PMC9330045_01
Bone marrow examination demonstrated eosinophils increased significantly. (A) Smear, Giemsa stain, 400x. (B) Smear, Giemsa stain, 1,000x. (C) Biopsy, H&E stain, 100x. (D) Biopsy, H&E stain, 400x.
fgene-13-948744-g001.jpg
PMC9330045_01_fgene-13-948744-g001.jpg
F1
Bone marrow (BM) examination showed significantly increased eosinophils (Figure 1). Cytogenetics showed an abnormal karyotype with 45, XX, -13 (1); 45, XX, -16 (1); 46, XX (18) (Supplementary Figure S1).
FDG-PET showed positive FDG uptake in multiple enlarged lymph nodes on 9 April (A) and 30 July (B), respectively. FDG-PET, positron-emission tomography with 18F-fluorodeoxyglucose.
fgene-13-948744-g002.jpg
PMC9330045_01_fgene-13-948744-g002.jpg
F2
As shown in Figure 2A, the FDG-PET on 9 April 2020 showed positive FDG uptake in multiple enlarged lymph nodes throughout the abdominal cavity and in the duodenum, terminal ileum, and colon. Two gastrointestinal specimens on 12 April 2020 and 3 May 2020 showed eosinophil invasion (Supplementary Figure S2). The FDG-PET on 30 July 2020 showed multiple enlarged lymph nodes in the body (Figure 2B).
Neoplastic cells in the specimen of the retroperitoneal lymph node showed intermediate-sized nuclei, copious pale/clear cytoplasm, and abundant clear cytoplasm (A,B). Immunohistochemistry of the neoplastic cells showed CD3+
(C), CD4+
(D), CD5+, CD8-, ICOS+ (E), Bcl-6+ (F), PD-1+ (G), Bcl-2+, Ki-67+ (70-80%), CD56-, TIA-1-, CD20-, CD79a-, CD10-, immunoblots CD30+, follicular dendritic cells CD21+
(H), and scattered lymphocytes EBER+ (I).
fgene-13-948744-g003.jpg
PMC9330045_01_fgene-13-948744-g003.jpg
F3
As shown in Figure 2A, the FDG-PET on 9 April 2020 showed positive FDG uptake in multiple enlarged lymph nodes throughout the abdominal cavity and in the duodenum, terminal ileum, and colon. The sample of the retroperitoneal lymph node showed that the neoplastic T cells had intermediate-sized nuclei, copious pale/clear cytoplasm, and abundant clear cytoplasm (Figures 3A, B). TIA-1-, CD20-, CD79a-, CD10-, immunoblasts CD30+, follicular dendritic cells CD21+, and scattered lymphocytes EBER+ (Figures 3C-I).
Comparison of VAFs before and at diagnosis. (A) VAF of the RHOA and TP53 mutations in different specimens at different periods. Five samples were involved, including one gastric, two intestinal, and two lymph node samples. (B) Map of clonal evolution. Four samples were collected, including two intestinal and two lymph node samples. VAF, variant allele frequency.
fgene-13-948744-g004.jpg
PMC9330045_01_fgene-13-948744-g004.jpg
F4
As shown in Figure 2A, the FDG-PET on 9 April 2020 showed positive FDG uptake in multiple enlarged lymph nodes throughout the abdominal cavity and in the duodenum, terminal ileum, and colon. TP53 Q100X mutation sites, with the variant allele frequencies (VAFs) of 16.00% and 20.60%, respectively. As shown in Figure 4, the VAFs of RHOA and TP53 gene mutations were 0.015% and 4.127%, respectively, in the gastric specimen on 12 April 2020. Also, they were both <0.001 in the intestinal specimen on 12 April 2020 and increased at a frequency of 0.023% and 1.198% on 3 May 2020. They were 1.299% and 3.303% in the abdominal lymph node specimen on 17 April 2020 and were elevated by 16.00% and 20.60%, respectively, on 6 August 2020 (Figure 4A). From the diagram of clonal evolution, the RHOA A161E mutation site was detected nearly 4 months before diagnosis in the lymph node specimen (Figure 4B), indicating that dynamic monitoring based on sequencing platforms at multiple time points may facilitate early detection of disease diagnosis in AITL.