Hodgkin’s Lymphoma

Definition of Hodgkin’s Lymphoma

Hodgkin’s lymphoma, also known as Hodgkin lymphoma and previously known as Hodgkin’s disease, is a type of lymphoma, which is a cancer originating from white blood cells called lymphocytes. It was named after Thomas Hodgkin, who first described abnormalities in the lymph system in 1832.

Hodgkin’s lymphoma is characterized by the orderly spread of disease from one lymph node group to another and by the development of systemic symptoms with advanced disease. When Hodgkins cells are examined microscopically, multinucleated Reed–Sternberg cells (RS cells) are the characteristic histopathologic finding.

Hodgkin’s lymphoma may be treated with radiation therapy, chemotherapy, or hematopoietic stem cell transplantation, with the choice of treatment depending on the age and sex of the patient and the stage, bulk, and histological subtype of the disease. The disease occurrence shows two peaks: the first in young adulthood (age 15–35) and the second in those over 55 years old.

The overall 5-year relative survival for 2001–2007 from 17 SEER geographic areas was 83.9%. Since many patients are young, they often live 40 years or more after treatment. However, few studies follow patients as long as 25 years, and those studies are of older treatments with more life-threatening adverse effects. There is insufficient data available about the long-term outcomes of newer, less-toxic regimens and ones which limit radiation exposure. Radiation treatments, and some chemotherapy drugs, pose a risk of causing potentially fatal secondary cancers, heart disease, and lung disease 40 or more years later. Modern treatments greatly minimize the chances of these late effects.

Patients with a history of infectious mononucleosis because of Epstein-Barr virus may have an increased risk of HL, but the precise contribution of Epstein-Barr virus remains largely unknown.

Cause of Hodgkin’s Lymphoma

There are no guidelines for preventing Hodgkin’s lymphoma; the cause is unknown or multifactorial. A risk factor is something that statistically increases one’s chance of contracting a disease or condition. Risk factors for Hodgkin’s lymphoma include:

Sex: male
Ages: 15–40 and over 55
Family history
History of infectious mononucleosis or infection with Epstein-Barr virus, a causative agent of mononucleosis
Weakened immune system, including infection with HIV or the presence of AIDS
Prolonged use of human growth hormone
Exposure to exotoxins, such as Agent Orange

Signs and Symptoms of Hodgkin’s Lymphoma

Patients with Hodgkin’s lymphoma may present with the following symptoms:

Lymph nodes: the most common symptom of Hodgkin’s is the painless enlargement of one or more lymph nodes, or lymphadenopathy. The nodes may also feel rubbery and swollen when examined. The nodes of the neck and shoulders (cervical and supraclavicular) are most frequently involved (80–90% of the time, on average). The lymph nodes of the chest are often affected, and these may be noticed on a chest radiograph.
Itchy skin
Night sweats
Unexplained weight loss
Splenomegaly: Enlargement of the spleen occurs in about 30% of people with Hodgkin’s lymphoma. The enlargement, however, is seldom massive and the size of the spleen may fluctuate during the course of treatment.
Hepatomegaly: Enlargement of the liver, due to liver involvement, is present in about 5% of cases.
Hepatosplenomegaly: the enlargement of both the liver and spleen caused by the same disease.
Pain following alcohol consumption: classically, involved nodes are painful after alcohol consumption, though this phenomenon is very uncommon, occurring in only two to three percent of people with Hodgkin’s lymphoma, thus having a low specificity. On the other hand, its sensitivity is high enough for it to be regarded as a pathognomonic sign of Hodgkin’s lymphoma. The pain typically has an onset within minutes after ingesting alcohol, and is usually felt as coming from the vicinity where there is an involved lymph node. The pain has been described as either sharp and stabbing or dull and aching.
Back pain: nonspecific back pain (pain that cannot be localized or its cause determined by examination or scanning techniques) has been reported in some cases of Hodgkin’s lymphoma. The lower back is most often affected.[citation needed]
Red-coloured patches on the skin, easy bleeding and petechiae due to low platelet count (as a result of bone marrow infiltration, increased trapping in the spleen etc. – i.e. decreased production, increased removal)
Systemic symptoms: about one-third of patients with Hodgkin’s disease may also present with systemic symptoms, including low-grade fever; night sweats; unexplained weight loss of at least 10% of the patient’s total body mass in six months or less, itchy skin (pruritus) due to increased levels of eosinophils in the bloodstream; or fatigue (lassitude). Systemic symptoms such as fever, night sweats, and weight loss are known as B symptoms; thus, presence of fever, weight loss, and night sweats indicate that the patient’s stage is, for example, 2B instead of 2A.
Cyclical fever: patients may also present with a cyclical high-grade fever known as the Pel-Ebstein fever, or more simply “P-E fever”. However, there is debate as to whether or not the P-E fever truly exists.

Risk Factors for Hodgkin’s Lymphoma

Risk factors for Hodgkin’s lymphoma include:

Sex: male
Ages: 15–40 and over 55
Family history
History of infectious mononucleosis or infection with Epstein-Barr virus, a causative agent of mononucleosis
Weakened immune system, including infection with HIV or the presence of AIDS
Prolonged use of human growth hormone
Exposure to exotoxins, such as Agent Orange

Diagnosis of Hodgkin’s Lymphoma

Hodgkin’s lymphoma must be distinguished from non-cancerous causes of lymph node swelling (such as various infections) and from other types of cancer. Definitive diagnosis is by lymph node biopsy (usually excisional biopsy with microscopic examination). Blood tests are also performed to assess function of major organs and to assess safety for chemotherapy. Positron emission tomography (PET) is used to detect small deposits that do not show on CT scanning. PET scans are also useful in functional imaging (by using a radiolabeled glucose to image tissues of high metabolism). In some cases a Gallium Scan may be used instead of a PET scan.

Pathology

Macroscopy

Affected lymph nodes (most often, laterocervical lymph nodes) are enlarged, but their shape is preserved because the capsule is not invaded. Usually, the cut surface is white-grey and uniform; in some histological subtypes (e.g. nodular sclerosis) a nodular aspect may appear.
A fibrin ring granuloma may be seen.

Microscopy

Microscopic examination of the lymph node biopsy reveals complete or partial effacement of the lymph node architecture by scattered large malignant cells known as Reed–Sternberg cells (RSC) (typical and variants) admixed within a reactive cell infiltrate composed of variable proportions of lymphocytes, histiocytes, eosinophils, and plasma cells. The Reed–Sternberg cells are identified as large often bi-nucleated cells with prominent nucleoli and an unusual CD45-, CD30+, CD15+/- immunophenotype. In approximately 50% of cases, the Reed–Sternberg cells are infected by the Epstein–Barr virus.

Characteristics of classic Reed–Sternberg cells include large size (20–50 micrometres), abundant, amphophilic, finely granular/homogeneous cytoplasm; two mirror-image nuclei (owl eyes) each with an eosinophilic nucleolus and a thick nuclear membrane (chromatin is distributed close to the nuclear membrane).

Variants:

Hodgkin cell (atypical mononuclear RSC) is a variant of RS cell, which has the same characteristics, but is mononucleated.
Lacunar RSC is large, with a single hyperlobated nucleus, multiple, small nucleoli and eosinophilic cytoplasm which is retracted around the nucleus, creating an empty space (“lacunae”).
Pleomorphic RSC has multiple irregular nuclei.
“Popcorn” RSC (lympho-histiocytic variant) is a small cell, with a very lobulated nucleus, small nucleoli.
“Mummy” RSC has a compact nucleus, no nucleolus and basophilic cytoplasm.

Hodgkin’s lymphoma can be sub-classified by histological type. The cell histology in Hodgkin’s lymphoma is not as important as it is in non-Hodgkin’s lymphoma: the treatment and prognosis in classic Hodgkin’s lymphoma usually depends on the stage of disease rather than the histotype.

Prevention from Hodgkin’s Lymphoma

Since it is not yet known what causes lymphoma, there is no general way to prevent it.

Avoiding the lymphoma risk factors, like smoking, can be helpful in reducing your risk of the disease. There are some risk factors, such as family history or age, which cannot be avoided. Infection with HIV, the virus that causes AIDS, is known to increase risk, so one way to limit your risk is to avoid known risk factors for HIV, such as intravenous drug use or unprotected sex with many partners.

Treatment of Hodgkin’s Lymphoma

Patients with early stage disease (IA or IIA) are effectively treated with radiation therapy or chemotherapy. The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. Patients with later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. Patients of any stage with a large mass in the chest are usually treated with combined chemotherapy and radiation therapy.

It should be noted that the common non-Hodgkin’s treatment, rituximab (which is a monoclonal antibody against CD20) is not routinely used to treat Hodgkin’s lymphoma due to the lack of CD20 surface antigens in most cases. The use of rituximab in Hodgkin’s lymphoma, including the lymphocyte predominant subtype has been reviewed recently.

Although increased age is an adverse risk factor for Hodgkin’s lymphoma, in general elderly patients without major comorbidities are sufficiently fit to tolerate standard therapy, and have a treatment outcome comparable to that of younger patients. However, the disease is a different entity in older patients and different considerations enter into treatment decisions.

For Hodgkin’s lymphomas, radiation oncologists typically use external beam radiation therapy (sometimes shortened to EBRT or XRT). Radiation oncologists deliver external beam radiation therapy to the lymphoma from a machine called a linear accelerator. Patients usually describe treatments as painless and similar to getting an X-ray. Treatments last less than 30 minutes each, every day but Saturday and Sunday.

For lymphomas, there are a few different ways radiation oncologists target the cancer cells. Involved field radiation is when the radiation oncologists give radiation only to those parts of the patient’s body known to have the cancer. Very often, this is combined with chemotherapy. Radiation therapy directed above the diaphragm to the neck, chest and/or underarms is called mantle field radiation. Radiation to below the diaphragm to the abdomen, spleen and/or pelvis is called inverted-Y field radiation. Total nodal irradiation is when the therapist gives radiation to all the lymph nodes in the body to destroy cells that may have spread.

Adverse effects

The high cure rates and long survival of many patients with Hodgkin’s lymphoma has led to a high concern with late adverse effects of treatment, including cardiovascular disease and second malignancies such as acute leukemias, lymphomas, and solid tumors within the radiation therapy field. Most patients with early-stage disease are now treated with abbreviated chemotherapy and involved-field radiation therapy rather than with radiation therapy alone. Clinical research strategies are exploring reduction of the duration of chemotherapy and dose and volume of radiation therapy in an attempt to reduce late morbidity and mortality of treatment while maintaining high cure rates. Hospitals are also treating those who respond quickly to chemotherapy with no radiation.

In childhood cases of Hodgkin’s lymphoma, long-term endocrine adverse effects are a major concern, mainly gonadal dysfunction and growth retardation. Gonadal dysfunction seems to be the most severe endocrine long-term effect, especially after treatment with alkylating agents and/or pelvic radiotherapy.