Immunological demarcation and intralesional immune cell infiltration of human hepatic hemangiomas and hepatic epithelioid hemangioendotheliomas. (A) HE stain of HH/adjacent liver interface and magnified region of interest with characteristic immunological demarcation. Scale bar: 200 µm (low) and 100 µm (high). (B) HE stain of HEHE/adjacent liver interface and magnified region of interest with indistinct lesion border. Scale bar: 800 µm (low) and 200 µm (high). (C) HH-TMA cohort as previously published.6 TMA contained patient material from 98 HH and 80 HH margins. HEHE cohort contained 9 HEHEs and 9 margins. (D) Immune cell detection within HH/HEHE cores by a trained cell classifier. Magnified regions of interest and full cores of HE, overlaid cell detections, and cell densities are displayed. Scale bar: 400 µm (low) and 100 µm (high). (E) Violin plots of quantified immune cell detections reveal significantly enriched immune cell density in HH margins but not HH centers, while HEHE margins remain statistically not significant. Wilcoxon rank-sum test (***p <0.001, n.s.). (F) Immunohistochemistry of HH/HEHE whole slides against sinusoidal EC markers STAB1, STAB2, CD32, and LYVE-1. The majority of HH ECs are negative for sinusoidal EC markers, while a higher proportion of HEHE ECs retain partial sinusoidal marker expression. Scale bar: 100 µm. (G) Barplots showing the percentual distribution of marker-positive ECs in HH/HEHE whole slides. The majority of HH ECs are negative for STAB1, STAB2, CD32, and LYVE-1, while a majority of HEHE ECs retain STAB1 (HH n = 47, HEHE n = 13). Abbreviations: EC, endothelial cell; HEHE, hepatic epithelioid hemangioendothelioma; HH, hepatic hemangioma; LYVE-1, Lymphatic Vessel Endothelial Hyaluronan Receptor 1; STAB1, Stabilin1; STAB2, Stabilin2; TMA, tissue microarray.