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Hodgkin's Lymphoma (Disease)

Pathology || Types || Signs and Symptoms || Diagnosis || Staging || Treatment || Overview || Related Articles || References and Resources
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Pathology





We have to first define what lymphoma is before discussing Hodgkin's disease. Lymphoma is a cancer that develops from cells in the body known as lymphocytes. Lymphocytes are a subcategory of white blood cells, which are the cells that help ward off infection. There are two different types of lymphocytes: B-cells and T-cells. Almost all lymphomas, including Hodgkin's disease, stem from B-cells.

In Hodgki's disease a B-cell, for unknown reasons, becomes cancerous. The cell then makes many clones of itself. These cells bundle together to form a solid tumor known as a lymphoma.

Why B-cells in Hodgkin's lymphoma become cancerous is not entirely known. One belief is that infection with Epstein-Barr virus (the same virus that causes infectious mononucleosis - "kissing disease") can cause the cells to turn cancerous in genetically susceptible people. Other theories are that certain genetic translocations may be the underlying factor. As of yet, no particular theory has significant supporting data to call it the "cause".

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Types

Reed-Sternberg Cell

There are different subcategories of Hodgkin's lymphoma. They are based on several unique histopathological (ie: what it looks like under a microscope) characteristics, and are important in determining prognosis.

The histopathological features the pathologist looks for are the number of Reed-Sternberg cells, as well as the number of lymphocytes present in the biopsy specimen. A Reed-Sternberg cell is a funny shaped cell with two nuclei that looks like an "owl's eyes" (see image to the right). They are believed to form when two cells merge together under the influence of certain proteins produced by the Epstein-Barr virus.

The first subcategory, and most common type, is nodular sclerosing Hodgkin's lymphoma. In this type, there are very few Reed-Sternberg cells with a moderate number of lymphocytes. It commonly occurs in younger individuals, and with treatment, the prognosis is excellent.

The second subcategory is mixed cellularity Hodgkin's lymphoma. This type has many Reed-Sternberg cells, and a moderate number of lymphocytes when viewed under the microscope. It has an intermediate prognosis.

The third subcategory is lymphocyte predominant Hodgkin's. It has very few Reed-Sternberg cells and many lymphocytes. It occurs most commonly in males less than 35 years of age. It is also one of the few types that is not associated with Epstein-Barr virus infection.

The last subcategory is lymphocyte depleted. It is the rarest form of Hodgkin's lymphoma. It typically affects older males.

Hodgkin's Types
Unfortunately it has the worst prognosis of the four types types.

The image to the left is one way of organizing the different Hodgkin's types and their prognosis based on age, number of RS cells, and prognosis. LP = lymphocyte predominant, NS = nodular sclerosing, MC = mixed cellularity, LD = lymphocyte depleted.

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Signs and Symptoms

The classic presentation of Hodgkin's lymphoma is painless enlargement of the lymph nodes. This is similar to non-Hodgkin's lymphoma, and the only way to differentiate the two is through biopsy.

Systemic manifestations may occur and include night sweats, fever, and weight loss. However, these are more common in patients with disseminated (ie: metastatic) disease. Interestingly, a pathognomonic (ie: seen exclusively in Hodgkin's lymphoma) feature that occurs in some cases is pain of the involved nodes after drinking alcohol. Finally, a symptom known as Pel-Ebstein fevers are also specific for the disease. A Pel-Ebstein fever is a cyclical fever that occurs for several weeks at a time followed by a fever free period.

Other signs related to the immune system can be seen in patients with Hodgkin's lymphoma. A condition known as cutaneous anergy can occur. Anergy refers to a lack of response by the cell mediated immune system. For example, in patients with tuberculosis a reaction will occur underneath the skin when they get a TB test. This reaction is the result of their cell mediated immunity reacting to the tuberculosis components injected underneath the skin. However, in anergic patients no reaction would be seen, even if they have tuberculosis! This can also occur in patients with Hodgkin's disease.

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Diagnosis

Hodgkin's Disease PET-CT
Diagnosis of Hodgkin's lymphoma is made by looking at a biopsy specimen underneath the microscope. The most common way of obtaining a specimen is through biopsy of a lymph node. This involves placing a needle into the node, usually under ultrasound guidance. Tissue is then aspirated and sent to the lab for analysis. Differentiating Hodgkin's from other types of lymphomas is important because it determines the best treatment options.

Additional studies are often performed to determine the number and location of involved lymph nodes. One such study is a positron emission tomograph (PET) combined with a CT scan. Any lymph nodes involved "light up" on the scan. An example, with the arrows pointing to involved nodes, is shown to the right.

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Staging

Staging of Hodgkin's lymphoma is based on a system known as the Ann Arbor Classification. It is divided into four stages. In stage 1 disease a single lymph node, or single organ is involved. In stage 2 disease involvement of multiple (two or more) lymph node regions on the same side of the diaphragm is present. In stage 3 disease involvement of nodes on both sides of the diaphragm is present; the spleen or other limited organ involvement may also be present. In stage 4 disease multiple organs are involved; interestingly, lymph node involvement is not necessary for a stage 4 diagnosis, although it is commonly present. Finally, each stage is further divided into "A" and "B" depending on whether or not symptoms are present. If symptoms are present, the stage is upgraded to a "B".

Ann Arbor Classification (simplified)
Stage 1 Single lymph node or organ
Stage 2 Multiple lymph nodes on same side of diaphragm
Stage 3 Lymph nodes on both sides of diaphragm
Stage 4 Multiple organs involved

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Treatment

Like most cancers treatment is highly dependent on the stage of the disease. In most cases chemotherapy and radiation are used. Radiation is directed at involved lymph nodes, as well as lymph nodes that are uninvolved, but nearby. Common chemotherapeutic agents used include: adriamycin, bleomycin, vinblastine, vincristine, prednisone, procarbazine, and mechlorethamine.

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Overview

Hodgkin's lymphoma is a cancer of white blood cells known as B-cells. There are numerous subcategories depending on its histopathological characteristics. Patients often have painless enlarged lymph nodes. Some patients have fever, weight loss, and other non-specific symptoms. Staging is based on the Ann-Arbor method. Treatment usually involves a combination of chemotherapy and radiation.

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Related Articles

- Blood types

- Sickle cell disease

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References and Resources

(1) Herbst C, Engert A. Meta-analyses of early-stage hodgkin lymphoma. Acta Haematol. 2011;125(1-2):32-8. Epub 2010 Dec 8.

(2) Josting A. Prognostic factors in Hodgkin lymphoma. Expert Rev Hematol. 2010 Oct;3(5):583-92.

(3) Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Seventh Edition. Philadelphia: Elsevier Saunders, 2004.

(4) Armitage JO. Early-stage Hodgkin's lymphoma. N Engl J Med. 2010 Aug 12;363(7):653-62.

(5) Gocheva L. Radiation therapy in Hodgkin's disease - decades of steady progress. J BUON. 2010 Apr-Jun;15(2):226-34.

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