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, accounting for 60% to 80% 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, and 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 5-year survival. That said, the treatment can be challenging. Support, as well as long-term management, are important.

Doctor examining older man's lymph nodes
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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%) and nodular lymphocyte predominant Hodgkin lymphoma (around 5%).

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 (NSHL), also called nodular sclerosis classic Hodgkin lymphoma (NSCHL)
  • Mixed cellularity
  • Lymphocyte-rich
  • Lymphocyte-depleted

It's important to note that NSHL is different and treated differently than nodular lymphocyte-predominant Hodgkin lymphoma even though the names appear similar.

Characteristics of NSHL

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.


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 mediastinum (chest), neck, and axilla (armpits). Of these sites, over 50% occur in the chest.


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 when they are examined with a microscope.

The name "nodular sclerosing" is derived from the appearance of lymph node tissue, which contains a large amount of scar or fibrous tissue (sclerosis).


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% 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% or more of body weight over a six-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, along with a burning sensation is common in Hodgkin lymphoma and has been coined the "Hodgkin itch." It's most common in the lower legs and may begin even before the diagnosis is made. However, itching is not one of the B symptoms.

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.
  • 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 an 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 the 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.

Rates of NSHL do not appear to be different based on sex or ethnic background.


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

  • Blood tests: Such as a complete blood count (CBC, blood chemistry tests, and erythrocytic sedimentation 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 lymphomas is very important to determine the best treatment options (NSHL is most often diagnosed at stage II).

A positron emission tomography combined with computed tomography (PET/CT) scan 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 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

The size of the mass is also part of the description of the tumor.

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.


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.

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 is the mainstay of treatment for NSHL. With early-stage disease, common regimens include ABVD or dose-escalated BEACOPP (the letters 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 treatment 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.


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.

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 that aren't well enough established to be FDA-approved are sometimes available through clinical trials.

Treatment 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 include hair loss, bone marrow suppression (reduced levels of white blood cells, red blood cells, and platelets), and nausea and vomiting. Fortunately, advances have made these side effects much more tolerable than 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 secondary cancer (cancer due to chemotherapy drugs or radiation), with the most common tumors being breast cancer, lung cancer, and thyroid cancer.

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.


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


NSHL may recur. Roughly half of all recurrences will occur within two years, with 90% of recurrences occurring within five years.


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 magnetic resonance imaging (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.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

By Indranil Mallick, MD
 Indranil Mallick, MD, DNB, is a radiation oncologist with a special interest in lymphoma.