College of American Pathologists

2011—June Case of the Month

Posted June 03, 2011


CAP Foundation June 2011 Online Case of the Month

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A 52-year-old man presented with abdominal pain and weight loss. A CT scan showed diffuse thickening of the anterior peritoneum over the small bowel. Laparotomy revealed an area of adherent small bowel with diffuse nodularity of the serosal surface. The area of nodularity was 14.0 x 11.0 cm in area and up to 1.5 cm in thickness with a fleshy, tan-white cut surface.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2008, Case 17, and is malignant mesothelioma.

Criteria for Diagnosis and Comments: The section shows a cellular proliferation infiltrating the peritoneum. The tumor has a diffuse growth pattern composed of cells with abundant eosinophilic cytoplasm and enlarged, round nuclei with an open chromatin pattern. The moderately pleomorphic tumor cells are arranged as small clusters or individual cells in a background of loose edematous stroma. Nuclear atypia and prominent nucleoli are present; however, necrosis and mitotic figures are rare to absent. The histology and tumor site are suggestive of malignant mesothelioma of the epithelioid type and the immunohistochemical profile supports the diagnosis. The tumor cells were calretinin (+), cytokeratin 5/6 (+), CEA (-), TTF-1(-), CD-117 (-), MOC 31 (-), and CD-34 (-).

Malignant mesotheliomas are much less common in the peritoneum than in the pleura. They probably account for less than 20% of all malignant mesotheliomas. There is a male predilection (2:1) and most patients are middle aged or elderly. The most common symptoms include abdominal discomfort, weight loss and ascites. There appear to be some differences in biologic behavior reported for male patients as compared to female patients. The majority of the male patients have shown a short (<2 years) survival, while select studies have shown a longer survival (>4 years or longer) in women. Younger patients have also been associated with improved survival.

The histologic features of peritoneal malignant mesothelioma are generally similar to those of pleural mesotheliomas; however, there seems to be a lower incidence of sarcomatoid and biphasic mesotheliomas than in the pleura. Psammoma bodies are a rare finding in peritoneal mesothelioma and most commonly indicate serous papillary carcinoma of other organs. The definitive diagnosis of mesothelioma requires correlation of histopathologic findings, radiography, clinical presentation and ancillary techniques. Electron microscopy remains a viable method of diagnosis for the epithelioid variant. Ultrastructurally, mesothelioma shows elongated surface microvilli and a lack of cytoplasmic secretory vacuoles. In practice, however, immunohistochemistry has become the technique of choice for supporting the diagnosis.

A specific marker for mesothelioma remains elusive, and use of a panel of stains that incorporates two positive markers and two negative markers is the preferred approach. The commonly used positive markers include cytokeratin 5/6, calretinin, and Wilms tumor gene-1 (WT1). Negative markers are usually epithelial antibodies such as CEA, MOC31 and TTF-1. These stains will aid in differentiating mesothelioma from metastatic adenocarcinomas. Negative markers should also include other stains tailored to the differential diagnosis for a given case, such as ER/PR receptors, BRST1, and other markers associated with specific lines of differentiation. For the case presented herein the addition of CD117 and CD34 were used to rule out a gastrointestinal stromal tumor given the location of the lesion in the bowel wall. TTF1, CEA and MOC31 aided in ruling out pulmonary and other types of adenocarcinoma.

The differential diagnosis for peritoneal malignant mesothelioma includes mesothelial hyperplasia, metastasis of adenocarcinomas to the peritoneum, serous borderline tumors and papillary serous carcinomas of the ovary or mesothelium, and gastrointestinal stromal tumors. Mesothelial hyperplasia is a common incidental finding in the peritoneum of women with chronic salpingitis and endometriosis. Mesothelial hyperplasia can be difficult to differentiate from malignant mesothelioma histologically and immunohistochemically. The gross appearance of the lesion is important for making this distinction; mesothelial hyperplasia usually presents either as multiple minute nodules or plaques or as an incidental microscopic finding. The presence of grossly visible nodules with cytologic atypia, necrosis and infiltration of the fat favors a diagnosis of mesothelioma.

Metastatic colorectal adenocarcinoma is a possibility in a peritoneal mass. Metastatic colorectal adenocarcinomas would show greater atypia and pleomorphism than peritoneal mesothelioma. Areas of necrosis should also be prominent. Immunohistochemical studies are helpful in this setting by demonstrating CEA and MOC 31 positivity in colonic adenocarcinoma with negative calretinin and CK 5/6 staining. Metastatic pulmonary adenocarcinoma is similar to colorectal carcinoma in that it should show a greater degree of atypia and pleomorphism than mesothelioma. Mitotic figures and necrosis would also be expected in pulmonary adenocarcinoma. The immunohistochemical profile would again show CEA and MOC 31 positivity as well as nuclear staining for TTF-1. Serous borderline tumors and papillary serous carcinoma of the ovary or peritoneum can pose the most significant differential diagnosis in women. In particular, WT1, a marker associated with malignant mesothelioma, can show strong nuclear positivity in serous carcinomas as well as peritoneal mesothelioma. Use of additional stains such as estrogen and progesterone receptor antibodies can be of help, as the latter are not expressed in malignant mesothelioma.

Finally, gastrointestinal stromal tumor (GIST) is included in the differential diagnosis of peritoneal mesothelioma as it shares many of the clinical and pathologic features. Clinically GIST is seen in middle aged to older patients and presents with similar vague abdominal complaints. The tumor originates from the muscularis propria of the GI tract, most commonly in the stomach or small bowel. The tumor can be composed of epithelioid cells that can resemble the cells of well-differentiated epithelioid mesothelioma. The immunohistochemical profile will serve to distinguish GIST from mesothelioma since GIST will show positivity for CD-34 and CD-117, and be negative for epithelial and mesothelial-associated markers.

Supplementary Questions: For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Which tumor exhibits CD-117 and CD-34 immunoreactivity and can have an epithelioid morphology? A. Gastrointestinal stromal tumor
B. Malignant mesothelioma
C. Mesothelial hyperplasia
D. Metastatic colorectal adenocarcinoma
E. Metastatic pulmonary adenocarcinoma
2. Which is a common incidental finding in the peritoneum of women with chronic salpingitis and endometriosis? A. Gastrointestinal stromal tumor
B. Malignant mesothelioma
C. Mesothelial hyperplasia
D. Metastatic colorectal adenocarcinoma
E. Metastatic pulmonary adenocarcinoma
3. Nuclear staining for TTF-1 is a common pattern of immunoreactivity for which tumor? A. Gastrointestinal stromal tumor
B. Malignant mesothelioma
C. Mesothelial hyperplasia
D. Metastatic colorectal adenocarcinoma
E. Metastatic pulmonary adenocarcinoma


  1. Clement P.B. Tumors of the peritoneum. In: Fletcher C.D.M. ed. Diagnostic Histopathology of Tumors. Vol. 1. 3rd edition. Boston, MA. Elsevier. 2007; 881-899.
  2. Hassan R, Alexander R. Nonpleural Mesothelioma: Mesothelioma of the Peritoneum, Tunica Vaginalis, and Pericardium. Hematol Oncol Clin N Am. 2005; 19:1067-1087.
  3. Suster S, Moran C. Applications and Limitations of Immunohistochemistry in the Diagnosis of Malignant Mesothelioma. Adv Anat Pathol. 2006; 13:316-329.
  4. Suster S, Moran C. Malignant Mesothelioma: current status of histopathologic diagnosis and molecular profile. Expert Rev Mol Diagn. 2005; 5:715-723.
  5. Travis W. D., Brambilla E., Muller-Hermelink H.K., Harris C.C. World Health Organization Classification of Tumours. Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart. IARC Press, Lyon. 2004.

Nicholas Dietz, MD
Medical College of Wisconsin
Milwaukee, WI

Saul Suster, MD, FCAP
Surgical Pathology Committee
Medical College of Wisconsin
Milwaukee, WI