver. Consequently, a thoracoscopic pleuro-pericardial window was performed. Intraoperatively, adherent blood clots were observed on the pericardial surface, and histopathologic evaluation continued to show a nonspecific inflammatory pattern. Prednisone 40 mg/day was added to her anti-inflammatory regimen, resulting in clinical improvement and a marked reduction in inflammatory markers. Despite initial stabilization, the patient returned 3 weeks later with recurrent pericardial effusion and signs of tamponade. A surgical pericardiectomy was ultimately performed ( Figure 2 ). Unfortunately, she developed multiorgan failure and died shortly after surgery. Final histopathological examination of the resected pericardium revealed biphasic pericardial mesothelioma, predominantly of the epithelioid subtype, with a high mitotic index. ( Figure 3 ) Inmunohistochemistry was positive for Keratin (AE1-AE3), Calretinin, WT1, D2-40, and negative for TTF and Napsin A, confirming the mesothelial origin of the tumor ( Figure 4 ).

Pericardium with diffuse nodular thickening due to primary mesothelioma.

Biphasic mesothelioma with predominant epithelioid component, nuclear grade III, high mitotic index.

Immunohistochemistry staining for mesothelial lineage.

Question 3

Regarding the clinical course and prognosis of primary pericardial mesothelioma, which statement is most accurate?

• A.

  Median survival after symptom onset is approximately 6 months, largely due to delayed diagnosis and advanced presentation

• B.

  Early surgical pericardiectomy significantly improves long-term survival and is considered curative in most cases

• C.

  Most patients remain asymptomatic until the development of distant metastases, usually after several years

Question 1: correct response

Rapid reaccumulating of a pericardial effusion with recurrent tamponade shortly after drainage indicates failure of percutaneous management and need for escalation of care. Surgical pericardial window (A) is preferred, as it provides sustained drainage and enables direct visualization and pericardial biopsy, which is particularly important when malignancy is suspected. Although the procedure requires a cardiac surgeon and carries a theoretical risk of tumor seeding in malignant disease, its diagnostic and therapeutic benefits generally outweigh this concern in rapidly recurrent effusions.

Repeat pericardiocentesis (B) with placement of an indwelling catheter is a less invasive alternative and can provide temporary symptom relief; however, it does not allow tissue sampling and may be insufficient in cases of aggressive or malignant processes.

Percutaneous balloon pericardiotomy (PBP) is a less invasive alternative that creates a pericardial–pleural communication and can be effective in patients who are poor surgical candidates. However, it does not allow direct tissue sampling or inspection of the pericardium, limiting its diagnostic yield. ^,,,,

Question 2: correct response

Recurrent pericardial effusion shortly after creation of a pericardioperitoneal window should raise strong suspicion for mechanical failure of the drainage pathway (B), most commonly due to obstruction of the surgically created tract or catheter. Although inflammatory pericardial disease or evolving constrictive physiology may also contribute to recurrent symptoms, these conditions typically follow a more gradual clinical course. ^,

In contrast, the rapid reaccumulating of fluid within weeks of the procedure, particularly after an initial period of improvement, strongly suggests loss of patency of the pericardioperitoneal window. Obstruction may occur due to fibrin deposition, inflammatory adhesions, clot formation, or tumor-related blockage when malignancy is a concern. Once the window becomes nonfunctional, pericardial fluid reaccumulates and may again lead to features of tamponade.

Recognizing this mechanism is essential, as management often requires repeat imaging, reassessment of drainage patency, and consideration of repeat surgical intervention or alternative drainage strategies, rather than simply intensifying anti-inflammatory therapy. Early identification prevents progressive hemodynamic compromise and facilitates timely definitive treatment. ^,,

Question 3: correct response

Primary pericardial mesothelioma (PPM) accounts for fewer than 2% of all mesotheliomas, yet it remains the most common primary malignancy of the pericardium. Due to its rarity, nonspecific clinical presentation, and poor prognosis, no standardized treatment guidelines currently exist. In contrast to pleural and peritoneal mesotheliomas, PPM has no consistent or well-established association with asbestos exposure. ^,,

Clinically, PPM often manifests with hemorrhagic pericardial effusion, pericardial constriction, or cardiac tamponade, with symptoms typically resulting from these complications. Onset is generally insidious, contributing to diagnostic delays and advanced disease at the time of presentation. Median survival following symptom onset is approximately 6 months. Local invasion and metastatic spread to the pleura, lungs, mediastinum, or distant organs are observed in up to 50% of cases.

Mesothelioma arises from mesothelial cells lining serous cavities. Stromal or fat invasion remains a key histological criterion for malignancy. According to the World Health Organization (WHO) classification, mesothelioma is divided into three subtypes: epithelioid (characterized by plump, rounded cells), sarcomatoid (spindle-shaped cells), and biphasic, which combines elements of both.

Diagnosis is particularly challenging in the epithelioid subtype, as it may closely mimic reactive mesothelial proliferations Immunohistochemical staining is essential for diagnosis, with markers such as CK5/6, Calretinin, WT-1, and D2-40 used to identify mesothelial lineage. Loss of BRCA1-associated protein 1 (BAP1) expression is a useful ancillary marker of malignancy in a subset of mesotheliomas. Cytologic diagnosis from pericardial fluid is limited in sensitivity, ranging from 32% to 76%. In our case, final histology confirmed a biphasic mesothelioma with predominant epithelioid features and a high mitotic index.

In our patient, multiple pericardial biopsies obtained during both the initial pericardio-peritoneal window and the subsequent pleuro-pericardial window failed to establish a definitive diagnosis. This likely reflects the multifocal nature of PPM and the tendency of early lesions to exhibit nonspecific chronic inflammation or reactive mesothelial hyperplasia. Definitive diagnosis was only achieved after surgical pericardiectomy allowed for a larger and deeper tissue specimen.

Cardiac magnetic resonance (CMR) plays a central role in the evaluation of suspected cardiac tumors. PPM typically appears isointense on T1-weighted sequences, heterogeneous on T2-weighted sequences, and demonstrates gadolinium enhancement. Computed tomography (CT) may reveal pericardial thickening or extracardiac extension. Positron emission tomography (PET/CT) is valuable not only for initial detection but also for disease staging. In our case, CMR showed only mild pericardial thickening without contrast enhancement and did not contribute to the diagnosis. PET/CT, which might have provided additional information, was not performed.

Due to its rarity, nonspecific presentation, and rapid progression, PPM is usually diagnosed at an advanced stage. No standardized management exists; pericardiectomy is mainly palliative for recurrent effusion or constriction. Despite intervention, overall outcomes remain poor. Further research is urgently needed to better define diagnostic strategies and effective therapies for this aggressive and understudied malignancy.