Congenital hepatic fibrosis and its mimics: a clinicopathologic study of 19 cases at a single institution

Abstract

Background: Congenital hepatic fibrosis (CHF) is a rare inherited form of ductal plate malformation associated with polycystic kidney disease. The diagnosis requires histopathologic confirmation, but can be challenging to distinguish from other undefined fibrocystic liver diseases. We aimed to describe the clinicopathologic features of congenital hepatic fibrosis (CHF), with comparisons to other entities that may clinically and/or histologically mimic CHF.

Methods: Nineteen cases that carried a clinical and/or histologic impression of CHF were identified at our institution, of which the histology was reassessed and reappraised into two categories: CHF (n=13) and mimics (n=6). The clinicopathologic features between the two groups were analyzed and compared.

Results: The CHF group was further sub-classified into those with clinical suspicion (CHF-c, n=8) and those as incidental histology findings (CHF-i, n=5). Patients of CHF-i were much older than CHF-c or mimics (P<0.05). Male and female were equally affected. Six of 8 CHF-c (66.7%) had concurrent kidney diseases, including 5 polycystic kidney diseases. Five of 6 mimics (83.3%) had various kidney diseases, including nephronophthisis, Alport syndrome, renal agenesis, and nephrolithiasis. None of the CHF-i patients had kidney disease, but 3 were associated with hepatic carcinomas. Histology analysis demonstrated characteristic triads (bile duct abnormalities, portal vein hypoplasia, and fibrosis) in all CHF cases. One mimic had paucity of intrahepatic bile ducts, while the other 5 mimics showed abnormal portal veins and nodular regenerative hyperplasia consistent with hepatoportal sclerosis (HPS).

Conclusions: Our study demonstrates classic histology triad of CHF despite a wide spectrum of clinical presentations. HPS is unexpectedly a clinical mimicker of CHF, which can be distinguished histologically.

Keywords: Congenital hepatic fibrosis; Hepatoportal sclerosis; Nodular regenerative hyperplasia; Portal hypertension.

Fig. 1

Representative histology of congenital hepatic fibrosis. a Case 1. Broad fibrous bands containing abnormal bile duct profiles with anastomosing and ectasia separate the parenchyma into nodules without hepatocyte regeneration. b Case 3. The portal tract is expanded with prominent fibrosis. There are centrally located bile ducts with luminal dilatation and numerous smaller bile ducts at the limiting plate. The portal vein is hardly appreciated. c Case 9. The bile ducts are ectatic and irregular. The portal veins are small and the portal arteries are prominent and supernumerous. d Case 4. Trichrome stain highlights the portal fibrosis with embedded abnormal bile ducts. Magnification: 100x

Fig. 2

Mimics of CHF with histologic features of hepatoportal sclerosis. a-b Case 15. Biopsy (a) showing portal vein abnormalities with alternating obliteration/hypoplasia in some portal tracts, but dilation and herniation in other portal tracts. Reticulin stain in explant liver (b) confirms nodular regenerative hyperplasia. c Case 17. Sinusoidal dilatation with Kupffer cell hyperplasia and iron deposit. d Case 19. Focal and mild bile duct abnormalities that mimics ductal plate malformation. Magnification: 100x

Fig. 3

Paucity of intrahepatic bile ducts in a patient with nephronophthisis (case 14). a-b The liver shows thin delicate portal/periportal fibrosis and eccentrically located portal veins with dilatation and herniation. Bile duct is missing in approximately 68% portal tracts. c-d In one portal tract there are residual bile ducts highlighted by CK19 immunohistochemistry, somewhat resembling ductal plate malformation. Magnification: a-b: 100X, c-d: 200x

Fig. 4

Carcinomas associated with congenital hepatic fibrosis. Case 11 (a-b) showing numerous cystically dilated bile ducts in hilar area (a) and hepatocellular carcinoma (b, upper half) with adjacent portal tracts (b, lower half). Case 12 (c-d) showing background congenital hepatic fibrosis (c) and hepatocellular carcinoma (d. upper half) with adjacent portal tracts (d, lower half). Case 13 (e-f) showing background congenital hepatic fibrosis (e) and incidental findings of cholangiocarcinoma (f) involving a benign dilated duct. Magnification: a: 20X; b, c, e, f: 100X; d: 40X