Papillary Mesothelioma

Well-differentiated papillary mesothelioma (WDPM) is a rarely observed subtype of epithelial mesothelioma, the cancer’s most common cell type. Compared to most other forms of mesothelioma, WDPM is far less aggressive. Its growth pattern is slow and the cancer does not typically metastasize(spread) to other parts of the body.

Although from a medical standpoint these tumors are practically benign, a lack of sufficient data makes doctors uncertain about their long-term behavior. It is unclear if WDPM can develop into malignant mesothelioma, a disease that is much more invasive and widespread. At this point researchers are also unsure whether or not the disease is linked to asbestos exposure.

The majority of well-differentiated papillary mesothelioma tumors develop in the abdomens of women, specifically in the peritoneal cavity. Although less common, doctors have found WDPM tumor growth on several of the body’s protective membranes, including the linings of the lungs (pleura), heart (pericardium) and testicles (tunica vaginalis).

Many cases of WDPM have no symptoms, but the disease has been known to cause pain andexcessive fluid buildup in the pleura or abdomen of some patients. Well-differentiated papillary mesothelioma of the tunica vaginalis can cause scrotal swelling or the formation of testicular lumps. In one study of 22 WDPM cases, only two patients reported to their doctors with symptoms. One patient experienced acute abdominal pain, and the other had chronic pelvic pain.

Because this mesothelioma subtype has not been studied extensively, no effective course of therapy has been established. Despite this obstacle, long-term survival is not uncommon. A 2012 study of 25 women with WDPM of the peritoneum described an average survival of 47.5 months, and one patient lived with the disease for 29 years before dying of another cause.

Characteristics of WDPM

The primary characteristics of well-differentiated papillary mesothelioma are described right in the disease’s name. The phrase well-differentiated refers to the tumor’s grade, which doctors use to characterize a cancer’s severity. Well-differentiated tumors are low grade, meaning their cancer cells resemble healthy cells and grow and multiply at a slow rate. The cancer does not invade nearby tissues or spread throughout the body. In many cases WDPM is completely inactive, showing no signs of cell division.

The word papillary describes the microscopic growth pattern of the tumor’s cells, which features small finger-like projections called papillae. These projections are lined by a single layer of flat mesothelial cells and can appear uniform, coarse or branching. The papillae sometimes create round swirls of calcium known as psammoma bodies.

To the naked eye, WDPM tumors form white or grey nodules ranging from less than 1 centimeter in size to more than 3 centimeters. The tumors are smaller than 1 centimeter in more than half of all cases. WDPM can develop as a solitary mass or arise in many sites, the latter being known for more aggressive behavior.

Diagnosis and Related Challenges

Because well-differentiated papillary mesothelioma rarely causes symptoms, doctors usually discover tumor growth incidentally during an unrelated pelvic or abdominal surgery. WDPM can sometimes be found with an imaging test like CT scan, but this technique isn’t sensitive enough to detect tumors smaller than 1 centimeter in size.

The only definitive procedure for diagnosing WDPM and other mesotheliomas is biopsy, the collection of a tissue sample for laboratory analysis. It is important for doctors to collect a comprehensive sample to prevent misdiagnosis because highly aggressive malignant mesothelioma tumors sometimes feature areas of papillary cell growth. Other indications that a suspected WDPM is actually malignant mesothelioma include tumor invasion of underlying tissue and a rapid progression of disease.

WDPM is also easily confused with these several other cancers and conditions

• Reactive mesothelial hyperplasia
• Adenomatoid tumor
• Peritoneal carcinomatosis
• Tuberculous peritonitis
• Serous papillary carcinoma of the ovary
• Serous papillary carcinoma of the peritoneum

If doctors make an inaccurate diagnosis, patients may receive aggressive treatments that do not improve the outcome of WDPM. Another way doctors can prevent misdiagnosis is by collecting fluid samples from patients and testing for certain biomarkers associated with the disease. Well-differentiated papillary mesothelioma will test negative for carcinoembryonic antigen (CEA) and positive for the markers cytokeratin (CK), calretinin and HMBE-1.

Treatment Options for WDPM

With only a limited amount of research on the management of well-differentiated papillary mesothelioma, doctors have yet to reach a consensus on the most effective course of treatment. Therapy usually involves some combination of the main types of mesothelioma treatment:

• Surgery
• Chemotherapy
• Radiation Therapy

The first procedure that most peritoneal WDPM patients receive is an exploratory laparotomy. In this type of surgery, doctors make a large incision in the patient’s abdomen to determine a diagnosis or perform cytoreductive surgery, which aims to remove most of the tumor. Some physicians, however, claim that laparotomy is too risky for an unaggressive cancer like WDPM, and instead prefer a series of biopsies to make an accurate diagnosis.

Various approaches to chemotherapy have been explored for WDPM treatment. One patient with WDPM tumors of both the pleura and peritoneum was successfully treated with carboplatin. The drug was administered intravenously and also injected directly into the pleural and peritoneal cavities. One year after diagnosis the patient showed no signs of disease.

Several patients have been given radiation therapy after a primary treatment of chemotherapy, but some doctors state this method should be avoided unless there are clear signs of cancer progression. In one study of 22 cases of well-differentiated papillary mesothelioma of the peritoneum, several patients given this therapy did not survive. The doctors could not determine if the tumor was the cause of death for these patients.

Some WDPM patients have also received cytoreductive surgery followed by heated chemotherapywith mixed results. This treatment involves heating chemotherapy drugs slightly higher than the patient’s body temperature to improve the treatment’s effectiveness. One patient treated with this method survived 15 months after the therapy and another was alive 40 months later. A third patient died of disease progression 13 months after treatment.

Researchers hope that additional data on well-differentiated papillary mesothelioma gained from long-term follow-ups and additional studies will eventually reveal the optimal treatment plan for the disease.

WDPM Prognosis and Survival Rates

The survival outlook for patients with well-differentiated papillary mesothelioma is drastically better than the outlook of patients with most other mesothelioma cell types. While only 5 to 10 percent of malignant mesothelioma patients survive five years after diagnosis, several patients with WDPM have survived for decades.

This can be explained by the slow growth of WDPM tumors and the absence of metastasis in most cases. Further, WDPM is a subtype of epithelial mesothelioma, the cell type that typically responds best to treatment.

In one study of 11 patients with WDPM of the pleura, survival ranged from 36 to 180 months. The average survival was 74 months, and 30.8 percent of the patients were alive 10 years after diagnosis. And in a 2012 study of 25 women with WDPM of the peritoneum, researchers observed an average survival of 74 months. With follow-up times spanning from five to 144 months, 22 of the patients survived with no evidence of well-differentiated papillary mesothelioma.