Large Cell Neuroendocrine Carcinoma Primarily in the Pericardium: A Case Report and Literature Review
A 40-year-old Chinese woman presented with a 3-month history of progressive chest pain, dyspnea, and a 2-week history of abdominal distension. Her symptoms began in June 2015 with retrosternal pain exacerbated by deep inspiration, accompanied by mild pericardial effusion observed on echocardiography (left ventricular ejection fraction: 63%). By July, her symptoms worsened despite normal routine blood tests, liver function, renal function, and thyroid studies. By September, she developed severe dyspnea at rest, orthopnea, palpitations, reduced urine output, bilateral lower limb edema, and significant abdominal distension. Echocardiography revealed moderate pericardial effusion unresponsive to diuretics, prompting hospital admission.
On examination, her blood pressure was 107/91 mmHg, heart rate 103 beats/min, and she appeared acutely ill with Kussmaul’s sign, distant heart sounds, pulsus paradoxus, shifting dullness, and jugular venous distension. Echocardiography confirmed massive pericardial effusion (indicative of cardiac tamponade) and inferior vena cava dilation (26 mm). Emergency pericardial puncture and catheterization drained 250–400 mL of turbid, bloody fluid daily, alleviating symptoms. Pericardial fluid analysis showed elevated lactic dehydrogenase (1,500 U/L), CA125 (256 U/mL), and red blood cells but no tumor cells. Serum CA125 (560 U/mL) and tissue polypeptide-specific antigen (389 U/L) were elevated, while other tumor markers remained normal. Liver function abnormalities (ALT 646 U/L, total bilirubin 39 mmol/L) resolved with effusion drainage.
In October 2015, recurrent symptoms prompted reevaluation, revealing constrictive pericarditis (cubital vein pressure: 30 cmH2O). Contrast-enhanced CT and 18F-FDG PET/CT demonstrated hypermetabolic lesions in the pericardium and atrioventricular spaces (SUVmax 6.0), suggesting malignancy (Figure 1A–E). Pericardiectomy revealed a necrotic malignant tumor involving visceral and parietal pericardium, with no mediastinal lymph node metastasis (0/7 nodes). Histopathology showed sheets of large polygonal cells with abundant eosinophilic cytoplasm, prominent nucleoli, mitotic activity (>10 mitoses/2 mm²), and extensive necrosis (Figure 1F–H). Immunohistochemistry confirmed neuroendocrine differentiation: cytokeratin (AE1/AE3+), synaptophysin (partial+), CD56 (partial+), and Ki-67 proliferation index of 90%. Negative stains included chromogranin A, calretinin, and TTF-1 (Figure 1I–K). Somatostatin receptor imaging post-surgery revealed tracer uptake in aortic arch and descending aorta, with no distant metastases.
Primary pericardial large cell neuroendocrine carcinoma (LCNEC) represents an unprecedented diagnostic entity. LCNEC, a high-grade neuroendocrine tumor, typically arises in the lung but rarely occurs in extrapulmonary sites like the gastrointestinal tract, genitourinary system, or mediastinum. The 2015 WHO classification defines LCNEC by neuroendocrine morphology (organoid nesting, rosettes, trabeculae), mitotic rate (>10/2 mm²), necrosis, and expression of ≥1 neuroendocrine marker (synaptophysin, chromogranin A, or CD56). Differentiating LCNEC from small cell carcinoma, atypical carcinoid, or non-small cell carcinoma requires resection specimens due to overlapping cytologic features in biopsies.
This case highlights diagnostic challenges in pericardial malignancies. Initial pericardial fluid cytology failed to detect tumor cells, delaying diagnosis. Constrictive pericarditis and tamponade, typically associated with tuberculosis or autoimmune diseases, masked the underlying neoplasm. Elevated CA125, often linked to ovarian or peritoneal malignancies, further complicated the picture. Definitive diagnosis necessitated pericardiectomy, underscoring the role of surgical biopsy in refractory pericardial effusions.
LCNEC’s aggressive biology parallels small cell lung cancer (SCLC), with rapid progression and poor prognosis. Platinum-etoposide regimens, effective in SCLC, are empirically used for LCNEC, though evidence remains limited. Somatostatin receptor expression in this case suggests potential benefit from octreotide or peptide receptor radionuclide therapy (PRRT), though neither was administered. Radiotherapy may palliate local symptoms, while debulking surgery remains controversial.
The patient’s demographics contrast with typical pulmonary LCNEC, which favors older male smokers. Her nonsmoking status, lack of occupational exposures, and primary pericardial involvement emphasize LCNEC’s biologic heterogeneity. Despite pericardiectomy, disease progression led to death within 17 months, reflecting LCNEC’s dismal prognosis.
This case underscores the importance of considering malignancy in refractory pericardial effusions, particularly with elevated CA125 and constrictive physiology. Multidisciplinary collaboration, advanced imaging (e.g., 18F-FDG PET/CT), and timely surgical intervention are critical for diagnosing rare pericardial tumors. Immunohistochemistry remains indispensable for classifying neuroendocrine neoplasms, guiding therapeutic decisions, and prognostic stratification. Future studies must define optimal treatment protocols for extrapulmonary LCNEC to improve outcomes.
doi.org/10.1097/CM9.0000000000000586
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