Simultaneous occurrence of well differentiated papillary mesothelioma and endometrioid ovarian cancer: A case report

Highlights

► We present a case of endometrioid ovarian cancer with concomitant well differentiated papillary mesothelioma of the peritoneum. ► Endometrioid ovarian cancer with concomitant well differentiated papillary mesothelioma is an extremely rare surgical finding of uncertain prognostic significance. ► Treatment with carboplatin and gemcitabine was given with no evidence of disease six months after diagnosis.

Introduction

Ovarian cancer is the fifth most common cancer in women, causing more deaths than any other cancer of the female reproductive system. The American Cancer Society (2012) projects that there will be 22,280 new cases of ovarian cancer in 2012, as well as 15,500 deaths. Mesotheliomas, however, are uncommon, with about 3000 new cases diagnosed per year in the United States, an incidence of 0.96 in 100,000 (Howlader et al., 2012). Approximately 9% of mesotheliomas arise in the peritoneum and half are epithelial in origin (Antman et al., 2005). Well-differentiated papillary mesothelioma (WDPM) of the peritoneum, a variant of epithelial mesothelioma, is a rare pathologic finding. It is considered by most to be of low malignant potential, as described in a case report and a review of the literature by Hoekstra et al. (2005). Diagnosing WDPM concomitantly with another malignancy is extraordinarily rare. Very few reports have been published in the literature describing WDPM in association with gynecologic malignancies, and most of these involve endometrial cancers. We present a case of endometrioid ovarian adenocarcinoma in association with WDPM, which has not yet been reported in the literature to the best of our knowledge.

Case

Ms. DF, a 50-year-old nulliparous Caucasian female, was noted to have symptoms and clinical findings consistent with ovarian cancer while hospitalized for an unrelated diagnosis. A gynecological history revealed menometrorrhagia, abdominal pain, bloating, constipation, and weight loss for the past six months. On exam, a midline, mobile mass was noted above the umbilicus. CA 125 was 40,442. A transvaginal ultrasound showed bilateral complex ovarian masses with cystic and solid components, a 4 cm irregular mass in the lower uterine segment, and ascites.

One month later, surgical staging and debulking yielded intraoperative findings of numerous malignant appearing sheets of implants with extensive coating of the large and small bowels, spleen, liver, diaphragm, and pelvic peritoneum. Thin, sheet-like disease coated the majority of the small and large bowels, precluding optimal debulking. All multidimensional bulky disease was resected. Final pathology revealed negative pelvic washings and moderately to poorly differentiated adenocarcinoma consistent with endometrioid type involving the left ovary and fallopian tube with metastasis to the cervix and lower uterine segment. Lymphovascular space invasion was noted. On the uterine serosa, right ovary, large bowel, and small bowel there was florid papillary mesothelial proliferation consistent with well-differentiated papillary mesothelioma. A single nodule of metastatic adenocarcinoma was noted on the omentum along with extensive fibrous serosal adhesions with well-differentiated papillary mesothelioma. These findings were confirmed in consultation with a gynecologic pathologist. An implant on the omentum was sent for tumor sensitivity assays. Carboplatin and gemcitabine were chosen for treatment.

Ms. DF tolerated 6 cycles of carboplatin and gemcitabine. Serial CA 125 levels were followed, and they steadily decreased to 10.9 four months after surgical staging and debulking. A follow up CT scan showed no evidence of disease five months after surgical debulking. Consideration was given to a second look and hyperthermic intraperitoneal chemotherapy (HIPEC) but it was not opted for by the patient. She chose to proceed with conservative management.

Discussion

A diagnosis of concomitant endometrioid ovarian adenocarcinoma and WDPM is extraordinarily rare, with this being the first reported case to our knowledge. It has been reported that WDPM and papillary serous cancers of the ovary and peritoneum have overlapping morphological features making them histologically similar. WDPM is generally associated with histological findings of coarse papillary architecture with fibrovascular cores with occasional areas of tubulopapillary pattern (Hoekstra et al., 2005) (Fig. 1). Immunohistochemistry and electron microscopy can be used to confirm the diagnosis of WDPM and differentiate it from other histologically similar disease processes. Common immunohistochemical stains that are sensitive and specific for the differentiation of WDPM from other similar appearing pathologies are calretinin (Fig. 2), MOC-31, and estrogen receptors (ER) (Ordóñez, 2006). In this case, a battery of immunostains including ER, PR, calretinin, p53, p63, and WT1 were performed, even though the ovarian primary was not of papillary serous histology. The endometrioid ovarian cancer cells (Fig. 3) stained positive for p53, WT1, ER, and PR and stained negative for calretinin. The mesothelial cells were positive for calretinin and negative for p53, ER, and PR, confirming the presence of two separate diagnoses.

Fig. 1.

Well-differentiated papillary mesothelium: mesothelial papillations containing cores of fibrovascular stroma.

Fig. 2.

Papillary mesothelioma: mesothelial lining cells strongly positive for calretinin.

Fig. 3.

Endometrioid adenocarcinoma of the ovary: cribriform glands with cuboidal to columnar epithelium.

There are no formal recommendations for treatment of WDPM, especially when it is found in association with another primary cancer. Carboplatin and gemcitabine were chosen for treatment, carboplatin as the first line against the endometrioid ovarian cancer and gemcitabine for its effectiveness against epithelial ovarian cancers and mesothelioma. This regimen seemed to be active against both primary neoplasms, as serial CA 125 levels progressively decreased from 40,442 to 10.9 over four months and follow up CT scan obtained three months after completion of the chemotherapy regimen showed no evidence of disease, although it is possible that the WDPM spontaneously regressed as previously reported in the literature. After completion of the planned chemotherapy, the patient was offered a second look laparotomy with HIPEC. HIPEC was offered to the patient as the next line of treatment due to its support in the literature, with potentially longer disease free survival and less transformation of WDPM into malignant processes after treatment with HIPEC. Baratti et al. (2007) reported that cytoreduction and HIPEC with cisplatin and doxorubicin seem more effective than debulking surgery in preventing disease recurrence or transition or WDPM to aggressive malignancy.

Information regarding progression and prognosis of WDPM are lacking in the literature. While many reported cases portray WDPM as a clinically benign tumor of low malignant potential, a few case reports have described more aggressive behavior after long-term follow-up. In one case, a patient died from a large embolism of tumor cells to the pulmonary artery five years after diagnosis. At autopsy the patient had extensive retroperitoneal, anterior abdominal wall, diaphragmatic, and pericardial invasion (Burrig et al., 1990). A second case describes a patient who died of diffuse malignant mesothelioma approximately nine years after the diagnosis of WDPM, suggesting a malignant transformation at some point in the clinical course (Hejmadi et al., 2003). Cases describing more aggressive behavior seem to be in the minority, with a benign course or even spontaneous regression being more common with WDPM.

This case of endometrioid ovarian adenocarcinoma and concomitant WDPM presented a challenge in the diagnosis, treatment, and surveillance of Ms. DF and her disease. It is obvious that research is needed to gain more information about the behavior, progression, prognosis, treatment, and surveillance of patients diagnosed with WDPM, whether alone or in association with a malignancy. Because of its rarity, it will be difficult to perform any prospective trials in order to make recommendations regarding the management of WDPM.

Conflict of interest statement

The authors have no conflict of interest to report.

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Appendix A. Supplementary data

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