Focal nodular hyperplasia

Focal nodular hyperplasia (FNG) is the second most common (after hemangioma) benign liver tumor. The frequency of FNG reaches 25% among benign and 8% among all primary liver neoplasms. The tumor occurs at any age, but most often in women of 30-40 years (80-95%).

Causes of occurrence

There is no unambiguous opinion about the causes of FNG. The prevalence of women, as well as a large proportion of women (up to 85%) who used hormonal contraceptives, have long supported the hypothesis that these drugs are the cause of the disease. However, a survey of 216 women in France found that hormonal contraceptives had no effect on the incidence and size of the tumor. Currently, it is believed that FNG is the reaction of hepatocytes to local vascular malformations (congenital or acquired). Local changes in blood flow lead to the appearance of areas of the parenchyma with increased arterial blood supply and hyperplasia of liver cells. In favor of vascular genesis, the frequent combination of FNG with liver hemangiomas (up to 23%) and various vascular anomalies indicates. The appearance of FNG after abdominal trauma and chemotherapy was also noted, which is associated with damage to intrahepatic vessels. 
FNG does not transform into a malignant tumor. Complications are extremely rare. Due to the benign nature and favorable prognosis of the neoplasm, active treatment is not required. The need for surgery may arise with an increase in size, the appearance of symptoms or complications, as well as with difficulties in the differential diagnosis of FNG and malignant liver tumors. 

Classification 

In gastroenterology, there are two types of nodular liver hyperplasia: classical (diagnosed in 80% of cases) and non-classical. The classic type is characterized by the presence of three signs: an abnormal lobule structure, sinuous thick-walled vessels and bile duct hyperplasia; in 60% of cases, a central scar with altered vessels of different calibers is found. In the non-classical type, there is always duct hyperplasia, and one of the remaining signs (altered vessels or abnormal nodal architecture) may be absent. The non-classical type is divided into three subtypes: adenomatous hyperplastic, telangiectatic, and nodular liver hyperplasia with cellular atypia.

Symptoms 

Symptoms are absent in 50-80% of patients. Only sometimes the disease is manifested by pain or discomfort, palpable formation (2-4%) in the upper abdomen, enlarged liver (hepatomegaly) and fever (

Diagnostics

Most often, FNG is detected accidentally during an examination or surgical intervention for another disease. Consultation with a gastroenterologist usually reveals non-specific signs of the disease: dyspeptic phenomena, low-intensity pain syndrome. With an objective examination of the patient, a large tumor can be detected palpationally, in the case of a violation of the outflow of bile, the jaundice of the skin and sclera is determined. Laboratory methods of investigation do not reveal any signs specific for nodular hyperplasia of the liver. Rarely, there is a slight increase in the level of alanine aminotransferase, bilirubin. For the purpose of differential diagnosis with malignant neoplasms of the liver, the determination of cancer markers is mandatory: alphafetoprotein, CA 19-9, CEA.

The diagnosis of liver FNG is based on instrumental methods. FNG is more often represented by a single formation (76-93%), in 7-24% of patients, multiple formations are present. Usually the size of the tumor does not exceed 5 cm.

A characteristic feature of this pathology is a "star scar" in the center of the formation, but it is not detected in all patients, in addition, it can be detected in fibrolamellar carcinoma, intrahepatic cholangiocarcinoma and other diseases. This diagnostic limitation applies to all imaging techniques: Ultrasound of the liver, CT and MRI of the liver. When conducting ultrasound of the abdominal organs, the only sign of nodular hyperplasia of the liver may be a displacement of the vessels, sometimes the hypoechoic rim of the tumor is determined (vessels and parenchyma compressed by the formation).

It is more informative to perform computer or magnetic resonance imaging of the abdominal organs with intravenous contrast. However, the first method is associated with radiation exposure and is undesirable for patients of young childbearing age; magnetic resonance imaging is the method of choice, however, there are relative and absolute contraindications to this method. Before choosing a method of examination, you should always consult the department of radiation diagnostics, where the doctor will tell you the most appropriate method for each specific case.

Non-invasive techniques are specific only for the classic type of nodular liver hyperplasia. In atypical cases, it is difficult to make a clear diagnosis and exclude the malignant nature of the tumor.

The most reliable non-invasive method for diagnosing the benign formation is magnetic resonance imaging with a hepatospecific contrast agent (see Primovist).

If it is impossible to establish a diagnosis in the course of non-invasive studies, a biopsyis performed , with large diagnostic criteria being the presence of thick-walled vessels, a fibrous layer, proliferating ducts, a nodular type of tumor; small criteria are perisinusoidal fibrosis and sinusoidal dilatation.

Example: 

Patient K., 45 years old, went on an outpatient basis to the magnetic resonance imaging office to verify the formation of the liver.

Anamnesis: since 2013. the patient was diagnosed with a liver hemangioma. Ultrasound in 2014 revealed an increase in the size of the formation to 80x60x50mm.

Laboratory parameters: alpha fetoprotein 2.37 (0.5-5.5 IU / ml norm)

Morphological verification after a puncture biopsy in an oncological hospital is shown. However, due to the large size of the formation and the risk of hemorrhage, the patient's puncture was refused and embolization of the feeding artery was performed, after which the size of the formation decreased and the contours were deformed.

According to MSCT with contrast – CT, the picture of the volume formation of the liver may correspond to focal nodular hyperplasia (differentiate with adenoma and liver cancer).

Since after embolization of the feeding vessel and "compression" of the formation, the contours and structure are deformed, and we expect to see a different picture from the "classical" one in focal nodular hyperplasia, the only way to non-invasively verify the nature of the tumor is to detect or exclude signs of malignancy.

That is why in the MRI room, the patient is offered to perform an MRI with the hepatotropic contrast agent Primovist. Despite its higher cost, compared to a conventional contrast agent, it is recommended to use it to exclude the presence of malignant cells and confirm the presence of healthy hepatocytes in the structure.

Figure 1. According to the MRI data, we visualize a large formation with uneven bumpy contours, actively accumulating a contrast agent and having an increased signal during diffusion and a reduced signal at ADC (indirect signs of a malignant structure). However, in the delayed hepatospecific contrast phases (at the 10th, 20th, and 30th minutes), we see that the formation retains the same intensity as the liver, i.e., their structure is identical and is represented by healthy hepatocytes. In this case, the operation is not shown. The patient has been sent home. It is recommended to monitor the growth of education once a year by ultrasound

This case is very revealing. Because with the primary correct choice of the examination method and the contrast agent, it would allow the patient to avoid many "unnecessary" and uninformative diagnostic procedures and worries about the possibly malignant nature of the formation. And in some cases, such an error in diagnosis and ambiguity could lead to an unjustified traumatic operation.