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. 2024 Jan 11;8(1):e0359. doi: 10.1097/HC9.0000000000000359

FIGURE 4.

FIGURE 4

Immunologic characterization of the human HEHE/adjacent liver parenchyma interface. (A) Low and high magnification of HE, ARG1, VIM, CD31, CD34 and FVIII at the HEHE/adjacent liver interface. Scale bar: 400 µm (low) and 100 µm (high). (B) Low and high magnification of CD3, CD4, CD8, CD20, CD79A, CD68, CD117, CD163 and MPO at the HEHE/adjacent liver parenchyma interface. Scale bar: 400 µm (low) and 100 µm (high). (C) Depiction of ARG1+, VIM+, CD3+, CD8+, MPO+ and CD163+ cell density overlay at the HEHE/adjacent liver interface. ARG1 highlights hepatocytes, and CD3, CD8 and CD163 show clear immunologic demarcation at the liver lesion interface. Spatial cell distribution of CD3, CD8 and MPO reveals high-density foci of marker-positive cells also within HEHE. Scale bar: 400 µm. (D) Percentual distribution of ARG1, VIM, CD3, CD8, CD20, CD79A, CD68, CD163 and MPO in the distant liver, HEHE/adjacent liver parenchyma interface (margin), and HEHE centers. Wilcoxon rank-sum test of HEHE centers versus tissue area of interest (*p < 0.05, **p < 0.01, ***p < 0.001, n.s. = not significant). (E) Heat maps displaying pairwise correlation metrics of marker-positive cells (%) in HEHE centers and at the HEHE/adjacent liver interface. Spearman correlation coefficient displayed as a color code from 1 (blue) to −1 (red; *p < 0.05, **p < 0.01, ***p < 0.001). (F) Barplot depicting percentual infiltration of marker-positive immune cells in HH/HEHE in an entity-specific comparison. Comparison of HH (overall) versus HEHE (overall) by Wilcoxon rank-sum test (*p < 0.05, **p < 0.01, ***p < 0.001, n.s. = not significant). (G) Graphical abstract summarizing the main results of this study. Abbreviations: ARG1, Arginase 1; FVIII, FVIII-related antigen; HE, hematoxylin eosin; HEHE, hepatic epithelioid hemangioendothelioma; HH, hepatic hemangioma. MPO, Myeloperoxidase; VIM, Vimentin.