Myeloid and lymphoid vacuolation in <scp>VEXAS</scp> syndrome

A 70-year-old Chinese male presented with unexplained fever, relapsing polychondritis, macrocytic anemia, acute necrotising lymphadenitis, skin papules that were in keeping histologically Kikuchi-Fujimoto disease, and pulmonary embolism secondary to extensive unprovoked right lower limb deep vein thrombosis. Given the recent discovery of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome,1 Sanger sequencing was performed on patient's peripheral blood buccal swab specimens, where p.Met41Leu missense mutation [NM_153280.3:c.121A?C; ClinVar accession number SCV001450457] detected but not swab, consistent a somatic X-linked codon 41 UBA1 gene which confirmed diagnosis. He subsequently treated hydroxychloroquine, methotrexate prednisolone improvement his autoimmune features. retrospective review bone marrow examination, previously ordered July 2019 exclude haematologic disease due constitutional symptoms, performed. The full count showed hemoglobin concentration 9.5 g/dL, white cell 6.3 x 109/L platelet 351 × 109/L. Peripheral film examination dysplastic neutrophils occasional forms showing vacuolation. Bone aspirate moderately hypocellular fragments adequate trilineage hematopoiesis. Dysplastic features seen both myeloid erythroid series no increased blasts. Iron stores markedly ringed sideroblasts seen. In series, cytoplasmic vacuolation observed predominantly myelomonocytic precursors (Image top left (A), center (B), (C)) lesser extent (D)) giant platelets bottom (E), (F)). Interestingly, plasma cells as well (G), (H)). Cancer cytogenetics revealed normal 46XY karyotype. Other causes for hematopoietic including copper deficiency,2 zinc excess3 history alcohol use4 excluded. While previous report,5 occurring exclusively cells, our patient. This observation is plausible, given findings Beck et al.1 early progenitor show mosaicism apart from precursors, abundant mutant lymphoid progenitors isolated marrow. Dysfunction UBA1, specifically may affect first step ubiquitin conjugation (ubiquitination) targets cellular proteins degradation via proteasomes accumulation intracellular vacuoles ensue mutation. contrast, study myelodysplastic syndrome by International Working Group Morphology MDS,6 be generally irregular shape, tendency coalesce, indistinct outlines, suggest presence glycogen (rather than lipids round vacuoles). also emphasized rarely recorded non-neoplastic conditions. Hematologists haematopathologists should mindful spectrum disorders, ranging commoner such heavy intake, rarer cases deficiencies or excess. pathognomic syndrome, elderly patients raise clinical suspicion warrant further genetic mutations. data support this are available corresponding author upon reasonable request.