Multiple areas of focal nodular hyperplasia in a pediatric patient following oncological therapy

Clinical History

An 11 year old male is status post resection, radiation, and bone marrow transplantation for a grade IV neuroblastoma 8 years previously, presents with abdominal pain and emesis.

Imaging Findings

A right upper quadrant US revealed multiple heterogeneous liver masses (Fig 1). Contrast enhanced CT showed multiple enhancing masses throughout the liver (Fig 2). A dynamically enhanced MRI revealed at least 12 liver lesions which were isointense with liver on T1 weighted sequences; hyperintense on T2 weighted sequences (Fig 3) and showed avid arterial enhancement (Fig 4) but rapid equilibration to the surrounding liver parenchyma during the portal venous phase of enhancement. These findings were not typical for metastatic disease and Focal Nodular Hyperplasia (FNH) was suspected. In order to confirm the diagnosis delayed imaging using gadobenate dimeglumine (Multihance, Bracco Inc.) was used; a hepato-specific contrast agent a proportion of which is excreted via the biliary system. This showed hyper intensity of all lesions some of which also demonstrated a central scar (Fig 5). These findings were in keeping with multiple FNH. One of the lesions was subsequently biopsied and confirmed the diagnosis.

Discussion

Focal Nodular Hyperplasia (FNH) is a relatively rare hepatic lesion in paediatric practice [1]. However, these lesions have been increasingly described occurring as a consequence of tumour therapy [2, 3, 4, 5, 6].
Histologically, classic FNH consists of multiple nodules of benign hepatocytes with abnormal architecture surrounding a central stellate scar with malformed vessels and bile duct proliferation [7,8]. While these lesions contain ductal components, they lack normal communicating bile ducts and exhibit chronic cholestasis [9,10]. It is currently accepted that FNH develops because of a hepatic vascular insult. Multiple aetiologies for this have been implicated including ischemia, arterio-venous malformations or vascular thrombosis [3,7]. It is assumed that the various oncological therapies mentioned above account for the originating vascular injury in the pediatric population group.

The imaging features of FNH are well described. On unenhanced CT, the typical appearance of FNH is a hypoattneuating or isoattenuating mass compared to the adjacent liver parenchyma. During the arterial phase of enhancement FNH shows avid homogeneous enhancement with lack of enhancement of the central scar during this phase. During the portal venous phase the typical lesion is isoattenuating to the adjacent liver parenchyma and the central scar may show enhancement during this phase [8,11].

Typical FNH findings on MRI are isointense to hypointense lesions on T1-weighted sequences, isointense to slight hyperintense lesions on T2-weighted sequences with hyperintensity of the central scar on T2-weighted sequences. The findings post intravenous gadolinium contrast injection are similar to post contrast CT findings with homogeneous enhancement during the arterial phase leading to hyperintensity compared to the liver parenchyma. During the portal venous phase of enhancement the lesions show isointensity to the surrounding parenchyma. As on CT there is enhancement of the central scar during later phases of enhancement [8,11,12].

Hepato-specific contrast agents can be helpful in better characterizing lesions suspected of representing FNH. Gadobenate dimeglumine is a paramagnetic gadolinium-based contrast agent which behaves like traditional gadolinium contrast agents in that they undergo a vascular-interstitial distribution after initial injection. However unlike traditional agents a proportion of gadobenate dimeglumine has a benzyloxymethyl group which is taken up by hepatocytes and excreted via the biliary tracts [13]. Because FNH are composed of hepatocytes and abnormally formed bile ducts, they take up gadobenate dimeglumine but excrete it more slowly than surrounding normal liver parenchyma leading to hyperintensity that persists on delayed imaging beyond 3 hours [12]. Metastatic disease to the liver does not exhibit enhancement on delayed imaging post gadobenate dimeglumine administration because cells of non hepatic origin have no specific cellular uptake of gadobenate dimeglumine [13].

In the context of a previous history of paediatric malignancy it is important to be able to exclude disease recurrence in the context of a new liver lesion. It is essential for general and paediatric radiologists to be aware that FNH may behave in this manner and that MR using gadobenate dimeglumine can help distinguish FNH from metastatic disease.

Differential Diagnosis List

Final Diagnosis

Multiple areas of focal nodular hyperplasia developing after chemotherapy/radiation therapy.

URL:	https://www.eurorad.org/case/7651
DOI:	10.1594/EURORAD/CASE.7651
ISSN:	1563-4086