PMC9354849_01
Important events of the patient according to the timeline.
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F1
Figure 1 summarizes the important events of this patient according to the timeline.
Histopathology of biopsy. (A-H) the first biopsy of the right inguinal lymph node which is diagnosed as angioimmunoblastic T-cell lymphoma and (I-P) the second biopsy of the right neck lymph node which is diagnosed as Epstein-Barr virus + diffuse large B-cell lymphoma. (A) a large number of diffuse medium-sized atypical lymphocytes proliferated with vascularity was observed. (B) increased extrafollicular follicular dendritic cell meshwork was observed. Immunohistochemical staining demonstrated that the lymphocytes were positive for CD3 (C), CD4 (D), PD-1 (E), and CXCL13 (F). (G) both the medium-sized T lymphocytes and scattered large B cells were positive for Ki67. (H) B cells were positive for EBER. Abnormal hyperplasia of large cells was observed (I), and the cells were positive for CD20 (J), Ki-67 (K), and LMP1 (L) and negative for CD3 (M). (N) the small lymphocytes were positive for TIA-1. (O) only the scattered small lymphocytes were positive for CD4, and the histiocytes were weakly positive for CD4. (P) most of the large B cells were positive for EBER.
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F2
A biopsy of the right inguinal lymph node demonstrated a large number of diffuse medium-sized atypical lymphocytes proliferated with vascularity (Figure 2A), together with increased extrafollicular follicular dendritic cell meshwork (Figure 2B). Immunohistochemical (IHC) staining demonstrated that the lymphocytes were positive for CD3 (Figure 2C), CD4 (Figure 2D), BCL6, CD10, PD-1 (Figure 2E), CXCL13 (Figure 2F), and Ki-67 (75%) (Figure 2G) staining. CD20, PAX5, CD30, Ki-67, and EBV-encoded RNA (EBER), as detected by the IHC staining and in situ hybridization (Figure 2H). Capillary electrophoresis showed that the cells were negative for IgH and TCR gene rearrangements. TFH disappeared following 157 days of the first lymph node biopsy, together with abnormal hyperplasia of large cells (Figure 2I), which showed diffuse or focal distribution and were positive for CD20 (Figure 2J), CD79a, CD30, BCL6, BCL2, c-MYC, Ki-67 (Figure 2K), and LMP1 (Figure 2L) and negative for EBNA2 and CD3 (Figure 2M) staining. The small lymphocytes were positive for CD5, CD2, CD7, CD8, CD43, TIA-1 (Figure 2N), GrB, and Ki-67 (30%) and negative for CD10, PD-1, CXCL13, CD56, and CD30. The scattered small lymphocytes were positive for CD4, and histiocytes were weakly positive for CD4 (Figure 2O). In addition, the large B cells were positive for EBER (Figure 2P) and PD-L1 staining, as well as IgH gene rearrangement.
Mutated genes of the primary and progression samples.
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Mutations in 10 genes were detected in both primary and transformed samples, while RHOA (G17V) mutation disappeared and mutations in JAK2 and TRIP12 genes emerged in the transformed sample (Figure 3).
Differences of 22 types of immune cells between the primary and progression samples.
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Then, 22 kinds of immune cell populations in the TME of the primary and transformed samples were compared by CIBERSORT deconvolution algorithm (v 1.03) as previously described. The numbers of memory B cells, TFH cells, regulatory T cells (Treg), and CD4+ T-memory resting cells were decreased in the transformed sample as compared with the primary sample, while the numbers of CD8+T cells, activated CD4+ memory T cells, gammadeltaT cells, activated NK cells, and M2 macrophages were increased (Figure 4).