Moderators: Dr. Kelly Butnor and Dr. Francoise Galateau-Salle
Section 4 -
Well-Differentiated Papillary Mesothelioma
Victor L. Roggli
Duke University Medical Center
Durham, North Carolina
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
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
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.
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. 
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.  The mesothelial nature of the
lining cells has been confirmed ultrastructurally. 
In the strictest definition, invasion is not observed in WDPM. However, some otherwise typical cases
may show limited invasion.
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,
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.
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. More recent data suggests that on
occasion these tumors can prove fatal.
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,
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
- 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. Extensive myxoid change in well-differentiated papillary mesothelioma of the pelvic peritoneum. Ann Diagn Pathol 2002; 6: 164-7.
- Churg A, Cagle PT, Roggli VL. Tumors of the serosal membranes. In: AFIP Atlas of Tumor Pathology. Series 4, Fascicle 3. Washington, DC: American Registry of Pathology, 2006: 61-64.
- Churg A, Roggli VL, Galateau-Salle F, Cagle P, Gibbs A, Henderson D, Vignaud JM, Inai K, Praet M, Ordonez N, Hammar S, Pugatch B, Testa J, Knuutila S, Gazdar A, Saracci R. Tumours of the Pleura, CH 2, In: World Health Organization Classification of Tumours, Pathology & Genetics, Tumours of the Lung, Thymus, and Heart. Lyon: WHO, 2004, pp. 125-144.
- Jayaram G, Ashok S. Fine needle aspiration cytology of well-differentiated papillary mesothelioma. Report of a case. Acta Cytolog 1988; 32: 563-6.
- Haba T, Wakasa K, Sasaki M. Well-differentiated papillary mesothelioma of the pelvic cavity: A case report. Acta Cytolog 2003; 47: 88-92.
- Hejmadi R, Ganesan R, Kamal NG. Malignant transformation of a well-differentiated peritoneal papillary mesothelioma. Acta Cytolog 2003; 47: 517-8.
- Burrig KF, Pfitzer P, Hort W. Well-differentiated papillary mesothelioma of the peritoneum: a borderline mesothelioma. Report of two cases and review of the literature. Virch Arch A Pathol Anat Histopathol 1990; 417: 443-7.
- Hoekman K, Tognon G, Risse EK, Bloemsma CA, Vermorken JB. Well-differentiated papillary mesothelioma of the peritoneum: a separate entity. Eur J Cancer 1996; 32A: 255-8.
- Galateau-Salle F. Well-differentiated papillary mesothelioma. Histopathology 2002; 41 [Suppl 2]: 154-6.
- Galateau-Salle F, Brambilla E, Cagle PT, Churg AM, Colby TV, Gibbs AR, Hammar SP, Hasleton PS, Henderson DW, Inai K, Praet M, Roggli VL, Travis WD, Vignaud JM. Pathology of Malignant Mesothelioma, Springer: London, 2006, pp. 150-1.
- Roggli VL, Oury TD, Moffatt EJ. Malignant mesothelioma in women. In: Anatomic Pathology, 1997, Vol. 2 (Rosen PP, Fechner RE, eds.), ASCP Press, Chicago, 1998, pp. 147-63.
- Roggli VL, Sharma A, Butnor KJ, Sporn T, Vollmer RT. Malignant mesothelioma and occupational exposure to asbestos: A clinicopathological correlation of 1445 cases. Ultrastruct. Pathol. 2002; 26: 55-65.