Hodgkin Lymphoma

What Hodgkin lymphoma is

Lymphomas are cancers of lymphocytes, the white blood cells that fight infection. In Hodgkin lymphoma, a small number of large cancerous B cells, called Reed-Sternberg cells, sit inside a lymph node surrounded by many normal immune cells that they attract. The disease usually starts in one group of nodes, often in the neck or chest, and spreads in an orderly way to neighboring groups. That predictable pattern is one reason it responds so well to treatment.

Types

• Classic Hodgkin lymphoma (about 95%): includes nodular sclerosis (the most common, typical in young adults with a chest mass), mixed cellularity, lymphocyte-rich and lymphocyte-depleted subtypes.
• Nodular lymphocyte-predominant Hodgkin lymphoma (about 5%): grows slowly, often in a single node group, and is treated differently, sometimes with surgery or radiation alone.

Hodgkin vs non-Hodgkin lymphoma

Symptoms

Early signs of Hodgkin lymphoma

• A painless, rubbery, swollen lymph node in the neck, above the collarbone, in the armpit or the groin. Unlike infection-related nodes, it does not shrink after a few weeks.
• Fatigue
• Itching all over the body, sometimes intense

B symptoms

Doctors call three symptoms "B symptoms" because they affect staging and treatment:

• unexplained fever above 38 °C (100.4 °F)
• drenching night sweats
• unexplained weight loss of more than 10% of body weight in 6 months

Symptoms from enlarged nodes in the chest

A mass in the middle of the chest can cause a cough, chest discomfort or breathlessness. Very large masses can press on the main vein from the head and arms, causing facial and arm swelling.

An unusual clue

A small number of people feel pain in the affected lymph nodes within minutes of drinking alcohol. It is rare but quite specific to Hodgkin lymphoma.

Causes and risk factors

The exact cause is unknown, and it is not contagious. Factors linked to higher risk include:

• Past Epstein-Barr virus infection, especially infectious mononucleosis (glandular fever), found in the tumor cells of many cases
• Age 20 to 39 or over 65
• Family history: a parent, brother or sister with Hodgkin lymphoma raises risk, though the absolute risk stays low
• Weakened immune system: HIV infection, organ transplant medicines, some autoimmune diseases
• Higher socioeconomic status in childhood in some studies, possibly from later exposure to common infections

Diagnosis

1. Examination and history: size, location and duration of lumps, and B symptoms.
2. Excisional or core needle biopsy of a lymph node. Removing a whole node is preferred, because a fine needle aspirate rarely provides enough tissue to show Reed-Sternberg cells.
3. Blood tests: blood count, ESR (a marker of inflammation that affects prognosis), liver and kidney function, and tests for HIV and hepatitis.
4. PET-CT scan to stage the disease and later to check how well treatment is working.
5. Heart and lung function tests before treatment, because some drugs can affect them.
6. Fertility counseling before treatment for people who may want children.

Many causes of swollen nodes are far more common, including viral infections, mononucleosis, dental infections, tuberculosis and sarcoidosis. A node that persists beyond a few weeks without explanation should be assessed.

Hodgkin lymphoma stages

Staging uses the Lugano system, based on the older Ann Arbor classification:

Letters add detail: A means no B symptoms, B means B symptoms are present, and bulky marks a large mass. Doctors group stages into early favorable, early unfavorable and advanced, which guides treatment.

Treatment for Hodgkin lymphoma

Treatment is planned by a hematologist-oncologist and adapted to how the disease responds on an interim PET scan.

Early-stage disease (I and II)

Usually 2 to 4 cycles of chemotherapy such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), sometimes followed by low-dose radiation to the involved area. If the interim PET scan is clear, radiation may be safely omitted to reduce long-term side effects.

Advanced disease (III and IV)

Six cycles of combination therapy. Options now include chemotherapy combined with immunotherapy, such as nivolumab with AVD or brentuximab vedotin with AVD, which have improved outcomes over ABVD in trials, or the more intensive escalated BEACOPP-based regimens used in some countries.

Relapsed or resistant disease

• Second-line chemotherapy followed by high-dose chemotherapy and an autologous stem cell transplant (using your own stem cells)
• Brentuximab vedotin, an antibody targeting CD30 on Reed-Sternberg cells
• Checkpoint inhibitors (nivolumab, pembrolizumab), which work well because Hodgkin cells often depend on PD-1 pathways to evade the immune system
• A donor (allogeneic) transplant in selected cases

Many people are still cured after a relapse.

During treatment

Chemotherapy can cause fatigue, nausea, hair loss, numb fingers and a low white blood cell count. Any fever during treatment needs urgent attention. Bleomycin can irritate the lungs, so report a new cough or breathlessness.

Survival rates

According to NCI SEER data, the overall 5-year relative survival is about 89%:

Survival is highest in children and young adults and lower in people over 65, who tolerate intensive treatment less well. These figures are averages from people treated years ago, and modern regimens are expected to do better.

Long-term effects and survivorship

Because most people are cured young, late effects of treatment matter:

• Second cancers, especially breast cancer after chest radiation in women treated before about age 30, and lung cancer in smokers
• Heart disease from doxorubicin and chest radiation
• Underactive thyroid after neck radiation
• Reduced fertility, more likely with intensive regimens
• Lung scarring from bleomycin

Survivors should have a long-term follow-up plan, including earlier breast screening if they had chest radiation, regular heart checks, thyroid tests, and no smoking.

Frequently asked questions

What are the early signs of Hodgkin lymphoma?

The most common early sign is a painless lump in the neck, armpit or groin that does not go away after a few weeks. Others include tiredness, itching, fevers, drenching night sweats and unexplained weight loss. A cough or breathlessness can occur if nodes in the chest are enlarged.

Is Hodgkin lymphoma curable?

Yes. It is one of the most curable cancers. Most people with early-stage disease are cured with chemotherapy, sometimes with radiation, and most with advanced disease are cured too. Even after a relapse, a stem cell transplant or newer immunotherapy cures many people.

What is the survival rate for Hodgkin lymphoma?

About 89% of people are alive 5 years after diagnosis, according to US national data. Survival is over 90% for disease found in one area and above 80% even when it has spread to distant organs. Outcomes are best in younger patients.

What causes Hodgkin lymphoma?

The exact cause is not known. Risk is higher after Epstein-Barr virus infection, especially mononucleosis, with a weakened immune system such as HIV, and in people with a close relative who had it. It is not caused by anything a person did, and it is not contagious.

Does Hodgkin lymphoma show up in blood tests?

Not directly. Blood tests may show anemia, a high white cell count or a raised ESR, but they cannot diagnose Hodgkin lymphoma. A biopsy of an affected lymph node is required, followed by a PET-CT scan to see where the disease is.

Can you have children after Hodgkin lymphoma treatment?

Many people can. ABVD-based treatment usually preserves fertility, while more intensive regimens and pelvic radiation carry a higher risk. Freezing sperm, eggs or embryos before treatment is offered when time allows, so ask about fertility preservation at diagnosis.