Contributions
Abstract: PB1849
Type: Publication Only
Background
With the emergence of targeted therapy, the precise classification of B-cell disorders has become critical. Indeed, a B-cell disorder presenting an altered TP53 gene should be treated by BCR inhibitors if it is a chronic lymphocytic leukemia (CLL), but by immunochemotherapy if it is a marginal zone lymphoma (MZL).
For B-cell disorders without tumoral syndrome, the diagnosis relies only on the analysis of circulating lymphocytes. Most of the time, cytologic, phenotypic, cytogenetic and molecular data allow to correctly classify those patients according to the WHO classification. However, for a few patients, the comprehensive analysis of tumoral cells doesn’t allow to retain a precise diagnosis.
Aims
The aim of this study was to better characterize the clinical presentation and outcome of patients with absolute lymphocytosis that cannot be precisely classify in the WHO classification.
Methods
We describe a monocentric retrospective cohort of patients presenting a lymphocyte count > 5 G/L, but without clinically detectable tumoral syndrome. We excluded patients with evident diagnosis according to the WHO classification, such as CLL, mantle cell lymphoma, or splenic MZL. Overall, 18 patients fulfilling these criteria were identified between 1999 and 2015 in our tertiary care center. We have reviewed cytological, phenotypical, cytogenetical and molecular features of these patients. For 8 patients, a panel of 94 genes was sequenced.
Results
Most patients were old (median age: 79 year-old) and without clinical signs or cytopenia. Cytological and phenotypical features were intermediate between CLL and MZL (notably with the RMH score <3 and positive CD5 staining for 16/18 cases). Cytogenetic analysis highlighted a chromosome 12 trisomy for 13/18 cases, and other alterations found in CLL (17p deletion, 13q deletion). Sequencing of the gene panel highlighted molecular anomalies found in both CLL and MZL, with frequent mutations of TP53 (3/8 patients). The disease seems relatively indolent as 5/18 patients were treated after a median follow-up of 4 years.
Conclusion
We have identified a group of patients presenting biological features intermediate between CLL and MZL. These B-cell disorders are characterized by a high frequency of chromosome 12 trisomy and a relatively indolent evolution. As these cases cannot be definitively classified in a category of the WHO classification, the choice of the first line treatment might be problematic: for patients presenting a TP53 alteration, if they are classified as CLL, ibrutinib is indicated, but this is not the case if they are classified as MZL. Other case series are mandatory to precise the optimal treatment of this B-cell disorder with intermediate features between CLL and MZL.
Session topic: 5. Chronic lymphocytic leukemia and related disorders – Biology & Translational Research
Keyword(s): B cell lymphoma, Chronic Lymphocytic Leukemia, WHO classification
Abstract: PB1849
Type: Publication Only
Background
With the emergence of targeted therapy, the precise classification of B-cell disorders has become critical. Indeed, a B-cell disorder presenting an altered TP53 gene should be treated by BCR inhibitors if it is a chronic lymphocytic leukemia (CLL), but by immunochemotherapy if it is a marginal zone lymphoma (MZL).
For B-cell disorders without tumoral syndrome, the diagnosis relies only on the analysis of circulating lymphocytes. Most of the time, cytologic, phenotypic, cytogenetic and molecular data allow to correctly classify those patients according to the WHO classification. However, for a few patients, the comprehensive analysis of tumoral cells doesn’t allow to retain a precise diagnosis.
Aims
The aim of this study was to better characterize the clinical presentation and outcome of patients with absolute lymphocytosis that cannot be precisely classify in the WHO classification.
Methods
We describe a monocentric retrospective cohort of patients presenting a lymphocyte count > 5 G/L, but without clinically detectable tumoral syndrome. We excluded patients with evident diagnosis according to the WHO classification, such as CLL, mantle cell lymphoma, or splenic MZL. Overall, 18 patients fulfilling these criteria were identified between 1999 and 2015 in our tertiary care center. We have reviewed cytological, phenotypical, cytogenetical and molecular features of these patients. For 8 patients, a panel of 94 genes was sequenced.
Results
Most patients were old (median age: 79 year-old) and without clinical signs or cytopenia. Cytological and phenotypical features were intermediate between CLL and MZL (notably with the RMH score <3 and positive CD5 staining for 16/18 cases). Cytogenetic analysis highlighted a chromosome 12 trisomy for 13/18 cases, and other alterations found in CLL (17p deletion, 13q deletion). Sequencing of the gene panel highlighted molecular anomalies found in both CLL and MZL, with frequent mutations of TP53 (3/8 patients). The disease seems relatively indolent as 5/18 patients were treated after a median follow-up of 4 years.
Conclusion
We have identified a group of patients presenting biological features intermediate between CLL and MZL. These B-cell disorders are characterized by a high frequency of chromosome 12 trisomy and a relatively indolent evolution. As these cases cannot be definitively classified in a category of the WHO classification, the choice of the first line treatment might be problematic: for patients presenting a TP53 alteration, if they are classified as CLL, ibrutinib is indicated, but this is not the case if they are classified as MZL. Other case series are mandatory to precise the optimal treatment of this B-cell disorder with intermediate features between CLL and MZL.
Session topic: 5. Chronic lymphocytic leukemia and related disorders – Biology & Translational Research
Keyword(s): B cell lymphoma, Chronic Lymphocytic Leukemia, WHO classification