PMC9218563_01
Clinical course of the patient. CRP, C-reactive protein; Hb, hemoglobin; IgG, immunoglobulin G; MCV, mean corpuscular volume; MM, multiple myeloma; PSL, prednisolone; RP, relapsing polychondritis; TP, total protein.
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His previous clinical course is shown in Figure 1. The inflammation of the auricular region and CRP decreased, and the patient did not show relapse of any symptoms (Figure 1).
(A) Result of 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography. There is marked FDG accumulation in the ribs, vertebrae, and ilium. (B) A floppy left ear. Our patient had prominent redness and pain in the left auricular region. (C) Histological findings of a biopsy specimen from the left auricle. Inflammatory cell infiltration of neutrophils around the auricular cartilage is observed (C-1). In addition, granuloma formation consisting of fibrosis and hypervascularization suggestive of chronic inflammation is observed (C-2) (hematoxylin and eosin staining, (C-1) original magnification x40, (C-2) original magnification x100). (D) Bone marrow smear findings. (D-1) Clonal expansion of plasma cells is shown by the yellow arrows. The bone marrow dysplasia suggesting MDS is not observed. (D-2) Vacuolization in granulocytic precursor cells are shown by green arrow. (May-Giemsa staining, (D-1) original magnification x400, (D-2) original magnification x1000).
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A skeletal survey via 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography showed diffuse FDG uptake in the ribs, vertebrae, and ilium (Figure 2A). Physical examination revealed a floppy appearance of both the ears (Figure 2B), whereas there were no abnormal findings in his nasal and tracheal cartilages, eyes, and skin. Biopsy was performed on the skin and cartilage of the left auricle, and the histological findings showed cellular infiltrates of lymphocytes, neutrophils, and plasma cells, especially at the cartilage-skin interface, and a reduced number of chondrocytes in areas of cartilage destruction (Figure 2C). Re-evaluating the BM smear at the time of MM diagnosis revealed scattered granulocyte precursor cells containing cytoplasmic vacuoles (Figure 2D) in addition to the clonal expansion of plasma cells (Figure 2D).
Sanger sequencing (exome sequencing) of genomic DNA from peripheral blood (red arrows) revealed that the patient had the electropherogram's peak of a somatic variant in UBA1 (NM_003334.3:c.122T>C:p.Met41Thr). To further validate the low-prevalence somatic variants in UBA1, peptide nucleic acid-clamping polymerase chain reaction was performed. The pathogenic variant at c.122T>C:p.Met41Thr is seen (red arrows) in a condition where the wild-type allele was not amplified.
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Genomic DNA from peripheral blood leukocytes was subjected to Sanger sequencing and peptide nucleic acid-clamping PCR of UBA1, identifying a somatic variant (NM_003334.3:c.122T>C:p.Met41Thr) (Figure 3) that strongly supported the diagnosis of VEXAS syndrome.