Definition
• Metastasis of extrapleural malignancies to pleura
Pathogenesis
• Pleural involvement can result from lymphatic spreading (from mediastinal and transdiaphragmatic lymphatics), hematogenous spreading, or direct extension from adjacent sites
Clinical features
Epidemiology
• Pleural metastasis of extrapleural malignancies account for the majority of the 150,000 malignant pleural effusions reported yearly
• Metastasis from lung carcinoma is the most common, accounting for 60,000 cases, followed by breast carcinoma and then lymphoma
Presentation
• Dyspnea and pleurodynia secondary to pleural effusion
• Radiological evidence of pleural effusion with multiple small nodules and/or thickening of pleura
Prognosis and treatment
• Poor prognosis; pleural involvement signifies an advanced stage of primary malignancy
• Lung cancer patients with pleural involvement have an 85% mortality rate over 6 months
Pathology
Gross
• Multiple white, firm pleural nodules or masses
• Malignant melanomas may be seen with pigmented lesions
Histology
• Morphological features are similar to that of the primary tumor
• Metastasis from lung adenocarcinoma
– Glandular, acinar, tubulopapillary, micropapillary, and solid variants
– Greater pleomorphism, higher nuclear–cytoplasmic ratio, and eccentric, prominent nucleoli when compared with malignant mesothelioma
• Metastasis from nonpulmonary tumors
– Papillary carcinoma of the thyroid and ovary may be seen with papillary architecture and psammoma bodies
– Colonic adenocarcinoma with tall tumor cells and central necrosis within glands
Immunopathology/special stains
• Consistent with immunoreactivity of primary tumor
• Lung adenocarcinoma: TTF-1, Ber-Ep4, and CEA
• Lung squamous cell carcinoma: CK5/6- and p63-positive; TTF-1-negative
• Breast carcinoma: ER/PR-positive
• Thyroid carcinoma: TTF-1 and thyroglobulin
• Leiomyosarcoma: SMA
• Renal cell carcinoma: CD10
• Peripheral nerve sheath tumors: S100
• Malignant melanoma: HMB45, S100
• Leukemia/lymphoma: lymphoid markers
• Thymoma: CD5
Main differential diagnoses
• Malignant mesothelioma
• Reactive mesothelial hyperplasia
Fig 1 Metastases to pleura. Gross photographs showing parietal pleura with multiple white-tan pleural nodules (A) and studding of the visceral pleura surface with innumerous white-tan metastatic deposits (B).
Fig 2 Metastases to pleura. Metastatic lung adenocarcinoma growing along pleural surface and invading pleural connective tissue, mimicking malignant mesothelioma (A); there is immunopositivity with TTF-1 (B), CEA (C), and Ber-Ep4 (D) staining.
Fig 3 Metastases to pleura. Metastatic lobular breast carcinoma with characteristic single file invasion (A) and immunopositivity with ER (B) staining.
Fig 4 Metastases to pleura. Metastatic colon cancer (A and B). Dissociated tumor cells are difficult to differentiate from reactive mesothelial cells; immunostains are positive for CK20 (C) and MOC31 (D).