- Risk Factors
- Recognizing Symptoms
- Classification & Staging
- Orthodox Treatment
- Side Effects of Orthodox Treatment
Hodgkin's disease is a cancer that originates in the nodes
of the lymphatic system, the collection of organs, tissues,
and vessels that produce infection-fighting cells and carries
them throughout the body.
Hodgkin's disease can occur throughout life but is most common
in early adulthood (ages 15 to 40, peaking in people between
25 and 30). The rate at which new cases are diagnosed has
remained stable over the past five decades, while death rates
have fallen more than 60 percent since the early 1970s because
of advances in treatment. The majority of patients with Hodgkin's
disease can be cured with current therapy.
The organs and tissues that make up the lymphatic system
include the lymph nodes, thymus, spleen, tonsils and adenoids,
bone marrow, and tissues in the gastrointestinal tract. Lymph
(fluid from these tissues) contains proteins, immune cells,
and waste products, and travels throughout the body in the
vessels of this system. The lymph nodes (small bean-shaped
organs in the neck, groin, underarms, and inside the pelvis,
abdomen, and chest) produce and store white blood cells called
lymphocytes, as do other lymphatic tissues. There are three
kinds of lymphocytes: B lymphocytes (or B cells), T lymphocytes
(or T cells), and natural killer (NK) cells. Each of these
types of cells performs a unique job in the battle against
infectious agents, targeting a very particular range of pathogens.
Hodgkin's disease arises when one of these cells (most often
a B cell) undergoes a transformation from a normal cell into
a malignant cell, one capable of uncontrolled growth and spread.
The malignant cell begins producing identical copies of itself,
or clones, in the lymph nodes. Over time these malignant cells
can spread to neighboring groups of lymph nodes, and if not
treated, may spread to other parts of the body. In Hodgkin's
disease, the tumors spread from lymph node group to lymph
node group via the lymphatic vessels. The most common site
of involvement is the lymph nodes in the chest; this region
is called the mediastinum.
Physicians distinguish Hodgkin's disease from other types
of lymphoma, in part, by examining tissue samples under a
microscope; biopsied tissue from patients with Hodgkin's disease
includes a certain number of cells called Reed-Sternberg cells
(named after the two physicians who first described them).
These cells are bigger than normal cells and have large, pale
nuclei (the site in each cell where chromosomes -- genetic
material -- are located). Researchers have recently discovered
that Reed-Sternberg cells almost always originate from B cells.
Risk factors for different types of cancer are those traits
that increase the likelihood that an individual will develop
disease. Risk factors include certain kinds of behavior such
as smoking, inherited (genetic) traits, and exposure to cancer-causing
agents in the environment. There is only a very small chance
that a person who has one of the few known risk factors for
Hodgkin's disease will develop the disease.
People whose immune systems are compromised -- as a result
of inherited genetic diseases, HIV infection, or administration
of immunosuppressive drugs as after an organ transplant --
have a slightly higher than average risk of developing Hodgkin's
disease. New research shows that viruses and bacteria may
play a role in initiating the disease. In about half of patients
with Hodgkin's disease the tumors can be shown to express
proteins associated with the Epstein-Barr virus.
Members of families in which one or more people have been
diagnosed with Hodgkin's disease also have a slightly higher
than average risk of developing the disease.
Hodgkin's disease can arise in lymph nodes almost anywhere
in the body, and symptoms of the disease depend on its location.
If Hodgkin's disease develops in lymph nodes that are close
to the skin in the neck, underarms, and groin, symptoms are
likely to include a persistent, painless swelling of the nodes.
If the disease develops in the chest, symptoms may include
cough, shortness of breath, and chest pain. When Hodgkin's
disease involves lymph nodes in the pelvis or abdomen, symptoms
may include a feeling of fullness or abdominal swelling.
Lymph nodes swell for many reasons, most often as a result
of an infection; swollen lymph nodes are usually not caused
by Hodgkin's disease. Physicians may treat a patient who has
a persistent swelling with antibiotics. If this treatment
does not reduce the swelling, the physician may order a biopsy
of the swollen node.
Other generalized symptoms of Hodgkin's disease include fever,
fatigue, night sweats, unexpected weight loss, and itchy skin.
A rare but almost diagnostic symptom is pain induced by the
ingestion of alcohol. Like swollen lymph nodes, these symptoms
(except for the last) are associated with a wide range of
conditions and illnesses. But if these problems persist, consult
Physicians use several kinds of tests to diagnose Hodgkin's
disease. These tests help determine the patient's exact type
of Hodgkin's disease and uncover other features that are helpful
in deciding on the most effective course of treatment.
During a biopsy, physicians remove a small amount of tissue
for analysis. There are several types of biopsies, including:
Excisional or incisional biopsy, in which the physician
cuts through the skin to remove an entire node (excisional)
or a small amount of tumor tissue (incisional). This is considered
the gold standard for the diagnosis of Hodgkin's disease.
Bone marrow aspiration, in which the physician withdraws
a small sample of bone marrow through a syringe. This test
is unlikely to result in a new diagnosis of Hodgkin's disease,
but it can help determine the extent of the spread of Hodgkin's
Physicians use imaging tests to determine the location
of tumors in the body. Chest x-rays can detect tumors in the
chest and lungs. Using computed tomography (CT scan), physicians
can take pictures of the body from a number of angles; these
pictures are then combined to produce detailed images of the
inside of the body. Magnetic resonance imaging (MRI) uses
magnets and radio waves to produce detailed pictures of soft
tissue and organs. In gallium scans and positron emission
tomography scans using fluorodeoxyglucose (FDG-PET), a radioactive
substance is injected into the body and attracted to cancerous
sites in the body. Using a special camera, physicians can
see where the radioactive material migrated, and determine
the extent of the spread of Hodgkin's disease.
In addition, physicians can use a number of tests that help
them determine specific features of the cells in biopsied
tissue including genetic abnormalities such as chromosomal
rearrangements -- which are common in lymphomas -- and whether
the cells have receptors for specific antigens (which helps
both identify the cells' origins and determine the patient's
prognosis). These tests include:
cytogenetic studies to determine chromosome changes
immunohistochemistry studies, in which antibodies
are used to distinguish between types of cancer cells
flow cytometry, in which prepared cells are passed
through a laser beam for analysis
molecular genetic studies (highly sensitive DNA and
RNA tests to determine specific genetic traits of cancer cells)
New diagnostic tests and procedures are emerging from work
on the human genome and gene expression analysis; these are
likely to be important in the future but are currently experimental.
Classification & Staging
When diagnosing Hodgkin's disease, physicians classify the
patient's disease (determine its type) and stage the disease
(discover if and how far it has spread from its site of origin).
This information is crucial in selecting a treatment and delineating
the patient's prognosis, or outlook.
The systems physicians have used to classify Hodgkin's disease
have evolved as understanding of the disease has progressed.
The current system is the WHO/REAL system (for World Health
Organization/Revised European American Lymphoma classification).
Under this system, lymphomas are divided according to a number
of characteristics: the appearance of the cells, their genetic
features, their chemistry, and their clinical behavior.
The WHO/REAL system describes two main types of Hodgkin's
Nodular lymphocyte-predominant Hodgkin's lymphoma, which
accounts for 5 percent of cases of Hodgkin's disease
Classical Hodgkin's lymphoma, which accounts for 95 percent
In nodular lymphocyte-predominant Hodgkin's disease, which
affects more men than women, the lymph nodes contain mostly
reactive lymphocytes and malignant B cells called popcorn
cells or lacunar cells.
Classical Hodgkin's disease is further divided into three
Nodular sclerosis Hodgkin's lymphoma: In this form of the
disease, which accounts for 70 to 80 percent of cases, the
lymph nodes usually contain scar tissue (sclerosis), normal
and reactive lymphocytes, and Reed-Sternberg cells.
Mixed cellularity Hodgkin's lymphoma: In this form of the
disease, which accounts for 20 percent of cases, the lymph
nodes contain Reed-Sternberg and inflammatory cells, and sclerosis
Lymphocyte depletion Hodgkin's lymphoma: There are two types
of this form of the disease, one with layers of malignant
cells, the other with few Reed-Sternberg cells and lymphocytes.
In recent years, the incidence of this form has declined for
reasons that are not clear.
Classical and nodular lymphocyte-predominant Hodgkin's disease
each have particular genetic and clinical features that distinguish
them from each other. The cells of each type of disease display
different, particular antigen receptors on their surfaces.
Classical Hodgkin's disease is commonly distributed along
the mediastinum (the space in the chest cavity behind the
sternum and in between the two sacs that contain the lungs)
and a late relapse following treatment is rare. In patients
with nodular lymphocyte-predominant Hodgkin's lymphoma, the
disease is more commonly found in the lymph nodes in peripheral
sites such as the neck or under the arm; the disease usually
progresses slowly, and late relapses are not uncommon but
patients generally fare well despite these relapses.
Once physicians have gathered all the information available
from diagnostic tests, they will stage the disease, or determine
the extent of its spread. Physicians stage Hodgkin's disease
as follows, using the Modified Ann Arbor Staging system.
Stage I: Disease is limited to one site or group of lymph
Stage II: Disease is found in more than one site, but is
limited to one side of the diaphragm.
Stage III: Disease is found in lymph nodes both above and
below the diaphragm.
Stage IV: Disease has spread outside the lymph nodes to other
organs (for example, lung, liver, bone marrow).
Staging can be further modified according to the absence
or presence of so-called B symptoms. Although Hodgkin's disease
responds better to treatment when diagnosed early, patients
with one or more of the following factors tend to have poorer
outcomes than patients without these factors:
B symptoms: Fever higher than 100.5, drenching night sweats,
and loss of more than 10 percent of the patient's baseline
Bulky disease: A tumor larger than 10 centimeters.
Disease found in more than four sites.
If the stage includes the letter B (e.g., stage IIIB), B symptoms
are present; if it includes the letter A, those symptoms are
absent. Stages I and II, and IIIA are considered early-stage
disease. Stages IIIB and IV are considered advanced-stage
Physicians generally treat classical Hodgkin's lymphoma with
combined chemotherapy and radiotherapy, and nodular lymphocyte-predominant
Hodgkin's lymphoma with involved-field radiotherapy -- radiation
limited to the area where disease is detected.
For early-stage disease of both types, physicians are working
to reduce both the size of the area exposed to radiation and
the dose of radiation; to avoid chemotherapy that may lead
to late complications; and to combine fewer cycles of more
effective and less toxic agents such as ABVD (doxorubicin
[Adriamycin], bleomycin, vinblastine, and dacarbazine) with
For advanced-stage disease, the standard of care is combination
chemotherapy: ABVD or Stanford V (an intensive, short-course,
seven-drug regimen). The role of radiotherapy combined with
ABVD is still controversial; current studies indicate that
additional radiotherapy reduces relapse rates but does not
improve overall survival. Stanford V is most often administered
as a combination program with chemotherapy followed by radiation
For patients whose disease recurs, physicians choose different
approaches depending on the nature of the initial treatment.
For those who relapse after radiotherapy alone, treatment
with standard-dose chemotherapy has a high rate of success.
For patients whose relapse follows chemotherapy or a combination
of treatment modalities, treatment could include stem cell
Side Effects of Orthodox Treatment
As early as 1902, physicians used radiotherapy to treat Hodgkin's
disease, and investigators developed chemotherapeutic regimens
for the disease in the mid-1960s. These decades of experience
have allowed researchers to observe and understand the later
complications of various treatment approaches.
High-dose radiation and toxic chemotherapeutic regimens such
as MOPP (mechlorethamine, vincristine [Oncovin], procarbazine,
and prednisone) and etoposide have been linked to second tumors
-- solid tumors including breast, lung, cancer, thyroid, and
skin cancers, as well as hematologic cancers such as non-Hodgkin's
lymphoma and leukemia. Patients may also experience cardiac
complications such as coronary heart disease after high-dose
radiotherapy. Following treatment -- and throughout their
lives -- people who have had Hodgkin's disease should make
sure that their physicians carefully monitor them for any
of these complications of treatment.