PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of bmjcrBMJ Case ReportsVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
 
BMJ Case Rep. 2010; 2010: bcr0220102704.
Published online 2010 September 29. doi:  10.1136/bcr.02.2010.2704
PMCID: PMC3027794
Unusual presentation of more common disease/injury

Spontaneous regression of focal nodular hyperplasia: a pathological report

Abstract

Focal nodular hyperplasia (FNH) is a benign tumour of the liver, occurring in 0.6–3% of the general population. Most lesions are diagnosed incidentally. With the increasing use and improvement of diagnostic imaging, FNH is being observed more often. It has been shown, using radiological approaches, that most FNH remain stable, or even regress, over a long follow-up period. In addition, it is extremely rare that FNH were discovered in elderly. However, to our knowledge, there is no pathological report illustrating the regression of FNH.

We report here a case showing the pathological changes occurring during the regression phase of FNH, with dense fibrous tissue mixed with arteries replacing hepatocytes nodules.

Background

Focal nodular hyperplasia (FNH) is a benign tumour of the liver, occurring in 0.6–3% of the general population.1 It consists of circumscribed nodules of the hyperplastic parenchyma surrounded by more or less continuous fibrous bands radiating from a stellate, fibrotic scar containing dystrophic vessels, mainly thick-walled arteries. Most lesions are diagnosed incidentally. Surgery is not recommended, except in few cases when the tumour compresses neighbouring organs, liver vessels or bile ducts. With the increasing use and improvement of diagnostic imaging, FNH is being observed more often. In the past, FNH has been one of the most challenging hepatic lesions for radiologists; however, recent technical advances in imaging have improved diagnostic accuracy.2 3 In rare cases, when imaging and liver biopsy have failed to confirm the diagnosis, final diagnosis is achieved only at the time of surgery.4 However, recently the pathological diagnosis of FNH has been greatly facilitated by the use of glutamine synthetase immunostaining.5 6

Follow-up studies have been performed only in small series of patients. It has been shown using radiological approaches that most FNH remain stable or even regress over a long follow-up period.79 In addition, it is extremely rare that FNH were discovered in elderly. However, to our knowledge there is no pathological report illustrating the regression of FNH.

Case presentation

A 60-year-old woman was admitted to a local hospital for an acute abdominal pain on 18 February 2009. On CT scan, a large subcapsular haematoma was discovered. There was no haemorrhagic shock. She was admitted to our digestive intensive care unit.

This overweight patient (body mass index 29) was treated for hypertension for a short period of time when she was 16 years old and then since 1994. She was also treated for high cholesterol level (past 10 years) and hypertriglyceridaemia (past 4 years). There was a family history of heart diseases (her mother, the father and brother of the mother; her brother had died at a young age of heart infarcts or arterial hypertension).

She smoked 1 pack of cigarettes/day (for 42 years) and took contraceptive pills for 20 years. She was menopaused at the age of 45 with a substitutive hormonal treatment until 2000.

In 2005 she had an MRI showing at least three FNH (figure 1), one located in the right lobe (58 mm), and two (40 and 30 mm) located in the left lobe, as well as liver steatosis. The three nodules had characteristic MRI pattern of FNH with strong arterial enhancement and typical central scar in particular.

Figure 1
2005 MRI showing typical FNHs. (A) Phase opposed T1 image showing nodules in segments VII (58 mm) and II (40 mm), appearing hyperintense in a steatotic liver. (B) Fat suppressed T2W scan showing both hyperintense lesions, with a high signal intensity ...

On the last MRI (2009) there was another tumour with strong arguments for a hepatocellular carcinoma (HCC) (data not shown) with an intrahepatic rupture (figure 2) and subcapsular haematoma. The three FNH were still present (figure 2) with a significant shrinkage (segment VII: 41 mm vs 58 mm diameter in 2005, segment II: 21 mm vs 40 mm, segment II (data not shown): 16 mm vs 30 mm). Furthermore in 2009, MRI features of the segment VII lesion had changed and were no more typical of FNH. This lesion was in particular heterogenous in T2W with an atypical hypointense central scar and did not exhibit the characteristic strong arterial enhancement after gadolinium-contrast injection. In the portal venous and delayed gadolinium-enhanced sequences, the lesion showed progressive enhancement suggestive of fibrous component.

Figure 2
2009 MRI. (A) Fat-suppressed T2W image shows a large subcapsular haematoma and shrinkage of the segment VII FNH (41 mm) which appears heterogenous with atypical hypointense central scar (arrow). (B) Gadolinium-enhanced fat-suppressed T1W sequence (arterial ...

The patient underwent a right hepatectomy and a segment II tumorectomy on 26 February 2009. The follow-up was uneventful except for a parietal abcess.

Pathological results

The resected liver portion had a weight of 2000 g. In the right lobe, the large subcapsular hematoma (15 × 10 cm) was in contact with a subcapsular multinodular necrotico haemorrhagic poorly limited tumour (figure 3). This tumour was a grade 3–4 Edmonson HCC (data not shown).

Figure 3
(A,B) Fresh resected specimen. (A) Cut section of the haematoma and part of the hepatocellular carcinoma (HCC); (B) cut section of the shrunked FNH; the haematoma is also visible (right).

Nearby the HCC, there was another whitish/brown, hard tumour (4 × 3 cm) (figure 3). At the microscopic level, part of the tumour was a recognisable FNH, with hepatocytes nodules surrounded by fibrotic bands, inflammatory infiltrate and mild ductular reaction (figures 4 and and5),5), and with a typical GS immunostaining (figure 6). The other part of the tumour was more fibrotic (figures 4 and and5),5), with numerous arteries exhibiting extremely thick walls and a very narrow lumen (figure 7). In this area devoid of hepatocytes, glutamine synthetase staining was negative (figure 6), and there was no ductular reaction (figure 8). In segment II, there was a typical FNH (figure 3) with large steatotic areas (data not shown) and the characteristic GS staining (figure 9). The non-tumoral liver was steatosic (80%) (data not shown).

Figure 4
The FNH is made of two parts: the fibrotic pink part in the middle limited by the dotted line and the peripheral part corresponding to a more classical aspect of FNH. The fibrotic parts contain mainly arteries (arrows).
Figure 5
The fibrotic zone (upper part) is devoid of glutamine synthetase (GS) staining, compared to the rest of the FNH.
Figure 6
There is no cytokeratin 7 (CK7) staining in the fibrotic area (upper part) compared to its periphery.
Figure 7
In the fibrotic area, there are many arteries with thick wall and narrow lumen. SMA, smooth muscle antibody.
Figure 8
No ductular reaction was observed in the area devoid of hepatocytes and with numerous arteries.
Figure 9
Cut section of segment three FNH (seen in the upper right corner). Glutamine synthetase (GS) well delineates the nodule. Compared to GS localisation in the non-tumoral liver, restricted to a few hepatocytes rows around hepatic veins, in FNH the staining ...

Differential diagnosis

In this case, no differential diagnosis was discussed. In the absence of a previous diagnosis of FNH, the other diagnosis to be discussed on the MRI were liver cell adenoma and metastasis.

Outcome and follow-up

In May 2010, the patient was in good health.

Discussion

Although FNH regression has been described in a couple of case reports,1014 there are only few data describing this phenomenon at the pathological level.79

In one study,9 the volumes of FNH were found stable in six cases, decreased in 10 cases and increased in two cases, using CT and MRI observation after a mean follow-up period of 37.6 months. In another report where sonographic follow-up was carried out,7 it was reported that size reduction of FNH occurred in 8 of 16 patients after a mean follow-up period of 33 months. In the last published series of patients,8 with the longest follow-up period (a mean of 42 months), most lesions (70.6%) were stable in size; only 1 lesion (2.9%) increased, and the others (26.5%) decreased or even disappeared over time.

FNH more frequently occurs in women between the ages of 20 and 50.4 Because of the female predominance and the young age at onset, a role of female hormones has been suggested, but definite evidence has not been provided yet. It has been considered previously that oral contraceptive use and pregnancy might be associated with the enlargement of FNH; however, one study indicated that use of contraceptive pills did not increase the incidence of FNH.15

Kuo et al8 investigated the possible factors associated with the evolution in FNH. Although there was no difference between FNH with or without regression, the significant factors associated with disappearance of FNH were older age (p < 0.05), nodule diameter <2 cm (p < 0.05) and longer follow-up time (p value not significant). Multiple logistic regression analysis revealed that older age and longer follow-up time were the independent factors associated with the disappearance of FNH. The association between the disappearance of FNH and older age might be explained by reduced female hormonal levels in older women.

In the present study, although all FNH decreased in size (MRI), on the resected specimen, one was still a classical type of FNH (segment II) and the other one was in the involution process and can be considered as a non-classical FNH.

To our knowledge, this is the first case report showing the pathological changes occurring during the regression phase, with dense fibrous tissue mixed with arteries replacing hepatocytes nodules. FNH is a polyclonal lesion thought to originate from a hyperplastic response to an anomalous vascular supply.16 The FNH involution is probably controlled by an arterial ischaemia leading to loss of hepatocytes and ducts, which are replaced by fibrotic tissue. The shrunk tissue contained numerous arteries with a very narrow lumen, compared to the extremely thick wall. The loss of hepatocytes explains why the so characteristic FNH glutamine synthetase staining5 was missing in such regressing FNH. In our case, this characteristic staining was nevertheless observed in the area with preserved hepatocytes.

The diagnosis of involuted FNH would probably be extremely difficult on a liver biopsy if the sampled tissue did not contain hepatocytes. It is likely that with the extensive use of modern imaging techniques, more and more non-diagnosis liver nodules will be identified and perhaps treated. More pathological data are needed to recognise those entirely benign nodules which indeed may completely disappear

Learning points

  • Spontaneous regression of FNH is a phenomenon rarely reported and may be accompanied by the loss of classical criteria for MRI diagnosis.
  • Pathological diagnosis may be difficult on liver biopsy sample.
  • Pathological changes occurring during the regression phase of FNH mainly include dense fibrous tissue mixed with arteries replacing hepatocytes nodules.

Footnotes

Competing interests None.

Patient consent Obtained.

References

1. Vilgrain V, Uzan F, Brancatelli G, et al. Prevalence of hepatic hemangioma in patients with focal nodular hyperplasia: MR imaging analysis. Radiology 2003;229:75–9. [PubMed]
2. Bonney GK, Gomez D, Al-Mukhtar A, et al. Indication for treatment and long-term outcome of focal nodular hyperplasia. HPB (Oxford) 2007;9:368–72. [PubMed]
3. Zech CJ, Grazioli L, Breuer J, et al. Diagnostic performance and description of morphological features of focal nodular hyperplasia in Gd-EOB-DTPA-enhanced liver magnetic resonance imaging: results of a multicenter trial. Invest Radiol 2008;43:504–11. [PubMed]
4. Bioulac-Sage P, Balabaud C, Bedossa P, et al. Pathological diagnosis of liver cell adenoma and focal nodular hyperplasia: Bordeaux update. J Hepatol 2007;46:521–7. [PubMed]
5. Bioulac-Sage P, Laumonier H, Rullier A, et al. Over-expression of glutamine synthetase in focal nodular hyperplasia: a novel easy diagnostic tool in surgical pathology. Liver Int 2009;29:459–65. [PubMed]
6. Rebouissou S, Couchy G, Libbrecht L, et al. The beta-catenin pathway is activated in focal nodular hyperplasia but not in cirrhotic FNH-like nodules. J Hepatol 2008;49:61–71. [PubMed]
7. Di Stasi M, Caturelli E, De Sio I, et al. Natural history of focal nodular hyperplasia of the liver: an ultrasound study. J Clin Ultrasound 1996;24:345–50. [PubMed]
8. Kuo YH, Wang JH, Lu SN, et al. Natural course of hepatic focal nodular hyperplasia: a long-term follow-up study with sonography. J Clin Ultrasound 2009;37:132–7. [PubMed]
9. Leconte I, Van Beers BE, Lacrosse M, et al. Focal nodular hyperplasia: natural course observed with CT and MRI. J Comput Assist Tomogr 2000;24:61–6. [PubMed]
10. Aufort S, Gallix BP, Perney P, et al. [Spontaneous regression of a focal nodular hyperplasia]. J Radiol 2003;84:705–8. [PubMed]
11. Côté C. Regression of focal nodular hyperplasia of the liver after oral contraceptive discontinuation. Clin Nucl Med 1997;22:587–90. [PubMed]
12. Meunier F, Boyer L, Abergel A, et al. Regression of a focal nodular hyperplasia after stopping oral contraceptives. J Radiol 1998;79:341–3. [PubMed]
13. Ohmoto K, Honda T, Hirokawa M, et al. Spontaneous regression of focal nodular hyperplasia of the liver. J Gastroenterol 2002;37:849–53. [PubMed]
14. Ross D, Pina J, Mirza M, et al. Letter: Regression of focal nodular hyperplasia after discontinuation of oral contraceptives. Ann Intern Med 1976;85:203–4. [PubMed]
15. Mathieu D, Kobeiter H, Maison P, et al. Oral contraceptive use and focal nodular hyperplasia of the liver. Gastroenterology 2000;118:560–4. [PubMed]
16. Wanless IR, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology 1985;5:1194–200. [PubMed]

Articles from BMJ Case Reports are provided here courtesy of BMJ Group