Well-differentiated papillary mesothelial tumor (WDPMT) is a subtype of mesothelial tumor with a myxoid core and expanded papillae enveloped by a monolayer of mesothelial cells, which shows a bland cytology. Protheragen provides a wide range of services for WDPMT diagnostics and therapeutics development, including histopathological examination, immunohistochemistry, molecular diagnostics, preclinical research, and customized solutions.
Overview of Well-differentiated Papillary Mesothelial Tumor (WDPMT)
Well-differentiated papillary mesothelial tumor (WDPMT) is a distinct and rare lesion of the mesothelium that occurs most frequently within the peritoneum, pleura, and tunica vaginalis. WDPMT, previously called well-differentiated papillary mesothelioma, has a distinct papillary form where the core is myxoid and is covered by a single layer of bland mesothelial cells. WDPMT is considered to have a benign or passive biological behavior, although some WDPMT tumors may be associated with invasive features or could advance to more aggressive variants of mesothelioma. WDPMT tumors have an incidence that is mostly in women of childbearing age, and it is often found incidentally while treating other surgical conditions. The WDPMT diagnosis entails sifting through the differential diagnoses of malignant mesotheliomas, which share many features in common with WDPMT.
Fig.1 A well-differentiated papillary mesothelioma that has invaded the stalk. (Churg A.,
et al., 2022)
Diagnostics Development for WDPMT
Histopathological Examination
Histopathological evaluation remains fundamental for WDPMT diagnostics. The micromorphological features show distinctive expansile papillae containing a myxoid center and supported by a single layer of bland mesothelial cells. Further, the tumor’s mesothelial origin requires confirmation through immunostaining for calretinin, WT-1, cytokeratin 5/6, and D2-40. While WDPMT frequently expresses PAX-8, its presence can lead to misdiagnosis since PAX-8 is expressed in other gynecologic tumors.
Molecular Diagnostics
Molecular diagnostics are essential in differentiating WDPMT from other mesothelial proliferations. Mutations linked to WDPMT, such as CDC42 and TRAF7, can be detected with genetic sequencing. Moreover, BAP1, MTAP, and CDKN2A FISH testing can help differentiate true WDPMT from mesothelioma in situ, which can be morphologically similar to WDPMT but has different molecular genetics.
Therapeutics Development for WDPMT
- Chemotherapy
In more severe cases of WDPMT, symptomatic manifestations may occur, necessitates chemotherapy. Regimens containing cisplatin, especially those that combine cisplatin with pemetrexed, have shown success. For example, one patient with disseminated WDPMT successfully resolved all tumors with eight cycles of pemetrexed and cisplatin chemotherapy, which was well tolerated. Intraperitoneal (IP) chemotherapy has also been employed for WDPMT-related ascites and pleural effusion.
- Targeted Therapies
Targeted therapies are being investigated for WDPMT. Considering the specific genetic alterations found in WDPMT, like CDC42 and TRAF7, therapeutics that antagonize these pathways could be beneficial. However, further research is needed to validate the efficacy of these targeted therapies.
Table 1. Therapeutics of WDPMT.
| Therapeutics |
Drug Name |
Mechanism |
Description |
Stage |
| Chemotherapy (Systemic) |
Cisplatin |
Crosslinks DNA, preventing DNA replication and transcription. |
Cisplatin is a platinum-based chemotherapy agent commonly used in various cancers, including mesotheliomas. It is often combined with other drugs like pemetrexed for enhanced efficacy. |
Approved |
| Chemotherapy (Systemic) |
Pemetrexed |
Inhibits folate-dependent enzymes involved in DNA synthesis (e.g., thymidylate synthase). |
Pemetrexed is a multitargeted antifolate that disrupts cell division by inhibiting key enzymes in the folate metabolism pathway, often used in combination with cisplatin. |
Approved |
| Chemotherapy (Systemic) |
Adriamycin (Doxorubicin) |
Intercalates into DNA, disrupting its structure, and inhibits topoisomerase II, leading to cell death. |
Adriamycin is an anthracycline antibiotic used for chemotherapy. It induces apoptosis in cancer cells through interference with DNA replication and repair. |
Approved |
| Chemotherapy (Intraperitoneal) |
Cisplatin (Intraperitoneal) |
Same as systemic cisplatin, but delivered directly to the peritoneal cavity, providing high local concentrations. |
Intraperitoneal chemotherapy delivers drugs directly to the tumor site, offering localized therapy with reduced systemic toxicity. |
Approved |
| Chemotherapy (Intraperitoneal) |
Mytomycin C |
Inhibits DNA synthesis by alkylating and crosslinking DNA strands, resulting in cell death. |
Mytomycin C is an antibiotic chemotherapy agent used in intraperitoneal chemotherapy. It is typically used in combination with cisplatin for treating peritoneal cancers. |
Approved |
| Chemotherapy (Intraperitoneal) |
5-FU (Fluorouracil) |
Inhibits thymidylate synthase, preventing DNA synthesis and leading to cell death. |
5-FU is a commonly used chemotherapy drug for various cancers. It is often administered in combination with other chemotherapeutic agents. |
Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
At Protheragen, we specialize in offering a comprehensive suite of services dedicated to the development of diagnostics and therapeutics for WDPMT. Our expertise spans histopathological and molecular diagnostics, genetic sequencing, and FISH analysis, enabling us to accurately identify and characterize WDPMT with precision. Additionally, we provide robust preclinical research services, encompassing both in vitro and in vivo studies, to rigorously evaluate the efficacy of novel therapeutic agents. Our customized services are meticulously designed to meet the unique needs of each client, ensuring that our solutions are perfectly tailored to support the development of WDPMT diagnostics and therapies.
Disease Models
- TRAF7 Mutant Mouse Models
- CDC42 Mutant Mouse Models
- BAP1 Heterozygous Knockout Models
- Murine Mesothelial Cell Line-Derived Tumors
- TRAF7/CDC42-Overexpressing Zebrafish
The advantage of Protheragen's services lies in our comprehensive expertise, from basic research to preclinical development. We offer a seamless integration of diagnostics and therapeutics, enabling a holistic approach to WDPMT therapeutics development. Our commitment to excellence and innovation ensures that our clients receive the highest quality services. If you are interested in our services, please feel free to contact us.
References
- Churg, Andrew, and Francoise Galateau-Salle. "Well differentiated papillary mesothelial tumor: a new name and new problems." Modern Pathology 35.10 (2022): 1327-1333.
- Lee, Young Ki, et al. "Therapeutic strategies for well-differentiated papillary mesothelioma of the peritoneum." Japanese journal of clinical oncology 43.10 (2013): 996-1003.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
