Pulmonary lymphomas are a rare subset of lymphomas that primarily affect the lungs. Protheragen offers a suite of services designed to support the development of diagnostics and therapeutics for pulmonary lymphomas. Our services encompass advanced histopathological analysis, molecular diagnostics, and preclinical research.
Overview of Pulmonary Lymphomas
Pulmonary lymphomas are a rare and intricate subset of malignancies that originate in lung tissue. Classified as extranodal lymphomas, primary pulmonary lymphomas (PPL) constitute less than 0.5% of primary lung cancers and approximately 1% of all lymphomas. PPL is further divided into non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL), with NHL being the more common form. The clinical manifestations of PPL are often nonspecific, with symptoms such as cough, expectoration, chest pain, and fever, which makes early diagnosis difficult. Imaging studies, especially computed tomography (CT), are essential for identifying pulmonary lesions. However, definitive diagnosis relies on histopathological examination and immunohistochemistry (IHC).
Fig.1 Case of histopathological analysis of pulmonary lymphomas. (Hu M.,
et al., 2022)
Pathogenesis of Pulmonary Lymphomas
The etiology of pulmonary lymphomas is multifactorial and not yet fully elucidated. However, several key mechanisms have been identified. Most PPLs are B-cell lymphomas, often originating from bronchial-associated lymphoid tissue. Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype, frequently associated with chronic inflammation and autoimmune diseases. This suggests that chronic antigenic stimulation may play a role in the pathogenesis. Additionally, genetic mutations and chromosomal abnormalities have been implicated in the transformation of normal lymphocytes into malignant cells. For instance, translocations involving the immunoglobulin heavy chain gene and the BCL-2 oncogene are commonly observed in MALT lymphomas. Environmental factors, such as exposure to certain chemicals and infections, may also contribute to the development of pulmonary lymphomas.
Diagnostics Development for Pulmonary Lymphomas
Histopathological Examination
Histopathological analysis remains the gold standard for diagnosing pulmonary lymphomas. Biopsy specimens obtained through fine needle aspiration (FNA), video-assisted thoracoscopic surgery (VATS), or open surgical procedures are examined under a microscope. Hematoxylin and eosin (H&E) staining highlight the morphological features of the lymphoma cells, while immunohistochemistry (IHC) is used to identify specific cell markers. For example, CD20 and CD79a are commonly expressed in B-cell lymphomas, whereas CD3 and CD4 are markers for T-cell lymphomas.
Laboratory Tests
Laboratory tests play a supportive role in the diagnosis of pulmonary lymphomas. Elevated levels of lactate dehydrogenase (LDH) and β2-microglobulin (β2-MG) in the blood can indicate the presence of a malignancy. Flow cytometry is used to analyze the immunophenotype of cells in a sample, helping to differentiate between various types of lymphomas. Cytogenetic studies can identify chromosomal abnormalities, which are often associated with specific subtypes of lymphoma. These tests collectively contribute to a comprehensive diagnostic evaluation.
Therapeutics Development for Pulmonary Lymphomas
- Chemotherapy Regimens: The CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been widely used, with the addition of rituximab (R-CHOP) showing improved outcomes in B-cell lymphomas. Rituximab, a monoclonal antibody targeting CD20, enhances the efficacy of chemotherapy by promoting apoptosis in B-cell lymphoma cells.
- Targeted Therapies: Targeted therapies have revolutionized the therapeutic landscape for pulmonary lymphomas. Bruton's tyrosine kinase (BTK) inhibitors, such as ibrutinib, have shown significant efficacy in treating MALT lymphoma by inhibiting the BTK pathway, which is crucial for B-cell survival and proliferation.
- Immunotherapies: Immunotherapies leverage the body's immune system to combat lymphomas. Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, target the PD-1/PD-L1 pathway, enhancing the immune response against cancer cells.
Table 1. Therapeutics of Pulmonary Lymphomas.
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Chemotherapy |
Cyclophosphamide |
DNA synthesis |
Used to inhibit rapidly dividing cells, including cancer cells. Associated with pulmonary toxicity in some cases. |
Approved |
| Chemotherapy |
Bleomycin |
DNA |
Causes breaks in DNA strands, leading to cell death. High incidence of pulmonary toxicity. |
Approved |
| Immunotherapy |
Rituximab |
CD20 |
Monoclonal antibody targeting CD20 on B cells, used in combination with chemotherapy for B-cell lymphomas. |
Approved |
| Immunotherapy |
Brentuximab Vedotin |
CD30 |
Antibody-drug conjugate targeting CD30, effective in Hodgkin's lymphoma and some NHL subtypes. |
Approved |
| Targeted Therapy |
Idelalisib |
PI3K delta |
Inhibits PI3K delta, used in relapsed or refractory indolent NHL. |
Approved |
| Immunotherapy |
Nivolumab |
PD-1 |
Immune checkpoint inhibitor, enhances T-cell activity against tumor cells. |
Approved |
| Immunotherapy |
Pembrolizumab |
PD-1 |
Immune checkpoint inhibitor, similar mechanism to nivolumab. |
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 are dedicated to offering all-encompassing preclinical therapeutic development services specifically for pulmonary lymphomas. Our expertise lies in crafting a diverse array of diagnostic and therapeutic approaches that are meticulously customized to address the distinct requirements of every individual project.
Disease Models
- Lymph Node Organoids
- Fluorescein Isothiocyanate (FITC)-Induced Models
- Radiation-Induced Model
- Spontaneous Pulmonary Lymphoma Model
- Humanized Mouse Models
Our preclinical research services at Protheragen are designed to provide in-depth insights into the biology of pulmonary lymphomas. We specialize in establishing and characterizing patient-derived xenograft (PDX) models and cell line-derived xenograft (CDX) models that accurately recapitulate the pathological and genetic features of human PPL. If you are interested in our services, please feel free to contact us.
References
- Hu, Mingbin, et al. "Clinical analysis of 50 cases of primary pulmonary lymphoma: a retrospective study and literature review." Technology in Cancer Research & Treatment 21 (2022): 15330338221075529.
- He, Huayu, et al. "Clinicopathological characteristics and prognostic factors of primary pulmonary lymphoma." Journal of Thoracic Disease 13.2 (2021): 1106.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
