Chronic Lymphocytic Leukemia (CLL) Differential Diagnoses

Updated: Feb 08, 2022
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Diagnostic Considerations

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease; SLL is diagnosed when the disease is mainly nodal, and CLL is diagnosed when the disease is seen in the blood and bone marrow. CLL is diagnosed when >5000 monoclonal lymphocytes/mm3 are present for longer than 3 months; the bone marrow usually has more than 30% monoclonal lymphocytes and is either normocellular or hypercellular

Monoclonal B lymphocytosis is a precursor form of CLL that is defined by the following:

  • Monoclonal B cell lymphocytosis of < 5000 monoclonal lymphocytes/mm 3
  • All lymph nodes smaller than 1.5 cm
  • No anemia
  • No thrombocytopenia.

Mantle cell lymphoma can have a clinical presentation very similar to that of CLL, but it is more aggressive. Several features aid in the distinction of mantle cell lymphoma from CLL. Mantle cell lymphoma expresses CD5 and CD19 but not CD23 antigen, which is expressed in CLL. Mantle cell lymphoma typically expresses FMC-7. Importantly, expression of CD20 is bright in mantle cell lymphoma, whereas it is dim in CLL.

Anemia secondary to bone marrow involvement with CLL, splenic sequestration of red blood cells, and autoimmune hemolytic anemia associated with a positive Coombs test are included in the differential diagnosis of a patient with anemia who has CLL. Autoimmune anemia or thrombocytopenia should be distinguished from bone marrow suppression in the staging of CLL.

Another problem to be considered is splenic lymphoma with villous lymphocytes.

Differential Diagnoses