Pleural Effusion with Innumerable Pleural Masses: A Case of Sarcomatoid Malignancy with Diagnostic Ambiguity

Purpose: Pleural effusions with concurrent pleural masses present a diagnostic challenge, requiring differentiation between infectious and neoplastic etiologies. Sarcomatoid malignancies of the pleura, including sarcomatoid mesothelioma and sarcomatoid carcinoma, are rare and aggressive tumors with overlapping morphologic and immunohistochemical features. Accurate classification is critical as each entity has distinct prognosis and therapeutic implications. We present a case of a 74 y/o M with a large loculated pleural effusion and innumerable pleural masses, ultimately diagnosed with sarcomatoid neoplasm indeterminate between sarcomatoid mesothelioma and sarcomatoid carcinoma despite extensive imaging & immunohistochemical testing.

Methods/Materials: A 74 y/o M with HTN and tobacco use presented with progressive dyspnea following COVID infection. CT angiography revealed a large, loculated right pleural effusion with compressive atelectasis. Pleural fluid analysis demonstrated an exudative effusion with 430,000 RBC/μL and negative cytology. Following US-guided thoracentesis and chest tube placement, robotic thoracoscopy with right total decortication and pleural biopsy was performed after identification of innumerable pleural masses.

Results: Initial imaging showed large loculated pleural effusion with sanguineous fluid, concerning for complicated parapneumonic effusion versus malignancy. Follow-up CT chest imaging demonstrated extensive right-sided pleural thickening with enhancement, ipsilateral volume loss, and rapidly progressing mass invasion with multiloculated gas and fluid collections. Histopathology revealed a malignant spindle cell neoplasm positive for cytokeratin CAM5.2 and focal AE1/AE3, but negative for traditional mesothelial markers. The patient developed rapid disease progression and ultimately required hospice care.

Conclusions: This case highlights the diagnostic complexity when CT findings and immunohistochemistry yield indeterminate results. Early thoracoscopic biopsy with comprehensive immunohistochemical panels and multidisciplinary correlation of clinical, radiologic, and pathologic findings remain essential for optimal diagnosis and management of these aggressive malignancies.