Nodular regenerative hyperplasia of the liver: coral atoll-like lesions on ultrasound are characteristic in predisposed patients

Abstract

Nodular regenerative hyperplasia (NRH) is an uncommon liver disease characterised histologically by numerous small hyperplastic nodules that are not separated by fibrotic tissue. It is thought to be the result of obliterative vasculopathy, and it has been associated with chronic use of medications, toxic substances and a wide variety of systemic diseases. Imaging diagnosis of early-stage NRH remains problematic. The nodules are rarely discerned and their appearance and behaviour before and after contrast medium administration are heterogeneous and not specific. A review of the literature shows that ultrasound has succeeded on occasion in revealing small focal liver lesions in patients with NRH. To our knowledge, there has been no published data on the performance in this setting of last-generation ultrasound scanners and techniques such as contrast-enhanced ultrasound (CEUS). The question is an important one because abdominal ultrasound is widely used as a first-line imaging technique for the evaluation of liver disease, and this makes it particularly suitable as a potential tool for the early diagnosis of NRH. Owing to the prolonged subclinical period and the limited help provided by imaging, the diagnosis in vivo of NRH is currently frequently missed, and it is still made exclusively on the basis of liver biopsy. In conclusion, this report describes 4 cases of biopsy-proven NRH that have been diagnosed over the past 2 years by our group. All were characterised by known comorbidities that confer a predisposition to NRH and by a peculiar parenchymal ultrasound pattern that we refer to as the "atoll sign".

Figure 1

Case 1, (a) upper abdominal ultrasound scan of the right hepatic lobe performed with a 3.5 MHz convex probe. The scan revealed an atoll-like pattern consisting of clusters of small (11 mm) round isoechoic focal lesions with thin hyperechoic rims (arrows). (b) Upper abdominal ultrasound scan of the left hepatic lobe (performed with a 7.5 MHz linear probe). Detail of one of the focal lesions, which produces no “mass effect” at the liver surface. (c) Histological appearance of one of the focal lesions in the right lobe (ultrasound-guided fine-needle biopsy). Regenerative hyperplastic hepatocytes are arranged in plates more than one cell thick that in turn form micronodules. Some of hepatocytes display nuclear hypertrophy (HE 4×). (d) With reticulin staining, the regenerative hyperplasic nodules and their compression of surrounding tissues are easily visualised (20×). Note the absence of fibrosis between the nodules.

Figure 2

(a) Case 2, upper abdominal ultrasound scan on the right hepatic lobe (using a 3.5 MHz convex probe). Multiple lesions, isoechoic with a thin hyperechoic rim, are visible (arrows), the larger diameter of such lesions is 12 mm. (b) Case 2, histological sample from ultrasound-guided fine-needle biopsy on one of the focal lesions of the right liver lobe. Regenerative hyperplastic hepatocytes are arranged in micronodules with microacinar appearance (arrows) (HE stain, 40×). (c) Case 3, upper abdominal ultrasound scan on the right hepatic lobe (using a 3.5 MHz convex probe). Some round isoechoic lesions with a thin hyperechoic rim, with a larger diameter of 10 mm, are present (arrows). (d) Case 3, histological sample from ultrasound-guided fine-needle biopsy on one of the focal lesions of the right liver lobe. The nodular arrangement of multilayered regenerative hyperplasic hepatocytes is evident. Some of them show hypertrophic nuclei (HE 40×). (e) Case 4, upper abdominal ultrasound scan on the right hepatic lobe (3.5 MHz convex probe). Rare round focal lesions, isoechoic with a hyperechoic rim, with a larger diameter of 13 mm, are visible (arrows). (f) Case 4, reticulin staining clearly reveals both the nodular arrangement of hepatocytes and the absence of fibrosis between the nodules (40×).

Figure 3

The focal lesions of nodular regenerative hyperplasia resemble the ring-shaped coral island known as an atoll (aerial view of Ari atoll, Maldives).