Section 4 -

Well-Differentiated Papillary Mesothelioma Victor L. Roggli Duke University Medical Center Durham, North Carolina

Clinical History This 60-year-old woman presented with a several week history of progressive dyspnea. Chest x-ray and computed tomography showed a large right pleural effusion. Thoracentesis yielded 1350 ml of bloody fluid. A thoracoscopic biopsy was performed. The patient was a non-smoker who worked as an LPN. Her father worked for the railroad and her husband worked for a chemical company. Section 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Discussion Well-differentiated papillary mesothelioma (WDPM) is a distinct tumor with papillary architecture and a tendency toward superficial spread without invasion. These tumors have most commonly been reported in the peritoneal cavity of women, but also occur in the pleura, pericardium and tunica vaginalis testis. [1, 2, 3, 4, 5] Well-differentiated papillary mesotheliomas usually occur as diffuse lesions, but may rarely occur as localized masses. Localized variants of WDPM have been reported in the peritoneum, pleura, and pericardium. [6, 7, 8] WDPM of the pleura is often an incidental finding at the time of surgery, but may also present with pleural effusion, chest pain or pneumothorax. Grossly, the tumor most often appears as multiple nodules ranging from a few millimeters to several centimeters in diameter. However, some cases have only a single nodule. The involved pleural surface may have a velvety appearance caused by the presence of numerous small tumor nodules. Microscopically WDPM is characterized by stout fibrovascular cores covered by a single layer of flattened to cuboidal mesothelial cells. In some cases, the cores have a myxoid appearance. [9] Solid or tubular areas may also be observed. Psammoma bodies are occasionally seen and a central scar may be present, especially in the localized variant. The tumor cells are uniformly bland, and do not show mitotic figures, large nucleoli, or necrosis. Basal vacuoles may be present in the lining cells. Results of immunohistochemical staining are similar to those observed for the epithelial variant of diffuse malignant mesothelioma. These include positive staining of tumor cells for cytokeratins (including CK 7 and CK 5/6), calretinin (nuclear and cytoplasmic), WT-1 (nuclear), thrombomodulin, mesothelin and HBME-1 (membranous). In addition, the tumor cells stain negative for carcinoembryonic antigen (CEA), BerEP4, CD15, B72.3, MOC31, Bg8 and TTF-1. [10] The mesothelial nature of the lining cells has been confirmed ultrastructurally. [2] In the strictest definition, invasion is not observed in WDPM. However, some otherwise typical cases may show limited invasion. [2, 11] It should be noted that diffuse malignant mesotheliomas may have areas with a WDPM-like pattern, and such cases should not be designated as WDPM. Therefore, great caution needs to be employed when attempting to make a diagnosis of WDPM on a small biopsy specimen. Although cytologic features of WDPM have been described, [12, 13, 14] cytologic specimens may fail to identify an invasive component that could have important prognostic implications, and cytologic diagnosis is not recommended. Localized WDPM invariably pursues a benign course and complete surgical resection is curative. As a rule tumors with multiple small nodules are characterized by an indolent course with prolonged survival and in most instances these tumors do not shorten life expectancy. [1, 2, 15, 16] In the original description by Daya and McCaughey, almost all tumors were multiple and the few patients that died did so of other causes with persisting but innocuous tumor. [1]More recent data suggests that on occasion these tumors can prove fatal. [2, 17] The development of invasive foci within WDPM may herald a more aggressive clinical course. However, rapidly progressive disease suggests that the underlying process is actually a diffuse malignant mesothelioma with focal areas resembling WDPM, but that the diagnostic areas have not been biopsied. No association of localized WDPM and asbestos exposure has been reported. Asbestos exposure has been reported in some cases of multi-nodular WDPM, [2, 17, 18] but an association has not been established in epidemiological studies. With regards to the present case, it should be noted that exposure to asbestos as a household contact is the most common cause of mesothelioma among women in the United States. [19, 20] References: Daya D, McCaughey WT. Well-differentiated papillary mesothelioma of the peritoneum: a clinicopathologic study of 22 cases. Cancer 1990; 65: 292-6. Butnor KJ, Sporn TA, Hammar SP, Roggli VL. Well-differentiated papillary mesothelioma. Am J Surg Pathol 2001; 25: 1304-9. Shukunami K, Hirabuki S, Kaneshima M, Kamitani N, Kotsuji F. Well-differentiated papillary mesothelioma involving the peritoneal and pleural cavities: successful treatment by local and systemic administration of carboplatin. Tumori 2000; 86: 419-21. Chetty R. Well-differentiated (benign) papillary mesothelioma of the tunica vaginalis. J Clin Pathol 1992; 45: 1029-30. Barbera V, Rubino M. Papillary mesothelioma of the tunica vaginalis. Cancer 1957; 10: 183-9. McCaughey WTE, Kannerstein M, Churg J. Tumors and pseudotumors of the serous membranes. In: Atlas of Tumor Pathology. Series 2, Fascicle 20. Washington, DC: Armed Forces Institute of Pathology, 1985: 76-78. Yesner R, Hurwitz A. Localized pleural mesothelioma of epithelial type. J Thorac Surg 1953; 26: 325-9. Sane AC, Roggli VL. Curative resection of a well-differentiated papillary mesothelioma of the pericardium. Arch Pathol Lab Med 1995; 119: 266-7. Diaz LK, Okonkwo A, Solans EP, Bedrossian C, Rao MS. 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