Malignant Pleural Effusion with Metastasis to the Pericardial Sac

Abstract  
Malignant pericardial effusion is commonly linked to occult carcinoma, most frequently discovered as disease progression from primary lung cancer. Pericardial involvement typically remains undiagnosed, with only 1-20% of tumor-related autopsies documenting invasion of the pericardium. We present a 56-year-old male with massive pericardial effusion, uncovering a diagnosis of primary adenocarcinoma of the lung. Initially, he presented to the emergency department with shortness of breath. Past medical history includes chronic obstructive pulmonary disease and a 45 pack-year smoking history. A computerized tomography angiography of the chest was performed, revealing a possible left lower lobe pulmonary embolism. A large pericardial effusion was also found, with evidence of cardiac tamponade. He was emergently taken to the cardiac catheterization lab, where a pericardiocentesis was performed and 850 ml of hemorrhagic fluid was evacuated. Cytology of fluid from the left pleural cavity was performed. This specimen was found to contain numerous cohesive groups of metastatic adenocarcinoma cells. Pericardial sac tissue biopsy demonstrated non-small cell lung carcinoma (nsclc) adenocarcinoma. Immunohistochemical staining demonstrated ttf-1, ck7, and ck20 positivity, which confirmed primary pulmonary adenocarcinoma. Oncology was consulted and the patient was diagnosed with stage iva nsclc. Systemic chemotherapy was started with carboplatin, pemetrexed and pembrolizumab. Malignant pericardial effusions, although relatively rare, carry grave implications for patients, often manifesting with varied clinical presentations that demand prompt medical interventions. The patient's journey through diagnosis and treatment serves as a reminder of the challenges posed by advanced stage malignancies and their propensity to affect multiple organ systems, necessitating a multidisciplinary approach.

Keywords: malignant pericardial effusion; metastasis; pericardial sac  

Introduction 
Malignant pericardial effusion is commonly linked to occult carcinoma, most frequently discovered as disease progression from primary lung cancer. Pericardial involvement typically remains undiagnosed, with only 1-20% of tumor-related autopsies documenting invasion of the pericardium. Presentation of malignant pericardial effusions vary and can range from patients experiencing difficulty breathing, chest pain, cardiac arrhythmias, to life threatening cardiac tamponade¹. Although emergent procedures such as pericardiocentesis and surgical procedures such as pericardial window can correct cardiac tamponade, prognosis for these patients remains guarded due to a primary malignancy being the cause of these complications. Non-small cell lung cancer (nsclc) has been reported as the most frequent malignancy related to malignant pericardial effusion; this case report will describe a patient with primary lung adenocarcinoma presenting with significant pericardial effusion.  

Case presentation: 
A 56-year-old male presented to the emergency department (ed) with shortness of breath. He reported that his shortness of breath has been on-going from the past 3 months, and recently progressively worsened. One day prior to his ed visit, he reported that he could not walk up one flight of stairs without becoming severely short of breath. At this time, he reported having mild lightheadedness, but denied chest pain. Past medical history includes chronic obstructive pulmonary disease (copd) and a 45 pack-year smoking history. Abnormal laboratory findings are represented in (table 1).

While performing thoracentesis of the left pleural cavity, 10 ml of translucent orange pleural fluid was collected. This specimen was found to contain numerous cohesive groups of metastatic adenocarcinoma cells. A pericardial sac tissue biopsy was also performed. Immunohistochemically staining of this specimen demonstrated ttf-1, ck7, and ck20 positivity, which differentiate primary pulmonary adenocarcinomas from extra pulmonary adenocarcinomas that have metastasized to the lung.

The patient was consulted by hematology-oncology and a brain mri was ordered, which was negative for brain metastasis. Our patient was subsequently diagnosed with stage iva nsclc. Whole-body pet scan was ordered upon discharge from the hospital which showed an enlarging, hypermetabolic mass like consolidation in the left lower lobe, hypermetabolic cervical, left supraclavicular, mediastinal, hilar and sub carinal lymphadenopathy, likely metastatic, and multiple discrete foci of increased anechoic activity in the pelvis and cervical spine which that were also like metastatic. Systemic chemotherapy was started with carboplatin and pemetrexed, in combination with pembrolizumab. Cyanocobalamin 1000 mcg was given intramuscularly prior to starting chemotherapy. This regimen was adjusted accordingly following a brief elevation of liver transaminases.


Figure 4. First cxr post-discharge; left subclavian chest port with the tip in the svc. The heart is stable in size. There is pulmonary venous congestion without overt edema. Redemonstrated is a large mass like opacity in the left lower lobe with a small left pleural effusion. No pneumothorax. The right lung is clear.

Upon discharge, he was educated on the importance of taking his medications for copd, specifically his albuterol and ipratropium nebulizers. Four days after discharge from our facility, he received a single-lumen power port vascular catheter through the left subclavian vein for chemotherapy. An outpatient cxr showed mild pulmonary venous congestion without overt edema with a stable, large, mass-like opacity in the left lower lobe. Our patient was given close follow up with hematology-oncology, pulmonology, and primary care to optimize his management for stage iva nsclc.   

Discussion  
Pericardial effusion is defined as a collection of fluid in the pericardial sac, located around the heart. In healthy patients, the pericardial sac contains approximately 15 to 50 ml of serous fluid which serves to reduce friction between the pericardial membranes allowing them to glide smoothly among each other while the heart is contracting and relaxing². The management of pericardial effusions depends on size of the effusion, hemodynamic compromise, and the primary etiology of the effusion. In developed countries, most pericardial effusions are idiopathic, however, in underdeveloped countries, tuberculosis (tb) has been identified as the most common cause of this problem. Disease states that have been identified to cause pericardial effusions include neoplasm, systemic lupus erythematosus (sle), bacterial and viral infections such as chagas disease, dressler syndrome, and chronic renal failure requiring dialysis. Hydralazine and procainamide have been identified as medications that can also cause this problem¹.

Fluid accumulation, inflammation, and fibrous constriction are among the most common forms of pericardial disease. These conditions are usually associated with other cardiac pathologies or systemic disease. Normally, less than 50 ml of thin, clear, straw-colored fluid is present within the pericardial sac. In conditions that permit long-standing cardiac enlargement or allow for a slow accumulation of fluid, the pericardium has adequate time to remodel and adjust to the larger volume. This process permits the development of a slow accumulating pericardial effusion to be very substantial without restricting or compromising cardiac function. Most cases of chronic effusion (usually less than 500 ml of fluid) only become clinically significant once identified as globular enlargement of the heart shadow on chest radiography. However, rapidly developing fluid collections of only approximately 200-300 ml due to hemopericardium caused by ruptured myocardial infarction or aortic dissection, can present with significant compression of the atria and venae cavae. Rapid developing pericardial effusion can be much more clinically devastating by compromising cardiac filling, leading to life-threatening cardiac tamponade³.

Malignant pericardial effusion remains a rare presentation in patients with undiagnosed malignancy. The most prevalent cancer identified as a cause of malignant pericardial effusions is lung cancer, and breast cancer as the second most prevalent. Other common malignancies such as melanoma, mesothelioma, mediastinal lymphoma, and renal cell carcinoma have been seen to cause malignant pericardial effusion. It is believed that the pathogenesis of malignant pericardial effusion is due to local lymphatic invasion. Direct invasion into the mediastinum is thought to occur less frequently and believed to be due to hematogenous spread¹.

Pathologic examination of the pericardial and pleural fluid showed similar findings, both revealing numerous groups of metastatic adenocarcinoma cells. Immunohistochemistry (ihc) testing then redemonstrated ttf-1, ck7 and ck20 positivity which are known to be specific for primary pulmonary adenocarcinoma⁴. These ihc results ruled out extrapulmonary sources for primary malignancy, therefore reinforcing the diagnosis of metastatic adenocarcinoma of the lung; see (table 3) for details.

Adenocarcinoma of the lung, a prevalent subtype of non-small cell lung cancer, originates in the lung's epithelial cells and is characterized by glandular structures. Commonly associated with genetic mutations like egfr, alk rearrangements, and kras mutations, adenocarcinoma often presents in nonsmokers or former light smokers, predominantly in the lung's outer regions. Its diverse histological patterns, including acinar, papillary, and solid formations, contribute to its varied clinical manifestations such as persistent cough, shortness of breath, and weight loss. Diagnosis involves imaging, biopsy, and molecular testing to determine treatment options, which span surgery, chemotherapy, radiation, targeted therapy, and immunotherapy, with personalized strategies becoming increasingly essential³.

Table 3. Immunohistochemical details; our patients ihc results showed positive staining for ttf-1, ck7, and ck20^5,6.