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Year : 2019  |  Volume : 62  |  Issue : 2  |  Page : 261-265
Focal nodular hyperplasia of the liver in children: A report of 2 cases


1 Department of Pathology, IPGME and R, Kolkata, West Bengal, India
2 Department of GI Pathology, IPGME and R, Kolkata, West Bengal, India
3 Department of Paediatric Surgery, KPC Medical College, Kolkata, West Bengal, India
4 Department of Paediatric Surgery, NRS Medical College, Kolkata, West Bengal, India

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Date of Web Publication10-Apr-2019
 

   Abstract 


Focal nodular hyperplasia (FNH) is a benign non-neoplastic lesion of the liver usually found in adults. It is uncommon in children, comprising 2-10% of all pediatric liver tumours. In children, it can occur at all ages, with increased frequency between 6-10 years. We present two cases of FNH in childhood- the first being that of a 5-month-old infant, and the second in a 6-year-old boy. The possibility of congenital FNH had been excluded in the first case. The second case posed diagnostic difficulty initially and was wrongly treated for hepatoblastoma by neoadjuvant chemotherapy, but later correctly diagnosed to be FNH. Both the children are doing well on follow-up. Paediatric FNH though rare, should be kept in mind while dealing with a hepatic mass. Radiological features can be variable and needle sampling may not be sufficient to reach to a diagnosis. Histological examination with glutamine synthetase immunostaining should be performed in doubtful cases to differentiate FNH from other paediatric liver masses, as management differs.

Keywords: Focal nodular hyperplasia, hepatoblastoma, paediatric focal nodular hyperplasia, paediatric liver tumours

How to cite this article:
Islam N, Halder A, Ghosh R, Banerjee S, Mishra PK, Chatterjee U. Focal nodular hyperplasia of the liver in children: A report of 2 cases. Indian J Pathol Microbiol 2019;62:261-5

How to cite this URL:
Islam N, Halder A, Ghosh R, Banerjee S, Mishra PK, Chatterjee U. Focal nodular hyperplasia of the liver in children: A report of 2 cases. Indian J Pathol Microbiol [serial online] 2019 [cited 2019 Oct 21];62:261-5. Available from: http://www.ijpmonline.org/text.asp?2019/62/2/261/255821





   Introduction Top


Focal nodular hyperplasia (FNH) is a benign tumour-like lesion consisting of hyperplastic parenchymal nodules with abnormal vessels associated with a central stellate-shaped scar.[1] Most of them occur in women of reproductive age but cases have been described in men and children also. FNH accounts for less than 2% of paediatric hepatic tumours and 0.02% of all tumours.[2],[3],[4] Although there are case reports on congenital FNH, diagnosed on antenatal USG,[5],[6],[7] it is an unusual liver tumour in children younger than 2 years of age.[5] We present two cases of paediatric FNH— the first case being reported in a 5 month old infant. Initially, the second case posed diagnostic difficulty, but was correctly diagnosed after histopathological examination of the resected mass, highlighting the fact that it is difficult to establish the diagnosis of FNH in small tissue samples such as liver biopsy.


   Case Reports Top


Case 1

A 5-month-old male infant presented with diarrhea of two weeks duration. His perinatal history was unremarkable and he had been delivered by elective caesarian section at term gestation. His routine investigations were within normal limits but an ultrasonogram (USG) of the abdomen revealed a solid inhomogeneous mass in the left lobe of liver. On magnetic resonance imaging (MRI), the mass appeared to be mildly hypointense on T1 weighted sequence (T1W) and isointense on T2 weighted sequence (T2W), with homogeneous contrast uptake on the arterial phase [Figure 1]a. Serum alpha-fetoprotein (AFP) level was normal. The possibility of hepatoblastoma appeared less likely and hence no preoperative neoadjuvant chemotherapy was administered. The mass was surgically excised and sent for histopathological examination. Grossly the mass measured 9 cm in greatest dimension and appeared to be subdivided into smaller nodules by bands of connective tissue [Figure 1]b. Microscopic examination revealed bands of arborizing fibrous connective tissue septa subdividing the liver parenchyma into nodules of varying sizes [Figure 1]c. The nodules were composed of bland hepatocytes. The fibrous septa contained several thick walled vessels of arteriolar calibre, some with eccentric subintimal thickening. The fibrous septa appeared to originate from a central scar like area [Figure 1]d and [Figure 1]e. Immunohistochemistry for glutamine synthetase showed characteristic map-like areas with perivenular distribution, thus confirming the diagnosis of FNH [Figure 1]f. The last prenatal USG of the mother done at 37 weeks gestation was reviewed, which did not show any mass lesion in the liver of the fetus, thus excluding the possibility of congenital FNH. The child has been followed up for 2 years now and is doing well till date.
Figure 1: (a) Large lobulated hyperintense lesion in right lobe of liver on MRI. (b) Multinodular Liver SOL with prominent central stellate scar on cut surface (inset). (c) Bands of fibrous connective tissue septa subdividing the liver parenchyma into nodules (H and E, ×10). (d) Fibrous septa contain thick walled arterial branches and bile ducts (Masson trichrome, ×10). (e) Proliferating bile ductules within the fibrous septa. (H and E, ×10); Inset- thick walled arteriole with subintimal thickening. (f) Glutamine synthetase immunostaining shows the characteristic map like areas with perivenular distribution (×10)

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Case 2

A 6 year old male child presented in the outpatient department of Pediatric Surgery for evaluation of an abdominal swelling of one year duration. He had undergone a battery of investigations at a different institute including USG which revealed a space occupying lesion (SOL) in right lobe of liver measuring 4.5 cm × 3.2 cm. Serum AFP level was normal. A trucut biopsy had been performed from the SOL around three months back which suggested the possibility of hepatoblastoma, on the basis of which he had received two cycles of neoadjuvant chemotherapy with vincristine and doxorubicin. As there was no response to therapy, he had been referred to our institute where he had been re-evaluated. On physical examination, the child was anicteric but had pallor. Complete hemogram revealed a haemoglobin level of 7 gm% and total leucocyte count of 2500 per cumm. Per-abdominal examination revealed a huge, right upper quadrant lump extending from right subcostal region upto the umbilicus, crossing the midline. A repeat serum AFP was done which was again within normal limits. A contrast enhanced CT (CECT) scan was performed which showed a large mixed density mass in the right lobe of liver with presence of a focal hypodense area in the centre of the lesion. The mass showed homogeneous contrast enhancement while the hypodense area was non-enhancing [Figure 2]a. The slide or block of the trucut biopsy done previously was not available for review. As such, the child was prepared for surgery and the resected specimen was sent for histopathological examination.
Figure 2: (a) CECT scan showing a large mixed density mass with a focal hypodense area in the right lobe of liver. Capsular retraction is seen adjacent to the hypodense area, corresponding to the scar tissue. (b) Cut section of liver showing multiple nodules of varying sizes along with a stellate depressed scar (arrow) (c) Microscopy shows nodules of bland hepatocytes separated by thick fibrous bands with lack of portal tracts and central veins (H and E, ×4). (d) Section from the area of softening shows necrosis within the lesion (H and E, ×10); Inset- Glutamine synthetase immunostaining showing map like areas

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Grossly the mass measured 12.5 cm across and weighed around 1100 grams. On slicing, the mass was composed of several tan coloured nodules of varying sizes, bulging from the cut surface, with a central arborizing, depressed scar [Figure 2]b. There were no areas of hemorrhage but an ill-defined area of softening was noted at one place. Microscopy showed nodules of varying sizes composed of normal, uniform looking hepatocytes separated by fibrous bands, along with attenuated endothelial cells and Kupffer cells. Portal tracts and central veins were practically absent within the mass. No atypia, pleomorphism, mitotic figures or pericellular fibrosis were noted. Evidence of polymorph infiltration was noted focally. Sections from the 'scar' showed presence of proliferating bile ductules and large thick walled arterioles [Figure 2]c. The ill-defined area of softening showed areas of necrosis [Figure 2]d. A beta-catenin immunostain was done which showed negative nuclear immunoreactivity. Immunohistochemistry for glutamine synthetase was also done showed characteristic map like areas with perivenular positivity [[Figure 2]d, inset]. Based on these features, the diagnosis of FNH was made with a suggestion that the foci of necrosis were possibly due to the effect of chemotherapy.

A post-operative MRI of the child was done to exclude any post-operative collection in the abdomen, to check the viability of the residual liver tissue and to rule out any untoward vascular complications of the surgery. His post-operative scans were within normal limits. The patient has been doing well on a 4 years follow-up.


   Discussion Top


FNH was first detected and described by Edmondson in 1958.[8],[9] It is the second most common liver cell-derived benign tumor and its incidence is just lower than that of hepatic haemangiomas.[10] It rarely occurs in childhood and very rarely in children younger than 2 years, accounting for 0.02% of all tumors and less than 2% of hepatic tumors in pediatric age group.[2],[11] Although congenital FNH have been described in a few case reports,[5],[6],[7] its occurrence at 5 months of age, as in our first case, is extremely rare. Our second case highlights the diagnostic difficulty which may be encountered on USG and trucut biopsy in differentiation of FNH from other lesions. This may often lead to administration of unwarranted chemotherapy as seen in our case. While diagnosis of FNH on surgical specimens is made outrightly as seen in our first case, its diagnosis on core needle biopsy can be extremely challenging.

Primary liver neoplasms comprise 0.3–2% of all pediatric tumors with up to 75% of pediatric liver tumors being malignant. Hepatoblastoma (HB) is the most common hepatic malignancy in children, accounting for 91% of cases and primarily affecting patients who are younger than 5 years of age. The other rare pediatric liver tumors are infantile hemangioendothelioma, mesenchymal hamartomas (MH), undifferentiated embryonal sarcoma and fibrolamellar variant of hepatocellular carcinoma (FL-HCC).[12]

FNH most commonly presents as an incidentally discovered liver nodule on physical examination or during routine check-ups with normal liver enzymes.[8],[9] It is usually solitary, but 15-20% of cases may be multifocal.[13] Asymptomatic cases of FNH are usually followed up closely but symptomatic patients may require surgical intervention. Till date, only one patient with FNH had recurrence after operation.[4]

Pre-operative AFP levels are a part of any routine investigations in a case of liver SOL in a child. High levels of AFP are a strong pointer in favour of HB. AFP levels in FNH are usually normal[4] though there have been instances where FNH is associated with markedly high AFP.[14],[15] A small percentage of HBs, especially the small cell variants, can be associated with a low AFP level. MH may show a mild increase in the levels of AFP.[16]

It is important to differentiate FNH from the HB-fetal type, hepatocellular adenoma (HCA), well differentiated hepatocellular carcinoma (HCC) and macroregenerative nodules (MRN) on a core needle biopsy (CNB). Typical FNH often resembles biliary type cirrhosis. Atypical forms of FNH are difficult to differentiate from HCA and the presence of central stellate scar may be confused with FL–HCC and congenital hepatic fibrosis.[17]

In some institutions, neoadjuvant chemotherapy is given to HB patients on the basis of clinical presentation, elevated serum AFP levels and radiological findings. Nevertheless, a trucut biopsy or Fine Needle Aspiration (FNA) is often advised in all suspected HB patients for accurate diagnosis. Considering other hepatic tumours in children, MH which is a benign tumour can have mildly elevated serum AFP levels and extensive calcification. Moreover, radiological distinction from HB with extensive osteoid elements and mesenchymal component can be difficult. Although infrequent, HCCs can occur in patients younger than 3 years of age and usually have a worse prognosis than HB. Thus, to prevent the administration of unwarranted neoadjuvant chemotherapy to children suffering from a liver SOL, a tissue diagnosis either by a CNB or FNA is routinely performed in our institution.[18],[19]

Diagnosis of FNH can be difficult in CNBs, especially for pathologists with limited experience.[20] The fibrous septa and bile ductules may sometimes mimic cirrhosis, which is an unlikely diagnosis at this age group. HB and FL-HCC are the most common differentials of FNH and differentiating fetal type HB from FNH on a trucut biopsy alone can be quite difficult. Both these entities show similar histological features like absence of portal tracts, mitosis or nuclear atypia. This was possibly the very problem encountered in the second case by the pathologists of the different institute. Immunohistochemical staining with beta catenin may help in these cases, as the strong nuclear immunostaining characteristic of HB is not seen in FNH. Glutamine synthetase is an important immunostain for diagnosis of FNH, which shows characteristic map like positivity with perivenular distribution and thus helps in differentiating it from other proliferating liver masses. The clinicopathological differences between FNH and HB are summarized in [Table 1].[21],[22],[23] Intratumoral necrosis as seen in our second case could be attributed to the two cycles of neoadjuvant chemotherapy administered to the patient based on the diagnosis made on trucut biopsy.
Table 1: Summary of key differences between focal nodular hyperplasia and hepatoblastoma

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   Conclusion Top


We report two cases of FNH in childhood, of which the first case is a 5 month old infant, which is extremely rare. Diagnosis of FNH is often difficult on small biopsies as seen in our second case. FNH needs to be differentiated from other malignant hepatic tumours so that unwarranted neoadjuvant chemotherapy can be avoided. Immunostaining with beta catenin and glutamine synthetase can be helpful to differentiate FNH from HB and other liver SOLs.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgement

We are grateful to Prof. Puja Sakhuja and Dr. Kaushik Majumdar of G. B. Pant Institute of Post Graduate Medical Education and Research (Maulana Azad Medical College), New Delhi for their valuable help and support in performing the glutamine synthetase immunostaining of the two cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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De Ioris M, Brugieres L, Zimmermann A, Keeling J, Brock P, Maibach R, et al. Hepatoblastoma with a low serum alpha-fetoprotein level at diagnosis: The SIOPEL group experience. Eur J Cancer 2008;44:545-50.  Back to cited text no. 16
    
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Correspondence Address:
Aniket Halder
No. 430/2, Ratnavilla, Nabatirtha, P.O. Hridaypur, Barasat, 24 PGS (North), Kolkata - 700 127, West Bengal
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DOI: 10.4103/IJPM.IJPM_396_18

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