Functional and morphological heterogeneity in HHs and study design. (A)
CT scan of a patient with a large hemangioma located in the left liver
lobe (asterisk). Specified imaging phases show an inhomogeneous uptake
of contrast agent in the lesion. (B) Three-dimensional reconstruction of
the hemangioma margin of the same patient. Limited density range
visualization removes liver-specific signal and visualizes inhomogeneous
uptake of contrast agent in HH. (C) Native and venous phase density
surface plots of the same patient. Inhomogeneous contrast agent uptake
in the lesion can be observed. (D) H&E images of five HHs with
different intralesional morphology as displayed by vascular morphology
and degree of tissue regression. Scale bar: 200 µm (low) and 100 µm
(high). (E) Distribution of the regression score in HH centers and
marginal zones (0 = “none,” 1 = “slight,” 2 = “intermediate,” 3 =
“strong,” 4 = “very strong”; n=63). (F) Stitched
H&E overview of the TMA consisting of five slides in total covering
98 HH, 80 HH margins, and 78 distant liver tissues and 339 cores in
total. (G) Low magnification overview of a tissue microarray section
after positive cell detection of the respective marker panel used in
this study (see Table 1). MET, MYC, and BRAF V600E were not digitally scored
due to negative staining results. Abbreviations: HH, hepatic hemangioma;
CT, computed tomography; H&E, hematoxylin and eosin; TMA, tissue
microarray.