Sandbox: leukemia

Pathophysiology

CLL affects a particular lymphocyte, the B cell, which originates in the bone marrow, develops in the lymph nodes, and normally fights infection. In CLL, the DNA of a B cell is damaged, so that it can't fight infection, but it grows out of control and crowds out the healthy blood cells that can fight infection.

CLL is an abnormal neoplastic proliferation of B cells. The cells accumulate mainly in the bone marrow and blood. CLL is closely related to a disease called small lymphocytic lymphoma (SLL), a type of non-Hodgkin's lymphoma which presents primarily in the lymph nodes. The World Health Organization considers CLL and SLL to be "one disease at different stages, not two separate entities".

In the past, cases with similar microscopic appearance in the blood but with a T cell phenotype were referred to as T-cell CLL. However, it is now recognized that these so-called T-cell CLLs are in fact a separate disease group and are currently classified as T-cell prolymphocytic leukemias.

Acute lymphocytic leukemia (ALL) is a disease of children, but CLL is a disease of adults.

Uncommonly, CLL presents as enlargement of the lymph nodes without a high white blood cell count or no evidence of the disease in the blood. This is referred to as small lymphocytic lymphoma.

The increase in lymphocytes and precursors in the bone marrow impairs the production of other leucocytes causing a decrease in such cell types.

Differential

Hematologic disorders that may resemble CLL in their clinical presentation, behavior, and microscopic appearance include:

• Mantle cell lymphoma
• Marginal zone lymphoma
• Lymphoplasmacytic lymphoma
• B cell prolymphocytic leukemia (B PLL), which is a related but more aggressive disorder, has cells with similar phenotype but that are signficantly larger than normal lymphocytes and have a prominent nucleolus suggests a related.
• Hairy cell leukemia is also a neoplasm of B lymphocytes but differs significantly from CLL by its morphology under the microscope (hairy cell leukemia cells have delicate, hair-like projections on their surface) and marker molecule expression.

All the B cell malignancies of the blood and bone marrow can be differentiated from one another by the combination of cellular microscopic morphology, marker molecule expression, and specific tumor-associated gene defects. This is best accomplished by evaluation of the patient's blood, bone marrow and occasionally lymph node cells by a pathologist with specific training in blood disorders. A sophisticated instrument called a flow cytometer is necessary for cell marker analysis and the detection of genetic problems in the cells may require visualizing the DNA changes with fluorescent probes by fluorescent in situ hybridization (FISH). CLL is positive for CD5, CD19 & CD23; CLL is the only cell type that coexpresses CD5 & 19. It is negative for CD10 & cyclin D. CD20 is +/- as is sIg. 90% of B-CLL have bcl-2. The 2 most noteworthy lymphoproliferative diseases with CD5 positivity are CLL (which is CD23 positive) & mantle zone lymphoma (which is CD23 negative). Other CD5+ groups include peripheral & cutaneous T-cell lymphoma, lymphoblastic lymphoma, and adult T-cell leukemia/lymphoma.