Lymphoma is a blood cancer that develops in the lymphatic system. The lymphatic system helps fight infection, control the levels of fluid in the body, and get rid of waste.

The lymphatic system contains many specialized white blood cells called lymphocytes. There are two main kinds of lymphocytes: B cells and T cells. Hodgkin lymphoma (HL), also called Hodgkin’s lymphoma or Hodgkin’s disease, most often affects B cells. Non-Hodgkin lymphoma (NHL), also called non-Hodgkin’s lymphoma, can develop in B cells or T cells. Both HL and NHL are further broken down into subtypes based on other characteristics of the cancer cells.

Doctors determine lymphoma subtypes by examining cancer cells under a microscope and using tests to find out which types of proteins are made by the cells. Knowing which subtype of lymphoma you have is important for making treatment decisions. Different types of treatments may be more effective for different Hodgkin lymphoma subtypes.

Types of Hodgkin Lymphoma

Doctors group Hodgkin lymphoma into two main subtypes: classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma.

About 19 of 20 people with Hodgkin lymphoma have classical Hodgkin lymphoma. People diagnosed with classical HL usually have two different types of cancerous B cells, called Reed-Sternberg cells and Hodgkin cells.

About 1 out of 20 people with Hodgkin lymphoma have nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). The cancer cells that make up NLPHL are a type of Reed-Sternberg cell called lymphocyte-predominant cells or popcorn cells.

Classical Hodgkin Lymphoma

There are four subtypes of classical Hodgkin lymphoma (cHL):

• Nodular sclerosis Hodgkin lymphoma
• Mixed cellularity Hodgkin lymphoma
• Lymphocyte-rich Hodgkin lymphoma
• Lymphocyte-depleted Hodgkin lymphoma

All four subtypes of cHL are usually treated with chemotherapy, immunotherapy, and radiation therapy. These treatments are often very effective and lead to a positive outlook.

Nodular Sclerosis Classical Hodgkin Lymphoma

About 70 percent of people with classical Hodgkin lymphoma have nodular sclerosis classical Hodgkin lymphoma (NSCHL), making it the most common type of cHL. NSCHL most often affects teens and young adults, although people of all ages can develop this subtype. NSCHL occurs slightly more often in women.

A group of symptoms called B symptoms is common in NSCHL, affecting 40 percent of people. B symptoms include fever, drenching night sweats, and unexplained weight loss. Another common sign of NSCHL is nodular sclerosis, in which scar tissue builds up inside of cancerous lymph nodes and makes them feel hard. NSCHL usually affects lymph nodes inside the chest.

Treatments are often very effective for nodular sclerosis Hodgkin lymphoma. Many cases of this lymphoma can be cured, meaning all signs and symptoms disappear and don’t return.

Mixed Cellularity Classical Hodgkin Lymphoma

Between 20 percent and 25 percent of cHL cases are mixed cellularity classical Hodgkin lymphoma (MCCHL). This subtype is more likely to affect older adults as well as children younger than 10 years. MCCHL develops in men more often than in women. Risk factors for MCCHL include immune system disorders such as HIV. MCCHL usually develops within lymph nodes in the upper half of the body.

B symptoms are common in those with MCCHL. Additionally, people with MCCHL often have lymph nodes that contain many different cell types, including Reed-Sternberg cells.

Lymphocyte-Rich Hodgkin Lymphoma

Around 5 percent of people with cHL have lymphocyte-rich Hodgkin lymphoma. Men are more likely to develop this subtype than women.

People with lymphocyte-rich Hodgkin lymphoma are less likely to have B symptoms than people with other types. This subtype may lead to swollen lymph nodes that contain both Reed-Sternberg cells as well as normal-looking lymphocytes. The affected lymph nodes are usually in the upper part of the body.

Lymphocyte-Depleted Hodgkin Lymphoma

Lymphocyte-depleted Hodgkin lymphoma is very rare, occurring in less than 1 percent of people with cHL. Like with the mixed cellularity subtype, older adults and people infected with HIV are more likely to develop lymphocyte-depleted HL.

Many people with lymphocyte-depleted Hodgkin lymphoma have B symptoms. They also have lymph nodes that are full of Reed-Sternberg cells (but lack normal lymphocytes). This lymphoma subtype usually develops in lymph nodes in the abdomen. It often spreads to nearby organs like the spleen and liver.

Lymphocyte-depleted Hodgkin lymphoma is often not diagnosed until after cancer cells have spread to different parts of the body. Most people with this subtype are diagnosed with advanced-stage disease, which may be harder to treat.

Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is much less common than classical Hodgkin lymphoma. Most people with nodular lymphocyte-predominant Hodgkin lymphoma are between the ages of 30 and 50 years. Men are more likely than women to be diagnosed with NLPHL.

During the process of a lymphoma diagnosis, doctors use several tests to tell NLPHL cells apart from cHL cells. NLPHL cells grow in a different pattern and make different proteins compared to the cancer cells found in people with cHL. People with NLPHL often do not have B symptoms and their tumors are usually small. NLPHL most often develops in lymph nodes in the neck and armpit.

In 3 out of 4 people with NLPHL, lymphoma is diagnosed when it is still in the early stages. This means that the lymphoma has not yet spread beyond the original lymph nodes. Additionally, NLPHL often grows very slowly. People with this lymphoma subtype often have very good survival rates.

Doctors may not recommend aggressive treatment options for NLPHL. Many people with this lymphoma follow a “watch and wait” strategy, in which they do not receive any treatments until the disease grows worse or symptoms appear. Other people are treated with radiation alone, without chemotherapy drugs. These less aggressive approaches allow people to avoid the side effects of lymphoma treatment. However, doctors recommend chemotherapy for some cases of NLPHL, such as those diagnosed at a more advanced stage. NLPHL is sometimes also treated with the targeted therapy drug Rituxan (rituximab), although this drug is not officially approved for HL treatment.

NLPHL can often be cured. For some people, the lymphoma may relapse (come back) after many years. Additionally, for about 7 percent of people, NLPHL will turn into aggressive (fast-growing) non-Hodgkin lymphoma.

Other Ways of Describing Hodgkin Lymphoma

In addition to diagnosing the subtype of lymphoma, doctors will determine the stage to better describe the type of lymphoma. A lymphoma’s stage describes how far it has spread. Early-stage lymphoma affects only one or a couple of lymph nodes, and advanced-stage lymphoma may be found in many different locations in the body.

Doctors may also classify Hodgkin lymphoma as favorable or unfavorable. Favorable lymphoma has a good prognosis (outlook) and is unlikely to relapse. Unfavorable lymphoma may be more likely to come back after being treated. Cases of Hodgkin lymphoma are unfavorable if they have certain features. These may include lymphoma that grows outside of the lymph nodes, that affects multiple different groups of lymph nodes, or that causes B symptoms.

When making treatment decisions and estimating outlook, doctors will look at the lymphoma type and stage and whether the lymphoma is favorable. Doctors also consider a person’s age, overall health, and personal preferences.

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