Comprehensive morphologic characterization of bone marrow biopsy findings in a large cohort of patients with VEXAS syndrome: A single-institution longitudinal study of 111 bone marrow samples from 52 patients

Horatiu Olteanu; Mrinal Patnaik; Matthew J Koster; Jennifer L Herrick; Dong Chen; Rong He; David Viswanatha; Kenneth J Warrington; Ronald S Go; Abhishek A Mangaonkar; Taxiarchis Kourelis; Alexander Hines; Sarah E Gibson; Jess F Peterson; Kaaren K Reichard

doi:10.1093/ajcp/aqad186

Comprehensive morphologic characterization of bone marrow biopsy findings in a large cohort of patients with VEXAS syndrome: A single-institution longitudinal study of 111 bone marrow samples from 52 patients

Am J Clin Pathol. 2024 Feb 27:aqad186. doi: 10.1093/ajcp/aqad186. Online ahead of print.

Authors

Affiliations

¹ Division of Hematopathology, Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, US.
² Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, US.
³ Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN, US.
⁴ Department of Dermatology, Mayo Clinic, Rochester, MN, US.
⁵ Division of Hematopathology, Department of Pathology and Laboratory Medicine, Mayo Clinic, Phoenix, AZ, US.

PMID: 38413044
DOI: 10.1093/ajcp/aqad186

Abstract

Objectives: VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. Patients present with rheumatologic manifestations and cytopenias and may have an increased predisposition to myelodysplastic syndrome (MDS) and plasma cell neoplasms. Prior studies have reported on the peripheral blood and bone marrow findings in patients with VEXAS syndrome. Due to the protean clinical presentation and lack of specificity of morphologic features (eg, vacuoles in early erythroid and granulocytic precursors), an optimal screening methodology to identify these patients in a timely fashion is desirable.

Methods: To further evaluate and describe the salient diagnostic morphologic features in VEXAS syndrome, we carried out a comprehensive study of the largest single-institution cohort to date. Diagnostic and follow-up bone marrow biopsy specimens from 52 male patients with molecularly identified VEXAS syndrome underwent central review.

Results: Cytopenias were common in all cases, primarily macrocytic anemia, monocytopenia, and thrombocytopenia. Bone marrow aspirate and biopsy were often hypercellular, with an increased myeloid/erythroid ratio, granulocytic hyperplasia with left shift, erythroid left shift, and megakaryocyte hyperplasia, which exhibited a range of striking morphologic findings. Distinctly vacuolated myeloid and erythroid precursors were seen in more than 95% of cases.

Conclusions: Our data reveal potential novel diagnostic features, such as a high incidence of monocytopenia and distinct patterns of atypical megakaryopoiesis, that appear different from dysmegakaryopoiesis typically associated with MDS. In our experience, those findings are suggestive of VEXAS, in the appropriate clinical context.

Keywords: VEXAS syndrome; bone marrow; hematopathology; morphology.