Mesothelioma with signet ring cells is an uncommon and vicious form of mesothelioma, which is marked by the signet ring appearance of the tumor cells. Protheragen offers comprehensive diagnostic and therapeutic development services for signet ring cell mesothelioma. These services comprise the histopathological and immunohistochemical diagnostics, electron microscopy, molecular diagnostics, and the development of targeted therapies, as well as the development of immunotherapies.
Overview of Signet Ring Cell Mesothelioma
Signet ring cell mesothelioma is an aggressive, rare form of mesothelioma, a cancer that affects the pleura or the peritoneum. Unlike more common mesotheliomas, which have epithelioid or sarcomatoid histologies, signet ring cell mesothelioma has more distinctive features, like cells with eccentric, peripherally displaced nuclei and with abundant cytoplasmic vacuoles, which are particularly distinctive. The cells are given a unique signet ring appearance because of these vacuoles. In addition, the tumors are very difficult to diagnose because of their resemblance to other tumors, such as the metastatic signet ring cell carcinoma, which originates from the stomach, lung, or other parts of the gastrointestinal tract.
Fig.1 Pathological analysis of epithelioid signet ring cell mesothelioma. (Elahi M.,
et al., 2024)
Diagnostics Development for Signet Ring Cell Mesothelioma
Histopathological and Immunohistochemical Diagnostics
Histopathological examination is crucial for the diagnosis of signet ring cell mesothelioma. Light microscopy reveals cells with a characteristic signet ring appearance, marked by eccentric nuclei and clear cytoplasm. Immunohistochemical studies are essential for distinguishing signet ring cell mesothelioma from other tumors with similar morphology. Markers such as calretinin, keratin 5/6, WT1, and podoplanin are typically positive in mesotheliomas, while markers like CEA, MOC-31, and TTF-1 are negative. These immunohistochemical profiles help confirm the diagnosis and differentiate mesothelioma from metastatic adenocarcinomas.
Molecular Diagnostics
Molecular diagnostics involve the analysis of genetic mutations and molecular markers associated with mesothelioma. Techniques such as next-generation sequencing (NGS) can identify mutations in genes like BAP1 and NF2, which are implicated in the development of mesothelioma. Additionally, molecular diagnostics can detect the expression of specific proteins or the presence of viral DNA, such as Epstein-Barr virus (EBV), which may be associated with certain cases of mesothelioma. These molecular tools enhance the accuracy of diagnosis and provide valuable information for targeted therapy development.
Therapeutics Development for Signet Ring Cell Mesothelioma
- Chemotherapy remains the cornerstone of therapeutic for signet ring cell mesothelioma, although it is often less effective in patients with this rare variant. Standard chemotherapy regimens, such as cisplatin combined with pemetrexed, are typically employed. While these therapies have shown some success in treating mesothelioma in general, the response rate in signet ring cell mesothelioma remains poor, necessitating the need for new drug developments.
- Immunotherapy has emerged as a promising therapeutic modality for mesothelioma. Immune checkpoint inhibitors, such as pembrolizumab (anti-PD-1) and nivolumab, have shown efficacy in non-small cell lung cancer and may be applicable to mesothelioma as well. However, the response of signet ring cell mesotheliomas to immunotherapy remains under investigation, as the tumor microenvironment may present unique challenges.
- Targeted therapies that focus on specific molecular markers are under investigation for signet ring cell mesothelioma. The expression of mesothelin, a cell surface protein overexpressed in mesotheliomas, presents a potential therapeutic target. Agents like the antibody-drug conjugate, anetumab ravtansine, which targets mesothelin, may offer promising therapeutic options. However, further clinical trials are needed to determine their efficacy specifically for the signet ring cell variant.
Table 1. Therapeutics of signet ring cell mesothelioma. (Ordóñez N. G., 2013)
| Case |
Sex/age |
Tumor location |
Type of specimen |
Light microscopy |
Therapeutics |
| 1 |
M/45 |
Rt. pleura |
Pneumonectomy |
Epithelioid, solid, and focally tubulopapillary, 15% signet-ring cell |
Pneumonectomy |
| 2 |
M/57 |
Rt. pleura |
Pleural biopsy |
Epithelioid, solid, and tubular with myxoid stroma and 25% signet-ring cells |
Decortication+radiotherapy+chemotherapy, lower-lobe lobectomy |
| 3 |
M/51 |
Rt. pleura |
Pleural biopsy |
Epithelioid, solid, 25% signet-ring cell |
Chemotherapy+radiotherapy |
| 4 |
F/69 |
Rt. pleura |
Pneumonectomy |
Epithelioid, tubulopapillary, 25% microcystic, and signet-ring cell |
Pneumonectomy+radiotherapy |
| 5 |
M/62 |
Rt. pleura |
Pneumonectomy |
Epithelioid, solid, and tubulopapillary, 10% signet-ring cell |
Pneumonectomy+chemotherapy+radiotherapy |
| 6 |
M/68 |
Rt. pleura |
Pneumonectomy |
Epithelioid, solid, and focally papillary, 15% signet-ring cell |
Intrapleural chemotherapy+pneumonectomy |
| 7 |
M/62 |
Peritoneum |
Tumor resection |
Epithelioid, solid, and tubulopapillary, 25% signet-ring cell |
Tumor debulking+chemotherapy |
| 8 |
F/55 |
Lt. pleura |
Pneumonectomy |
Epithelioid. Solid and tubulopapillary, 15% signet-ring cell |
Pneumonectomy+radiotherapy |
| 9 |
M/57 |
Rt. pleura |
Decortication |
Epithelioid, deciduoid, 20% signet-ring cell |
Decortication and tumor debulking+chemotherapy |
| 10 |
M/55 |
Rt. pleura |
Lymphadenectomy |
Epithelioid, solid with focal, tubular areas, 25% signet-ring cell |
Talc pleurodesis+chemotherapy |
| 11 |
M/59 |
Peritoneum |
Peritoneal biopsies |
Epithelioid, solid, and tubulopapillary, 30% signet-ring cell |
Debulking (80% tumor resected) + chemotherapy |
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
Protheragen provides a wide range of services to support signet ring cell mesothelioma research and development. Our diagnostics development services include IHC marker development, molecular diagnostics, and ancillary studies. Therapeutic development encompasses chemotherapy, targeted therapy, and immunotherapy strategies.
Disease Models
- Primary Signet Ring Cell Mesothelioma Cell Culture
- NF2/INK4A/ARF/p53 Knockout Mouse Model
- Asbestos-Induced Pleural Mesothelioma
- Non-Human Primate Models
Protheragen's preclinical research services for signet ring cell mesothelioma are designed to accelerate the development of novel diagnostics and therapeutics. Our services include the establishment of in vitro and in vivo models, comprehensive molecular profiling, and high-throughput screening of potential therapeutic agents. If you are interested in our services, please feel free to contact us.
References
- Elahi, Morvarid, et al. "Cytologic diagnosis and differential diagnosis of histiocytic signet ring cells in effusion specimens." CytoJournal 21 (2024): 30.
- Satala, Catalin Bogdan, et al. "Signet-ring cell squamous cell carcinoma: A biphenotypic neoplasm of the gastro-esophageal junction with uncertain biological potential: Case report and literature review." International Journal of Molecular Sciences 24.11 (2023): 9535.
- Ordóñez, Nelson G. "Mesothelioma with signet-ring cell features: report of 23 cases." Modern Pathology 26.3 (2013): 370-384.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
