Nodular lymphocyte predominant Hodgkin lymphoma

by Jason Wasserman MD PhD FRCPC
September 27, 2024

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare type of lymphoma that affects a part of the immune system called the lymph nodes. It is a slow-growing cancer that starts in B cells, a type of white blood cell that helps the body fight infections. The World Health Organization recommends the term “nodular lymphocyte predominant Hodgkin lymphoma,” while the International Consensus Classification prefers the term “nodular lymphocyte predominant B cell lymphoma” for this same condition. Both names refer to the same disease.

What are the symptoms of nodular lymphocyte predominant Hodgkin lymphoma?

Symptoms of nodular lymphocyte predominant Hodgkin lymphoma can vary from person to person. Some common symptoms include:

• Swollen lymph nodes are often in the neck, under the arms, or groin.
• Feeling tired.
• Unexplained weight loss.
• Night sweats or fever.

Many people with NLPHL do not feel sick and may only notice swollen lymph nodes. Because other conditions can cause these symptoms, it is important to see a doctor for a proper diagnosis.

What causes nodular lymphocyte predominant Hodgkin lymphoma?

The exact cause of nodular lymphocyte predominant Hodgkin lymphoma is not known. It is thought to occur when specific changes happen in the DNA of B cells, causing them to grow out of control. However, it is not usually linked to known infections, lifestyle factors, or family history. Research is ongoing to better understand why this lymphoma develops.

How is this diagnosis made?

To diagnose nodular lymphocyte predominant Hodgkin lymphoma, doctors usually perform a biopsy, which involves removing a small piece of tissue from an enlarged lymph node. A pathologist, a doctor who examines tissues under a microscope, will examine the biopsy sample to identify the features of this cancer. They may also use special tests, such as immunohistochemistry, to look for specific proteins that help confirm the diagnosis.

What are the microscopic features of nodular lymphocyte predominant Hodgkin lymphoma?

When pathologists look at lymph nodes affected by nodular lymphocyte predominant Hodgkin lymphoma under a microscope, they notice several features:

• Nodular pattern: This lymphoma often has a “nodular” growth pattern. This means that groups of abnormal cells form small clusters within the lymph node.
• Large cells: These clusters contain large cells called “LP cells” (lymphocyte-predominant cells). These cells have nuclei (the cell’s control center) that may look folded or “popcorn-like” in shape, with pale surrounding material. These LP cells usually make up only a small part of the overall tumour.
• Non-cancerous cells: Surrounding these clusters are many normal B cells, T cells (another type of white blood cell), and other immune cells called histiocytes. Sometimes, the histiocytes form small groups called granulomas around the tumour clusters.
• Other features: Unlike some other lymphomas, nodular lymphocyte predominant Hodgkin lymphoma does not usually have specific cells like neutrophils and eosinophils (types of white blood cells) in the affected area. Sclerosis (scar tissue) is uncommon when the disease is first diagnosed, but it can appear if it returns. Additionally, a layer of normal lymph node tissue may still be present around the outside of the affected lymph node, showing changes like follicular hyperplasia (growth of certain parts of the lymph node) and transformation of germinal centers (areas where B cells develop).

Immunohistochemistry

Pathologists use immunohistochemistry (IHC) to identify specific proteins on the surface of cells. This can help confirm the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma. In this type of cancer, most cases show a group of markers related to B cells:

• Positive markers: Most nodular lymphocyte predominant Hodgkin lymphoma cells express proteins like CD20, CD79a, OCT2, BOB1, PU.1, BCL6, LMO2, and HGAL. Of these, OCT2 is often the most reliable. BCL6 and LMO2 are markers found in germinal center B cells, a stage in B cell development.
• Variable markers: Some cases may not show specific proteins, like CD20 or other B cell transcription factors. CD19 is often missing in nodular lymphocyte predominant Hodgkin lymphoma cells.
• Negative markers: LP cells in nodular lymphocyte predominant Hodgkin lymphoma do not usually show CD30 and are rarely positive for CD15. They also tend to be negative for CD10.
• Other markers: In some cases, LP cells express a protein called IgD, linked to a particular subtype of nodular lymphocyte predominant Hodgkin lymphoma.
• Background cells: The small B cells around the LP cells often have a “mantle zone” pattern, expressing a protein called IgD but not germinal center markers. Surrounding the LP cells are many T cells that express markers like CD3, PD1, CD57, BCL6, CXCL13, and ICOS. These T cells can form “rosettes” around LP cells.

How is nodular lymphocyte predominant Hodgkin lymphoma staged?

The Lugano system is the method most commonly used to stage lymphomas, including nodular lymphocyte predominant Hodgkin lymphoma. Staging describes how much of the body is affected by the lymphoma and helps guide treatment and predict outcomes.

The Lugano system divides lymphoma into four stages:

1. Stage I: The lymphoma is found in a single lymph node or area of a nearby organ (extranodal site).
2. Stage II: The lymphoma is in two or more lymph node areas on the same side of the diaphragm (the muscle that separates the chest from the abdomen) or has spread to a nearby organ.
3. Stage III: The lymphoma is in lymph node areas on both sides of the diaphragm or has spread to nearby organs.
4. Stage IV: The lymphoma has spread to one or more organs outside the lymph nodes, such as the liver, bone marrow, or lungs.

Additional letters are sometimes used to provide more details about the lymphoma:

• A or B: These letters indicate whether specific symptoms are present. “A” means no symptoms like fever, night sweats, or weight loss, while “B” means these symptoms are present.
• E: This means the lymphoma has spread to an organ outside the lymph nodes (extranodal).
• X: This indicates bulky disease, which means there is a large tumour, usually larger than 10 cm.

Understanding the stage of nodular lymphocyte predominant Hodgkin lymphoma helps doctors decide on the most appropriate treatment and gives patients an idea of what to expect during their care.

What is the prognosis for a patient diagnosed with nodular lymphocyte predominant Hodgkin lymphoma?

Nodular lymphocyte predominant Hodgkin lymphoma generally has a good prognosis. It is a slow-growing (indolent) lymphoma, which means it often responds well to treatment, and patients can live for many years after diagnosis. However, the disease can come back (relapse) after treatment, so regular follow-up with a doctor is important. Treatment plans depend on the stage of the disease and may include options such as radiation therapy, chemotherapy, or a combination of treatments.

While nodular lymphocyte predominant Hodgkin lymphoma can sometimes transform into a more aggressive type of lymphoma, this is uncommon. Most patients do well with appropriate management and care.