A 22 year-old female presented with ascites. Laparoscopic examination revealed a pelvic
mass involving the cecum. Diffuse peritoneal studding was also noted. A biopsy was obtained.
Diagnosis: Malignant mesothelioma, epithelial type, with prominent myxoid change
Case 3 - Figure 1 - Low magnification showing a cellular proliferation embedded in a myxoid background.
Case 3 - Figure 2 - Intermediate magnification showing infiltration into adipose tissue.
Case 3 - Figure 3 - Intermediate magnification showing neoplastic cells arranged in a cystic pattern and small cords.
Case 3 - Figure 4 - Higher magnification showing a uniform cellular proliferation composed of round to polygonal cells with eosinophilic cytoplasm, round nucleus and inconspicuous nucleoli. Scattered cells with a signet-ring appearance are present.
The low power magnification shows a prominent myxoid background with clusters of
epithelioid cells distributed haphazardly and arranged in cords, loose aggregates or in a cystic pattern.
At higher magnification, the cellular proliferation was composed of medium size cells with eosinophilic
cytoplasm, dark nuclei and inconspicuous nucleoli. Focally, they had a signet ring cell-like appearance.
No marked mitotic activity was noted and no necrosis and/ or hemorrhage was identified. The cellular
proliferation was very uniform throughout. At the periphery, infiltration of the adipose tissue was
Histochemical and Immunohistochemical Features:
Histochemical studies including colloidal iron, alcian blue at ph 2.5, periodic
acid-Schiff (PAS) with and without diastase as well as mucicarmine were performed. The myxoid background
and rare cytoplasmic vacuoles were positive for alcian blue and colloidal iron. Mucicarmine and PAS were
Immunohistochemical studies for calretinin and keratin 5/6 strongly decorated the cellular
proliferation while CEA, MOC-31, Ber-EP4, Leu M1 (CD15) and B72.3 were negative.
Peritoneal mesothelioma is an uncommon disease accounting for 17 to 32% of the
mesotheliomas in females.1-4 Just as their counterparts in the pleural cavity, these tumors may show
similar histopathological features and the diagnostic criteria are also similar.
Clinically, the patients' age range from 18 to 85 years (mean: 51.8 and 50.4 years in the
two largest studies). Most of the patients present with abdominal pain and ascites. No definitive
history of asbestos exposure has been documented in the largest series.5,6
Histologically, the diagnosis of mesothelioma traditionally has been one of exclusion.
Three main histological patterns have been recognized: 1) epithelial type; 2) sarcomatoid type; 3)
biphasic type. However, numerous other unusual variants of mesothelioma have been described including:
lymphohistiocytic type, with osseous and cartilaginous metaplasia, and with myxoid change.7
Immunohistochemically, the US/Canada mesothelioma panel recommends the use of Carcinoembryonic antigen
(CEA), B72.3, Leu-M1, Ber-Ep4, and keratin. Ideally, mesotheliomas should only be positive for keratin
and negative for the rest of carcinomatous epitopes. More recently, in a review of the
immunohistochemistry of mesothelioma, it has been stated that the use of keratin 5/6 and calretinin
should be part of the panel of immunohistochemistry.8 It is well known that Ber-Ep4 may be positive
in approximately 25% of cases of mesothelioma,9 thus casting some doubts about the specificity of this
antibody. However, the use of this panel of antibodies applies namely when the tumor is predominantly
epithelial. When the tumor is sarcomatoid, the use of broad-spectrum keratin may be the best and only
marker useful in the evaluation of mesothelioma,8 since there are conflicting reports about the
usefulness of keratin 5/6 and calretinin in that particular histological variant. In this latter
setting, the use of histochemical stains is also useless. Regarding the different variants of
mesothelioma, the same concept applies. In particular in our case in which there is a prominent myxoid
change, still the fact that the predominant cellular proliferation is epithelial, the use of
immunohistochemistry can provide important information in the proper classification of this neoplasm.
The differential diagnosis of peritoneal mesothelioma can be summarized with the following conditions:
1) Mesothelial hyperplasia; 2) Prominent inflammatory histiocytic reaction; 3) Peritoneal spread from a
carcinoma; 4) Primary peritoneal carcinoma. In cases of mesothelial hyperplasia the gross description
plays an important role since it would be unusual for mesothelial hyperplasia to present as diffuse
peritoneal nodules. From the histopathologic evaluation, in cases of mesothelioma one would expect to
have invasion into the adjacent tissue such as fibroconnective, muscular, or adipose tissue.10 Even
though immunohistochemistry cannot separate malignant mesothelioma from mesothelial hyperplasia, the use
of keratin may be useful in order to determine the extent of cellular proliferation and/or infiltration
into adjacent tissues.10 In cases of a marked inflammatory reaction of predominantly histiocytes, the
clinical history of pelvic inflammatory disease or previous abdomino-pelvic surgery may be helpful. In
such cases, an inflammatory pelvic reaction may present clinically with abdominal pain and peritoneal
nodules. However, the histologic evaluation of the lesion and the use of immunohistochemistry will help
us with the correct interpretation. For the latter two conditions, primary peritoneal carcinoma and
peritoneal spread from a carcinoma, clinical evaluation is of utmost importance. In addition, the use of
immunohistochemical markers (carcinomatous epitopes) in the evaluation of the neoplasm is essential in
order to arrive at the proper interpretation.
The behavior of peritoneal mesotheliomas, unlike those in the pleural cavity, is not
always aggressive. Unfortunately, there are not morphological features, which can be correlated with the
behavior of the tumor. It is possible that extent of disease may play an important role in the outcome.
Even though there is not standard treatment for mesotheliomas, surgery and chemotherapy have been used
with relative success.11,12
- Spitas R, Connelly RR, Tucker MA. Survival pattern of malignant mesothelioma: The SEER experience.
Int J Cancer 1988; 41:525-530.
- Antman K, Shemin R, Ryan L, et al. Malignant mesothelioma: prognostic variables in registry of 180
patients, the Dana-Farber Cancer Institute and Brigham and Women's Hospital experience over two decades,
1965-1985. J Clin Oncol 1988; 6:147-153.
- Dawson A, Gibbs AR, Pooley FD. Malignant mesothelioma. Thorax 1993; 48:269-274.
- Roggli VL, Oury TD, Moffatt EJ. Malignant mesothelioma in women. Anat Pathol 1997; 2:147-163.
- Kerrigan SAJ, Turnnir RT, Clement PB, et al. Diffuse malignant epithelial mesothelioma of the
peritoneum in women: a clinicopathologic study of 25 patients. Cancer 2002; 94:378-385.
- Sant'Ambrogio S, Malpica A, Ordonez NG, et al. Well differentiated papillary mesothelioma and
malignant mesothelioma of the peritoneum in women: a clinicopathological and immunohistochemical study
of 43 cases (submitted for publication).
- Battifora H, McCaughey WTE. Tumors of Serosal Membranes. Atlas of Tumor Pathology, Fascicle No. 15,
Bethesda, MD 1995.
- Moran CA, Wick M, Suster S: The role of immunohistochemistry in the diagnosis of malignant
mesothelioma. Sem Diag Pathol 2000; 17:178-183.
- Gaffey MJ, Mills SE, Swanson PE, et al: Immunoreactivity for Ber-Ep4 in adenocarcinoma, adenomatoid
tumors, and malignant mesothelioma. Am J Surg Pathol 1992; 16:593.
- Churg A, Colby TV, Cagle P, et al. The separation of benign and malignant mesothelial
proliferations. Am J Surg Pathol 2000; 24:1183-1200.
- Antman KH, Osteen RT, Klegar KL, et al. Early peritoneal mesothelioma: a treatable malignancy.
Lancet 1985; 8462:977-981.
- Eltabbakh GH, Piver MS, Hempling RE, et al. Clinical picture, response to therapy, and survival of
women with diffuse malignant peritoneal mesothelioma. J Surg Oncol 1999; 70:6-12.