What is Hodgkin's Disease

2.0  Overview

The purpose of this section is to provide an introduction to Hodgkin's disease. It describes how Hodgkin's Disease is recognized, the systems that are used to determine the type and extent of disease, and some of the history surrounding this disease. It also includes some information about the lymphatic system.

Without treatment, Hodgkin's is a fatal disease. Luckily, Hodgkin's generally responds well to modern chemotherapy and/or radiation treatments.

2.1  Hodgkin's Disease

Hodgkin's disease is a type of lymphoma. In other words, it is a cancer of the lymphatic system. Like all cancers, Hodgkin's disease affects the body's cells. Cells in the lymphatic system grow abnormally, reproduce, and can spread to other organs. As the disease progresses, the body's ability to fight infection decreases. Hodgkin's differs from non-Hodgkin's Lymphoma by the presence of an unusual cell called the Reed Sternberg cell in the affected tissue.

Hodgkin's usually starts in a lymph node. Left untreated, the lymph circulating through the lymphatic system spreads Hodgkin's to adjacent lymph nodes as well as other parts of the lymphatic system such as the spleen, liver, and bone marrow. Hodgkin's can also invade tissues outside of the lymphatic system such as the lungs. Since lymph tissue is widespread in the body, Hodgkin's disease can start almost anywhere.

Hodgkin's disease is rare. The incidence is about 3 cases per 100,000 people per year, and it accounts for less than 1 percent of all cases of cancer in the United States. It is most often seen in people aged 15 to 34 or over the age of 60. It afflicts a slightly higher percentage of men and whites than women and blacks. Hodgkin's is one of the most treatable cancers and with treatment it has a high survival rate.

2.2  The lymphatic system

The lymphatic system is a set of interconnected organs and tissues that helps the body fight diseases and infections. It consists of a network of thin tubes that branch, like blood vessels, into the tissues throughout the body. Lymphatic vessels carry lymph, a colorless, watery fluid that contains infection-fighting cells called lymphocytes (white blood cells).

Connected along this network of vessels are groups of small, bean shaped and sized organs called lymph nodes. The lymph nodes filter the lymph as it passes through the nodes. Lymph nodes are found in the neck, armpits, abdomen, and groin. The lymphatic system also includes the tonsils, thymus (important to the development of T-cells, a type of white cells), spleen (which is a gland that filters bacteria and old red blood cells from the body), and bone marrow (spongy tissue inside the bones).

2.3  Reed Sternberg cell

Hodgkin's disease is differentiated from non-Hodgkin's Lymphoma (NHL) by the presence of Reed Sternberg (R-S) cells. This is determined by a microscopic inspection of tissue that has been removed from the tumor(s).

The R-S cell is a very unusual and very large cell with more than one large nuclei. Each nucleus encloses a large nucleolus with an unusual clear space around it.

Click here to view a R-S cell from my pathology.

2.4  History of Hodgkin's Disease

On January 10th, 1832, a paper named "Some Morbid Appearances of the Absorbent Glands and Spleen" was presented to the Medical and Surgical Society in London. At the time, it wasn't considered a very important paper and only eight members were present to hear it.

This was a very important event for us though. This was the first time that lymphoma was clinically identified as separate from other diseases. This paper, written by a 34 year old Thomas Hodgkin described what was finally named Hodgkin's disease years after his 1866 death.

Hodgkin's disease has been called the "great white whale of hematopathology." For over a hundred years the mysteries of this illness proved illusive. Initially, it wasn't even known if Hodgkin's was cancer, an infection, or an inflammation. If fact, it's only in the last few years that modern molecular techniques have identified that the Reed Sterberg cell is probably an abnormal B lymphocyte.

So who was this man who was the first to get his hook into the whale? Hodgkin began his life as an English Quaker in 1798. He earned his medical degree in 1823 and spent his life pursuing both medical and social causes.

On the medical front he helped introduce the stethoscope to English medicine, helped produce the first accurate description of red bloods cells, did diabetes research, and spoke out about the medical ramifications of smoking.

Hodgkin was deeply religous and fervently worked on causes such as the better treatment of Canadian Indians and the abolishment of slavery.

Although Hodgkin's was the first to begin to understand Hodgkin's disease, he was not the only one to make important contributions to the understanding of this disease. Two other people who will forever have their names associated with Hodgkin's Disease are Reed and Sternberg. In 1898, Sternberg described 15 similar cases, which he thought were a kind of tuberculosis of the lymphatic system. However, he identified microscopically the cells that differentiate Hodgkin's from other lymphomas. Four years later, Reed described theses cells in detail. They are now called Reed-Sternberg (R-S) cells.

2.5  Symptoms and warning signs

The most common Hodgkin's symptom is a painless , non-tender swelling of the lymph nodes in the neck (cervical nodes), underarm (axillary nodes), or groin (inguinal nodes). In addition, common symptoms include intermittent or cyclic fevers, chills, sweats (especially at night), lack of appetite, weight loss, itching, tiredness, jaundice, or anemia. Unfortunately, most of these symptoms may also be caused by common illnesses such as flu. Alcohol induced pain in the diseased area is a classic, but somewhat rare Hodgkin's symptom. Depending on the location of the disease, other possible symptoms include cough, chest pain, shortness of breath, difficulty in swallowing, and rarely the coughing up of blood or bone or back pain.

The erythrocyte sedimentation (SED) rate is commonly high in Hodgkin's patients, and may be the only indication that active disease is present. Many Hodgkin's patients have normal SED rated though.

Also, since Hodgkin's disease reduces the body's ability to fight disease, patients have a tendency to develop various kinds of infections.

Lymphomatoid papulosis

Lymphoma Papulosis consists of small lesions or bumps that pop up on the skin. They come up one at a time and gradually fade. As one goes away, two pop up to take its place. They are usually on the legs, arms, and later go to the torso. Different studies give the patients between 10 and 30 % chance of developing lymphoma. The longer the condition lasts, the greater the chance of eventually developing lymphoma. The papulosis rarely goes away on its own.

It may last a lifetime, but usually goes on for about 10 years before becoming lymphoma. The strangely good news, is that if it turns to lymphoma, it is treatable. -- Paul McMullen <mcmul002@mailhost1.csusm.edu>

2.6  Staging

The purpose of staging is performed to determine the extent of the disease.
• Clinical staging is determined through the patient's

  • history
  • physical examination
  • laboratory work
  • chest and possibly other x-rays
  • chest, abdominal, and pelvic computerized tomography (CT) scans
  • gallium scans (not universally performed)
  • bipedal lymphangiogram (occasional)

• Pathologic staging includes
  • biopsy of at least one tumor site
  • bone marrow biopsy (BMB)
  • Staging laparotomy (sometimes performed when the results will allow a significant reduction in treatment)

A system called the Ann Arbor Staging Classification is used to give a rough idea of the extent of the disease. The four stages are as follows:

Stage I	I - Involvement of a single lymph node region -or- IE - Involvement of a single extra-lymphatic site
Stage II	II - Involvement of two or more lymph node regions on the same side of the diaphragm -or- IIE - Involvement of two or more sites on the same side of the diaphragm including localized involvement of an extra-lymphatic site
Stage III	III - Involvement of lymph node regions on both sides of the diaphragm -or- IIIE - also be accompanied by involvement of an extra-lymphatic site -or- IIIS - also accompanied by involvement of the spleen -or- IIISE - also accompanied by involvement of an extra-lymphatic site and spleen
Stage IV	Diffuse or disseminated involvement of one or more extra-lymphatic organs with or without associated lymph node involvement

Note, the E suffix is used when Hodgkin's extends to tissues beyond, but near, the major lymphatic sites. Stage IV refers to disease that is diffusely spread throughout a site outside the lymphatic system, such as the liver.

The stage is also given an A or B suffix. An A suffix is used unless one of the following specific "B" symptoms is present:

• Fever in excess of 38°C
• Weight loss exceeding 10% of body weight during the preceding 6 months
• Drenching night sweats

Note that the most significant "B" symptoms are fevers and weight loss. Night sweats alone do not imply an adverse prognosis.

Itching as a Hodgkin's symptom remains controversial and it is not considered a B symptom. However, when the itching is recurrent, generalized, and it comes and goes along with disease activity, it may be the equivalent of a B symptom.

If pathology proves involvement of one or more sites outside the lymphatic system, the symbol for the site of involvement, followed by a plus sign (+), is listed. Sites are identified by the following notations: N=nodes, H=liver, L=lung, M=bone marrow, S=spleen, P=pleura, O=bone, and D=skin.

2.7  Subtypes

While Hodgkin's disease is characterized by the presence of cancerous Reed Sternberg cells, these cells typically make up less than 1% of the tumor mass. Most of the mass consists of benign inflammatory cells including small T lymphocytes, histiocytes, plasma cells, eosinophils, and neutrophils. This inflammation is caused by cytokines produced by the tumor cells.

Subtypes are determined by the variants of the Reed Sternberg cells present as well as the structure of the inflammatory background.

There are four different subtypes of Hodgkin's Disease. A system called the Rye modification of the Lukes and Butler classification is used to delineate the four subtypes:

• lymphocyte predominance (approximately 5% of cases)
• nodular sclerosis (approximately 70%)
• mixed cellularity (approximately 20%)
• lymphocyte depletion (5%)

2.8  What causes Hodgkin's Disease?

The short answer is that the cause of Hodgkin's is not known. Immunodeficiency does increase the risk of getting Hodgkin's. However, other than being in one of the higher incidence age groups, there are no other significant and proven risk factors for the disease. Therefore, there are no known ways to prevent it.

However, research continues and there are some clues which may eventually help understand the causes of Hodgkin's Disease:

• The age distribution in other developed countries is similar to the United States distribution with a higher incidence in young adults (15-34 years) and older adults (50+ years). In developing countries, the young adult peak is replaced by a childhood (0-14 years) peak. This difference between developed and developing countries suggests that exposure to an infectious disease plays a role. In fact, Epstein-Barr virus does appear to play a role in the development of Hodgkin's disease, but the role of the virus is controversial, and no evidence of the virus is present in approximately half the cases.

• In Japan, the young adult peak is absent, presumably because of a reduced incidence of the nodular sclerosis subtype.

• The disease is more common among individuals with few or no siblings, among those having higher education, and among urban rather than rural dwellers.

• There may also be a genetic link, as there have been many reported incidences of family members of the same or different generation suffering from Hodgkin's. A sibling of an affected patient has a fivefold risk of developing the disease.