Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a type of Hodgkin lymphoma (HL), a kind of blood cancer. HL is one of the two main types of lymphoma.

Lymphomas originate in the lymphatic system, which is made up of multiple organs (including the lymph nodes, lymph channels, bone marrow, spleen, thymus, tonsils, and tissue in the digestive tract). The purpose of the lymphatic system is to remove waste and bacteria from the body and drain excess fluid from tissue.

What Is Nodular Lymphocyte-Predominant Hodgkin Lymphoma?

NLPHL is an indolent (slowly progressing) type of HL that affects B lymphocytes (or B cells), a type of white blood cell. NLPHL usually affects people aged 30 to 50 years old and is more common in men than women.

NLPHL is curable, but people may relapse years after complete remission. Very rarely, NLPHL can progress into an aggressive type of NHL called diffuse large B-cell lymphoma. NLPHL is uncommon, only accounting for 5 percent of all cases of HL.

Symptoms of Nodular Lymphocyte-Predominant Hodgkin Lymphoma

NLPHL, classical HL, and NHL can have many symptoms in common. Because it is a very slow-growing cancer, NLPHL is now thought of as being on the transition spectrum between HL and NHL. NLPHL is most often diagnosed when it is still an early-stage disease before most symptoms develop. The most typical symptom seen in people with NLPHL, and often the only symptom, is painless, enlarged lymph nodes. Although there are lymph nodes throughout the body, groups of superficial lymph nodes that lie just beneath the skin in the neck, groin, and armpits are usually affected in people with NLPHL. Deep lymph nodes are less commonly affected in those with NLPHL.

All types of HL can have the same symptoms. Three symptoms, in particular — unexplained fever, night sweats, and unexplained weight loss are called B symptoms. B symptoms are systemic symptoms that affect the whole body. The presence of these symptoms is important to help determine the stage of HL and its prognosis. B symptoms are not often found in people with NLPHL.

Common Symptoms of NLPHL

Swollen lymph nodes are new or persistent painless lumps, usually in the neck, armpits, and groin.

Less Common Symptoms of NLPHL

Below are some symptoms of NLPHL that are less common than swollen lymph nodes:

• B symptoms (unexplained fever, night sweats, unexplained weight loss)
• Fatigue that does not improve with rest
• Coughing or chest pain
• Shortness of breath
• Abdominal pain or fullness
• Unexplained itching that may worsen after consuming alcohol or exposure to heat

How Is Nodular Lymphocyte-Predominant Hodgkin Lymphoma Diagnosed?

Diagnosis of NLHPL, like other types of lymphoma, begins with a thorough medical history and physical examination to identify what signs and symptoms you have, as well as any risk factors for lymphoma. Additional tests used to diagnose and stage NLPHL include biopsies of tumors and bone marrow, imaging tests, and blood tests. An accurate diagnosis is important to determine the best treatment approach.

Physical Exam

A thorough physical exam for NLPHL and other types of lymphoma includes careful palpation (feeling by hand) of the neck, armpits, and groin for swollen lymph nodes. Palpation of the abdomen is also important to check for enlargement of the spleen.

Biopsy

A biopsy to take out all or part of an enlarged lymph node is necessary to diagnose NLPHL. Tissue and cells from a biopsy are analyzed for the presence of lymphocyte-predominant (LP) cells, a specific type of Reed-Sternberg cell, the hallmark of this form of HL. Cancer cells are also tested for specific DNA mutations and proteins on the cell surface.

The surgical removal of an entire lymph node (excisional biopsy) is the best way to identify and diagnose NLPHL. Biopsies using a needle lymph node or a bone marrow biopsy and aspirate (collection of liquid bone marrow) may be performed in some cases.

Imaging

Imaging tests can help find tumors throughout the body and may include one or more of the following:

• CT scans use X-rays to look for tumors and enlarged organs throughout the body.
• Positron emission tomography uses a radioactive tracer, usually given by intravenous injection, to identify potential cancer cells by their high metabolism. It may be repeated early in the treatment plan to assess how rapidly the lymphoma is responding.
• MRI is similar to CT but uses a very strong magnetic field to produce images of the soft tissues in the body.

Blood Tests

The most important blood tests for NLPHL (and classical HL) are complete blood count and erythrocyte sedimentation rate. Blood tests for liver and kidney function — as well as tests for HIV and hepatitis B and C infection — are also needed to help decide what treatment options are best.

Complete Blood Count

Complete blood count testing measures the amount of red blood cells (erythrocytes), hemoglobin, white blood cells (leukocytes), and platelets in a blood sample. Further analysis, called differential analysis, also looks at which types of white blood cells are present and if they show any abnormalities.

Erythrocyte Sedimentation Rate

Erythrocyte sedimentation rate is a measure of inflammation in the body and is important in the diagnosis of HL.

Stages of NLPHL

Staging of NLPHL involves classifying the spread of the disease and which organs are affected, in order to determine the appropriate treatments as well as disease prognosis. Most cases of NLPHL are diagnosed at stage 1. Advanced-stage NLPHL that spreads to other parts of the body is rare. Stages of NLPHL and other types of HL using the Lugano classification system are:

• Stage 1 and stage 2 — Early-stage or limited-stage NLPHL, involving lymph nodes and/or one organ outside the lymphatic system on the same side of the diaphragm (either above or below)
• Stage 3 and stage 4 — Advanced-stage lymphoma that has spread to both sides of the diaphragm and may include organs outside of the lymphatic system

A letter may be used to denote additional classification of these stages:

• A — No B symptoms are present.
• B — Symptoms are present.
• E — The lymphoma started in a single body organ outside the lymphatic system.
• S — Cancer cells are found in the spleen.

What Causes Nodular Lymphocyte-Predominant Hodgkin Lymphoma?

NLPHL is caused by genetic mutations that occur in specific genes inside B lymphocytes, the type of lymphocyte responsible for producing antibodies. Mutations that “turn on” oncogenes (potentially cancer-causing genes) or “turn off” tumor suppressor genes (genes that help prevent cancer) can lead otherwise normal cells to become cancer cells. It is not known what causes these mutations, but there are several identified risk factors for developing NLPHL:

• Past infection with Epstein-Barr virus, a virus that causes infectious mononucleosis
• A compromised immune system, including people with HIV
• Family history of NLPHL or other types of lymphoma

How Does Nodular Lymphocyte-Predominant Hodgkin Lymphoma Differ From Other Lymphomas?

The primary distinguishing feature of NLPHL is the presence of "popcorn cells" in the lymph nodes, also sometimes found in the blood and bone marrow. Reed-Sternberg cells are a unique type of abnormal lymphocyte seen in people with all types of HL. A specific type of Reed-Sternberg cells (LP cells) are seen in people with NLPHL, but not in those with other types of lymphoma.

LP cells have a unique appearance that looks similar to a popped kernel of popcorn. Unlike other types of HL cells, LP cells consistently express the CD20 marker on their surface, which is important for determining effective treatment.

NLPHL has several distinguishing features:

• Primarily affects superficial lymph nodes
• Enlarged lymph nodes are often the only symptom
• Usually detected at an early stage
• Slow growing
• Defined by the presence of lymphocyte-predominant “popcorn” Reed-Sternberg cells
• NLPHL cancer cells have CD20 surface markers

Treatment of Nodular Lymphocyte-Predominant Hodgkin Lymphoma

The best treatment plan for NLPHL is determined by the stage and extent of the disease, as well as a person’s age and overall health. Early-stage NLPHL, like other indolent types of lymphoma and leukemia, may not require immediate treatment. When treatment is required, it can involve one or more of the following: radiation, chemotherapy, and targeted drug therapy.

Surgery

Surgery to remove affected lymph nodes can be a part of both diagnosis and treatment, especially if the enlarged lymph nodes are limited to one area of the body. Surgery may be followed by other treatments or active surveillance, also called “watch and wait.”

Watch and Wait

When NLPHL is discovered at an early stage in an asymptomatic person (not experiencing any symptoms) the watch-and-wait approach may be the best course of treatment. This approach involves active surveillance, regular blood tests, and follow-up with a doctor, to see if the disease progresses.

Radiation

Involved site radiation therapy uses localized radiation focused on affected lymph nodes and other tumors. A similar type of radiotherapy, involved field radiation therapy, is sometimes used. Involved site radiation therapy may be used alone in people with early NLPHL who do not have any B symptoms. Involved site radiation therapy may also be used after surgery or chemotherapy to destroy any remaining cancer cells.

Chemotherapy

Several chemotherapy regimens can be used to treat NLPHL, either alone or with the addition of targeted therapy (rituximab) or radiation. Rituximab is an anti-CD20 antibody, which this type of HL uniquely possesses. Chemotherapy is more likely to be used in people with NLPHL who have B symptoms or more advanced disease (stages 3 and 4). Some commonly used chemotherapy regimens for NLPHL include:

• ABVD — Doxorubicin (Adriamycin), bleomycin (Blenoxane), vinblastine, and dacarbazine (DTIC-Dome)
• CHOP — Cyclophosphamide (Cytoxan), doxorubicin, vincristine (Oncovin), and prednisone. R-CHOP also includes rituximab (Rituxan).
• CVP — Cyclophosphamide, vinblastine, and prednisone

Targeted Drug Therapy

Targeted drug therapies are designed to attack cancer cells while leaving healthy cells alone. The monoclonal antibody drug rituximab targets cells expressing the CD20 surface protein and marks them for destruction by healthy immune cells. Because NLPHL cells have this protein, rituximab is frequently used in combination with chemotherapy and radiation or sometimes used alone.

Nodular Lymphocyte-Predominant Hodgkin Lymphoma Prognosis

The prognosis (outlook) of NLPHL is overall very good. Because NLPHL is slow growing and usually found at an early stage, effective treatments have an excellent chance to cure the disease. Even people with more advanced NLPHL and recurrent NLPH are usually very responsive to treatment. The five-year survival rate for all types of HL combined is 87 percent, and the survival rate of early-stage NLPHL is more than 90 percent, making NLPHL one of the more survivable types of cancer.

Talk With Others Who Understand

MyLympomaTeam is a social network for people with lymphoma. On MyLymphomaTeam, more than 10,000 members come together to ask questions, give advice, and share their stories with others who understand life with nodular lymphocyte-predominant Hodgkin lymphoma.

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