What is Hodgkin Lymphoma?
Hodgkin lymphoma, originally known as Hodgkin disease, is a comparatively rare type of cancer originating from certain white blood cells, which has a high possibility of being cured. This cancer can be further categorized into two main types: classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Both types have differences in their pathology, which is the study of the disease, and symptoms.
Approximately 95% of all Hodgkin lymphoma cases fall under the classical type, which again can be broken down into four sub-sections: nodular sclerosis, lymphocyte-rich, mixed cellularity, and lymphocyte-depleted. Hodgkin lymphoma has four main characteristics. It usually starts in the lymph nodes in the neck; it has a tendency to affect young adults more frequently; it features large cells known as Hodgkin and Reed-Sternberg cells mixed with a variety of non-cancerous inflammatory cells. Lastly, a type of white blood cells called T lymphocytes, are often seen around the cancer cells.
The good news is Hodgkin lymphoma typically has a very positive outcome, with around 80% of patients achieving a cure.
What Causes Hodgkin Lymphoma?
While we don’t know the exact cause of Hodgkin lymphoma, a type of cancer, there are certain factors that might increase the risk of getting it. These include having certain infections like Epstein-Barr (EBV) and Human immunodeficiency virus (HIV), autoimmune diseases, and a weak immune system. There’s also evidence that if a family member has had Hodgkin lymphoma, you might be more likely to get it too.
EBV is often found in certain types of Hodgkin lymphoma, namely the mixed cellularity and lymphocyte-depleted subtypes. It’s thought that its presence might be linked to a failure in the immune system’s ability to keep diseases in check.
That said, no other viruses have been identified as major contributors to the development of the disease. Those who’ve had a transplant, are taking medications that suppress their immune system, or have HIV are at a higher risk of getting Hodgkin lymphoma. HIV patients typically experience a more severe form of the disease, unusual locations of affected lymph nodes, and have generally worse outlooks.
Research also indicates that if a person with Hodgkin lymphoma has a sibling of the same sex, that sibling is ten times more likely to also develop the disease. This suggests that there might be a mix of genetic and environmental factors that contribute to whether or not someone gets Hodgkin lymphoma.
Risk Factors and Frequency for Hodgkin Lymphoma
Hodgkin lymphoma is a rare type of cancer that affects around 2.6 people out of every 100,000 in the United States. This type of cancer accounts for 11% of all lymphoma cases. Coincidentally, Hodgkin lymphoma is most common in two separate age groups: between 20 to 40 years old and those 55 years old and above. The disease is seen more often in males, particularly in children where 85% of cases are diagnosed in boys.
There are different types of Hodgkin lymphoma present, which appear to be more prevalent in certain demographic groups. For example, the nodular sclerosis type is frequently observed in young adults, while mixed cellularity affects older adults more.
- 70% of Hodgkin lymphoma cases are of nodular sclerosis type.
- Mixed cellularity type accounts for 25% of cases.
- 5% of cases are lymphocyte-rich Hodgkin lymphoma.
- Less than 1% of cases are lymphocyte-depleted Hodgkin lymphoma.
- Nodular lymphocyte-predominant Hodgkin lymphoma makes up approximately 5% of all Hodgkin lymphoma cases.
Signs and Symptoms of Hodgkin Lymphoma
Hodgkin lymphoma is a type of cancer that affects the lymphatic system, which is a part of the body’s immune system. Patients usually notice painless swelling in one or two areas in the upper chest, high fevers, major weight loss, and extreme night sweats. These symptoms, commonly known as B symptoms, are found in about 30% of patients, and are more prevalent during the later stages of the disease. Other symptoms could include itching, chest pain and shortness of breath due to significant enlargement of nodes, and pain in the lymph nodes after drinking alcohol.
Different subtypes of Hodgkin lymphoma show slightly different symptoms. The nodular sclerosis subtype mostly affects young adults and is usually detected in the early stages. Mixed cellularity Hodgkin lymphoma is found in both children and elderly patients and is often discovered at a more advanced stage. Lymphocyte depletion Hodgkin lymphoma mainly affects elderly patients and is often associated with an AIDS infection. The lymphocyte-rich and NLP-HL subtypes generally present as painless swollen lymph nodes in the neck.
Each subtype has unique features and distinct symptom profiles:
- Nodular sclerosis: Affects young adults and usually detected early
- Mixed cellularity: Found in children and elderly patients, commonly at a later stage
- Lymphocyte depletion: Mainly affects elderly, often associated with AIDS
- Lymphocyte-rich and NLP-HL: Mostly observed as painless neck swelling
Testing for Hodgkin Lymphoma
To definitively diagnose Hodgkin lymphoma, a biopsy, or sample, is taken from a lymph node or possibly affected organ. However, it’s important to be aware that common methods like fine-needle or core-needle biopsy often return non-specific results due to the small amount of cancer cells and lack of detailed structural information. So, if the suspicion of Hodgkin lymphoma is high, a more thorough biopsy should be done. Finding an RS or LP cell in the biopsy confirms the diagnosis.
After diagnosis, more tests are needed to figure out how far the disease has spread, which will guide the treatment plan and give an idea of the potential outcome.
These tests can include a complete blood count, a complete metabolic panel, testing for Hepatitis B and C, HIV, and the erythrocyte sedimentation rate. The level of LDH (lactate dehydrogenase) in the blood may provide clues about the extent of the disease. A heightened level of alkaline phosphatase could indicate that the liver or bones are involved. HIV testing is recommended because treating the infection can improve outcomes for individuals who are HIV-positive.
Levels of certain substances called cytokines in the blood, specifically IL 6, IL 10, and soluble CD 25, can be linked with systemic symptoms and reveal information about the prognosis.
Imaging tests like chest x-rays, CT scans of the chest, abdomen, and pelvis, and PET/CT scans can help to assess the stage of the disease. PET-CT scans are commonly used to assess the person’s response to treatment in cases of Hodgkin lymphoma and most other types of lymphoma. In summary, a complete and detailed examination is crucial for both diagnosing and determining the stage of Hodgkin lymphoma.
Treatment Options for Hodgkin Lymphoma
The treatment strategy for Hodgkin lymphoma varies depending on its type, stage, and the presence of certain factors that can affect the prognosis. The aim is to cure the disease while managing short and long-term complications. The Cotswolds modified Ann Arbor classification is commonly used to determine the disease’s stage.
A specific project was established to pinpoint seven factors that affect patients with severe Hodgkin lymphoma. These include: being over 45 years old, having severe disease (stage-IV), being male, having a white blood cell count over 15,000/mL, having a lymphocyte count under 600/mL, having albumin levels under 4.0 g/dL, and having hemoglobin levels under 10.5 g/dL.
Determining a patient’s risk of the disease recurring is done by categorizing them as low or high risk based on these factors. A PET scan helps assess a patient’s response to treatment and plan the best course of action moving forward.
Treatment for Hodgkin lymphoma is split into three categories depending on the disease’s severity and prognosis: early-stage with a positive prognosis, limited-stage with negative prognosis, and advanced-stage.
For patients in the early stages (stage I to IIA) with a favorable prognosis, a short chemotherapy regimen, typically two cycles of ABVD (drugs doxorubicin, bleomycin, vinblastine, and dacarbazine), followed by targeted radiation therapy is administered.
Patients with limited-stage disease but with unfavorable features like a significant chest disease, elevated ESR, and the disease spreading to other parts of the body are often treated with more extended chemotherapy cycles (4 to 6) followed by stronger doses of targeted radiation therapy.
Those with advanced-stage (stage IIB to IV) disease are assessed differently, using the International Prognostic Score (IPS) system. Depending on the IPS, different chemotherapy treatments can be recommended, but typically, ABVD is the standard for most patients. Radiation usually does not benefit these patients.
Even though most patients are cured with initial therapy, about 10% of patients with Hodgkin lymphoma treatment do not respond, and up to 30% will see the disease return even after initially achieving complete remission. For these patients, high-dose chemotherapy, followed by a transplant of their blood-forming stem cells, is the usual care standard. If this treatment path fails, doctors might then look at alternatives like brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplantation, or experimental treatments as options.
Future treatments for Hodgkin lymphoma may involve new frontline therapeutics that have proven effective in difficult-to-treat cases and the introduction of other potential treatments. Stem cell transplantation is often used in patients where the disease has returned or resisted initial treatments.
What else can Hodgkin Lymphoma be?
- Infectious mononucleosis (a type of viral infection)
- Peripheral T cell lymphoma (a type of blood cancer)
- ALK1+ anaplastic large cell lymphoma (a certain type of lymphoma)
- Non-Hodgkin lymphoma (another form of lymphoma or blood cancer)
- Diffuse large B cell lymphoma (one of the most aggressive types of lymphoma)
What to expect with Hodgkin Lymphoma
The outlook of a disease largely depends on several key factors, one of which is the stage of the disease. Currently, doctors use the stage of the disease along with other factors to assess the potential risk before starting treatment. In the case where the disease is caught early at stages 1 or 2a, there’s a roughly 90% chance of surviving for five years or longer. However, if the disease reaches stage 4, the five-year survival rate drops to about 60%.
Possible Complications When Diagnosed with Hodgkin Lymphoma
The heart can be affected by mantle radiotherapy, a treatment often used for certain types of cancer. This can cause conditions like inflammation of the heart lining (pericarditis), heart valve disease, and coronary artery disease. Some drugs, such as anthracyclines, can lead to heart muscle damage (cardiomyopathy).
Similar treatments can also harm the lungs. For instance, the drug bleomycin and radiation therapy can cause lung disease. Another major concern is the possibility of developing other cancers after treatment. For example, the most common cancer seen after treating patients with a type of cancer called Hodgkin lymphoma is lung cancer.
After alkylation therapy, a specific type of cancer treatment, there’s also a considerable worry about the development of a group of cancers that affect the bone marrow (myelodysplastic syndrome) or a type of blood cancer (acute myeloid leukemia).
Furthermore, other cancers that might pop up include breast cancer, soft tissue sarcoma, pancreatic cancer, and thyroid cancer. Infertility is an unfortunate side effect that impacts over 50% of patients undergoing these treatments.
Infections could happen as well, but these can often be handled by using standard antibiotic treatment. Also, last but not least, patients may face various struggles such as depression, peripheral neuropathy (nerve damage usually affecting the hands and feet), problems within the family, and issues with sexual wellbeing.
Common side effects of cancer treatments:
- Pericarditis, valvular heart disease, and coronary artery disease due to mantle radiotherapy
- Heart muscle damage from anthracycline drugs
- Lung disease induced by bleomycin and radiation therapy
- Increased risk of secondary malignancies, including lung cancer
- Myelodysplastic syndrome and acute myeloid leukemia post-alkylation therapy
- Possible development of breast, soft tissue sarcoma, pancreatic, and thyroid cancer
- Over 50% risk of infertility
- Potential infectious complications, manageable with antibiotics
- Depression, peripheral neuropathy, family issues, and disturbed sexual functioning
Recovery from Hodgkin Lymphoma
For those with Hodgkin lymphoma, long-term monitoring and regular check-ups are very important and include:
1. A yearly health check-up
2. Keeping heart health risks under control
3. Getting vaccinated if the spleen has been removed
4. Heart stress test or echocardiogram, which is a type of heart scan
5. Carotid ultrasound, a test for the two main blood vessels in the neck
6. Tests like TSH (for thyroid), a general chemistry panel, and Complete Blood Count (CBC)
7. Checking sugar and fat levels in the blood
8. For women, mammograms (breast x-rays)
9. A low-dose CT scan for the chest area to check for any signs of lung lesions or abnormalities