Peripheral Blood and Bone Marrow Findings in Treatment-Naive Patients With Cytopenia(s)/Myeloid Neoplasms Harboring Both a Germline and a Somatic DDX41 Mutation.

Document Type

Article

Publication Title

Applied immunohistochemistry & molecular morphology : AIMM / official publication of the Society for Applied Immunohistochemistry

Abstract

DDX41 -associated cytopenia(s)/myeloid neoplasms ( DDX41 -C/MNs) are an emerging pathologic entity. We examined the hematopathologic findings in DDX41 -C/MNs with both a germline and somatic DDX41 mutation ( DDX41 -C/MNs-GS). We reviewed the peripheral blood and bone marrow (BM) findings from treatment-naive patients with DDX41 -C/MNs-GS. Thirty cases were identified: 10% (3/30) were classified as clonal cytopenia(s) of unknown significance (CCUS), 17% (5/30) as myelodysplastic neoplasm/syndrome (MDS) with < 5% blasts, 20% (6/30) as MDS with 5% to 9% blasts, 20% (6/30) as MDS with 10% to 19% blasts, and 33% (10/30) as acute myeloid leukemia (AML). All patients were cytopenic; circulating blasts were rare (23%, 7/30). 63% (19/30) showed dysmegakaryopoiesis. Dyserythropoiesis and dysgranulopoiesis were uncommon; seen in 20% (6/30) and 7% (2/30), respectively. Sixty-six percent (19/29) of cases were normocellular; 43% (13/30) showed erythroid predominance. Flow cytometry revealed an unremarkable blast myeloid phenotype. Blasts were intermediate sized with round nuclei, distinct nucleoli, and light blue cytoplasm with azurophilic granules. The karyotype was predominantly normal (93%, 26/28). All germline mutations were deleterious: 53% (16/30) truncating and 47% (14/30) missense. The most common somatic variant was the R525H mutation in 70% (21/30). The BM diagnostic spectrum in DDX41- C/MNs that harbor both a germline and somatic DDX41 mutation is broad-ranging from CCUS to AML. We describe consistent hematopathologic findings that pathologists may expect in these cases.

First Page

371

Last Page

381

DOI

10.1097/PAI.0000000000001215

Publication Date

9-1-2024

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