Mixed cellularity Hodgkin lymphoma (MCHL) is a subtype of classical Hodgkin lymphoma characterized by a diverse mixture of different types of immune cells within the affected lymph nodes. Understanding what causes MCHL involves exploring a combination of viral, genetic, immune, and environmental factors that contribute to the abnormal growth of lymphatic cells.
At the core of MCHL’s development is the abnormal transformation of a specific type of white blood cell called the B lymphocyte. Normally, B lymphocytes play a crucial role in the immune system by producing antibodies to fight infections. However, in MCHL, these cells undergo genetic changes that cause them to grow uncontrollably and evade normal cell death processes. This leads to the formation of cancerous cells known as Reed-Sternberg cells, which are a hallmark of Hodgkin lymphoma.
One of the most significant contributors to the development of MCHL is infection with the Epstein-Barr virus (EBV). EBV is a common virus that infects most people at some point in their lives, often causing mild or no symptoms. However, in some cases, EBV infects B cells and integrates its genetic material into them, altering their behavior. This viral infection is particularly associated with the mixed cellularity subtype of Hodgkin lymphoma. EBV-infected cells can avoid immune detection and promote an environment that supports cancerous growth. The virus produces proteins that interfere with normal cell regulation, encouraging the survival and proliferation of abnormal B cells.
Genetic predisposition also plays a role in MCHL. Individuals with a family history of Hodgkin lymphoma have a higher risk of developing the disease, suggesting that inherited genetic factors can influence susceptibility. These genetic factors may affect how the immune system responds to infections like EBV or how cells regulate their growth and death. However, no single gene mutation has been identified as the sole cause; rather, it is likely a combination of multiple genetic variations that increase risk.
Immunodeficiency is another important factor. People with weakened immune systems, whether due to HIV infection, immunosuppressive medications, or congenital immune disorders, are more prone to developing Hodgkin lymphoma, including the mixed cellularity subtype. A compromised immune system is less capable of controlling EBV infection and eliminating abnormal cells, allowing cancerous cells to multiply unchecked.
Environmental and lifestyle factors may also contribute, although their roles are less clearly defined. Exposure to certain chemicals, radiation, or chronic infections could potentially influence the risk by causing DNA damage or chronic immune stimulation. However, these factors are not as strongly linked to MCHL as viral infection and immune status.
The mixed cellularity subtype is named for the variety of immune cells found within the tumor, including lymphocytes, eosinophils, plasma cells, and histiocytes, alongside the malignant Reed-Sternberg cells. This cellular diversity reflects the complex interaction between the cancerous cells and the immune system. The tumor microenvironment is shaped by signals from the Reed-Sternberg cells, which recruit and manipulate surrounding immune cells to create conditions favorable for tumor growth and survival.
In summary, mixed cellularity Hodgkin lymphoma arises from a combination of factors that disrupt normal immune cell function and regulation. Epstein-Barr virus infection is a major trigger, especially in individuals with genetic susceptibility or weakened immune defenses. These elements together lead to the uncontrolled growth of abnormal B cells and the characteristic mixed cellular environment seen in this subtype of Hodgkin lymphoma.
