Chronic lymphocytic leukemia FISH panel: impact on diagnosis

Area of Science:

• Hematology
• Cytogenetics
• Molecular Diagnostics

Background:

• Chronic lymphocytic leukemia (CLL) diagnosis traditionally relies on morphology and immunophenotyping.
• Interphase fluorescence in situ hybridization (FISH) offers a molecular alternative for detecting chromosomal abnormalities.
• Identifying specific genetic aberrations is crucial for prognosis and treatment stratification in CLL.

Purpose of the Study:

• To evaluate the utility of a comprehensive FISH panel in diagnosing CLL.
• To identify common and rare genetic abnormalities in a cohort of suspected CLL cases.
• To assess the role of FISH in differentiating CLL from other lymphoid malignancies and in cases with atypical morphology.

Main Methods:

• Analysis of 172 samples from 136 potential CLL cases using a FISH panel.
• Reflex testing with specific probes (CCND1, BCL2, BCL3, BCL11A, c-MYC, MALT1, IGH break-apart) triggered by 14q32 signals.
• Data analysis from 111 cases with sufficient information.

Main Results:

• 81 out of 111 (72.9%) analyzed cases exhibited at least one genetic abnormality.
• The most prevalent abnormalities were 13q deletion, trisomy 12, 11q deletion, and 17p deletion.
• Immunoglobulin heavy chain (IGH) abnormalities were found in 13 cases, including CCND1/IGH fusion in two cases reclassified as mantle cell lymphoma.

Conclusions:

• The FISH CLL panel is effective in detecting prognostic genetic aberrations in CLL.
• FISH aids in clarifying diagnoses, particularly in cases with unusual morphologic features.
• This molecular approach enhances diagnostic precision and supports risk-adapted therapy in CLL management.