Nodular sclerosis

Nodular sclerosis is a type of Hodgkin lymphoma, a cancer of the lymphatic system. The lymphatic system is part of the immune system that helps your body fight infections. It’s similar to the circulatory system, but instead of carrying blood, it transports lymph, a clear fluid filled with immune system cells called lymphocytes, throughout your body. Lymphoma occurs when those cells develop mutations, or changes, that cause them to divide and grow out of control.

Hodgkin lymphomas include two subtypes: classic Hodgkin lymphomas (cHL) and nodular lymphocyte-predominant Hodgkin lymphomas.

• According to the American Society of Clinical Oncology (ASCO), about 95 percent of people with Hodgkin lymphoma have cHL.
• According to the National Cancer Institute (NCI), 70 percent of all cHL cases are diagnosed as nodular sclerosis, making it the most common of the four cHLs subtypes.

Like most Hodgkin lymphomas, nodular sclerosis usually starts in a type of lymphocyte called a B-cell. B-cells make antibodies, which help the immune system fight off bacteria and viruses.

Nodular sclerosis usually starts in B-cells in lymph nodes located in the neck or in an area of the chest between the lungs. These B-cells change into much larger, cancerous cells called Reed-Sternberg cells. The presence of these cells help doctors make a diagnosis of Hodgkin lymphoma. To distinguish nodular sclerosis from other cHL types, doctors look for the thick bands of tissue that develop and create distinct sections in lymph nodes.

Although it is the most common type of classic Hodgkin lymphoma, nodular sclerosis is a rare cancer. An estimated 8,540 new cases of Hodgkin lymphoma will be diagnosed in 2022, according to the American Cancer Society, and an estimated 5,987 of them will be nodular sclerosis. Nodular sclerosis affects young adults more than other age groups. Most people are diagnosed between the ages of 15 and 34. It’s slightly more common in women than men. Nodular sclerosis tends to be easier to treat and has better survival rates than other types of Hodgkin lymphoma.

Causes and risk factors of nodular sclerosis

Nodular sclerosis (and Hodgkin lymphoma in general) is caused by changes in the DNA of B-cells that turn them into Reed-Sternberg cells. DNA is the genetic material that makes up the genes in every cell in the body. Cancer-causing mutations can be passed down from a parent to a child (inherited) or acquired during one’s lifetime.

Researchers believe Hodgkin lymphoma tends to be caused by acquired mutations rather than inherited mutations, though they aren’t sure exactly what happens to cause these mutations. Exposures to chemicals or toxic substances, or certain lifestyle factors (like smoking, for example), may play a role, or the mutations may happen spontaneously. Still, people with a brother, sister, or parent who has had Hodgkin lymphoma have a slightly increased risk of developing the disease.

Being infected with the Epstein-Barr virus (EBV), best known for causing mononucleosis, is also a risk factor. EBV seems to play a role in the mutations associated with Hodgkin lymphoma, although researchers aren’t sure exactly what role the virus plays. According to ASCO, lymphoma cells contain traces of the virus in about 20 to 25 percent of classic Hodgkin lymphoma cases in the U.S. However, EBV infection is extremely common, and most people infected with EBV don’t develop Hodgkin lymphoma.

Symptoms of nodular sclerosis

Nodular sclerosis doesn’t always cause noticeable symptoms. When they do occur, they may include:

• One or more lumps under the skin: People with nodular sclerosis may have swollen lymph nodes, especially in the section of the chest between the lungs called the mediastinum. Swollen lymph nodes are usually caused by conditions other than Hodgkin lymphoma, such as an infection. However, if the swelling doesn’t go away or gets worse over time, it’s important to tell your doctor.
• Fever without a known cause, drenching night sweats and unintentional weight loss in the past six months: Together, these are known as B symptoms, and they’re experienced by about 40 percent of patients, according to the Leukemia & Lymphoma Society.
• Coughing, difficulty breathing and chest pain: Swollen lymph nodes in the chest may cause these symptoms.
• Itchy skin
• Fatigue
• Poor appetite

Diagnosing nodular sclerosis

Your doctor will start with a physical exam. He or she will look and feel for enlarged lymph nodes and ask about your health history, any symptoms you’re having and any other medical conditions you may have.

If your doctor suspects nodular sclerosis, you may undergo the following tests:

Lymph node biopsy: To diagnose nodular sclerosis, the doctor will remove all or part of a lymph node and send the sample to the lab to be examined for cancer cells. This procedure is called an excisional biopsy if an entire lymph node is removed, or an incisional biopsy if only part of a lymph node is removed. If the lymph node is near the skin’s surface, you may only need local anesthesia to numb the area. Removing lymph nodes that are deeper in the body, such as those in the chest, usually requires general anesthesia so that you’ll be asleep. In the lab, a pathologist, who is an expert in diagnosing diseases, will examine the lymph node sample to check for cancerous cells and determine the exact type of cancer.

Blood tests: Different blood tests, such as a complete blood count (CBC), are used to help diagnose lymphoma. A CBC blood test counts the number of different kinds of blood cells. Lymphoma often changes blood cell counts. Blood samples may also be tested for other substances or diseases. For example, a lactic dehydrogenase (LDH) blood test checks levels of LDH, which tend to be higher when someone has lymphoma. In some cases, doctors may want to test for viruses such as HIV and hepatitis, so they can recommend an appropriate treatment plan.

Bone marrow aspiration and biopsy: A bone marrow biopsy can find out if the cancer has spread to the bone marrow. For this procedure, the doctor will insert a hollow needle into the hip bone to extract a sample of the bone and bone marrow. The sample is then analyzed in a laboratory to look for cancerous cells.

Imaging tests: These tests–such as X-rays, computed tomography (CT) scans and magnetic resonance imaging (MRI)–take detailed pictures of the inside of your body. They may help doctors find swollen lymph nodes that aren’t visible on the surface of the skin, determine if and where the cancer has spread, and to monitor the progress of treatment.

Treatment for nodular sclerosis

Treating nodular sclerosis often involves the expertise of multiple doctors, including:

• A hematologist, who treats diseases of the blood
• A medical oncologist, who uses drugs to treat cancer
• A radiation oncologist, who uses radiation therapy to fight cancer

Treatment may depend on factors such as the cancer’s stage as well as your age and overall health.

People with nodular sclerosis–both children and adults–tend to have positive outcomes, especially when the cancer is found early. People with this type of Hodgkin lymphoma tend to live longer than patients with other types.

The main treatment options for nodular sclerosis include:

Chemotherapy: Chemotherapy drugs are designed to kill cancer cells or stop their growth. The medicine travels through the bloodstream and fights cancer cells throughout the body. These drugs are typically delivered in either pill form or by injection, and they’re taken at specific times over several weeks or months, followed by a rest period to let the body recover. The treatment plan, which specifies the dose, timing and duration of chemotherapy, is called a regimen. Some people get chemotherapy by itself, while others may benefit from chemotherapy in combination with radiation therapy.

Radiation therapy: Some kinds of radiation, such as high-dose X-rays, destroy cancer cells or limit their growth. Patients with nodular sclerosis may undergo external radiation treatments using a machine that directs radiation in the form of high-energy X-rays or tiny particles called electrons to the area of the tumor. Your team will try to use a form of radiation that targets the affected lymph nodes as closely as possible to reduce the harm to nearby healthy cells. Patients with nodular sclerosis may receive radiation therapy after chemotherapy.

Targeted therapy: Targeted therapy uses drugs or specific substances that are designed to seek out or “target” cancer cells, thereby doing less damage to healthy cells than some other treatments. Some nodular sclerosis patients may receive a type of targeted therapy called monoclonal antibodies, which are man-made drugs designed to attack cancer cells and kill them or stop them from growing. In some cases, monoclonal antibodies and chemotherapy drugs are delivered together, so the monoclonal antibodies can transport chemotherapy drugs directly to the cancer cells.

Immunotherapy: This therapy helps treat cancer by boosting or guiding the disease-fighting powers of your immune system. Immunotherapies may be used to treat nodular sclerosis that hasn’t gone away completely or that comes back after treatment.

Stem cell transplant: A stem cell transplant allows patients to receive higher doses of chemotherapy, which is designed to kill cancer cells but also kills healthy blood cells. For a stem cell transplant, doctors will remove a sample of stem cells from your own blood or bone marrow. These stem cells are stored and preserved while you’re treated with intensive chemotherapy. After the chemotherapy regimen has ended, your stem cells are put back in your body where they can grow into healthy blood cells. Stem cell transplants may also use a donor’s stem cells, called an allogeneic transplant. Stem cell transplants come with risks and potential complications, but they may be an option for nodular sclerosis when the initial treatments haven’t worked or the cancer returns.