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Journal of Clinical Oncology, Vol 25, No 25 (September 1), 2007: pp. 4009-4011 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.12.3794
Pleural Metastases From Renal Cell Carcinoma 16 Years After ResectionDepartment of General Thoracic Surgery, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan
Department of Respiratory Medicine, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan
Department of Pathology, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan
Division of Thoracic and Visceral Organ Surgery, Gunma Graduate University School of Medicine, Maebashi, Gunma, Japan In September 2003, a 68-year-old man was admitted to our hospital because of a 1-month history of dyspnea. The patient received medical attention and he was diagnosed with a common cold. He had had a left radical nephrectomy for renal cell cancer in August 1987. Afterward, a diagnosis of clear cell carcinoma of the left kidney was made. Clinically, the disease was in stage 3, and histologically diagnosed as grade 2 clear cell type. Since then, the patient had experienced no recurrence. A roentgenography (Fig 1) and computed tomography of the thorax revealed a mass pleural effusion of the right thorax. On examination, vital signs were within normal limits. There was no elevation of tumor markers (carcinoembryonic antigen, alpha fetoprotein, squamous cell carcinoma antigen, neuron-specific enolase). The other laboratory data were within the normal range. After thoracentesis, about 1,000 mL of serosanguinous fluid was aspirated; pleural fluid cytologic examination was negative. A subsequent computed tomography (Fig 2) and magnetic resonance image demonstrated mesothelioma-like tumor, which was spreading in the left pleural space. It was difficult to confirm the diagnosis without a certain amount of biopsied specimen. Video-assisted thoracoscopic biopsy of the pleural mass was conducted in October 2003. Macroscopically, the nodules were present and protruded on the parietal pleura. Histological features of the biopsied specimen showed metastatic renal cell carcinoma (Fig 3). The lesion consisted of tumor cells with abundant clear cytoplasm and small round nuclei with atypia (hematoxylin and eosin stain; original magnification x400). The immunohistochemical study demonstrated positive reaction with periodical acid–Schiff stain (Fig 4). This finding was similar to those of the previously resected primary lesions (Fig 5). The tumor was diagnosed to be compatible with metastatic renal cell carcinoma, grade 2 clear cell type, of the pleura. Since the 13th postoperative day, 6 million U of interferon-alfa had been injected subcutaneously. The postoperative course was uneventful. The patient was discharged on the 22nd postoperative day. Interferon was discontinued because of disease progression. The patient received 60 Gy total lung irradiation in February 2004, but it was ineffective. The patient remained symptomatically stable for 10 months, but then deteriorated and died of respiratory failure in December 2004.
Renal cell carcinoma has an unpredictable behavior even after curative resection. While renal cell cancer commonly metastasizes to the lung, pleural metastasis is a rare clinical entity. Pleural lesions usually develop as a part of systemic metastases of renal cell cancer, accompanied by parenchymal spread.1 Late recurrence in the intrathoracic organ, especially lung, more than 15 years after radical nephrectomy has been reported.2 However, to our knowledge, this case, in which late recurrence developed at the pleura only, has not been reported previously. From 1959 to 1977, one study reported that 12% of 1,451 necropsied cases of renal carcinoma had pleural metastases, but none had solitary pleural metastases.3 All metastatic lesions existed mainly in the lungs; pleural metastases occurred secondary to invasion or dissemination from parenchymal lung lesions. Therefore, it was extremely rare to spread only parietal pleurae.4,5 There was only one individual report of solitary pleural metastasis in the literature.6 However, primary and metastatic lesions occurred simultaneously. What is more unusual about our case is that the disease-free interval between pleural metastasis and primary cancer was 16 years. In a review of the literature, there are no reports with long disease-free intervals in solitary pleural metastasis. Metastases to other sites, which are more common, may also be seen many years after resection of the primary malignancy in the kidney.2 Where had these tumor cells been for such a long time? In the past 10 years, there have been many studies on tumor dormancy that can account for long remissions or hidden metastatic tumor foci. It is known that tumors are dependent on angiogenesis, which is essential for the expansion of the primary tumor and required for growth of established metastases at distant sites. The cellular and molecular mechanisms ingeniously control malignant tumor cells during the dormancy. Metastases remain dormant when tumor cell proliferation is balanced by an equivalent rate of apoptosis.7 However, tumors switching one day to the angiogenic phenotype are grown and detected radiologically.8 We studied resected cases of pulmonary metastases with disease-free intervals longer than 10 years.9 In this report, we found tumor-doubling times ranging from 80 to 815 days; therefore, it might take more than several decades for some tumors to become radiologically detectable. How did tumor cells reach and grow at the pleura? It has been10 suggested that there was another route other than the recognized vein systems: the pulmonary, the caval, and the portal routes. The vertebral system of vein may have spread tumor cells from anal to various regions of the body without the previous vein systems. The fourth pattern is raised as the possibility of metastatic route in our case because of no metastatic lesions other than pleura. The pathway, by which renal cell carcinoma reached pleura, was also suggested.11 Therefore, it might have taken 16 years to reach pleura on opposite side of the primary lesion. This case suggests us that a pleural mass mimicking pleural mesothelioma could be metastasis from renal cell carcinoma, even if it appears a long time after radical nephrectomy. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Bennington JL, Kradjian RM: Distribution of metastases from renal cell carcinoma, in Bennington JL, Kradjian RM (eds): Renal Carcinoma. Philadelphia, PA, Saunders, 1967, pp 156-161 2. Yoshida J, Nagai K, Hasebe T, et al: Pulmonary metastasis of renal cell carcinoma resected sixteen years after nephrectomy. Jpn J Clin Oncol 25:20-24, 1995 3. Saitoh H: Distant metastases of renal adenocarcinoma. Cancer 48:1487-1491, 1981[CrossRef][Medline] 4. Kutty K, Varkey B: Incidence and distribution of intrathoracic metastases from renal cell carcinoma. Arch Intern Med 144:273-276, 1984[Abstract] 5. Singla R, Bhattacharya D, Chhabra SK, et al: Pleural effusion in renal cell carcinoma: A rare presenting feature. Indian J Chest Dis 29:29-35, 1987[Medline] 6. Taylor DR, Page W, Hughes D, et al: Metastatic renal cell carcinoma mimicking pleural mesothelioma. Thorax 42:901-902, 1987[Medline] 7. Holmgren L, O'Reilly MS, Folkman J: Dormancy of micrometastases: Balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nature Med 1:149-153, 1995[CrossRef][Medline] 8. Naumov GN, Bender E, Zurakowski D, et al: A model of human tumor dormancy: An angiogenic switch from the nonangiogenic phenotype. J Natl Cancer Inst 98:316-325, 2006 9. Kamiyoshihara M, Hirai T, Kawashima O, et al: Resection of pulmonary metastases in six cases with disease-free interval greater than 10 years. Ann Thorac Surg 66:231-233, 1998 10. Batson OV: The function of the vertebral veins and their role in the spread of metastases. Ann Surg 112:138-149, 1940[Medline] 11. Latour A, Shulman HS: Thoracic manifestation of renal cell carcinoma. Radiology 121:43-48, 1976[Abstract]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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