Background: Cardiac tamponade is a life-threatening oncologic and cardiovascular emergency requiring prompt recognition and immediate drainage. While the pericardium can accommodate slowly accumulating fluid, extreme effusions exceeding 50 mm are exceptionally rare.

Case Presentation: We report the case of a 77-year-old female with an intellectual disability and a history of two prior pericardiocenteses who presented with severe dyspnea and hemodynamic collapse (BP: 76/42 mmHg, HR: 125 bpm). Transthoracic echocardiography (TTE) in end-diastole demonstrated a massive, giant pericardial effusion measuring up to 82 mm from the apical long- and short-axis views. Pulsed-wave Doppler revealed profound respiratory variation (>25% across the mitral valve and >40% across the tricuspid valve), confirming overt cardiac tamponade. The inferior vena cava was severely dilated (32 mm) without inspiratory collapse. Emergent pericardiocentesis initially evacuated 1,500 mL of hemorrhagic fluid, culminating in a total of 2 liters drained within the first 24 hours. This provided immediate hemodynamic relief without any subsequent deterioration in cardiac function. Over the course of the hospital stay, continuous catheter drainage yielded a remarkable cumulative total of 5.5 liters. Thoracic CT identified a pulmonary mass and mediastinal lymphadenopathy. Serum CA-125 was significantly elevated; surprisingly, repeated pericardial fluid cytological examinations showed no malignant cells. Tissue biopsy could not be obtained due to patient refusal. A surgical pericardial window was created, and the patient was discharged in a stable condition.

Conclusion: This case highlights that giant effusions (82 mm) can induce massive pericardial distension and that elevated serum CA-125 levels in such settings may stem from mesothelial mechanical stretch rather than direct tumor secretion. It also reinforces the critical utility of quantitative PW-Doppler and comprehensive imaging in validating tamponade hemodynamics and navigating diagnostic dilemmas in recurrent effusions despite negative cytology