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Focal Nodular Hyperplasia

Focal Nodul Hyperpl of Liver

Focal nodular hyperplasia is a benign hepatic tumor that is typically asymptomatic. It is not usually associated with hemorrhage or malignant transformation.


Presentation

As most patients are asymptomatic, their tumors are discovered incidentally through radiographs or CT scans while undergoing assessment for other reasons. Rarely, patients experience abdominal pain, fullness, bloating, or fever. Furthermore, the physical exam may reveal signs such as hepatomegaly and/or a palpable mass on the right upper quadrant.

Gross examination of the dissected liver of the nodular hyperplasia features a stellate, or a star resembling scar, at the center of the lesion. Another finding is a condition in which the blood vessels are dilated, this is referred to as telangiectasia.

With regards to the size of the tumors, they are typically 3cm in diameter as the majority are less than 5cm. These masses may either exist on the surface of the liver or raise as pedunculated. Furthermore, when the lesion encompasses a lobe, it is known as Lobar Focal nodular hyperplasia.

Dry Cough
  • We present the case of a 78 years old man who presented to emergency room (ER) with a history of dry cough, chest pain and mild dyspnea.[ncbi.nlm.nih.gov]
Exertional Dyspnea
  • A 15-year-old girl had exertion dyspnea, focal nodular hyperplasia of the liver, portal vein hypoplasia, portopulmonary hypertension, mental retardation, and minor facial abnormalities.[ncbi.nlm.nih.gov]
Liver Dysfunction
  • She showed progressive liver dysfunction and ongoing cirrhosis, and so at the age of 10 years, she received living donor liver transplantation at our institute. The tumor was pathologically diagnosed as a FNH.[ncbi.nlm.nih.gov]
Chest Pain
  • We present the case of a 78 years old man who presented to emergency room (ER) with a history of dry cough, chest pain and mild dyspnea.[ncbi.nlm.nih.gov]
Flushing
  • MR perfusion [perfusion-weighted imaging (PWI)] consisted of a 3D free-breathing LAVA sequence repeated up to 5 minutes after injection of 7 mL Gd-BOPTA (MultiHance, Bracco, Italy) and 20 mL saline flush at a flow rate of 4 mL/s.[ncbi.nlm.nih.gov]
Pruritus
  • The operation and the follow-up were uneventful, allowing full recovery and disappearance of pruritus.[ncbi.nlm.nih.gov]
Confusion
  • The rarity and aberrant locations of such lesions cause confusion and may lower diagnostic confidence despite otherwise classic radiographic appearances.[ncbi.nlm.nih.gov]
  • Abstract Focal nodular hyperplasia (FNH) is a common benign liver tumor that is often confused with hepatic adenoma.[ncbi.nlm.nih.gov]
  • In conclusion, FNH can present as a hepatic nodule after orthotopic liver transplantation and should not be confused with hepatocellular carcinoma.[ncbi.nlm.nih.gov]
  • This finding should not be confused with steatohepatitic variant of HCC. Common typical features of FNH including thick-walled vessels, ductular reaction and thick fibrous bands are helpful for discrimination of FNH from HCC.[ncbi.nlm.nih.gov]
  • The prior numerous names associated with this condition depicts confusion regarding its pathogenesis. The consensus now proposes that FNH is the regenerative response to the hyperperfusion by the arteries located centrally in the nodules.[symptoma.com]
Dark Urine

Workup

In patients with an abdominal mass or an incidental finding, the assessment will include a thorough personal and family history, physical exam, and various imaging studies.

Laboratory tests

With regards to the laboratory workup, the liver functions tests (LFTs) are usually normal.

Imaging

One study is the color Doppler, which depicts the mass as a "comet tail" as it reflects the hypervascularization. The color Doppler will show vessels distributed throughout the liver.

Another imaging technique, ultrasonography, can identify the isoechoic tumor when it is exerting pressure on the nearby vasculature or structures. When applying enhanced contrast to the ultrasound imaging, the mass will be displayed as a stellar shaped, non-enhancing central lesion. This finding is the hallmark sign of FNH.

To exclude differentials such as hepatic adenomas and other pathologies of the liver, the low index enhanced sonography is a beneficial test. Employing this study is a priority especially since FNH can overshadow serious conditions that require urgent attention.

A CT scan will provide information about the tumor such as its size, location, and density. It also highlights the contouring of the liver and its stellar shaped central scarring. CT imaging will also depict the growth of the tumor but not its characteristics.

The nuclear scintigraphy test and the magnetic resonance imaging (MRI) with superparamagnetic iron oxide (SPIO) technique will reveal the tumor's characteristics. The former study utilizes sulfur colloid as the radiotracer, which is taken up by 60% of FNH lesions and many hepatic adenomas. In the latter technique, the lesion's Kupffer cells absorb SPIO, which suggests that the diagnosis is FNH.

Lymphocytic Infiltrate
  • Thirty-three resection specimens of steatotic FNH from 3 institutions were evaluated for degree of steatosis, background liver steatosis, ductular reaction, and lymphocytic infiltrate, as well as presence of thick fibrous bands, thick-walled vessels,[ncbi.nlm.nih.gov]
Liver Biopsy
  • The role of liver biopsy in children for the diagnosis of FNH is unclear. This study investigates the diagnostic accuracy of DI for FNH in children without comorbidities, compared to liver biopsy.[ncbi.nlm.nih.gov]
  • KEYWORDS: Differential diagnosis; Focal nodular hyperplasia; Hepatocellular adenoma; Hepatocellular carcinoma; Liver biopsy[ncbi.nlm.nih.gov]
  • The transjugular approach was used to perform a random liver biopsy to assess the amount of hepatic necrosis and to perform the focal lesion biopsy orienting the needle with sonography guidance.[ncbi.nlm.nih.gov]
  • No definite diagnosis could be obtained after serial imaging and liver biopsy. As a result of uncertainty in the imaging and needle biopsy results, the patient underwent complete tumor resection.[ncbi.nlm.nih.gov]
  • We recommend further investigations including liver biopsy if necessary when fatty tumours exhibit atypical MR findings.[ncbi.nlm.nih.gov]

Treatment

The treatment of FNH depends on the overall presentation of the disease. Asymptomatic and benign lesions do not typically warrant surgery. These patients are usually closely monitored with liver imaging to track the tumor's growth. It is important to note that most individuals with FNH do not require treatment or surgical intervention.

However, resection of the lesion and the affected areas is the mainstay therapy for those with the following features:

  • Large tumors (likely >5cm)
  • Multiple liver lesions
  • Tumor growth
  • Abnormal tumor behavior
  • Hepatomegaly or liver displacement
  • Symptoms
  • Abdominal hemorrhage

Note that infected liver tissue and maybe even an entire lobe of the liver may be resected.

Post-surgical surveillance

Following surgery, the patient is periodically evaluated for possible new tumors and their growth.

Other

Some clinicians may recommend the discontinuation of oral contraceptives and hormone replacement therapy. This is based on the thought that hormones contribute to tumor growth and its subsequent rupture and hemorrhage.

Prognosis

This is a benign disease with an overall good prognosis. Moreover, FNH does not transform into a malignancy and rarely yields complications.

Etiology

There are several possible etiologies of FNH. One of the leading theories describes that this tumor arises from a hyperplastic process that occurs in the presence of underlying congenital blood vessel malformations. Further beliefs propose that vascular events such as clot formation or hemorrhage in the hepatic blood vessels lead to the development of FNH. Additionally, it is thought that liver inflammation may contribute to the formation of this tumor.

Another factor to consider is the role of estrogen since this disease is more predominant in women. An exogenous supply of this hormone has demonstrated an enlargement of the tumor size.

Epidemiology

With regards to patient demographics, FNH most commonly occurs in middle-aged individuals. Specifically, it is more predominant between 20 and 50 years of age [2] and accounts for up to 2% of hepatic tumors in the pediatric population [3]. Furthermore, it has a female preference in an 8-9:1 ratio [2] while approximately 15% of cases are found in men [4].

Sex distribution
Age distribution

Pathophysiology

Before the current understanding of FNH was established, it was characterized as a neoplasm, a hamartoma, an area of regeneration, and even as a consequence of an ischemic or hemorrhagic event. Since the pathogenesis was not elucidated in the past, the nomenclature of this tumor took numerous forms including solitary hyperplastic nodule, focal cirrhosis, hepatic hamartoma, hepatic pseudotumor, and hamartomatous cholangiohepatoma. The prior numerous names associated with this condition depicts confusion regarding its pathogenesis.

The consensus now proposes that FNH is the regenerative response to the hyperperfusion by the arteries located centrally in the nodules [5] [6] [7]. While it is unknown whether vascular events play a role, the portal vein sometimes perfuses the nodule due to the thrombotic events in the anomalous central artery [6].

To clarify the meaning, the International Working Party of the World Congresses of Gastroenterology labeled FNH as a regenerative nodule instead of dysplastic or neoplastic [8] as this description matches the current knowledge about the pathogenesis.

Some experts believe that FNH originates from polyclonal hepatocytes [9]. However, this is opposed by others [10].

The characteristics of FNH

The hallmark features of the tumor include the proliferation of hepatocytes and presence of fibrous tissue and Kupffer cells. The tumor growth exhibits increased numbers of hepatocytes, malformed vasculature, and the presence of bile duct elements.

Prevention

Since this condition is likely secondary to a congenital abnormity of hepatic blood vessels, there are no preventative measures.

However, it is important to be cautious about overall liver health, which involves lifestyle and dietary modifications. Examples include moderation of the intake of alcohol, fatty foods, and certain medications. Additionally, patients with FNH are usually advised to avoid the use of oral contraceptives and hormone replacement medications. This also applies to those at risk for developing this benign tumor.

Summary

Focal nodular hyperplasia (FNH) is the second most prevalent tumor of the liver, preceded by hepatic hemangioma [1]. The etiology of FNH is based on a hyperplastic process in response to an underlying congenital abnormality of the liver vasculature. Additionally, hormones are thought to play a role as FNH is more commonly seen in females.

Most cases of FNH are asymptomatic and present no serious complications. In fact, this condition is typically diagnosed incidentally on imaging as part of a workup for other medical issues. With regards to the minority of patients who do have clinical features, they may exhibit abdominal pain, bloating, hepatomegaly, and/or a palpable mass.

Evaluation of the patient includes a personal and family history, a complete physical exam, laboratory studies, and imaging. The latter may consist of color Doppler, ultrasonography with optimization such as enhanced contrast, and computed tomography (CT scan).

The treatment approach varies according to the presentation of the disease. Patients without clinical manifestations do not require surgical intervention. Moreover, these individuals are typically closely monitored for tumor growth through regular imaging. However, tumor resection is warranted for patients with the presentation of symptoms, tumor growth, liver enlargement, or hemorrhage.

While this condition is not preventable, those at risk or with small tumors are advised to abstain from hormone medications. Also, all individuals are advised to follow key lifestyle modifications for maintaining liver health.

Patient Information

What is focal nodular hyperplasia (FNH) of the liver?

FNH is a benign tumor of the liver that usually does not grow, bleed or become cancerous.

What causes the development of FNH?

This tumor is likely caused by abnormal blood vessels in the liver that have been present since birth. These congenital abnormalities lead to a distribution of blood, oxygen and nutrients to some liver cells more than others. Therefore, these cells are likely to grow into tumor-like masses.

Who does FNH affect?

It is more common in women than men especially in young and middle ages (between 20 and 50 years of age). Also, it may occur in children.

Why does FNH typically occur in women?

The most likely reason for this is the fluctuation of female hormones during the reproductive ages.

What are the signs and symptoms of this tumor?

FNH does not usually cause symptoms. In many cases, this tumor is found accidentally during imaging testing for other reasons or during a physical exam.

For those that do experience signs and symptoms, they may exhibit the following:

  • Abdominal pain
  • Feeling of fullness
  • Bloating (which is rare)
  • Abdominal hemorrhage (which is rare)
  • Enlarged liver and abdomen
  • Palpable mass in the right upper abdomen

How do you treat FNH?

Treatment of this benign tumor depends on the specific case. Since many will not experience symptoms or possess serious health risks, clinicians will keep a close eye and monitor the patient's condition. In addition to follow-up appointments, the patient will have regular liver imaging tests in order to track the growth of the tumor.

Some cases such as with symptomatic tumors will warrant surgical resection of the tumor and its surrounding areas. Further surgical indications include large tumor sizes, the presence of multiple tumors, the presence of an enlarged liver, and the development of bleeding.

Additionally, clinicians may recommend that patients discontinue use of oral contraceptives and hormone replacement therapy since hormones are thought to play a role in tumor growth.

What are the outcomes of this tumor?

Since this is a benign tumor that rarely becomes malignant, patients have a great prognosis. Also, surgery is not often required as most tumors do not produce symptoms.

Can FNH be prevented?

There are no preventative measures as this condition is likely a result of liver blood vessel abnormalities present from birth.

It is important to take good care of liver health in general by controlling the amount of alcohol and fatty acid intake. Moreover, the clinician can advise the patients with this condition to stop using oral contraceptives and hormone replacement medications.

References

Article

  1. Craig JR, Peters RL, Edmondson HA, Omata M. Fibrolamellar carcinoma of the liver: a tumor of adolescents and young adults with distinctive clinico-pathologic features. Cancer. 1980. Jul 15; 46(2):372-9.
  2. Wanless IR, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology. 1985; 5(6):1194.
  3. Reymond D, Plaschkes J, Lüthy AR, et al. Focal nodular hyperplasia of the liver in children: review of follow-up and outcome. J Pediatr Surg. 1995; 30(11):1590.
  4. Bioulac-Sage P, Balabaud C, Wanless IR. Diagnosis of focal nodular hyperplasia: not so easy. Am J Surg Pathol. 2001; 25(10):1322-5.
  5. Fukukura Y, Nakashima O, Kusaba A, et al. Angioarchitecture and blood circulation in focal nodular hyperplasia of the liver. J Hepatol. 1998;29(3):470-5.
  6. Wanless IR, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology. 1985; 5(6):1194-200.
  7. Kondo F, Nagao T, Sato T, et al. Etiological analysis of focal nodular hyperplasia of the liver, with emphasis on similar abnormal vasculatures to nodular regenerative hyperplasia and idiopathic portal hypertension. Pathol Res Pract. 1998; 194(7):487-95.
  8. International Working Party. Terminology of nodular hepatocellular lesions. Hepatology. 1995;22(3):983-93.
  9. Paradis V, Laurent A, Flejou JF, Vidaud M, Bedossa P. Evidence for the polyclonal nature of focal nodular hyperplasia of the liver by the study of X-chromosome inactivation. Hepatology. 1997; 26(4):891-5.
  10. Gaffey MJ, Iezzoni JC, Weiss LM. Clonal analysis of focal nodular hyperplasia of the liver. Am J Pathol. 1996;148(4):1089-96.

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Last updated: 2018-06-21 21:56