It is very important for patients to have an accurate diagnosis to ensure they are properly cared for. There are other lymphoid diseases which are biologically similar to CLL but do not have all of the same characteristics. These diseases are often rare and range from variations in the CLL cells to some types of lymphomas.

Hairy Cell Leukemia

Hairy cell leukemia (HCL) is a very unusual lymphoproliferative disorder distinguished by its appearance under the microscope. These leukemia cells have fine, “hairy” projections from their surfaces. Many HCL patients do not have any leukemic cells in the blood, but have marked enlargement of the spleen. HCL is typically a disease of middle-aged or older males. HCL differs from CLL with respect to management, and is now extremely treatable with of a group of drugs called nucleoside analogs and more recently with the addition of monoclonal antibodies such as rituximab.

Richter’s Transformation

Richter’s transformation is the development of high-grade Non-Hodgkin’s Lymphoma from CLL. The reasons for this transformation are unknown, but are under investigation. Richter’s occurs in a small percent of CLL patients, estimated at 5-10% and is more aggressive than CLL. Physicians usually treat Richter’s with the same therapies used for Non-Hodgkin’s Lymphoma.


Similar to leukemia, lymphoma is a disease which affects the immune system. The difference is that lymphoma occupies lymphoid organs, whereas leukemia starts in the bone marrow and primarily infiltrates the blood. On occasion, the lymphoma cells spill out of the lymphoid organs into the blood stream in a leukemic form. This is common in Mantle Cell Lymphoma and Marginal Zone Lymphoma and occurs less commonly with Follicular Lymphoma and similar diseases. Treatment for these disorders varies.

Interestingly, another form of lymphoma, small lymphocytic lymphoma (SLL), is identical to CLL.  Biologically, and from a prognosis and treatment point of view, CLL and SLL are the same disease, separated only by the white blood cell count. Unlike CLL, SLL stays in the lymphoid organs such as the lymph glands of the head, neck, armpit, groin or the abdomen.

Waldenström macroglobulinemia is a B-cell lymphoproliferative disorder in which the lymphocytic cells resemble plasma cells. This disease is associated with production of abnormal antibodies which themselves may cause a number of non-specific symptoms. A number of new treatment regimens containing rituximab have proven beneficial.

B-Cell Lymphocytosis

A small percentage of individuals will have a family of cells which are identical to CLL cells; however, the cells do not behave as a disease. This condition is now classified as monoclonal B-cell lymphocytosis (MBL) where there is an increased accumulation of these cells over time. However, unlike “typical” CLL, there is a balance between the cells being produced and the cells dying off. The likelihood of this particular classification of patients needing treatment is minimal (possibly 1% risk per year).

Finding the Right Expert

It is clear that the tools are present for accurate identification of CLL and other lymphoid disorders. Well trained hematologists, oncologists and pathologists can do this readily. However, patients need to know that not all oncologists see a large number of patients with these lymphoid diseases. It is often useful to have a second opinion by a lymphoid disease expert, either locally or at one of the major referral centers. It is important for patients to get an accurate prognosis and, if treatment is necessary, to make sure that the appropriate treatment for the appropriate patient is in place. The first treatment decision is important in every form of leukemia, lymphoma or other cancers.