What are the other Names for this Condition? (Also known as/Synonyms)

• HD (Hodgkin's Disease)
• Hodgkin Disease
• Hodgkin’s Lymphoma

What is Hodgkin Lymphoma? (Definition/Background Information)

• Lymphocytes are a type of white blood cells that are responsible for providing immunity in the human body. B-cells, T-cells, and NK cells are the 3 different types of lymphocytes
• When under certain circumstances, the lymphocytes grow and multiply abnormally, it leads to a condition called as a lymphoma, which is a common type of cancer. There are 2 types of lymphoma:
  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
• Hodgkin Lymphoma develops in the body's immune system, known as the lymphatic system. The function of the immune system is to protect the body from infections (bacterial, viral, or fungal), diseases, as well as from substances deemed foreign and harmful to the body
• Hodgkin’s Lymphomas are broadly categorized into 2 main groups, depending on the types of cells affected and the extent of their malfunction. These include:
  • Classical type of Hodgkin Lymphoma
  • Nodular lymphocyte predominant type of Hodgkin Lymphoma
• Both children and adults may be affected by Hodgkin Lymphoma; the condition is more common in the age group 15-40 years. The risk factors for developing the condition include a family history of the condition and being immune-compromised. Infection with Epstein-Barr virus, which causes mononucleosis, is believed to predispose an individual to Hodgkin Lymphoma as well
• The exact cause of this type of cancer is unknown. In the majority of cases, a mutation in a type of lymphocytes known as B-lymphocytes is reported. This mutation leads to enlargement of such lymphocytes, causing them to block the lymphatic system and the exclusion of healthy cells from the system
• Individuals with Hodgkin Lymphoma may experience non-specific symptoms such as fever, fatigue, swollen lymph nodes that are not painful (but may pain after intake of alcoholic beverages), itching all over the body, and unintended weight loss
• The diagnosis of Hodgkin Lymphoma may be established through a biopsy of the affected lymph node or the tumor. However, other tests and exams (such as blood tests and imaging studies) may be performed to examine the severity and extent of spread of the lymphoma
• The treatment of Hodgkin Lymphoma depends on the type, the stage of the condition, the size of the tumor, and if there are any pre-existing conditions (such as pregnancy). An individual may be recommended chemotherapy, radiation therapy, stem cell transplantation from his/her own body (autologous stem cell transplantation), or other treatment modes, to successfully combat the condition
• Treatments, such as radiation or chemotherapy, for the treatment of this lymphoma type can give rise to potential complications. These could include the formation of other types of cancer (thyroid cancer or leukemia), abnormalities with the thyroid gland function, heart and lung health issues, and infertility
• Currently, Hodgkin Lymphoma is not preventable, because the cause of this cancer type is not known. However, leading a healthy lifestyle with a balanced diet, regular physical activity, and not smoking, are generally considered good preventive methods to decrease the likelihood of contracting any disease, including cancer
• The prognosis of Hodgkin Lymphoma depends on the stage of the cancer when it is diagnosed, the extent of spread, and whether any internal organ is affected. If the cancer is diagnosed in its early stages, the prognosis is reported to be excellent. In many cases, the cancer is also considered curable when diagnosed during the later stages of the disease

The 2 main categories of Hodgkin Lymphomas include:

Classical types of Hodgkin’s Lymphoma: Individuals diagnosed with this type of disease are generally reported to have abnormal cells known as Reed-Sternberg cells in their lymph nodes. The majority of Hodgkin Lymphomas fall in the category of the classical type. This group of cancers is further divided into the following 4 subtypes:

• Nodular-Sclerosis Classical Hodgkin Lymphoma
  • It is the most predominant subtype; 60-80% cases of Hodgkin Lymphoma belong to this type
  • Generally the younger population are affected
  • The lymph nodes in the chest (mediastinum) and neck are most often affected 
• Mixed Cellularity Classical Hodgkin lymphoma
  • Constitutes 15-30% of Hodgkin Lymphoma cases
  • Occurs most often in older adults
  • Reed-Sternberg cells mixed with other cell types are observed in this subtype
• Lymphocyte-Rich Classical Hodgkin Lymphoma
  • About 5% of all cases of Hodgkin Lymphoma belong to this type
  • The lymphocytes appear very small under the microscope, with the presence of very few Reed-Sternberg cells
• Lymphocyte-Depleted Hodgkin Lymphoma
  • It is a rare type of cancer
  • Some cancers might contain fibrous tissue mixed with Reed-Sternberg cells
  • Others might contain many Reed-Sternberg cells, with abundant reticular lymphocytes (a type of lymphocytes)

Nodular Lymphocyte-Predominant type of Hodgkin Lymphoma: Individuals with this type of cancer present with very few Reed-Sternberg cells. There is also the presence of large abnormal cells called “popcorn” cells, owing to their appearance. These types of cancer are observed in about 5% of Hodgkin’s Lymphoma patients; they are generally localized and slow-growing.

General information on the lymphatic system: It is a component of the circulatory system and consists of the following components.

• Lymphocytes: These are the main white blood cells found in the lymph. They protect the body from infections, foreign entities, and tumors
  • Spleen: An organ located adjacent to the stomach that makes lymphocytes
  • Tonsils: Located at the back of the throat; this organ also makes lymphocytes
  • Thymus: An organ located in the chest, where lymphocytes grow and mature
  • Bone marrow: It is the soft center of the large bones that makes red blood cells, white blood cells, and platelets
• Lymph: Colorless liquid that carries lymphocytes through the lymphatic system
• Lymph vessels: A network of thin tubes that collect lymph from different parts of the body and return it to the bloodstream
• Lymph nodes: These structures, located along the lymph vessels in clusters and dispersed throughout the body (neck, underarms, and groin), store the lymphocytes

Additionally, there are lymph tissues, which are also located in the stomach, thyroid gland, brain, and skin.

Who gets Hodgkin Lymphoma? (Age and Sex Distribution)

• Hodgkin Lymphoma is observed in adults, as well as in children. This cancer is more prevalent in young individuals aged 15-40 years (predominantly in the 20s), and those over 55 years of age
• Children and teenagers are reported to account for 10-15% of Hodgkin Lymphoma cases
• Both male and female genders are affected; although, Hodgkin Lymphoma is more commonly observed in males
• The condition is found worldwide and no racial or ethnic predilection is observed in its occurrence

What are the Risk Factors for Hodgkin Lymphoma? (Predisposing Factors)

Studies have reported some risk factors for Hodgkin Lymphoma development and these include:

• A family history of the condition
• Being a male and age in the 20s
• Having been infected with Epstein-Barr virus (EBV, a causative organism for mononucleosis)
• Being immune-compromised due to conditions, such as HIV/AIDS, or other causes
• Obesity

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hodgkin Lymphoma? (Etiology)

The exact cause of Hodgkin Lymphoma is not known. However, the possible causes that are being actively researched upon include:

• Genetic mutation: The majority of these types of cancer ensue as a result of a genetic mutation in the B-lymphocyte.
  • This mutation is reported to facilitate uncontrolled proliferation of B cells, as well as their extended lifespan
  • These properties ensure that the abnormal cells outnumber and outlive normal healthy cells, leading to the cancer
• Epstein-Barr virus infection: Having been infected with EBV might lead to mutation(s) in the B-lymphocytes, causing the abnormal Reed-Sternberg cells to develop

What are the Signs and Symptoms of Hodgkin Lymphoma?

The following signs and symptoms may be reported in individuals with Hodgkin Lymphoma:

• Swollen lymph nodes that occur in the underarm, neck, groin, and other regions of the body; these are often painless
• Pain in the lymph nodes after alcohol ingestion; increased sensitivity to alcoholic drinks
• Fever
• Excessive night-time sweating
• Appetite loss
• Unexplained weight loss
• Fatigue
• Itching of skin

How is Hodgkin Lymphoma Diagnosed?

In order to diagnose Hodgkin’s Lymphoma accurately, a healthcare provider might perform or request many of the following tests and exams:

• A thorough physical examination
• An evaluation of the individual’s personal and family history (of lymphoma)
• An assessment of the signs and symptoms
• Blood tests that may include the following:
  • Complete blood count (CBC) to ascertain hemoglobin, red blood cells, white blood cells, and other components of blood
  • Blood chemistry to check for any abnormality in the amounts of certain chemicals in blood (released by organs and tissues)
  • Estimation of sedimentation rate to check for abnormality, which might denote an inflammation
• Tissue biopsy: Biopsies of the affected region including swollen lymph nodes (partial or whole), bone marrow, or tumors to check for any malignancy through various tests performed by a pathologist. Many different types of biopsies could be performed depending on the type and extent of the cancer
• Imaging studies of the affected region that may include x-rays, computed tomography (CT) scan, positron emission tomography (PET) scan, magnetic resonance imaging (MRI), and whole body bone scan

Note:

• If the affected individual is pregnant, only ultrasound imaging and MRI scan may be employed to assess lymphoma occurrence and/or spread
• Differential diagnoses, to eliminate other tumor types are often considered, before arriving at a definitive diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hodgkin Lymphoma?

The potential complications arising from Hodgkin Lymphoma could include those from the growth and spread of the lymphoma, as well as from the side effects of treatment measures (such as radiation or chemotherapy) employed.

• Complications as a result of the malignancy:
  • Headaches
  • Changes in vision
  • Numbness of face
  • Meningitis
  • Anemia
  • Intestinal blockage
  • Kidney disease
• Complications due to treatment of the cancer:
  • An allergic reaction to therapy
  • Fatigue, dizziness
  • Nausea, vomiting, and diarrhea
  • Heart, lung, and thyroid abnormalities
  • Infertility
  • Leukemia and other bone marrow diseases; development of other types of cancers
  • Vulnerability to infections owing to a weakened immune system
  • Birth defects in children, if the mother was pregnant and was treated with chemotherapy

Apart from the above complications, the condition can recur after being in remission, also known as Recurrent Hodgkin’s Lymphoma.

How is Hodgkin Lymphoma Treated?

Once a definitive diagnosis has been made, staging is used to describe how far the cancer has spread. The staging helps describe:

• The number of lymph nodes affected and their location(s)
• If the condition has spread to the internal organs

The following stages are used for adult Hodgkin Lymphoma:

Stage I: It is subdivided into stage I and stage IE.

• Stage I: The cancer is detected in a component of the lymphatic system, such as in the
  • Lymph node(s) at a particular site
  • Lymphatic tissue known as Waldeyer's tonsillar ring
  • Thymus
  • Spleen
• Stage IE: Cancer is detected in an organ or tissue that is not a component of the lymphatic system

Stage II: It is subdivided into stage II and stage IIE.

• Stage II: The cancer is detected in more than one lymph node groups, which could be located above or below the diaphragm
• Stage IIE: Apart from the cancer being detected in two or more lymph node groups, it has also spread to the organ or tissue adjacent to the lymph nodes

Stage III: It is subdivided into stage III, stage IIIE, stage IIIS, and stage IIIES.

• Stage III: The cancer is detected in lymph node groups, which could be located above or below the diaphragm
• Stage IIIE: Apart from the cancer being detected in two or more lymph node groups, it has also spread to the organ or tissue adjacent to the lymph nodes
• Stage IIIS: The cancer is detected in lymph node groups, as well as in the spleen
• Stage IIIES: The cancer is detected in lymph node groups, organ or tissue adjacent to the lymph nodes, as well as in the spleen

Stage IV: This is considered as an advanced stage of cancer, wherein the lymphoma is detected in several lymph nodes, organs, tissues, and at other locations, near and distant from the affected lymph nodes. The organs that have been found to contain metastasized cancer during this stage are the liver, lungs, bone marrow, and many others.

Grouping for treatment purposes: For the purpose of treatment, adult Hodgkin Lymphoma may be grouped into the following categories.

• Early favorable: Generally, stage I or stage II without certain risk factors that include large-sized tumor, cancer in multiple lymph nodes, cancer that has spread to the organs, and the presence of typical symptoms (fever, weight loss)
• Early unfavorable: They include stage I or stage II cancers with one or more risk factors such as:
  • Multiple lymph nodes with cancer (3 or more)
  • Large-sized tumor in the chest (about or larger than 10cm)
  • Cancer spread to the organs or tissues
  • Blood sedimentation rate being high (blood settles to the bottom of a tube at a faster rate than normal)
  • Fever
  • Weight loss
  • Night sweats
• Advanced favorable: Stage III or stage IV with not more than 3 risk factors such as:
  • Male gender
  • Age over 45 years
  • Low hemoglobin levels (below 10.5)
  • High white blood cell (WBC) number (at or above 15,000)
  • Low lymphocyte count (less than 8% of WBCs)
  • Stage IV Hodgkin’s Lymphoma
  • Low blood albumin (less than 4)
• Advanced unfavorable: Stage III or stage IV with 4 or more risk factors as mentioned under ‘advanced favorable’

Each stage of adult Hodgkin’s Lymphoma could include the following categories: 

• Category A: The patient does not have symptoms such as unintended weight loss, fever, or profuse sweating in the nights
• Category B: The patient has fever, night-sweats, and weight loss symptoms
• Category E: Cancer has spread to an internal organ or tissue, which is not a component of the lymphatic system (may be adjacent to the affected site)
• Category S: Cancer has spread to the spleen

Following a definitive diagnosis of Hodgkin’s Lymphoma, and determination of the extent and spread of the condition, some standard and some newer therapy regimens may be adopted such as:

• Chemotherapy: It is the treatment with drugs to either kill the cancer cells or stop their proliferation. The type of cancer, the size of tumor, and the extent of spread dictates the kind of chemotherapy recommended. Sometimes, a mixture of chemotherapeutic drugs may be necessary
• Radiation therapy: It is the use of high-energy radiation to kill cancer cells or stop the proliferation of malignant cells. This type of treatment is mainly of 2 types:
  • External, or the radiation emitting device is placed outside the body, and
  • Internal, when a radioactive source sealed in a container is placed directly near the cancer, inside the body
• Surgery: This modality may be used for diagnostic as well as for treatment purposes.
  • Laparotomy: An incision is made in the affected area to check for cancer in the internal organs. If a tumor is detected, then the same is removed during the procedure
  • Rarely, when feasible, a surgical excision of the tumor may be performed
• Transplantation of stem cells or bone marrow:
  • Stem cells are undifferentiated cells that are capable of differentiating into many different types of cells. While embryos are rich in these types of cells, adult humans also possess such cells. They have been used in medicine to heal and replenish damaged tissue. In cancer therapy, stem cells are being used for the generation of healthy blood-forming cells. High-dose chemotherapy and high-energy radiation therapy are known to harm the blood forming cells. In order to help patient make healthy blood cells following such therapies, stem cells could be harvested from the patient himself/herself (autologous), or from a close relative such as a sibling (allogeneic).  Stem cells are generally derived from circulating blood, umbilical cord blood, or bone marrow
  • Bone marrows (of large bones) are seats of generation for different types of blood cells. In order for the patient to have healthy circulating blood cells, the marrow could be harvested before therapy and re-injected into the patient. This procedure is known as bone marrow transplantation. It is reported that within a few weeks of transplantation, the healthy bone marrow cells start generating new white blood cells and red blood cells
  • Monoclonal antibody therapy: This is a kind of immune therapy, where cells from the immune system of a single type are propagated in the laboratory and introduced into the patient. The cells recognize the cancer cells by their unique chemical signature. It then attaches to the cancer cells and destroys them. The antibodies can be also be used to deliver drugs or radiation in a targeted manner, to the cancer cells

Pregnancy: If a pregnant woman develops Hodgkin’s Lymphoma, then the treatment options offered may vary from the above-mentioned list. It usually depends upon the site of the cancer, its rate of proliferation (how fast the cancer cells are growing), how advanced the pregnancy is, and, whether the woman wishes to continue with the pregnancy.

Some of the options offered during pregnancy may include:

Watchful waiting: Usually during the first trimester

• Watchful waiting is the term used for monitoring the pregnant patient without any treatment. If there is no change in her health status, the pregnancy may be allowed to advance till 32-36 weeks, when labor may be induced. The treatment could be commenced after delivery
• However, if any of the symptoms change, treatment might be initiated sooner than anticipated

Chemotherapy: Throughout the pregnancy period

• Chemotherapy may be recommended for pregnant women with a single drug or a combination of therapeutic drugs

Radiation therapy: During the first and second half of pregnancy

• If the affected area is above the diaphragm (a thin membrane separating the chest from the abdomen), radiation therapy may be attempted with a lead shield to protect the developing fetus
• This therapy may be recommended in the second half of the pregnancy to aid in breathing, if a large tumor is detected in the chest area

Note: A lead shield may not be able to protect the fetus from radiation and consequent developmental defects.

Steroid therapy during the second half of pregnancy: Since steroids help hasten lung growth and maturity in a developing fetus, steroid therapy may be recommended in a pregnant woman if labor is induced early, so that treatment for cancer can begin.

As elaborated previously, Hodgkin’s Lymphoma is divided into various groups to facilitate making the right treatment choices. The treatment options for the various groups are:

• Early favorable Hodgkin’s Lymphoma:
  • Chemotherapy (with a combination of several drugs, known as combination chemotherapy)
  • Radiation therapy to the affected parts
  • Combination chemotherapy and radiation therapy 
• Early unfavorable Hodgkin’s Lymphoma:
  • Chemotherapy (with a combination of several drugs)
  • Combination of chemotherapy and radiation therapy to affected parts of the body 
• Advanced favorable Hodgkin’s Lymphoma:
  • Combination chemotherapy
  • Combination of chemotherapy and radiation therapy to affected parts of the body 
• Advanced unfavorable Hodgkin’s Lymphoma:
  • Combination chemotherapy
  • Clinical trials for new therapeutic drugs, as well as combination of drugs and stem cells

Treatment options for recurrent Hodgkin’s Lymphoma could include:

• Combination chemotherapy
• Radiation therapy
• Chemotherapy and radiation therapy
• Chemotherapy with stem cell transplant
• Chemotherapy, transplantation, and radiation therapy
• Clinical trial therapies including therapeutic drugs, radiation, stem cell transplantation, and monoclonal antibodies, either singly or in combination of various therapies
• Medical care to alleviate symptoms and offer emotional support; to help improve the quality of life

How can Hodgkin Lymphoma be Prevented?

The exact cause of Hodgkin Lymphoma is unknown, and hence, no guidelines exist for the prevention of this type of cancer. However, by addressing some risk factors that are common to many illnesses as well as to cancer, the condition may be avoided. It includes the following factors:

• Adhering to a healthy diet, including eating fresh vegetables and fruits
• Regular physical activity
• Smoking cessation
• Regular visits to a healthcare professional, especially with advancing age
• If an individual is diagnosed with this lymphoma type, keeping accurate documentation filed, can help start follow-up care without any delay; especially in case of cancer recurrence
• Follow-up visits with a healthcare professional as recommended, for monitoring health after cancer treatment

What is the Prognosis of Hodgkin Lymphoma? (Outcomes/Resolutions)

• The prognosis of Hodgkin Lymphoma is considered to be good, with early diagnosis and prompt treatment. The 5-year survival rates reported for individuals diagnosed with stage I and stage II cancers are 90-95%
• This type of cancer is reported to be one of the most curable types of cancer, since it is also curable when diagnosed during the later stages of lymphoma development
• Several factors may contribute to the final outcome of the condition and these include:
  • Stage of tumor: Early stages with localized cancer are reported to have better outcomes than later stages
  • Age: Younger patients are known to have a better outcomes than older patients
  • Health: Overall good health of an individual portrays a better outcome than poor health
  • Tumor size: Individuals with smaller-sized tumors generally have better outcomes than those with larger tumors
  • Metastasis: If the cancer has spread to other parts of the body, particularly to the vital internal organs, the recovery may be hampered
  • Response: When an individual’s body tolerates harsh cancer therapies and responds favorably to the treatments undertaken, then the outcome is generally improved
  • Removability of tumor: When the tumor can be surgically removed (and completely), it can have an impact on the outcome
  • Recurrence: If the tumor is recurrent, then the outcome may not be favorable

Additional and Relevant Useful Information for Hodgkin Lymphoma:

For more information on clinical trials, please visit the following website: http://www.clinicaltrials.gov.