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
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引用次数: 0
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.
期刊介绍:
The American Journal of Clinical Pathology (AJCP) is the official journal of the American Society for Clinical Pathology and the Academy of Clinical Laboratory Physicians and Scientists. It is a leading international journal for publication of articles concerning novel anatomic pathology and laboratory medicine observations on human disease. AJCP emphasizes articles that focus on the application of evolving technologies for the diagnosis and characterization of diseases and conditions, as well as those that have a direct link toward improving patient care.