Clinical Features / Diagnostics

About half of cases of CLL remain asymptomatic for a long period, resulting in late or incidental diagnosis.

• Weight loss, fever, night sweats, fatigue (B symptoms)

• Painless lymphadenopathy

• Hepatomegaly and/or splenomegaly may occur.

• Repeated infections

  • Severe bacterial infections (e.g., necrotic erysipelas)

  • Mycosis (candidiasis)

  • Viral infections (herpes zoster)

• Symptoms of anemia and thrombocytopenia

• Dermatologic symptoms

  • Leukemia cutis

  • Chronic pruritus

  • Chronic urticaria

• Diagnostic criteria

  • Persistent (≥ 3 months) lymphocytosis (≥ 5000 cells/mm3)

  • CLL immunophenotype confirmed by flow cytometry, including:

    • Expression of CD5, CD19, CD20, CD23

    • Light chain restriction (kappa or lambda)

• Additional findings: may further support the diagnosis

  • Cytopenias

    • Anemia: may be caused by AIHA

    • Thrombocytopenia

    • Granulocytopenia

  • Peripheral blood smear may show:

    • High percentage of small mature lymphocytes

    • Smudge cells (Gumprecht shadows): mature lymphocytes that rupture easily; appear as artifacts on a blood smear

Prognostic markers in CLL

• Indications for testing

  • Confirmed CLL diagnosis

• Methods

  • Cytogenetic testing

    • FISH to assess for common structural chromosomal aberrations in CLL, e.g., del(17p)

    • Immunoglobulin heavy chain variable region (IGHV) mutational status

    • TP53 mutational status

  • Serum studies: β2-microglobulin and LDH

• Interpretation

  • Adverse prognosis: e.g., del(17p) , del(11q), TP53 mutation, elevated β2-microglobulin, elevated LDH

  • Intermediate prognosis: trisomy 12 [1]

  • Favorable prognosis: IGHV mutation , isolated del(13q)

• Bone marrow aspiration and biopsy

  • Not routinely required for diagnosis

  • Consider in patients with cytopenias to determine the cause.

  • Typical findings in aspirate include a high percentage of small mature lymphocytes.

Rai staging system.

• Acute lymphoblastic leukemia (ALL)

• Autoimmune hemolytic anemia (AIHA)

• Mantle cell lymphoma

• Hairy cell lymphoma