Table 4.

Evaluation of six histologically proven FNH’s, Tumor A–F, respectively

	Tumor A	Tumor B	Tumor C	Tumor D	Tumor E	Tumor F
CK 19	Moderately positive: only lesion periphery shows a limited number of pre-existent bile-ducts and some ductular proliferation	Positive: lesion periphery shows stronger CK19 positivity due to ductular proliferation but no pre-existent bile-ducts. Lesion centre is almost completely negative for CK 19	Positive: areas with ductular proliferation of CK19 positive bile-ducts and pre-existent bile-ducts	No expression: only a few normal pre-existent bile-ducts, while normal parenchyma is strongly positive	Biopsy → insufficient tissue to perform CK19 staining	Positive: both pre-existent bile-ducts and bile-duct proliferation
CK 7	Markedly positive: mostly ductular proliferation around the tendrils of the fibrous scar, less ductular metaplasia	Strongly positive (++): in lesion centre mainly due to ductular metaplasia and only limited due to ductular proliferation. Lesion periphery also reveals combination of ductular metaplasia and proliferation	Strongly positive (++): especially the areas with ductular metaplasia and dedifferentiated hepatocytes due to bile flow obstruction show strong CK7 positivity. Little ductular proliferation	Strongly positive (++): positive throughout lesion, caused by well-differentiated ductular proliferation. There are no signs of metaplasia	Biopsy → insufficient tissue to perform CK7 staining	Slightly positive (±): ductular metaplasia
CD34	Positive (+); more CD34 expression than normal parenchyma, but not diffuse and therefore not suspicious for HCC	Positive (+); especially around the fibrous tissue, but not diffuse and therefore not suspicious for HCC	Strongly positive (++) around the vessels, but not diffuse and therefore not suspicious for HCC	Slightly positive (±): vascularization around fibrous septa is slightly positive, the rest of lesion is negative	Biopsy → insufficient tissue to perform CD34 staining	Biopsy → insufficient
Histological features	Central scar with extensive fibrous tissue visible in the core of the lesion. Only lesion periphery shows no fibrous tissue	No typical central scar, but increased fibrous tissue throughout lesion	Central scar (fibrous tissue)	No central scar, but areas of scar tissue	Cirrhotic intratumor transformation	Large fibrous component
		Inflammatory component in lesion centre	Vascular proliferation (large vessels with thickened vascular walls)	Many fibrous tissue septae	Many fibrous tissue septae	Increased number of bile-ducts compared to surrounding parenchyma
	Cirrhotic intratumor transformation with inflammatory component in lesion centre	Strong proliferation of well-differentiated bile-ducts especially in lesion periphery	Multiple areas of fibrous tissue	Vascular malformation and degeneration	Strong infiltration with lymphocytes	Both well-differentiated and de-differentiated bile-ducts
			Strong infiltration with lymphocytes	Strong infiltration with lymphocytes	Bile-duct proliferation	Considerable infiltration with lymphocytes
	Bile-duct proliferation, especially in lesion periphery	Extensive ductular metaplasia	Bile-duct proliferation	Strong bile-duct proliferation
Histology conclusion	Typical FNH	Typical FNH	FNH due to vascular malformation with secondary ischemia	FNH due to vascular malformation with secondary ischemia	Typical FNH	Typical FNH
FNH-type (radiology)	Hypo-intense-with-ring type FNH	Hypo-intense-without-ring type FNH	Inhomogeneous hyperintense type FNH	Inhomogeneous hyperintense type FNH	Inhomogeneous hyperintense type FNH	Iso-intense type FNH