We often think of cancer as a hard nodule that forms in an organ. For example, lumps in the breast tissue or abnormal growth in the liver. This type of cancer is known as solid cancer, and it is perhaps the most common but not the only type. There’s another type of cancer affecting non-solid tissues such as the blood cells, especially white blood cells.
Leukemia and lymphoma are tumors affecting the bone marrow and the lymphatic system, respectively. They sometimes cause what we traditionally know as a tumor, but other times they behave differently from what we expect.
In this article, we’re covering the topic of lymphoma from a very wide perspective. After reading, you will understand what it is, the types of lymphoma, and what is different about them. You will also learn about its causes, how it is detected, and what to do about it.
Lymphoma cancer overview
Lymphoma is the name given to a heterogeneous group of cancers that develop in the lymphatic and reticuloendothelial systems. The lymphatic system includes the lymph nodes and lymphatic vessels. The reticuloendothelial system includes white blood cells such as macrophages and monocytes, which clear the body from toxins and particles by engulfing and destroying them. The most common lymphoma types are Hodgkin and Non-Hodgkin lymphoma, but there are many others, including more than 30 categories, types, and subtypes.
For many years, doctors believed that lymphomas were different from leukemias because the former develops in the lymphatic system, and the latter is caused by alterations in the bone marrow. That is what traditionally happens and one of the distinctions between lymphoma and leukemia. However, it is not always true, and lymphoma can sometimes have characteristics usually attributed to leukemia. Thus, in some patients, the distinction between lymphoma and leukemia can be vague.
You can find lymphoma by other names, especially lymphocytic cancer or lymphatic cancer. This is the name because lymphoma involves lymphocytes, a type of white blood cell. These cells usually work to protect the body against infection, and we have two types of lymphocytes for that: B lymphocytes, which produce antibodies that detect and destroy pathogens, and T lymphocytes, which kill bacteria directly and without intermediates. B or T cells can be transformed into lymphoma, and they usually grow and collect in lymph nodes throughout the body or in the spleen. Thus, we can see tissue growths, traditionally associated with the lymphatic tissue, until cancer spreads to other parts of the body.
Types of lymphoma
There are two categories of lymphoma: Hodgkin lymphoma and Non-Hodgkin lymphoma. Both types of lymphoma have the same symptoms and a very similar appearance. They grow in the lymph nodes and cause similar symptoms. The main distinction between Hodgkin and non-Hodgkin lymphoma is only seen under the microscope when a biopsy sample is taken.
The differences are as follows:
- Hodgkin Lymphoma: This type of lymphoma usually develops in the third or fourth decade of life and affects only B lymphocytes. The primary physical manifestation is swollen lymph nodes, and they start in the neck, armpits, chest, and other areas of the upper body. The distribution of lymph nodes taken by the disease is usually contiguous or found in clusters. It is highly treatable because most cases are diagnosed at an early stage, and 70-80% of patients are cured. This type of lymphoma has distinct features, usually causing a mediastinal mass and symptoms such as itching and pain induced by alcohol consumption.
- Non-Hodgkin Lymphoma: This type of lymphoma encloses everything that is not Hodgkin lymphoma, and it is typically diagnosed in patients over 50 years with an increasing incidence as we grow older. There are over 30 subtypes, and they can develop from B cells or T cells. In most cases, the lymph nodes taken by the disease are not contiguous. Thus, the disease spreads to different areas and different lymph nodes. It is not as specific as Hodgkin lymphoma, and the presentation in patients is often vague. Thus, it is not as easy to diagnose, and patients usually reach an advanced stage before detecting and treating the disease. There are more complications in Non-Hodgkin lymphoma, including uric acid and phosphate elevation, electrolytic disturbances, and tumor lysis syndrome when the intracellular contents are released from rapid cell death.
What causes lymphoma cancer?
The cause of lymphoma depends on the type. As you will see, they have a few causes in common but differ in other elements.
Hodgkin lymphoma is a transformation of B-cells into a type of cell called Reed-Sternberg cell. These cells have two nuclei instead of one and have other characteristics on their own. The exact reason why B cells transform into Reed-Sternberg cells is not entirely understood. Similarly, Non-Hodgkin lymphoma usually develops in B cells, but around 15% of cases arise from T cells. Instead of an exact cause, many risk factors contribute to the development of both Hodgkin and non-Hodgkin lymphoma:
- Genetic susceptibility: Patients with Hodgkin lymphoma are likely to have a family history of the disease. There’s a genetic predisposition, and specific genes are involved, according to studies.
- Occupational risk factors: Certain occupations increase the risk of Hodgkin lymphoma, especially woodworking. Exposure to substances plays a significant role in these cases, probably contributing to the causes. Insecticides, herbicides, and other chemicals also lead to a higher risk of Non-Hodgkin lymphoma.
- Certain drugs and therapies: Patients under chemotherapy or radiation therapy can develop Hodgkin lymphoma after curing of their primary cancer. Phenytoin treatment can also lead to the development of this B-cell transformation
- Viral infections: Certain viruses apparently trigger susceptible cells to transform into Reed-Sternberg cells. That is especially the case of the Epstein-Barr virus or the infection with herpesvirus type 6 and Mycobacterium tuberculosis. Viral infections trigger both Hodgkin and non-Hodgkin lymphoma.
- Immunosuppression: Patients with a dysfunction of the immune system are more likely to trigger Hodgkin and Non-Hodgkin lymphoma. For example, patients with infection with HIV and those taking immunosuppressants after an organ transplant. It is also common in patients with congenital problems that lead to immunosuppression, such as Chédiak-Higashi syndrome or Klinefelter syndrome.
- Autoimmune problems: Certain autoimmune condition also leads to the development of Hodgkin lymphoma. This is particularly the case in celiac disease, systemic lupus erythematosus, and rheumatoid arthritis.
- Infection with Helicobacter pylori: This infection causes severe gastrointestinal problems and may lead to gastric cancer. It also increases the risk of Non-Hodgkin lymphoma.
- Chronic inflammation: Enduring chronic inflammation in organs or body tissues can lead to hyperplasia of reactive lymph nodes and Non-Hodgkin lymphoma.
Signs and symptoms
The signs and symptoms of lymphoma are almost the same in both types, with minor variants. Here’s a list of the clinical manifestations of both Hodgkin and non-Hodgkin lymphoma:
- Swollen lymph nodes: This is often the initial manifestation of the disease in both categories. In Hodgkin lymphoma, swollen lymph nodes are found in the upper body, including the thoracic area, the upper limbs, the armpits, and the neck. In this type, swollen lymph nodes can be adjacent or nearby. In contrast, non-Hodgkin lymphoma can be found in any part of the body, including the upper or lower body. The distribution of swollen lymph nodes does not follow a pattern.
- Hepatosplenomegaly: This is the clinical name of an increase in the liver’s size and the spleen. It is a significant finding in both Hodgkin and non-Hodgkin lymphoma but more relevant in the physical exam of the latter. The spleen is a part of the lymphatic system and often grows very large.
- Compression or obstruction symptoms: Swollen lymph nodes are often close to blood vessels, nerves, and other structures inside of the body. As they keep growing, they will potentially cause compression or obstruction symptoms. For example, when causing compression in the superior vena cava, the blood return to the heart is compromised, and the patient can develop facial edema and shortness of breath. If the biliary tree is compromised, the patient will have jaundice. In case of bowel obstruction, symptoms will be constipation and vomiting. When the lymph drainage is compromised, the patient will develop fluid retention in the lower extremities. Nerve compression is also possible, causing sensory or motor disturbances such as tingling or muscle weakness.
- Abdominal pain: This symptom is often reported when the liver and the spleen are very large. They activate nearby nerve terminals and cause diffuse abdominal pain. It can also be a part of the compression symptoms listed above.
- Fever and chills: Lymphocytes taken by the disease are a part of the immune system, and fever is an immune system function. As a part of the illness, aberrant B and T cells can release substances into the blood, similar to what happens during an infection. This triggers fever as a defense mechanism, and chills are reported when we reach the peak of high temperature.
- Weight loss: This symptom is the same as many other types of cancer. These cells have an accelerated metabolism and consume our resources and calories very fast. Even patients with adequate nutrition can potentially experience weight loss.
- Fatigue: The extra consumption of energy and nutrients by cancer also leads to the sensation of tiredness or fatigue in these patients. This symptom is more prevalent in patients with anemia, which is also possible in Hodgkin and non-Hodgkin lymphoma.
- Itching: This symptom is significant to differentiate the main categories of lymphoma. Only Hodgkin’s lymphoma causes itching, known by doctors as pruritus.
- Skin manifestations: They are particularly common in non-Hodgkin lymphoma and affect the legs or the scalp. The skin lesions look like reddened and raised nodules, plaques, or papules. The location can also be diffuse depending on the subtype of lymphoma.
- Shortness of breath: This is a very important sign, usually associated with compression by swollen lymph nodes. They could either compress the superior vena cava or the airways. When they compress the superior vena cava, the blood flow does not return to the heart, and there is congestion of blood to the airways and other parts of the upper body. When there is compression of the airways, it is usually a mediastinal mass pushing the airways apart and causing breathing problems.
Diagnosis
In most cases, the diagnosis is made by evaluating the patient’s signs and symptoms and the pattern of swollen lymph nodes. Several studies are made to obtain an accurate diagnosis:
- Blood tests: They are essential to diagnose alterations in white blood cell count, anemia, and other blood problems. Blood chemicals such as lactate dehydrogenase can be helpful to evaluate the type and aggressiveness of lymphoma.
- Biopsy: When malignancy is suspected, doctors can take a sample of a swollen lymph node to examine the tissue under a microscope. A biopsy is easier if the mass is felt under the skin. If the mass is found deep inside body tissues, a good quality sample often requires a surgical biopsy or laparoscopy with a more complex procedure. Reed-Sternberg cells should be found to diagnose Hodgkin lymphoma, while non-Hodgkin lymphoma has a very heterogeneous appearance under the microscope.
- Imaging studies: They can be very helpful to detect the spread of the disease and provide a follow-up throughout the treatment process to see how the disease is responding. X-rays are more useful in the chest to detect mediastinal masses. Other studies include a CT scan or MRI scan if we want more accurate images.
- Bone marrow biopsy: In many cases, it is essential to evaluate what is happening in the bone marrow and if the alteration comes from there. The procedure is uncomfortable but necessary sometimes to distinguish between leukemia and lymphoma.
Treatment options
Treatment of Hodgkin and non-Hodgkin lymphoma depends on the stage and subtype of lymphoma. It also depends on you because your doctor will recommend treatment, and you’re free to accept the treatment regime or not.
Medical treatment starts with induction therapy, which is more aggressive and has side effects that you need to discuss with your doctor. The goal of induction therapy is to obtain a remission of the disease (stop growing and return affected tissues to normal). When you reach the remission stage, mild treatment is established for maintenance to prevent a recurrence of the disease.
This treatment involves radiation therapy and chemotherapy:
- Radiation therapy: It is beneficial in patients with early-stage disease. It is targeted to a particular area or organ affected by the disease.
- Chemotherapy: It is imperative in more advanced cases and used in combination with radiation therapy. This systemic therapy enters the bloodstream and attacks cancer cells regardless of the location.
- Other therapies: There is biological therapy against lymphoma that includes monoclonal antibodies, vaccines, and other means to stimulate the immune system and make your own bodywork against cancer.