Lymphoma is the most common form of blood cancer. The two main types of lymphoma are Hodgkin lymphoma and non-Hodgkin lymphoma. Lymphoma occurs when lymphocytes, a type of white blood cell, grow abnormally. The body has two main types of lymphocytes that can develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). These cancerous lymphocytes can travel to many parts of the body, including the lymph nodes, spleen, bone marrow, blood or other organs, and can accumulate to form tumors.
Hodgkin lymphoma, formerly known as Hodgkin's disease, is less common than non-Hodgkin lymphoma. According to the National Cancer Institute, approximately 9,000 new cases of Hodgkin lymphoma are projected each year. Although the cancer can occur in both children and adults, it is most commonly diagnosed in young adults between the ages of 15 and 35 and in older adults over age 50.
Hodgkin lymphoma is divided into two main classifications: classical Hodgkin lymphoma and lymphocyte predominant Hodgkin lymphoma. There are four main subtypes of classical Hodgkin lymphoma (which accounts for roughly 95 percent of all cases of Hodgkin lymphoma) and two subtypes of lymphocyte predominant Hodgkin lymphoma. The subtypes of each form of Hodgkin lymphoma are described below.
Classical Hodgkin Lymphoma Subtypes
Nodular Sclerosis: Nodular Sclerosis is the most common subtype of Hodgkin lymphoma, accounting for between 60 percent and 80 percent of all cases of Hodgkin lymphoma. In nodular sclerosis Hodgkin lymphoma, the involved lymph nodes contain areas composed of Reed-Sternberg (R-S) cells mixed with normal white blood cells. The lymph nodes often contain prominent scar tissue, hence the name nodular sclerosis (scarring). The disease is more common in women than men, and it usually affects adolescents and adults under 50. The majority of patients diagnosed with this subtype are cured with current treatments.
Mixed Cellularity: Mixed Cellularity accounts for roughly 15 percent to 30 percent of all cases of Hodgkin lymphoma. It is found more commonly in men than women. The disease is characterized by the involved lymph nodes containing many R-S cells in addition to several other cell types. This subtype primarily affects older adults and may be associated with HIV and the Epstein-Barr virus. More extensive disease is usually present by the time this subtype is diagnosed.
Lymphocyte Depletion: Lymphocyte Depletion accounts for fewer than five percent of all Hodgkin lymphoma cases. It is characterized by few normal lymphocytes but abundant R-S cells. This subtype is aggressive and usually not diagnosed until the disease is widespread.
Lymphocyte-Rich: Lymphocyte-Rich accounts for less than five percent of all Hodgkin lymphoma cases. The disease may be diffuse (spread out) or nodular (knot-like) in form and is characterized by the presence of numerous normal lymphocytes and very few abnormal cells and classical R-S cells. Lymphocyte-rich Hodgkin lymphoma is usually diagnosed at an early stage in adults and has a low rate of relapse.
Lymphocyte Predominant Hodgkin Lymphoma Subtypes
Nodular Lymphocyte Predominant: Nodular Lymphocyte Predominant Hodgkin lymphoma accounts for five to 10 percent of all Hodgkin cases. It primarily affects more men than women and is usually diagnosed in people under the age of 35. In nodular lymphocyte predominant Hodgkin lymphoma, most of the lymphocytes found in the lymph nodes are normal (not cancerous). Typical R-S cells are usually not found in this subtype, but large, abnormal B-cells can be seen, as well as reactive small B-cells, which may be distributed in a nodular (knot-like) pattern within the tissues. This subtype is usually diagnosed at an early stage and is not very aggressive. In many ways, this form of Hodgkin lymphoma resembles low-grade (indolent) B-cell non-Hodgkin lymphoma.
Diffuse Lymphocyte Predominant: Diffuse Lymphocyte Predominant Hodgkin lymphoma is extremely rare. In fact, the existence of this subtype has been questioned. Most cases are in fact nodular lymphocyte predominant Hodgkin lymphoma with an ill-defined nodular pattern. Unlike nodular lymphocyte predominant Hodgkin lymphoma, fewer small benign B-cells are found. The lymphatic tissue is dominated instead by reactive, non-malignant T-cells. Disease recurrence is common in this Hodgkin lymphoma subtype.
Relapsed and Refractory Hodgkin Lymphoma
While the vast majority of Hodgkin lymphoma patients will be cured of their cancer with first-line treatment, some patients will relapse (the lymphoma returns following remission) or become refractory (the lymphoma is resistant to primary treatment). For classical Hodgkin lymphoma, most relapses typically occur within the first three years following diagnosis, although some relapses occur much later.
Exactly why an individual patient relapses is not known, but there are a number of clinical and laboratory factors that are associated with an increased risk of relapse. The International Prognostic Score includes seven factors that predict which Hodgkin lymphoma patients are at high risk for relapse. They include: late stage disease, age, gender, hemoglobin level, albumin level, white blood cell count and lymphocyte level. Additional markers used to predict which patients are at high risk for relapse include advanced age, bulky-mass tumors, multiple nodal sites and serologic markers, such as elevations of Interleuken 10, Interleuken 6 and soluble CD30.