Diagnostic and therapeutic challenges in hairy cell leukemia-variant: where are we in 2021?

ABSTRACT

Introduction

Hairy cell leukemia-variant (HCL-V) is a rare B-cell neoplasm arising or homing primarily in the spleen. It has been considered in the WHO classification of Hemopoietic and Lymphoid Tumors as a provisional entity since 2008 and included under the umbrella of unclassifiable splenomegalic B-cell leukemia/lymphomas. The diagnosis is a challenge to hematopathologists and management of these patients by the clinicians is difficult due to the lack of diagnostic and therapeutic guidelines and prospective studies.

Areas covered

This manuscript is a comprehensive review of the clinical features, pathology, immunophenotypic profile, genomic alterations and therapeutic options of HCL-V. Diagnostic and therapeutic dilemmas are extensively outlined considering the information derived from a literature search covering from 1980 to 2019. Integration of all the data is needed and recommended for establishing the diagnosis of this leukemia.

Expert opinion

More extensive information of genomic aberrations underlying the pathogenesis of the disease would be a solid stone for the diagnosis. To this end, a collaborative work among scientists and pathologists from different centers is required and expected. In turn, this might have a relevant clinical translation by allowing to identify putative targets for therapy and to improve the outlook of these patients.

KEYWORDS:

• Hairy cell leukemia variant
• TP53
• MAP2K1
• gene mutations
• immunophenotype
• diagnosis
• treatment

Article highlights

• HCL-V is included as a provisional entity in the WHO classification under the umbrella of unclassifiable splenic B cell leukemia/lymphoma

• It is considered to be biologically unrelated to typical HCL

• It has overlapping histological features with splenic diffuse red pulp lymphoma (SDRPL) but different cytology and outcome

• The diagnosis is a challenge to hematopathologists. This should be made on a constellation of features that includes cytology, flow cytometry, bone marrow histology and if available splenic histology

• Mutations of TP53 are frequent. MAP2K1 gene mutations have been documented with variable frequency whilst mutations on the BRAF gene have not been reported

• Age, anemia and TP53 mutations seem to be adverse prognostic factors for survival

• Unlike typical HCL, responses to single agent purine analog are not satisfactory. The best available option is chemoimmunotherapy

• The clinical course is chronic and median survivals range from 7 to 9 years

Disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.