Brief Overview about Chronic Lymphocytic Leukemia Markers and Diagnosis

Abstract

Background: Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) is an indolent malignancy characterized by increased production of mature but dysfunctional B lymphocytes. CLL/SLL is defined as a monoclonal lymphoproliferative disease characterized by the proliferation and accumulation of morphologically mature but immunologically dysfunctional B-cell lymphocytes that are smudge cells, as noted on peripheral smear. The primary disease sites include peripheral blood, spleen, lymph nodes, and bone marrow. CLL and SLL are identical from a pathologic and immunophenotypic standpoint. Both CLL and SLL originate from B-cell lymphocytes but present with different manifestations depending on where the abnormal cells are found.  Usually, the initial leukemic phase represents CLL, where the cells are present in the blood.  This eventually progresses to the lymphoma phase, representing SLL, where the cells are found in the lymph nodes. The term SLL is commonly used to represent the lymphoproliferative process limited to the lymph nodes. The first and foremost laboratory abnormality found in CLL is lymphocytosis in peripheral blood and bone marrow. The first step in the diagnosis of CLL is a peripheral blood smear. The peripheral blood smear shows an absolute lymphocyte count of greater than 5000/mcL and smudge cells that confirm CLL. Although the diagnostic criteria for CLL are >=5000/mcL B lymphocytes on peripheral smear, a large proportion of patients present with an absolute lymphocyte count > 100,000/mcL. In patients with SLL, peripheral blood smear shows an absolute lymphocyte count of less than 5000/mcL along with lymphadenopathy but without cytopenias. However, lymph node biopsy is required to confirm the diagnosis of SLL. The peripheral blood smear shows leukemic cells, which are small, mature lymphocytes with a darkly stained nucleus, condensed chromatin, and indistinguishable nucleoli with a narrow rim of basophilic cytoplasm. Classical "smudge" cells ("basket" cells) are also seen on peripheral blood smear; these are pathognomic of CLL. The smudge cells are more fragile than normal lymphocytes that are disrupted during the process of being spread on a glass slide.