Pleuropulmonary Blastoma (PPB) is a formidable challenge in pediatric oncology. At Protheragen, we are dedicated to advancing the development of therapies for rare and aggressive childhood cancers like PPB. Our comprehensive services in diagnostic and therapeutic development are designed to bring innovative solutions to researchers and pharmaceutical companies.
Overview of Pleuropulmonary Blastoma (PPB)
Pleuropulmonary Blastoma (PPB) is a rare and highly aggressive pediatric malignancy that primarily targets children under six years of age. This intrathoracic tumor is characterized by primitive blastema and a malignant mesenchymal stroma that exhibits multidirectional differentiation. PPB is categorized into three types: Type I (cystic), Type II (cystic/solid), and Type III (solid). The clinical presentation is often nonspecific, with symptoms such as difficulty in breathing, cough, fever, and chest pain, which frequently lead to misdiagnosis as respiratory tract infections or pneumothorax. Histologically, PPB is distinguished by its mixed blastoma and sarcomatous elements, which are distinct from the malignant epithelial and mesenchymal tissue seen in adult-type pulmonary blastoma.
Fig.1 Histopathology images (A) Nodules of blastema-like cells. H&E x100. (B) Pleomorphic bizarre giant cells. H&E x 100. (Madaan P. K.,
et al., 2021)
Pathogenesis of Pleuropulmonary Blastoma (PPB)
The pathogenesis of Pleuropulmonary Blastoma (PPB) is intricately connected to mutations in the DICER1 gene, situated on chromosome 14q13.2. This gene encodes a crucial enzyme responsible for the production of mature microRNAs. Mutations in DICER1 can disrupt the normal regulation of gene expression, thereby promoting tumorigenesis. It is estimated that around 66% of PPB patients harbor heterozygous mutations in the DICER1 gene. PPB is also identified as a component of the DICER1 syndrome, which encompasses other neoplasms such as cystic nephroma, pineoblastoma, and pituitary blastoma. While the precise molecular pathways underlying PPB development are still being explored, the DICER1 mutation stands out as a pivotal factor.
Diagnostics Development for Pleuropulmonary Blastoma (PPB)
Histopathological Examination
Histopathological examination confirms the diagnosis of PPB. Type I lesions appear as cystic structures, Type II as mixed cystic and solid lesions, and Type III as purely solid lesions. The presence of blastematous foci, spindle cell proliferation, and areas of necrosis are characteristic features. Immunohistochemistry and molecular diagnostic techniques, including genetic testing for DICER1 mutations, are increasingly being used to support diagnosis and understand the underlying genetic basis.
Molecular Diagnostics
Molecular diagnostic techniques are indispensable in the diagnosis and management of Pleuropulmonary Blastoma (PPB). Genetic testing for DICER1 mutations is crucial for confirming the diagnosis and identifying patients at risk for associated neoplasms. These techniques also aid in differentiating PPB from other pediatric lung tumors and guiding appropriate therapeutic strategies.
Therapeutics Development for Pleuropulmonary Blastoma (PPB)
- Chemotherapy
Chemotherapy regimens for PPB commonly include drugs such as vincristine, actinomycin-D, doxorubicin, cisplatin, cyclophosphamide, and irinotecan. These agents target rapidly dividing cancer cells and help prevent recurrence and metastasis. The specific regimen depends on the type and stage of the tumor, as well as the presence of metastases.
- Radiation Therapy
Radiation therapy is reserved for patients with residual disease or in cases where the tumor is nonresectable. It helps control local disease and prevent recurrence. The use of radiation therapy is carefully considered due to its potential long-term effects, especially in young children.
- High-Dose Chemotherapy and Stem Cell Rescue
High-dose chemotherapy followed by autologous stem cell rescue (ASCR) is an emerging approach for managing recurrent or refractory PPB. This strategy aims to overcome dose-limiting toxicity and facilitate chemotherapy dose escalation, improving outcomes for cases with advanced disease.
Table 1. Chemotherapy of pleuropulmonary blastoma (PPB).
| Drug Name |
Target |
Description |
Stage |
| Vincristine |
Microtubules |
Alkylating agent that disrupts cell division |
Approved |
| Actinomycin-D |
RNA polymerase |
Antibiotic that inhibits DNA synthesis |
Approved |
| Doxorubicin |
Topoisomerase II, DNA, and mitochondria |
Anthracycline antibiotic that intercalates DNA |
Approved |
| Cisplatin |
DNA |
Platinum-based compound that cross-links DNA |
Approved |
| Cyclophosphamide |
DNA, RNA, and proteins |
Alkylating agent that disrupts DNA synthesis |
Approved |
| Irinotecan |
DNA topoisomerase I |
Topoisomerase inhibitor that causes DNA damage |
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
Protheragen offers comprehensive diagnostics and therapeutics development services for Pleuropulmonary Blastoma (PPB). Our services encompass a wide range of preclinical research activities, including histopathological examination and molecular diagnostics. We provide tailored solutions to meet the specific needs of our clients, ensuring that each project is designed to achieve optimal outcomes.
Disease Models
- KCMC-PPB-1 Cell Line Models
- PPB Organoid Models
- KCMC-PPB-1 Cell Line Transplantation Mouse Models
- FGF/NCAM1 Pathway Model
Protheragen's preclinical research services for PPB are designed to accelerate the development of effective diagnostics and therapeutics. Our team of experts utilizes state-of-the-art technologies and methodologies to conduct thorough analyses, from initial disease modeling to advanced drug efficacy studies. If you are interested in our services, please feel free to contact us.
References
- Madaan, Prateek K., et al. "Pleuropulmonary blastoma: a report of three cases and review of literature." Radiology Case Reports 16.10 (2021): 2862-2868.
- Chidiac, Charbel, et al. "Patient Characteristics, Treatment, and Survival in Pleuropulmonary Blastoma: An Analysis from the National Cancer Database." Children 11.4 (2024): 424.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
