Liver & intrahepatic bile ducts
Benign / nonneoplastic
Focal nodular hyperplasia
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 6 March 2019
Last staff update: 20 September 2023 (update in progress)
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Focal nodular hyperplasia liver
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Savari O, Tomashefski JF. Focal nodular hyperplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumorFNH.html. Accessed September 30th, 2023.
Definition / general
- Focal nodular hyperplasia (FNH) is a benign nonneoplastic hepatic lesion, arising in a noncirrhotic liver parenchyma
- Can be divided into classical (80%) and nonclassical or atypical (showing unusual features such as steatosis, large cell changes, Mallory bodies or cholestasis) (Am J Surg Pathol 1999;23:1441)
- Multiple FNH syndrome is defined as the presence of at least 2 FNH lesions associated with other vascular or nonvascular lesions, such as hepatic hemangioma, an arterial structural defect, vascular malformation, meningioma or astrocytoma (Hepatology 1995;22:983)
Essential features
- Solitary, well demarcated, unencapsulated, subcapsular hepatic nodule with central stellate scar on gross examination
- Nodule with histologic features of biliary type cirrhosis with ductopenia in a background of noncirrhotic liver
- Immunoreactivity for glutamine synthetase with a map-like pattern of staining
Terminology
- Also known as focal cirrhosis, pedunculated adenoma, solitary hyperplastic nodule, mixed adenoma, hamartoma and hamartomatous cholangiohepatoma
ICD coding
- ICD-10: K76.89 - other specified diseases of liver
Epidemiology
- Most common in young adults, with rare reports of occurrence in childhood
- More common in females than males (F:M = 8:1)
- Accounts for ~8% of all primary liver tumors in adults (Dig Surg 2010;27:24)
- Prevalence of 4 - 30 per 1,000 in adults and 0.2 per 1,000 in persons < 18 years (Dig Surg 2010;27:24)
Pathophysiology
- Pathogenesis is not fully understood but is thought to occur as the result of a hyperplastic response to a vascular anomaly (Am J Surg Pathol 1999;23:1441)
- Vascular endothelial growth factor is increased due to arterial hyperperfusion, which leads to activated hepatic stellate cells, which are responsible for fibrosis and characteristic central scar formation
Etiology
- Etiology is ascribed to several vascular lesions, including hepatic hemangioma, Budd-Chiari syndrome and hereditary hemorrhagic telangiectasia
- Development is not associated with oral contraceptives but larger and more symptomatic lesions are observed among patients taking oral contraceptives
- Association with chemotherapy has been reported in children (J Pediatr Surg 2015;50:382)
Clinical features
- Usually asymptomatic
- Lesion is often incidentally discovered during abdominal imaging or rarely as an abdominal mass identified during physical examination (HPB (Oxford) 2005;7:298)
Diagnosis
- Diagnosis is usually made by imaging; patients typically undergo regular followup (Clin Mol Hepatol 2016;22:199)
Laboratory
- Abnormal liver function tests and gamma glutamyl transferase (GGT) have been reported in 12% of cases (Dig Surg 2010;27:24)
Radiology description
- Well demarcated solitary hepatic lesion with a central scar in contrast CT scan and MRI
- Angiography demonstrates "wheel spoke" appearance with the vessels radiating out from the center of the tumor (Clin Mol Hepatol 2016;22:199)
Radiology images
Images hosted on other servers:
Ultrasound and MRI
Prognostic factors
- Benign hepatic lesion with excellent prognosis
- There are rare case reports of fibrolamellar hepatocellular carcinoma arising from focal nodular hyperplasia (J Reprod Med 2005;50:633)
Case reports
- 3 year old girl with pedunculated focal nodular hyperplasia (Proc (Bayl Univ Med Cent) 2018;31:97)
- 15 year old boy treated with transarterial embolization (BMJ Case Rep 2015 Jul 10;2015)
- 23 year old man with lesion mimicking a soft tissue sarcoma liver metastasis (Surg Case Rep 2017;3:59)
- 31 year old woman with vasooclusion and focal nodular hyperplasia after longterm oral contraceptives (BJR Case Rep 2017;4:20170070)
- 2 cases of fibrolamellar hepatocellular carcinoma arising in a background of focal nodular hyperplasia (J Reprod Med 2005;50:633)
- Liver ectopic pregnancy complicating a focal nodular hyperplasia (Pathology 2018;50:478)
Treatment
- Symptomatic focal nodular hyperplasia and any change in lesion size or number should prompt consideration of surgical resection (Clin Mol Hepatol 2016;22:199)
- Transarterial embolization is an alternative approach if surgery is not possible (BMJ Case Rep 2015 Jul 10;2015)
Gross description
- Well demarcated but unencapsulated solitary lesion
- Nodular appearance that is lighter in color than the surrounding liver parenchyma
- Although usually a solitary nodule, it may be multifocal
- Often located in the subcapsular region
- Ranges in size from 1 to 10+ cm, although most nodules measure < 5 cm
- Cut surface often shows a characteristic central scar with radiating fibrous septa, dividing the mass into smaller nodules
- Rarely can present as a pedunculated mass (Proc (Bayl Univ Med Cent) 2018;31:97)
Gross images
Contributed by Omid Savari, M.D. and Hanni Gulwani, M.D.
Well circumscribed subcapsular mass
Well
circumscribed
mass with central
stellate scar
Microscopic (histologic) description
- Overall resembles a biliary type of cirrhosis with ductopenia in a background of noncirrhotic liver
- Bland hepatocytes surrounded by fibrous septa that contain artery branches and variable degree of bile ductular reaction (most important distinguishing features) and variable amount of mixed inflammatory infiltrate
- Portal tracts are absent except at the periphery of the lesion
- Hepatocytes are usually similar to those in the surrounding liver
- Hepatocyte plates are 1 - 2 cells thick and are supported by an intact reticulin framework
- Mallory hyaline and other features of chronic cholestasis such as feathery degeneration and accumulation of excess copper may be found adjacent to the fibrous septa
- Nuclear pleomorphism, prominent nucleoli and mitotic figures are absent in classical focal nodular hyperplasia (FNH) but cytologic atypia may be seen in variant forms
- Medium to large sized, thick walled muscular vessels, often present in fibrous bands, which often exhibit myointimal myxoid or fibromuscular hyperplastic changes
- In one study by Nguyen BN et al., different histologic variants are described (Am J Surg Pathol 1999;23:1441):
- Classical
- Nonclassical:
- Telangiectatic: absence of a central scar and lack of architectural nodular distortion; hepatic plates are 1 cell thick and rather frequently appeared atrophic; plates are separated by sinusoid dilatation, sometimes alternating with areas of marked ectasia
- Mixed hyperplastic and adenomatous form: presence of 2 alternating aspects, 1 resembling telangiectatic type FNH, the other simulating adenoma
- FNH with cytologic atypia: atypical hepatocytes have an enlarged nucleus with an irregular nuclear contour, hyperchromasia, coarse granular chromatin and conspicuous nucleoli
- FNH with steatohepatitis-like changes: may show overlapping features with steatohepatitic variant of hepatocellular carcinoma, such as widened cell plates or hepatocyte rosettes (Am J Surg Pathol 2017;41:277)
Microscopic (histologic) images
Contributed by Omid Savari, M.D.
Fibrous septae
Absent portal tracts
Nodular hepatocyte arrangement
Ductular reaction
Bland hepatocytes
Lack of atypia
Muscular vessels
Trichrome
Cytology description
- In classical focal nodular hyperplasia (FNH), hepatocytes without significant atypia, arranged in trabeculae that are 2 cells thick
- Bile ductular cells are helpful findings on cytology to differentiate FNH from hepatocellular adenoma (World J Surg Oncol 2004;2:5)
Positive stains
- Glutamine synthetase: patchy and map-like pattern (Arch Pathol Lab Med 2015;139:537)
- Arginase: positive in hepatocytes
- HepPar1: positive in hepatocytes
- CK7 and CK19: positive in the ductular reactions
Negative stains
Molecular / cytogenetics description
- mRNA expression alteration of the angiopoietin genes (ANGPT1 and ANGPT2) (Clin Mol Hepatol 2016;22:199)
- Angiopoietin genes (ANGPT1 and ANGPT2) are involved in vascular maturation process
- ANGPT1/ANGPT2 ratio increased compared with normal liver, cirrhosis and other liver tumors
- Nonclonal β catenin activation, without mutations, has been shown to occur, contributing to hepatocellular hyperplasia and regeneration (Clin Mol Hepatol 2016;22:199)
Sample pathology report
- Liver, right lobe lesion, needle core biopsy:
- Liver parenchyma with features suggestive of focal nodular hyperplasia (see comment)
- Comment: There is a history of an incidentally discovered right liver lesion. A well differentiated hepatocellular lesion with fibrous septa containing medium sized muscular arteries and inflammation is seen. Reticulin highlights normal hepatocyte cell plates. Glutamine synthetase demonstrates patchy staining of hepatocytes. CD34 shows patchy sinusoidal staining and beta catenin highlights normal membranous staining. Glypican 3 is negative. The morphology and immunoprofile are suggestive of focal nodular hyperplasia.
- Liver parenchyma with features suggestive of focal nodular hyperplasia (see comment)
Differential diagnosis
- Hepatocellular adenoma:
- No stellate scar, no ductular reaction, homogeneous parenchyma, perivascular and patchy glutamine synthetase expression
- Fibrolamellar hepatocellular carcinoma:
- Although grossly has similar features, microscopically, sheets of tumor cells with marked atypia and abundant eosinophilic cytoplasm are characteristic
- Cirrhosis:
- Diffuse changes in liver parenchyma
Additional references
Board review style question #1
Which immunohistochemistry stain is helpful to differentiate focal nodular hyperplasia from hepatocellular adenoma?
- Arginase
- HepPar1
- Glutamine synthetase
- Glypican 3
Board review style answer #1
C. Glutamine synthetase with map-like staining can differentiate focal nodular hyperplasia from hepatocellular adenoma.
Comment Here
Reference: Focal nodular hyperplasia
Comment Here
Reference: Focal nodular hyperplasia
Board review style question #2
Which histologic feature helps to differentiate focal nodular hyperplasia from hepatocellular adenoma?
- Atypical hepatocytes
- Lack of portal tracts
- Portal tract chronic inflammation
- Presence of ductular reaction in fibrous bands
Board review style answer #2
D. Presence of ductular reaction in fibrous bands is an important histologic feature that can help to distinguish focal nodular hyperplasia from hepatocellular adenoma.
Comment Here
Reference: Focal nodular hyperplasia
Comment Here
Reference: Focal nodular hyperplasia
