Hepatocellular adenoma
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Hepatocellular adenoma (also known as hepatic adenoma or hepadenoma) is a rare, benign
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
tumor. It most commonly occurs in people with elevated systemic levels of estrogen, classically in women taking estrogen-containing oral contraceptive medication.


Signs and symptoms

About 25–50% of hepatic adenomas cause pain in the
right upper quadrant The human abdomen is divided into quadrants and regions by anatomists and physicians for the purposes of study, diagnosis, and treatment. The division into four quadrants allows the localisation of pain and tenderness, scars, lumps, and other ...
or
epigastric In anatomy, the epigastrium (or epigastric region) is the upper central region of the abdomen. It is located between the costal margins and the subcostal plane. Pain may be referred to the epigastrium from damage to structures derived from the f ...
region of the abdomen. Since hepatic adenomas can be large (8–15 cm), patients may notice a palpable mass. However, hepatic adenomas are usually asymptomatic, and may be discovered incidentally on imaging ordered for some unrelated reason. Large hepatic adenomas have a tendency to rupture and bleed massively inside the abdomen. If not treated, there is a 30% risk of bleeding. Bleeding may lead to hypotension,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
, and sweating ( diaphoresis).


Related Conditions

Hepatic adenomas are related to
glycogen storage diseases A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by an enzyme deficiency affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells. GSD has ...
,
type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...
, as well as
anabolic steroid Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects ...
use.


Diagnosis

Hepatic adenoma is usually detected by
imaging Imaging is the representation or reproduction of an object's form; especially a visual representation (i.e., the formation of an image). Imaging technology is the application of materials and methods to create, preserve, or duplicate images. ...
, typically an ultrasound or CT, as a hyperenhancing liver nodule. Given that several liver tumors appear similarly on these imaging modalities, a multi-phase contrast-enhanced imaging study such as CT or
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
may be used to provide more information. The significance of making a specific diagnosis is that, unlike other benign liver tumors such as hemangioma and focal nodular hyperplasia, hepatic adenomas have a small but meaningful risk of progressing into a
malignancy Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
. Although imaging provides supportive information, a definitive diagnosis of hepatic adenoma requires
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
of the tissue.


Radiologic differential diagnosis

* Echinococcal cyst * Focal fatty change *
Focal nodular hyperplasia Focal nodular hyperplasia (FNH) is a benign tumor of the liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and ...
*
Hepatoblastoma Hepatoblastoma is a malignant liver cancer occurring in infants and children and composed of tissue resembling fetal liver cells, mature liver cells, or bile duct cells. They usually present with an abdominal mass. The disease is most commonly di ...
* Infiltrative liver disease * Inflammatory pseudotumor *
Leiomyosarcoma Leiomyosarcoma is a malignant (cancerous) smooth muscle tumor. A benign tumor originating from the same tissue is termed leiomyoma. While leiomyosarcomas are not thought to arise from leiomyomas, some leiomyoma variants' classification is evolvi ...
*
Lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include en ...
* Nodular regenerative hyperplasia


Subtypes

Hepatic adenomas may be sub-classified according to morphologic appearance by microscopy, immunohistochemical staining, and genetic mutational analysis: * Inflammatory (40%–50%) * HNF1α-inactivated (35%–40%) * β-catenin–activated - with exon 3 versus exon 7/8 mutation * β-Catenin–activated inflammatory - with exon 3 versus exon 7/8 mutation * Unclassified Although the significance of this categorization is still under research, the subtypes may indicate differential risk of hemorrhage or malignant transformation.


Pathologic diagnosis

Hepatic adenomas are, typically, well-circumscribed nodules that consist of sheets of
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
s with a bubbly vacuolated
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
. The hepatocytes are on a regular reticulin scaffold and less or equal to three cell thick. The histologic diagnosis of hepatic adenomas can be aided by
reticulin Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue composed of type III collagen secreted by reticular cells. Reticular fibers crosslink to form a fine meshwork (reticulin). This network acts as a support ...
staining Staining is a technique used to enhance contrast in samples, generally at the microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissues), in cytology (microscopic study of cells), and in th ...
. In hepatic adenomas, the reticulin scaffold is preserved and hepatocytes do not form layers of four or more hepatocytes, as is seen in
hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...
. Cells resemble normal hepatocytes and are traversed by blood vessels but lack portal tracts or central veins. Image:Hepatic adenoma high mag.jpg, Micrograph of hepatic adenoma.
H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin-eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diag ...
Image:Hepatic adenoma low mag reticulin.jpg, Micrograph of hepatic adenoma.
Reticulin Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue composed of type III collagen secreted by reticular cells. Reticular fibers crosslink to form a fine meshwork (reticulin). This network acts as a support ...
stain File:Histopathology of inflammatory hepatocellular adenoma.jpg, Inflammatory hepatocellular adenoma


Treatment

Some authors feel that all hepatocellular adenoma should be resected, because of the risk of rupture causing bleeding and because they may contain malignant cells. Current recommendations are that all hepatic adenomas should be resected, as long as they are surgically accessible and the patient is a reasonable operative candidate. Patients with adenomas should avoid oral contraceptives or hormonal replacement therapy. Pregnancy could cause the adenoma to grow faster, so patients with hepatic adenomas should avoid pregnancy.


Epidemiology

The majority of hepatic adenomas arise in women aged 20–40, most of whom use oral contraceptives. Other medications which also alter circulating hormone levels, such as anabolic or androgenic steroids,
Barbiturates Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as we ...
,
clomifene Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. Use results in a greater chance of twins. It is taken by mouth once a day, with a course ...
, have also been implicated as risk factors. Incidence of adenomas may be increased in metabolic diseases, including
tyrosinemia Tyrosinemia or tyrosinaemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms of untreated tyrosinemia include liver and kidney disturbances. Without treatment, tyrosinemi ...
and
type 1 diabetes mellitus Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...
, and
glycogen storage disease A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by an enzyme Deficiency (medicine), deficiency affecting glycogen synthesis, glycogen breakdown, or glycolysis, glucose breakdown, typically in musc ...
s (types 1 and 3), as well as in
beta-thalassemia Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to cl ...
and
hemochromatosis Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosi ...
.


References


External links


University of Utah—Pathology Images
{{DEFAULTSORT:Hepatocellular Adenoma Hepatology