A routine blood test was performed in a 47-year-old mother of three children working as a house keeper and revealed a mild elevation of γ glutamyltransferase (46 IU N<39). On ultrasound (March 2009) a liver nodule of 55 mm diameter was discovered in segment VII. Liver stiffness was measured by the acoustic radiation force impulse imaging method. The median (M) speed of 10 measurements was 2.55 m/s (19.57 kPa) with interquartile range (IQR)/M=0.40 in the tumoural liver and 1.05 m/s (3.3 kPa) with IQR/M=0.19 in the non-tumoural liver.
MRI features were more indicative of an HCA than of a FNH (). Indeed, this large hypervascular lesion of the segment VII did not in particular exhibit any central scar and was heterogenous in all sequences. Furthermore, part of the lesion had high signal intensity on T2W sequences with persistent enhancement in the gadolinium-enhanced delayed phase. This feature was suggestive of sinusoidal congestion and, therefore, the diagnosis of inflammatory HCA was raised.
Figure 1 MRI. (A) Axial fat suppressed T1W sequence shows a 55 mm diameter heterogenous nodule in the segment VII. (B) Axial fat suppressed T2W image shows heterogeneity of the lesion with a large hyperintense central area not suggestive of focal nodular hyperplasia (more ...)
The patient had been on oral contraceptive (Diane 35, Adepal) for more than 20 years until the last 11 months (tube ligation). Aside a lombar scoliosis and a discal hernia, her past history was unremarkable. Preoperative blood tests, including transaminases, alkaline phosphatase, bilirubin, glycaemia, cholesterol, triglycerides, ferritin, fibrinogen, C reactive protein (CRP), were normal.
The surgical specimen weighed 66 g. A needle biopsy (trucut) was performed into the nodule before cutting the fresh specimen. The tumour was tan, with an irregular surface and congestive darker areas. The non-tumoural liver was limited to a small rim. Several samples of the tumour and non-tumour tissue were immediately frozen in liquid nitrogen and stored at −80 °C and others were routinely processed for light microscopy and diagnosis purposes. The following stains were performed: H&E, Masson's trichrome, Perls, Gordon Sweet, as well as immunostains: cytokeratins 7 (CK7) and 19, liver fatty acid binding protein (LFABP), serum amyloid A (SAA), CRP, glutamine synthetase (GS) and β catenin.
Macroscopically, the tumour exhibited a vague nodularity (), better seen after formol fixation, but without any fibrous scar. At the microscopic level (needle biopsy and surgical specimen), the lesion corresponded to a benign hepatocellular proliferation with two parts: a dilated and a compact area (, and ).
Figure 2 (A) Biopsy specimen performed on the resected nodule at low magnification. (B) H&E staining at high magnification: dilated sinusoids are visible (right) associated with thick walled arteries. This aspect could suggest the diagnosis of hepatocellular (more ...)
Figure 3 In this area, (A) trichrome (TRI) staining and (B) α smooth muscle (SMA) immunostaining, two zones are easily identified: one with dilated sinusoids and one compact. (C,D) Illustrate zones in the vicinity of A and B. Overall, there is little fibrotic (more ...)
Figure 4 (A,B,C) are identical zones with different stainings. (A) Heavy glutamine synthetase (GS) staining focalised in the compact zone (right) is faintly present in the dilated zone (left); in this zone, dilated sinusoids surround areas containing many arteries (more ...)
The dilated area was composed of atrophic hepatocytes bordered by dilated sinusoids and centred by arteries (, and ). In some areas, sinusoids were massively dilated with almost no hepatocytes lining. In the centre of these areas, abnormal arteries were surrounded by a lymphocytic reaction containing ductules (CK7 and 19 positive) themselves surrounded by collagen bundles ().
In the compact area (–) there were major vascular abnormalities made of (1) numerous isolated dystrophic arteries with a thick wall, surrounded by a thin rim of collagen with no portal veins, and rare ductules; (2) hepatic veins with different aspects: normal, surrounded by congestive areas, partially or completely occluded among oedematous fibrous tissue, or haemorrhagic areas, or in contact with arteries, linked to other hepatic veins by very thin bundles of collagen ( and ).
Figure 5 Compact zone. (A) Illustrates the typical aspect of glutamine synthetase (GS) in focal nodular hyperplasia (compact zone). This staining is sharply different in the non-tumoural liver (NTL) where the staining is limited around the hepatic veins. (C) Numerous (more ...)
Compact zone. The veins in (A) and (B) are occlude and in part recanalised. (C,D) The lumen of this artery surrounded by connective tissue is not visible. SMA, α smooth muscle. TRI, trichrome.
Compact zone. (A,B,C,D) Illustrate the contact between arteries and veins. SMA, α smooth muscle.
The delimitation of the normal tissue was not clear.
LFABP, SAA, CRP and β catenin immunostaining was normal (not shown). In the compact area, GS pattern (, and ) was highly suggestive of FNH diagnosis as previously reported;7
this immunostaining was fainter in the dilated area. The non-tumoural liver was normal ().
The final report was FNH with major sinusoidal dilatation. Additional comments indicate that the FNH was lacking the key usual features such as central scar and fibrotic bands.
Gene expression was examined by quantitative reverse transcriptase-PCR. Results were normalised to the mean expression level of normal liver samples. ANGPT1/ANGPT2, NTS/HAL, GLUL and GPR49 were 73, 980, 7 and 9, respectively. CRP, SAA, LFABP and UGT2B7 were in the normal limit.