Clinical and Pathologic Spectrum of DDX41-Mutated Hematolymphoid Neoplasms. Issue 5 (30th April 2021)

• Record Type: Journal Article
• Authors: Goyal, Tanu; Tu, Zheng Jin; Wang, Zhen; Cook, James R
• Is Part Of: American journal of clinical pathology. Volume 156:Issue 5(2021)
• Page Start: 829
• Page End: 838
• Publication Date: 2021-04-30
• Subjects: DDX41 -- Germline predisposition -- Hematolymphoid malignancies; Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqab027
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: Objectives: This study seeks to further characterize the clinicopathologic spectrum of DDX41 -mutated hematolymphoid malignancies. Methods: We identified DDX41 mutations from a cohort of known or suspected hematologic disorders and reviewed the corresponding clinical, genetic, phenotypic, and morphologic findings. Results: DDX41 mutations were identified in 20 (1.4%) of 1, 371 cases, including 8 cases of acute myeloid leukemia (AML), 5 cases of myelodysplastic syndrome (MDS), 2 cases of therapy-related MDS/AML, 1 case of primary myelofibrosis, 1 case of chronic myeloid leukemia, 1 case of clonal cytopenia of uncertain significance (CCUS), 1 case of T-cell large granular lymphocytic leukemia (T-LGL), and 1 case of multiple myeloma. DDX41- mutated neoplasms were morphologically heterogeneous with a median cellularity of 20% (range, 10%-100%). Megakaryocyte dysplasia occurred in 7 (35%) of 20 cases and trilineage dysplasia in 1 (5%). Frequently comutated genes include a second, somatic DDX41 mutation (8/19, 42%) followed by mutations in TET2 (20%), DNMT3A (20%), ASXL1 (20%), and CUX1 (20%). Karyotypes were noncomplex in 17 (89%) of 19. Conclusions: This report extends the spectrum of DDX41- mutated disorders to include CCUS, T-LGL, and plasma cell disorders. The morphologic features are heterogeneous and nonspecific, highlighting the importance of DDX41 testing during routine workup of hematolymphoid neoplasms.