Unclassifiable Isolated Monoclonal Lymphocytosis: Comprehensive Description of a Retrospective Cohort.

Degaud Degaud,Grange Grange,Huet Huet,Callet-Bauchu Callet-Bauchu,Manzoni Manzoni,Sujobert Sujobert,Traverse-Glehen Traverse-Glehen,Davi Davi,Ghesquières Ghesquières,Baseggio Baseggio,Salles Salles

doi:10.3390/cancers11101495

Abstract

According to the World Health Organization (WHO) classification, the nosology of B-cell neoplasms integrates clinical, morphological, phenotypic, and genetic data. In this retrospective analysis, we identified 18 patients with isolated neoplastic lymphocytosis that could not be accurately classified within the WHO classification. Most of them were asymptomatic at the time of diagnosis and the evolution was relatively indolent, as only five patients required treatment after a median follow-up of 48 months. The neoplastic B-cells expressed CD5 in most cases, but the Royal Marsden Hospital score was strictly below 3. Trisomy 12 was the most frequent cytogenetic abnormality. High-throughput sequencing highlighted mutations found in both chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL). Similarly, the immunoglobulin heavy chain variable region repertoire was distinct from those reported in CLL or MZL. However, as treatment choice is dependent on the correct classification of the lymphoproliferative disorder, a histological diagnosis should be performed in case patients need to be treated.

Highlights

As stated in the fourth edition of the World Health Organization (WHO) classification of hematological malignancies, “classification is the language of medicine” [1]
Cytological examination of blood smears found in all patients both chronic lymphocytic leukemia (CLL)-like and marginal zone lymphoma (MZL)-like atypical lymphocytes [13]
The IGH variable region (IGHV) repertoire, which was mostly mutated, seemed distinct from those reported in CLL [10], MZL [9], or in the recently described clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) [24]

Summary

Introduction

As stated in the fourth edition of the World Health Organization (WHO) classification of hematological malignancies, “classification is the language of medicine” [1]. The classification of lymphoid neoplasms integrates clinical, morphological, phenotypic, and genetic data to associate a malignant cell to its supposed normal counterpart. The accuracy of classification is even more important with the use of targeted therapies, as their authorization is restricted to specific nosological entities with a given molecular alteration [2]. Lymphocytosis (defined as an absolute lymphocyte count above 5 G/L) is a frequent clinical presentation of B-cell neoplasms. Lymphocytosis can represent the dissemination in the blood of an overt lymphoma, or can be the only detectable manifestation of the neoplasm. In the latter case, accurate diagnosis relies exclusively on the characterization of the circulating lymphocytes, based on cytology, immunophenotyping, cytogenetics, and/or molecular biology. The diagnosis of chronic lymphocytic leukemia (CLL) requires a Royal Marsden Hospital (RMH) score [3,4] of three or more

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Conclusion