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Small Lymphocytic Lymphoma (SLL) represented 6.7% of non-Hodgkin lymphomas in the International Lymphoma Study Group Classification Project. The average age of patients with SLL was 65 years, and 53% of the patients were male. The average age of patients with Chronic Lymphocytic Leukemia (CLL), the most common type of chronic leukemia, is 65 years, and the male to female ratio is reported to be approximately 2:1. Recent advances in our understanding of CLL/SLL have led to the realization that CLL/SLL is a heterogeneous disorder with a highly variable clinical course

A significant recent discovery has been that outcome of leukemic CLL/SLL patients can be predicted based on the mutational status of the immunoglobulin heavy chain variable region (IgVH) genes. CLL/SLL can now be broadly divided into 2 groups based on the mutational status of IgVH: those cases with unmutated IgVH regions having an unfavorable clinical course, and those with mutated IgVH having a favorable clinical course. Patients with un mutated IgVH genes were found to have a median survival of 95 months compared with 293 months for those with mutated IgVH genes. Gene expression profiling of CLL/SLL has revealed characteristic patterns of gene expression that correlate with the mutational status of the IgVH genes. ZAP-70, a protein tyrosine kinase normally expressed in T-cells that plays an important role in T-cell receptor signaling, was found to be expressed in CLL/SLL with unmutated IgVH genes. Consequently, ZAP-70 has been suggested as a surrogate marker for IgVH mutational status. Comprehensive investigations in CLL/SLL have confirmed that cases with ZAP- 70 expression usually carry unmutated IgVH genes and patients with these neoplasms have a shorter time to disease progression and a reduced overall survival compared with those without ZAP-70 expression

In Summary, part of the essential work up for cases with CLL/SLL is performing ZAP-70 immunostaining. Expression of this marker indicate a poor outcome in such a relatively indolent tumor and requires more aggressive therapy

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Dr. Hussam Abu-Farsakh

American Board of Anatomic & Clinical Pathology, and Cytopathology