CD19 negative precursor B acute lymphoblastic leukemia (B-ALL)-Immunophenotypic challenges in diagnosis and
Kiran Ghodke1, Asma Bibi1, Nikhil Rabade1
1Hematopathology Laboratory, Department of Pathology, Tata Memorial Centre, Mumbai, India.
Insights
Extremely rare cases of B-cell acute lymphoblastic leukemia (B-ALL) lacking CD19 expression were identified. This CD19 negative B-ALL presents diagnostic challenges for immunophenotyping and monitoring residual disease.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- CD19 is a standard B-cell marker crucial for diagnosing B-cell malignancies.
- Flow cytometric immunophenotyping (FCI) relies heavily on CD19 for B-acute lymphoblastic leukemia (B-ALL) diagnosis and monitoring.
- CD19 negative B-ALL is exceptionally rare, posing diagnostic and therapeutic challenges.
Observation:
- Three cases of B-ALL with severely down-regulated CD19 expression were identified.
- Leukemic blasts expressed other B-cell markers (CD10, CD20, CD22, CD79a) and CD34.
- Morphological and standard cytogenetic analyses did not reveal significant differentiating features.
Findings:
- Confirmed diagnosis of B-ALL in three patients despite absent CD19 expression.
- CD19 negativity was consistent across different antibody clones.
- No recurrent genetic translocations were detected in these cases.
Implications:
- Highlights the critical need for awareness of CD19 negative B-ALL to avoid misdiagnosis.
- Emphasizes potential difficulties in monitoring minimal residual disease using CD19.
- Suggests the importance of comprehensive immunophenotyping panels beyond CD19 for accurate B-ALL assessment and targeted therapy development.
Background:
CD19 is a B-cell specific marker, expressed on all stages of B-lymphocytes including plasma cells. It is widely used in the flow cytometric immunophenotyping (FCI) of B-cell and plasma cell malignancies. The analysis approach of FCI for the diagnosis and monitoring of B-cell acute lymphoblastic leukemia (B-ALL) is totally based on the CD19-based primary gating strategy and it would be challenging to study B-ALL without CD19 expression. Since CD19 negative B-ALL are extremely rare, we report three cases of B-ALL with negative expression of CD19 and discussed its implication in the diagnosis, residual disease monitoring and future targeted therapy.
Methods:
Peripheral blood (PB) and bone marrow (BM) samples from three cases suspicious of acute leukemia were studied for morphology, cytochemistry, immunophenotyping and cytogenetics. FCI was performed using a comprehensive six to eight-color multiparametric assay. The cytogenetic studies for standard recurrent genetic translocations were performed by FISH & Karyotyping.
Results:
The three cases studied were diagnosed as B-ALL based on the expression of CD10, CD20, CD22, CD34, and CD79a by leukemic blasts. CD19 was studied using two different clones (i.e. J3-119 & HIB-19) and found to be severely down regulated in all three cases. There were no significant differentiating features in morphology. Cytogenetic studies were negative for recurrent translocations.
Conclusion:
We report three cases of extremely rare CD19 negative B-ALL. Lack of awareness of negative CD19 expression in B-ALL can leads to incorrect immunophenotypic diagnosis and monitoring of B-ALL, especially in laboratories using limited markers. © 2016 International Clinical Cytometry Society.
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