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Diagnosing Chronic Lymphocytic Leukemia


A definite diagnosis requires at a minimum: lymphocytosis, characteristic morphology of blood smear using light microscopy, and characteristic immunophenotype.

Close to 80% of the patients have a lymph node tumor when the diagnosis is made and about half of the patients have splenomegaly. It is very common to find leukemic organ infiltration in almost all organs during autopsy, but this is rarely the cause of clinical symptoms.  

The diagnosis requires evidence of lasting lymphocytosis ( > 5 x 109/l). When the diagnosis is made, the lymphocyte value is most often > 40 x 109/l and sometimes > 100 x 109/l. The leukemic cells resemble normal lymphocytes and are 1.5–2 times larger than erythrocytes. They have very sparse basophilic cytoplasm and most often have a round-oval nucleus with condensed chromatin without a distinct nucleolus.

Diagnostic criteria for chronic lymphocytic leukemia


The diagnosis requires lasting (> 6 months) lymphocytosis > 5 x 109/l. Patients with clonal B-cell lymphocytosis between 3 and 5 x 109/l and morphology consistent with chronic lymphocytic leukemia may develop clinical symptoms. For lymphocytosis < 10 x 109/l, detection of monoclonal lymphocyte population with characteristic immunophenotype is necessary to make the diagnosis. 

Lymphocyte morphology

In typical lymphocytic leukemia, >90% of the cells are small or medium lymphocytes with condensed chromatin (like pine tree bark), diffuse or no nucleolus, and with very sparse cytoplasm (high nuclei/cytoplasm ratio). In 15% of patients, the morphology is atypical due to the high number of prolymphocytes (>10%, but <55 %) or low nucleus/cytoplasma ratio).


CD19, CD20, CD23, CD5, k or l light chains. CD5 expression cannot be detected in 5–10% of cases and membrane-bound Ig cannot be found in an equivalent amount of cases.


CLL Score
Marker CLL (score) Other leukemia/NHL score
mIg Weak/negative (1) Moderate/strong (0)
CD5 Positive (1)        Negative (0)
CD23 Positive (1) Negative (0)
CD79b or CD22 Weak/negative (1) Moderate/strong (0)
FMC7 Negative (1) Positive (0)

Score 4–5 in about 90% of cases with chronic lymphocytic leukemia, score 0–1 in about 90% of cases of the other leukemia and about 75% of cases with leukemized NHL. The remaining have a score of 2.

Bone marrow aspirate

More than 30% lymphocytes in a smear with not too few cells (not obligatory).

The diagnosis is confirmed by evidence of monoclonal population of B-cells with characteristic immunophenotype and morphology in blood.

About 15% of patients have anemia, normocytic and normochromic, at the debut of the disease. In 20%, a positive direct antiglobulin test can be detected (DAT+) at some point during the disease course due to the production of IgG auto-antibodies in non-neoplastic B lymphocytes. Only 8% of patients develop autoimmune hemolytic anemia.

Thrombocytopenia is observed in almost all patients with advanced illness, which is due to reduced thrombopoiesis. Also, immune-mediated thrombocytopenia occurs due to thrombocyte-specific auto-antibodies at any time during the course of the disease.

Hypogammaglobulinemia is detected early in the disease course in at least half of patients and in about 5% of the patients, a monoclonal gammopathy can be detected, usually of the IgM type. The paraprotein has the same specificity as that which is detected on the surface of the leukemic cells.  

Bone marrow is always infiltrated by leukemic cells, but the growth pattern varies.

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