Hodgkin’s lymphoma is a cancer of the lymphatic system, the network of vessels, nodes, and organs that helps your body fight infection. It stands apart from other blood cancers because of a unique hallmark: the presence of abnormal cells called Reed-Sternberg cells, which are large, distinctive cells visible under a microscope. About 8,500 new cases are diagnosed each year in the United States, and it is one of the most curable forms of cancer, with five-year survival rates above 80% even in advanced stages.
What Makes Hodgkin’s Lymphoma Different
The defining feature of Hodgkin’s lymphoma is the Reed-Sternberg cell. These cells are unusually large, sometimes exceeding 50 micrometers in diameter (a typical white blood cell is around 10 to 15 micrometers). Under a microscope, they have a distinctive “owl-eye” appearance, with at least two nuclear lobes and prominent, bright-colored structures inside each one.
What’s surprising is that these cancerous cells make up only about 1% of the actual tumor. The remaining 99% consists of normal immune cells: T-cells, B-cells, eosinophils, macrophages, and others that have been recruited to the site. Reed-Sternberg cells essentially hijack the immune system, sending and receiving signals that create a supportive environment for the cancer to thrive. Tumors with fewer surrounding T-cells and a higher proportion of Reed-Sternberg cells tend to behave more aggressively.
Types of Hodgkin’s Lymphoma
There are two main categories, and they behave quite differently.
Classical Hodgkin’s Lymphoma
About 95% of cases fall under classical Hodgkin’s lymphoma, which contains Reed-Sternberg cells and is further divided into four subtypes:
- Nodular sclerosis is the most common subtype, especially in young adults. It typically starts in lymph nodes in the neck or chest and features thick bands of scar tissue running through the affected nodes. It’s often caught at an early stage.
- Mixed cellularity is more common in older adults and tends to involve multiple groups of lymph nodes at diagnosis. The affected tissue contains a mix of Reed-Sternberg cells and various other blood cells.
- Lymphocyte-rich is rare. Affected lymph nodes contain many small lymphocytes but very few Reed-Sternberg cells.
- Lymphocyte-depleted is the rarest subtype, accounting for roughly 1% of all Hodgkin’s lymphoma. The tissue is dense with fibrous material and Reed-Sternberg cells but has relatively few normal immune cells.
Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma
This type accounts for about 5% of cases. Instead of classic Reed-Sternberg cells, it features abnormal cells informally called “popcorn cells” because of their shape. It’s typically slower growing, often found in just one group of lymph nodes (stage 1), and requires different treatment. One thing to be aware of: in some cases, it can transform into a type of non-Hodgkin’s lymphoma after about 10 years.
Who Gets It
Hodgkin’s lymphoma has an unusual age pattern. Unlike most cancers, which become more common as you get older, Hodgkin’s lymphoma peaks twice: first in young adults around age 20 to 30, and again in people over 70. The first peak is dominated by the nodular sclerosis subtype, while the second peak more often involves mixed cellularity.
The Epstein-Barr virus (the virus that causes mono) plays a role in a significant portion of cases. Historically, EBV was detectable in the majority of Hodgkin’s tumors, though that proportion has been declining over recent decades. The connection is strongest in children, older adults, and people in developing countries. Having a sibling with Hodgkin’s lymphoma also increases your risk, suggesting a genetic component, and people with weakened immune systems face higher odds.
Symptoms to Recognize
The most common first sign is a painless, swollen lymph node, usually in the neck, armpit, or groin. Many people notice a lump that doesn’t go away after a few weeks. Some people experience pain in their lymph nodes after drinking alcohol, which is uncommon but fairly specific to Hodgkin’s lymphoma.
Doctors pay close attention to a specific cluster called “B symptoms,” which appear in up to 30% of patients and signal more advanced or aggressive disease:
- Unexplained weight loss of more than 10% of body weight over six months
- Drenching night sweats that soak through clothing or bedsheets
- Fevers above 100.4°F (38°C) that come and go without an obvious infection
B symptoms are more common in stages 3 and 4 and in the mixed cellularity and lymphocyte-depleted subtypes. Other symptoms can include persistent fatigue, itchy skin, and a cough or chest discomfort if lymph nodes in the chest are enlarged.
How It’s Diagnosed and Staged
A definitive diagnosis requires a biopsy, typically of an enlarged lymph node. Pathologists look for Reed-Sternberg cells (or popcorn cells in the lymphocyte-predominant type) and test them for specific surface markers. Imaging scans, usually PET-CT, then map out how far the disease has spread.
Staging follows the Lugano classification system, which has four stages based on how many lymph node regions are involved and whether the cancer has moved beyond the lymphatic system:
- Stage I: A single lymph node region is affected.
- Stage II: Two or more lymph node regions on the same side of the diaphragm (the muscle separating your chest from your abdomen) are involved.
- Stage III: Lymph node regions on both sides of the diaphragm are affected, or the spleen is involved along with nodes above the diaphragm.
- Stage IV: The cancer has spread beyond the lymphatic system into organs like the bone marrow, liver, or lungs.
A tumor is considered “bulky” if it’s larger than 10 centimeters or takes up more than a third of the chest width on imaging. Bulky disease at stage II is treated more like advanced disease. Each stage also gets a letter: “A” means no B symptoms are present, “B” means they are.
Treatment and Cure Rates
Hodgkin’s lymphoma is one of the most treatable cancers. The backbone of treatment is combination chemotherapy, sometimes followed by radiation to specific areas. The specific regimen depends on the stage, the presence of B symptoms, and certain risk factors.
For early-stage disease, treatment typically involves a shorter course of chemotherapy followed by targeted radiation. For advanced disease, more intensive or prolonged chemotherapy is standard. Doctors increasingly use a response-adapted approach: a PET-CT scan is performed early in treatment, and if the cancer is responding well, the remaining treatment may be dialed back to reduce side effects. If it’s not responding, treatment can be escalated.
PET-CT results are scored on a five-point scale called the Deauville scale, where scores of 1 to 3 generally mean no active disease remains, while scores of 4 or 5 suggest residual cancer that may need additional treatment.
The five-year survival rates from SEER data (2016 to 2022) reflect just how treatable this cancer is:
- Stage I: 92.7%
- Stage II: 95.4%
- Stage III: 87.7%
- Stage IV: 82.8%
Stage II actually has a slightly higher survival rate than stage I, likely because early-stage disease detected in younger patients with favorable biology tends to cluster in stage II.
When Standard Treatment Doesn’t Work
For the minority of patients whose cancer returns or doesn’t respond to initial chemotherapy, newer targeted therapies have dramatically improved outcomes. One approach uses an antibody-drug conjugate that zeroes in on a protein (CD30) found on Reed-Sternberg cells, delivering a toxic payload directly to the cancer. Another uses a checkpoint inhibitor, a drug that strips away a cloaking mechanism Reed-Sternberg cells use to hide from the immune system.
When these two therapies are combined as a first rescue treatment, 85% of patients respond, with 67% achieving a complete response. Among those who then proceed to a stem cell transplant, the three-year survival rate is 91%. Side effects are generally manageable. The most common are nausea and infusion-related reactions, mostly mild. About 18% of patients develop immune-related side effects requiring additional treatment.
Long-Term Health After Treatment
Because Hodgkin’s lymphoma often strikes young adults and cure rates are high, long-term survivorship matters enormously. Treatments that save lives in the short term, particularly radiation to the chest, can create health risks that emerge years or even decades later.
Breast cancer is the most significant concern for women treated with chest radiation at a young age. Women who received radiation between ages 10 and 19 have a cumulative breast cancer risk of 15% to 33% by 25 years after treatment. For those treated in their twenties, the risk is 15% to 25%. This is why survivors are typically enrolled in early breast screening programs.
Heart disease is another serious late effect. In one study of long-term survivors, five out of twelve deaths were from cardiac causes. Even among survivors who feel well, imaging often reveals subtle damage: thickened heart valves, mild regurgitation, or changes in how the heart wall moves. Lung problems are also common, with about 24% of women in one follow-up study showing signs of airway obstruction and 10% showing restrictive lung changes.
Secondary cancers beyond breast cancer also occur. In one cohort of 131 long-term survivors, nearly 10% developed a second cancer, including lung cancer, esophageal cancer, and skin cancers in the radiation field. Modern treatment protocols have evolved significantly to reduce these risks, using lower radiation doses, smaller treatment fields, and in many cases eliminating radiation entirely when chemotherapy alone achieves a complete response. But for anyone treated in earlier decades, ongoing monitoring for these late effects is an essential part of life after Hodgkin’s lymphoma.