An Overview of Nodular Sclerosing Hodgkin Lymphoma

Nodular sclerosing Hodgkin lymphoma (NSHL) is the most common type (and most curable type) of Hodgkin lymphoma in developed countries and accounts for 60 to 80 percent of these cancers. The first symptom is usually enlarged lymph nodes, and the diagnosis is made by a lymph node biopsy. NSHL occurs most commonly between the ages of 15 and 35 and affects equal numbers of males and females. Treatment most often includes chemotherapy with or without radiation, but monoclonal antibody therapy or a stem cell transplant may be needed in the advanced stages or with a recurrence. The prognosis is very good, in general, with roughly 90 percent of people being alive after 5 years and likely cured. That said, the treatment can be challenging and support, as well as long term management, are important.

Types of Lymphomas

There are two main categories of lymphoma, including Hodgkin and Non-Hodgkin lymphoma. Hodgkin lymphoma (also referred to as Hodgkin disease) is in turn broken down into two groups; classic Hodgkin lymphoma (roughly 95 percent) and nodular lymphocyte predominant Hodgkin lymphoma (around 5 percent).

Classic Hodgkin lymphoma is broken down into four subtypes based on pathology (how the tumor looks under the microscope) and includes:

  • Nodular sclerosing Hodgkin lymphoma
  • Mixed cellularity
  • Lymphocyte-rich
  • Lymphocyte-depleted

It's important to note that nodular sclerosing Hodgkin lymphoma (also called nodular sclerosis classic Hodgkin lymphoma or NSCHL) is different and treated differently than nodular lymphocyte-predominant Hodgkin lymphoma even though the names appear similar.

Characteristics of Nodular Sclerosing Hodgkin Lymphoma

Nodular sclerosing Hodgkin lymphoma differs from other subtypes of classic Hodgkin lymphoma based on the appearance of the cells, and the most likely areas of the body where they occur.

Origin

Hodgkin lymphomas arise in a type of lymphocytes called B lymphocytes or B cells and begin in lymph nodes. Lymph nodes are like outposts that occur at various points along the lymphatic channels that run throughout the body.

While Hodgkin lymphomas may arise in any lymph nodes, NSHL is found most often in lymph nodes in the chest (mediastinum), neck, and armpits (axilla). Of these sites, over 50 percent occur in the chest.

Pathology

Under the microscope, the abnormal B lymphocytes found in NSHL are referred to as Reed Sternberg cells. These cells are larger than normal B cells and have two nuclei; giving the cell the appearance of an owl's face. The name "nodular sclerosing" is derived from the appearance of lymph node tissue, which contains a large amount of scar or fibrous tissue (sclerosis).

Symptoms

Concerns over "swollen glands" are what usually alert a person with NSHL to see a doctor, but many people have nonspecific symptoms such as fatigue and loss of appetite as well.

Enlarged Lymph Nodes

The most common symptom with NSHL is painless, enlarged lymph nodes. When these occur in the neck or armpits, they are often detected by feeling the nodes. In the chest, enlarged lymph nodes may cause obstruction of the airways, leading to a cough, chest pain, shortness of breath, or recurrent respiratory tract infections. With NSHL, it's thought that the swelling in lymph nodes occurs due to activation of other immune cells in the nodes rather than from a large number of cancerous B cells.

While lymph nodes affected by NSHL are usually painless, an odd symptom of pain in lymph nodes after drinking alcohol may occur. It's not known exactly why this occurs, but may be related to the expansion of blood vessels in the nodes.

B Symptoms

Roughly 40 percent of people with NSHL will also have what has been coined the B symptoms.of lymphoma. These include:

  • Fever: A persistent or intermittent fever may occur without any obvious infection or cause.
  • Unintentional weight loss: Unexpected weight loss is defined as the loss of 10 percent or more of body weight over a 6 month period.
  • Drenching night sweats: The night sweats associated with Hodgkin lymphoma are often different than "normal" hot flashes, and people may awaken and need to change their sleepwear several times during the night.
  • Itching: Itching, along with a burning sensation is significant enough that it has been coined the "Hodgkin itch," Itching (pruritis) is most common in the lower legs, and may begin even before the diagnosis is made.

Causes and Risk Factors

The exact causes of NSHL are unknown, but several risk factors have been identified. These include:

  • Age: NSHL is most common in adolescents and young adults.
  • Sex: NSHL has an equal incidence in males and females.
  • Ethnic background: There does not seem to be a racial or ethnic predilection to the disease.
  • Epstein-Barr virus infection: Infection with the virus that causes mononucleosis is common.
  • Family history: NSHL is more common in those who have a family history of the disease, but it's not certain if this is due to heredity or instead common infection with the Epstein-Barr virus.
  • Higher socioeconomic background: NSHL is more common in developed countries.
  • Immunosuppression: People infected with HIV are more likely to develop NSHL, and the disease is more common in those who have had a previous stem cell transplant.
  • Obesity
  • Smoking: Smoking is a risk factor for Hodgkin lymphoma, and it's thought that the toxins in tobacco may work along with Epstein-Barr virus to induce the mutations that lead to NSHL.
  • Low ultraviolet radiation exposure: Unlike other subtypes of Hodgkin lymphoma, the incidence of NSHL does not appear to be lower in regions where ultraviolet sun exposure is higher.

    Diagnosis

    The diagnosis of lymphoma is made with a lymph node biopsy. Other tests that may be done include:

    • Blood tests such as a CBC, blood chemistry tests, and sed rate (ESR)
    • Immunohistochemistry (looking for CD15 and CD30, proteins found on the surface of Hodgkin lymphoma cells)
    • Bone marrow biopsy: People with early-stage NSHL may not need this test done

    Staging

    Staging lymphomas is very important to determine the best treatment options (NSHL is most often diagnosed at stage II).

    A PET scan (PET/CT) is most sensitive in determining the extent of these cancers, as cancer may be found even in normal-sized lymph nodes.

    NSHL is assigned a stage and category based on symptoms, findings on physical exam, results of the lymph node biopsy, results of imaging tests such as PET/CT, and bone marrow test results (when needed).

    Stages include:

    • Stage I: Lymphomas that involve only one lymph node or a group of adjacent nodes
    • Stage II: Lymphomas that involve two or more lymph node regions on the same side of the diaphragm
    • Stage III: Lymphomas that involve lymph nodes on both sides of the diaphragm
    • Stage IV: Lymphomas that involve lymph nodes on both sides of the diaphragm and/or involve organs including the spleen, lungs, liver, bones, or bone marrow

    Categories include:

    • Category A: No symptoms are present
    • Category B: B symptoms are present (unexplained fevers, night sweats, weight loss)
    • Category E: Involvement of tissues beyond the lymphatic system
    • Category S: Involvement of the spleen

    Bulky vs. Non-bulky: Tumors are also assigned either an A or B based on whether they are bulky or not (bulky tumors are those that are 10 cm in diameter or involve a third or more of the diameter of the chest.

    Differential Diagnosis

    One type of non-Hodgkin's lymphoma, primary mediastinal large B-cell lymphoma (PMBL), may also be found in the chest and can look similar under the microscope. Immunohistochemistry tests may be done to tell the difference as the two diseases are treated in different ways.

    Treatments

    The treatment of NSHL is based more on the stage of the disease than the type of Hodgkin lymphoma. Options will depend on the number of lymph nodes affected and their locations, as well as the presence of lymphoma in other tissues.

    With early-stage lymphomas (stage I or stage II) chemotherapy with or without radiation is often curative, yet (unlike many solid tumors), a cure may be possible even with advanced lymphomas.

    Before Starting Treatment: Fertility Preservation and Pregnancy

    For those who would like to have children after treatment, it's important to be aware of the effects of Hodgkin lymphoma on fertility. There are different options for preserving fertility for those who are interested.

    For those who are pregnant when diagnosed, the management of Hodgkins during pregnancy also requires special consideration.

    Chemotherapy

    Chemotherapy is the mainstay of treatment for NSHL. With early-stage disease, common regimens include ABVD or dose escalated BEACOPP (the letter represent the different chemotherapy drugs) with or without radiation.

    Radiation Therapy

    Radiation may be given to areas of lymph node involvement after chemotherapy.

    Monoclonal Antibodies

    Monoclonal antibody with the drug Adcentris (brentuximab) is now available for those who have resistant or recurrent tumors. Adcentris may also be used along with chemotherapy (ABVD) with advanced stage lymphomas.

    Stem Cell Transplants

    For people who have lymphomas that relapse, high dose chemotherapy followed by stem cell transplant may be used. Stem cell transplants, in this case, are most often autologous (using a person's own stem cells).

    Nonmyeloablative stem cell transplants are another option for some people who might not tolerate the high dose chemotherapy used with a conventional stem cell transplant.

    Clinical Trials

    For people who relapse or have lymphomas that aren't responding to the above treatments (refractory tumors), other options are available. A type of immunotherapy referred to as immune checkpoint inhibitors may be used. Drugs in this category include Opdivo (nivolumab) and Keytruda (pembrolizumab) and are expected to improve survival for those with difficult-to-treat lymphomas.

    Side effects

    Fortunately, people with Hodgkin lymphomas often receive less toxic chemotherapy and have radiation delivered to smaller fields than in the past.

    Short Term Side Effects: The immediate side effects of chemotherapy are fairly well known, with hair loss, bone marrow suppression (reduced levels of white blood cells, red blood cells, and platelets), and nausea and vomiting most common. Fortunately, advances have made these side effects much more tolerable in the past. Side effects of radiation therapy include skin redness and fatigue. When radiation is delivered to the chest, inflammation of the lungs and esophagus may occur.

    Long Term Side Effects: Since many people with nodular sclerosing Hodgkin lymphoma are young, and the survival rate is high, the long-term effects of cancer treatment become very important.

    One of the greatest concerns is the risk of secondary cancers in Hodgkin lymphoma survivors. People who have been treated for Hodgkin lymphoma are roughly 4.6 times more likely to develop a secondary cancer (cancer due to chemotherapy drugs or radiation), with the most common tumors being breast cancer, lung cancer, and thyroid cancer.

    It was thought that with less toxic chemotherapy and more precise radiation fields this risk would decrease, but it appears that secondary cancers are actually increasing.

    Coping and Support

    Even though NSHL has a good survival rate, the treatment to get to that point can be challenging and sometimes grueling. Support is critical, and in addition to reaching out to friends and family, many people find it helpful to become involved in a support group. The internet provides an opportunity for people to connect with others with their subtype of Hodgkin lymphoma.

    Prognosis

    Nodular sclerosing Hodgkin lymphoma has a higher survival rate than other types of classic Hodgkin lymphoma, with the 5-year survival rate being greater than 90 percent.

    Recurrence

    Like solid tumors, NSHL may recur, but unlike tumors such as breast cancer, most recurrences occur early on. Roughly half of all recurrences will occur within two years, with 90 percent of recurrences occurring within 5 years.

    Survivorship

    The concept of survivorship and survivorship care is relatively new but critical with cancers such as NSHL that often occur in young people and have high survival rates.

    For those who are diagnosed as children, issues such as fatigue, growth delays, thyroid problems, and hearing loss may arise.

    For everyone who has been treated for NSHL, the risk of secondary cancers is present.

    It's important to be aware of survival guidelines for Hodgkin lymphoma and what this might mean for you, as well as to stay abreast of these as more is learned.

    For example, at the current time, it's recommended that women who have received radiation therapy to the chest for Hodgkin lymphoma between the ages of 10 and 30 have breast MRI screening in addition to mammograms.

    When you have completed treatment, your oncologist should fill out a survivorship care plan for you outlining some of these recommendations.

    A Word From Verywell

    Nodular sclerosing Hodgkin lymphoma is often curable, but the treatment is challenging. In addition, late side effects may occur and lifelong monitoring is needed. What this means is that support is crucial throughout the journey. Learning to ask for and accept help, and connecting with the Hodgkin community to find your "tribe" are invaluable as you face this disease.

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