Hodgkin's Lymphoma Staging and Classification

Hodgkin's lymphoma – formerly known as Hodgkin's disease – is a cancer of the lymphatic system, which is part of your immune system. It may affect people of any age, but is most common in people between 20 and 40 years old and those over 55.

In Hodgkin's lymphoma, cells in the lymphatic system grow abnormally and may spread beyond it.

Hodgkin's lymphoma is one of two common types of cancers of the lymphatic system. The other type, non-Hodgkin's lymphoma, is far more common.

Advances in diagnosis and treatment of Hodgkin's lymphoma have helped give people with this disease the chance for a full recovery. The prognosis continues to improve for people with Hodgkin's lymphoma.

Hodgkin’s lymphoma is divided into two major types according to how the lymph cells look under a microscope and whether Reed-Sternberg cells are present. Knowing the type of lymphoma helps doctors determine your best treatment.

Different types of Hodgkin lymphoma can grow and spread differently and may be treated differently.

Classic Hodgkin lymphoma

Classic Hodgkin lymphoma (cHL) accounts for more than 9 in 10 cases of Hodgkin lymphoma in developed countries.

The cancer cells in cHL are called Reed-Sternberg cells. These cells are usually an abnormal type of B lymphocyte. Enlarged lymph nodes in people with cHL usually have a small number of Reed-Sternberg cells with a lot of normal immune cells around them. These other immune cells cause most of the swelling in the lymph nodes.

Classic HL has 4 subtypes:

Nodular sclerosis Hodgkin lymphoma or NSCHL: This is the most common type of Hodgkin disease in developed countries. It accounts for about 7 out of 10 cases. It's most common in teens and young adults, but it can occur in people of any age. It tends to start in lymph nodes in the neck or chest.

Mixed cellularity Hodgkin lymphoma or MCCHL: This is the second most common type, found in about 4 out 10 cases. It's seen mostly in people with HIV infection. It's also found in children or the elderly .It can start in any lymph node but most often occurs in the upper half of the body.

Lymphocyte-rich Hodgkin lymphoma: This sub-type isn't common. It usually occurs in the upper half of the body and is rarely found in more than a few lymph nodes.

Lymphocyte-depleted Hodgkin lymphoma: This is a rare form of Hodgkin disease. It's seen mainly in older people and those with HIV infection. It's more aggressive than other types of HL and likely to be advanced when first found. It's most often in lymph nodes in the abdomen (belly) as well as in the spleen, liver, and bone marrow.

Nodular lymphocyte-predominant Hodgkin lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for about 5% of cases. The cancer cells in NLPHL are large cells called popcorn cells (because they look like popcorn), which are variants of Reed-Sternberg cells. You may also hear these cells called lymphocytic and histiocytic (L&H) cells.

NLPHL usually starts in lymph nodes in the neck and under the arm. It can occur in people of any age, and is more common in men than in women. This type of HL tends to grow more slowly and is treated differently from the classic types.

Hodgkin lymphoma can develop at any age, but it mostly affects young adults in their early 20s and older adults over the age of 70. Slightly more men than women are affected.

Lymph tissue is in many parts of your body, so Hodgkin lymphoma can start almost anywhere.

The major sites of lymphoid tissue are:

Lymph nodes: Lymph nodes are bean-sized collections of lymphocytes and other immune system cells. They're found throughout the body, including inside the chest, abdomen (belly), and pelvis. They're connected to each other by a system of lymphatic vessels.

Bone marrow: The bone marrow is the liquid, spongy tissue inside certain bones. New blood cells (including some lymphocytes) are made there.

Lymph vessels: A network of tiny tubes (a lot like blood vessels) that connect lymph nodes and carry immune cells in a clear fluid called lymph. Lymph is collected from around the body and put into the bloodstream.

Thymus: The thymus is a small organ behind the upper part of the breastbone and in front of the heart. It's important for T lymphocyte development.

Spleen: The spleen is an organ that's under the lower ribs on your left side. The spleen is part of your immune system. It makes lymphocytes and other immune system cells. It also stores healthy blood cells and filters out damaged blood cells, bacteria, and cell waste.

Adenoids and tonsils: These are collections of lymph tissue in the back of your throat. They help make antibodies against germs that are breathed in or swallowed.

Digestive tract: The stomach, intestines, and many other organs also have lymph tissue.

Although Hodgkin lymphoma can start almost anywhere, most often it starts in lymph nodes in the upper part of the body. The most common sites are in the chest, neck, or under the arms.

Hodgkin lymphoma most often spreads through the lymph vessels from lymph node to lymph node. Rarely, late in the disease, it can invade the bloodstream and spread to other parts of the body, such as the liver, lungs, and/or bone marrow.

The most common symptom of Hodgkin lymphoma is a swelling in the neck, armpit or groin. The swelling is usually painless, although some people find that it aches.

The swelling is caused by an excess of affected lymphocytes (white blood cells) collecting in a lymph node (also called lymph glands). Lymph nodes are pea-sized lumps of tissue found throughout the body. They contain white blood cells that help to fight infection.

However, it's highly unlikely that you have Hodgkin lymphoma if you have swollen lymph nodes, as these glands often swell as a response to infection.

Other symptoms

Some people with Hodgkin lymphoma also have other more general symptoms. These can include:

1. Night sweats
2. Unintentional weight loss
3. A high temperature (fever)
4. A persistent cough or feeling of breathlessness
5. Persistent itching of the skin all over the body

Other symptoms will depend on where in the body the enlarged lymph glands are. For example, if the abdomen (tummy) is affected, you may have abdominal pain or indigestion

A few people with lymphoma have abnormal cells in their bone marrow when they're diagnosed. This may lead to:

1. Persistent tiredness or fatigue
2. An increased risk of infections

excessive bleeding – such as nosebleeds, heavy periods and spots of blood under the skin

In some cases, people with Hodgkin lymphoma experience pain in their lymph glands when they drink alcohol.

Hodgkin lymphoma is caused by a change (mutation) in the DNA of a type of white blood cell called B lymphocytes, although the exact reason why this happens isn't known.

The DNA gives the cells a basic set of instructions, such as when to grow and reproduce. The mutation in the DNA changes these instructions so the cells keep growing, causing them to multiply uncontrollably.

The abnormal lymphocytes usually begin to multiply in one or more lymph nodes in a particular area of the body, such as your neck or groin. Over time, it's possible for the abnormal lymphocytes to spread into other parts of your body, such as your:

1. Bone marrow
2. Spleen
3. Liver
4. Skin
5. Lungs

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some cancer risk factors, like smoking or being overweight, can be changed. Others, like a person’s age or family history, can’t be changed.

A few risk factors make a person more likely to develop Hodgkin lymphoma (HL), but it’s not always clear why these factors increase risk. Having a risk factor, or even many, does not mean that you'll definitely get the disease. And many people who get HL have few or no known risk factors.

Factors that can increase the risk of Hodgkin's lymphoma include:

Your age: Hodgkin's lymphoma is most often diagnosed in people between 15 and 30 years old and those over 55.

A family history of lymphoma: Having a blood relative with Hodgkin's lymphoma or non-Hodgkin's lymphoma increases your risk of developing Hodgkin's lymphoma.

Being male: Males are slightly more likely to develop Hodgkin's lymphoma than are females.

Past Epstein-Barr infection: People who have had illnesses caused by the Epstein-Barr virus, such as infectious mononucleosis, are more likely to develop Hodgkin's lymphoma than are people who haven't had Epstein-Barr infections.

The stage describes how many areas of the body are affected by lymphoma and where these are. This information helps doctors plan the right treatment for you.

The stage of a lymphoma is usually described using numbers from 1 to 4:

Stage 1: there is only one area of lymphoma. This may affect one group of lymph nodes or another part of the lymphatic system.

Stage 2: there are two or more areas of lymphoma on the same side of the diaphragm (the sheet of muscle underneath the lungs).

Stage 3: there are areas of lymphoma above and below the diaphragm.

Stage 4: there are areas of lymphoma outside and separate from the lymphatic system. For example, this could be in organs such as the bone marrow, liver or lungs.

Stages 1 and 2 are also called early-stage, limited lymphoma. If stage 1 or 2 lymphoma has grown into nearby areas of tissue, this is called extra-nodal disease. The letter E may be added after the stage number to show it is extra-nodal disease.

Stages 3 and 4 are also called advanced lymphoma.

Your doctor will ask you about your personal and family medical history. He or she may then have you undergo tests and procedures used to diagnose Hodgkin's lymphoma, including:

A physical exam: Your doctor checks for swollen lymph nodes, including in your neck, underarm and groin, as well as a swollen spleen or liver.

Blood tests: A sample of your blood is examined in a lab to see if anything in your blood indicates the possibility of cancer.

Imaging tests: Your doctor may recommend imaging tests to look for signs of Hodgkin's lymphoma in other areas of your body. Tests may include X-ray, CT and positron emission tomography.

Removing a lymph node for testing: Your doctor may recommend a lymph node biopsy procedure to remove a lymph node for laboratory testing. He or she will diagnose classical Hodgkin's lymphoma if abnormal cells called Reed-Sternberg cells are found within the lymph node.

Removing a sample of bone marrow for testing: A bone marrow biopsy and aspiration procedure involves inserting a needle into your hipbone to remove a sample of bone marrow. The sample is analyzed to look for Hodgkin's lymphoma cells.

Other tests and procedures may be used depending on your situation.

Which Hodgkin's lymphoma treatments are right for you depends on the type and stage of your disease, your overall health, and your preferences. The goal of treatment is to destroy as many cancer cells as possible and bring the disease into remission.

Chemotherapy

Chemotherapy is a drug treatment that uses chemicals to kill lymphoma cells. Chemotherapy drugs travel through your bloodstream and can reach nearly all areas of your body.

Chemotherapy is often combined with radiation therapy in people with early-stage classical type Hodgkin's lymphoma. Radiation therapy is typically done after chemotherapy. In advanced Hodgkin's lymphoma, chemotherapy may be used alone or combined with radiation therapy.

Chemotherapy drugs can be taken in pill form or through a vein in your arm, or sometimes both methods of administration are used. Several combinations of chemotherapy drugs are used to treat Hodgkin's lymphoma.

Side effects of chemotherapy depend on the drugs you're given. Common side effects are nausea and hair loss. Serious long-term complications can occur, such as heart damage, lung damage, fertility problems and other cancers, such as leukemia.

Radiation therapy

Radiation therapy uses high-energy beams, such as X-rays and protons, to kill cancer cells. For classical Hodgkin's lymphoma, radiation therapy is often used after chemotherapy. People with early-stage nodular lymphocyte-predominant Hodgkin's lymphoma may undergo radiation therapy alone.

During radiation therapy, you lie on a table and a large machine moves around you, directing the energy beams to specific points on your body. Radiation can be aimed at affected lymph nodes and the nearby area of nodes where the disease might progress. The length of radiation treatment varies, depending on the stage of the disease. A typical treatment plan might have you going to the hospital or clinic five days a week for several weeks. At each visit, you undergo a 30-minute radiation treatment.

Radiation therapy can cause skin redness and hair loss at the site where the radiation is aimed. Many people experience fatigue during radiation therapy. More-serious risks include heart disease, stroke, thyroid problems, infertility and other cancers, such as breast or lung cancer.

Bone marrow transplant

Bone marrow transplant, also known as stem cell transplant, is a treatment to replace your diseased bone marrow with healthy stem cells that help you grow new bone marrow. A bone marrow transplant may be an option if Hodgkin's lymphoma returns despite treatment.

During a bone marrow transplant, your own blood stem cells are removed, frozen and stored for later use. Next you receive high-dose chemotherapy and radiation therapy to destroy cancerous cells in your body. Finally your stem cells are thawed and injected into your body through your veins. The stem cells help build healthy bone marrow.

People who undergo bone marrow transplant may be at increased risk of infection.

Other drug therapy

Other drugs used to treat Hodgkin's lymphoma include targeted drugs that focus on specific vulnerabilities in your cancer cells and immunotherapy that works to activate your own immune system to kill the lymphoma cells. If other treatments haven't helped or if your Hodgkin's lymphoma returns, your lymphoma cells may be analyzed in a laboratory to look for genetic mutations. Your doctor may recommend treatment with a drug that targets the particular mutations present in your lymphoma cells.