Imaging Pearls ❯ Liver ❯ Hepatic Adenoma
|
-- OR -- |
|
- “Modern classification schemes identify five subtypes of hepatic adenoma. The first, hepatocyte nuclear factor 1α (HNF-1α)-inactivated, is relatively indolent, accounts for 30–40% of all adenomas, and is associated with a lower risk for both malignant transformation and hemorrhage. By comparison, the β catenin-activated adenoma subtype (~10% of all adenomas) can be associated with significant cellular atypia at pathology and can have a rate of malignant transformation of 46% in series evaluating specific activating mutations. Inflammatory adenomas comprise approximately 40% of all hepatic adenomas, are due to aberrant regulation of the Janus kinase, and are more common in obese patients. They have a risk of malignant transformation but this risk is much lower than in the β catenin-activated subtype.”
Nontraumatic Liver Hemorrhage
Amudan J. Srinivasan and Andrew B. Peitzman F. Coccolini, F. Catena (eds.),
Textbook of Emergency General Surgery, https://doi.org/10.1007/978-3-031-22599-4_64 - “Sonic hedgehog adenomas account for fewer than 5% of cases, but are associated with higher rates of spontaneous hemorrhage without elevated risks of malignancy. Finally, unclassified adenomas comprise the remainder of these lesions and do not have unifying histologic or molecular features.”
Nontraumatic Liver Hemorrhage
Amudan J. Srinivasan and Andrew B. Peitzman F. Coccolini, F. Catena (eds.),
Textbook of Emergency General Surgery, https://doi.org/10.1007/978-3-031-22599-4_64 - “Accounting for fewer than 2% of all primary hepatic malignancies, angiosarcoma is a mesenchymal tumor that is classically associated with exposure to vinyl chloride, thorium dioxide/thorotrast, or anabolic steroids, though the majority of these lesions occur in patients who have no significant exposure history. They are vascular by nature, arising from endothelium, and this in combination with their aggressive growth predisposes these lesions to intraperitoneal hemorrhage—it is estimated that 15–25% of cases will have NLH at the time of initial presentation. The tumor is frequently advanced or metastatic at the time of diagnosis, and this confers an overall poor prognosis, with median survival around 1 year from diagnosis. Their appearance on CT can be variable, but they are generally hypoattenuating masses with peripheral nodular arterial enhancement. Some may show evidence of heterogeneity within the mass, with regions of hyperattenuation. Following stabilization, there is a reasonable argument to be made for the resection of a hemorrhagic primary lesion in the elective setting, though the oncologic benefit of such an operation may be unclear if there are metastatic lesions.”
Nontraumatic Liver Hemorrhage
Amudan J. Srinivasan and Andrew B. Peitzman F. Coccolini, F. Catena (eds.),
Textbook of Emergency General Surgery, https://doi.org/10.1007/978-3-031-22599-4_64 - Etiologies of nontraumatic liver hemorrhage
- “The liver is a common site for metastatic disease due in large part to its dual blood supply as well as its exposure to the near-complete venous drainage of the gastrointestinal tract. Overall, metastatic liver lesions are much more common than primary liver tumors, though they represent a relatively small fraction of hepatic lesions associated with intraperitoneal hemorrhage. Nonetheless, there are case reports within the literature that discuss hemorrhage from a variety of primary tumor types, including nasopharyngeal, breast, lung, pancreas, colon, lymphoma, and melanoma. While not formally studied, it has been theorized that peripheral and subcapsular lesions are more likely to produce NLH due to the propensity for a capsular tear from the mass effect of tumor growth. On imaging, metastatic lesions are usually multiple well-defined rounded tumors that can have variable imaging characteristics based on the specific primary but are usually hypoechoic on ultrasound and hypoattenuating and hypoenhancing on CT. As metastatic lesions usually derive blood supply from the hepatic arterial distribution, they are reasonable candidates for embolization, though the patient’s overall prognosis is usually poor in the setting of metastatic disease.”
Nontraumatic Liver Hemorrhage
Amudan J. Srinivasan and Andrew B. Peitzman F. Coccolini, F. Catena (eds.),
Textbook of Emergency General Surgery, https://doi.org/10.1007/978-3-031-22599-4_64 - “The HELLP syndrome is an idiopathic clinical entity that is thought to share a pathologic etiology with preeclampsia/eclampsia, characterized by microangiopathic hemolytic anemia, elevations in transaminases, and thrombocytopenia. Approximately 4–12% of cases of severe pre-eclampsia have an associated component of HELLP syndrome. Though the suspected root cause of preeclampsia is abnormal placental development, perhaps at the vascular interfaces of maternal/fetal circulation, it is believed that some component of endothelial damage is associated with the development of HELLP. This endotheliopathy and corresponding microangiopathy can create perturbations in hepatic sinusoidal flow, causing congestion and hepatocyte necrosis. In this setting, spontaneous hepatic hemorrhage can occur and can breach the liver capsule causing NLH. This can be extremely morbid, with mortality ranging from 18% to 86% depending on cohort, though it is rare even in the context of HELLP syndrome—less than 1–2% of all HELLP cases. Most commonly occurring in the right hepatic lobe (75%), most likely due to the greater tissue mass in that lobe, it presents most commonly between 28 and 36 weeks of gestation . HELLP-associated NLH should be strongly suspected in any pregnant patient presenting with acute hemodynamic instability and an acute abdomen.”
Nontraumatic Liver Hemorrhage
Amudan J. Srinivasan and Andrew B. Peitzman F. Coccolini, F. Catena (eds.),
Textbook of Emergency General Surgery, https://doi.org/10.1007/978-3-031-22599-4_64
- “Approximately 7% of benign HAs will progress to HCC. Whenever a distinctive nodule is noted within a HA lesion, the suspicion for malignancy should be high. The probability of developing cancer is highest if the patient is male, has a β-catenin subtype, or has a large tumor > 5 cm. The most significant risk factor is male sex, which increases the chance of malignant transformation into HCC by ten- fold, with a 10-year cumulative risk of up to 60%. The risk of HCC increases exponentially with tumor size, yet is unrelated to the number of HAs. The β-catenin subtype is most frequently implicated in malignant transformation, with an incidence of up to 50%.”
A Scoping Review of the Classification, Diagnosis, and Management of Hepatic Adenomas
Hassan Aziz et al.
Journal of Gastrointestinal Surgery (2022) 26:965–978 - "Patients with HA require surveillance imaging as HCC can develop in a pre-existing lesion over many years. HA patients taking exogenous androgens (for example, patients with Fanconi anemia) should especially be monitored for signs of malignancy. OCPs and liver glycogen diseases have also been implicated in the pathogenesis of HA but have not been as strongly associated with malignant transformation. HA-related HCC has a better prognosis than other HCC variants because it is usually detected at an early stage and resected with negative margins. Furthermore, patients with HA tend to have a relatively normal background liver, while patients with HCC tend to have significant liver disease.”
A Scoping Review of the Classification, Diagnosis, and Management of Hepatic Adenomas
Hassan Aziz et al.
Journal of Gastrointestinal Surgery (2022) 26:965–978 - "Given that spontaneous regression of HAs after discontinuing OCPs may occur, often the first step in the management of HAs in asymptomatic women without evidence of β-catenin activation is the cessation of estrogen-containing medications. A subsequent 6-month observation period, even in patients with HAs ≥ 5 cm, may be a reasonable approach. To this point, Klompenhouwer et al. reported that 58.5% of HAs regressed to less than 5 cm at a median of 104 weeks after cessation of OCPs. Larger tumors took longer to regress, and there was no correlation between complications and observation time, suggesting that post-hormonal surveillance can be extended up to 12 months. For individuals with a nodule ≥ 5 cm or a lesion that demonstrates continued growth on repeat imaging, surgical resection is warranted.”
A Scoping Review of the Classification, Diagnosis, and Management of Hepatic Adenomas
Hassan Aziz et al.
Journal of Gastrointestinal Surgery (2022) 26:965–978
- “Hepatic adenomatosis is a benign disease defined as the presence of multiple adenomas in a normal liver. It is an uncommon condition and there are less than a hundred reported cases in the literature. The etiology is unknown, although it has been associated with the use of oral contraceptives, anabolic steroids, certain storage diseases and some genetic mutations linked to maturity onset diabetes of the young. The coexistence of hepatic adenomatosis and nonalcoholic steatohepatitis has been recently described in two patients suffering from metabolic syndrome. This association is particularly interesting due to the growing prevalence of nonalcoholic fatty liver disease in developed countries and the possibility of a common causal pathway.”
Nonalcoholic steatohepatitis and hepatic adenomatosis: casual or causal relationship?
Pérez-Carreras M et al.
Rev Esp Enferm Dig. 2018 Mar;110(3):204-206 - OBJECTIVE. The objective of our study was to investigate the relationship between hepatic adenoma and liver steatosis.
RESULTS. Hepatic steatosis was present in 14 of 24 patients (58%) with hepatic adenoma versus seven of 24 patients (29%) with hemangioma (p = 0.042). Steatosis was more common in patients with multiple hepatic adenomas (9/11, 82%) than in those with a single hepatic adenoma (5/13, 38%) (p = 0.047).
CONCLUSION. Hepatic adenomas occur in patients with hepatic steatosis.
Multiple Hepatic Adenomas Associated with Liver Steatosis at CT and MRI: A Case-Control Study
Furlan A, Federle MP et al.
AJR 2008; 191:1430–1435 - “The goal of our study was to investigate the association between hepatic adenoma and liver steatosis. According to our results, the presence of liver fat deposition at CT and MRI was more frequently detected among the study group of patients with hepatic adenoma than in the control group of patients with hepatic hemangioma. In addition, in the study group, patients with multiple adenomas more fre- quently had signs of a fatty liver than patients with a single adenoma. These results suggest that liver steatosis may play a role in the development of multiple hepatic adenomas.”
Multiple Hepatic Adenomas Associated with Liver Steatosis at CT and MRI: A Case-Control Study
Furlan A, Federle MP et al.
AJR 2008; 191:1430–1435 - “Investigators have reported that, in patients with diabetes, the accumulation of glycogen within the cells, related to the defect in hepatic catabolism, can play a role in the hyperplastic reaction leading to the genesis of hepatic adenomas. The obesity epidemic has paralleled the rapid increase in the prevalence of type 2 diabetes. In our study, there was a significant increased incidence of diabetes in the adenoma group versus the control group; however, no difference could be found between patients with a single adenoma and those with multiple adenomas.”
Multiple Hepatic Adenomas Associated with Liver Steatosis at CT and MRI: A Case-Control Study
Furlan A, Federle MP et al.
AJR 2008; 191:1430–1435 - “In conclusion, the results of our study show the association of liver steatosis and hepatic adenoma in a case-control setting, which is a suitable study design for uncommon condi- tions such as hepatic adenoma. Multiple ade- nomas were especially correlated with ste- atosis. In view of the increasing incidence of hepatic steatosis and obesity, this group of he- patic adenoma patients might be of growing importance and needs special attention.”
Multiple Hepatic Adenomas Associated with Liver Steatosis at CT and MRI: A Case-Control Study
Furlan A, Federle MP et al.
AJR 2008; 191:1430–1435
- “Hepatic adenomatosis is a benign disease defined as the presence of multiple adenomas in a normal liver. It is an uncommon condition and there are less than a hundred reported cases in the literature. The etiology is unknown, although it has been associated with the use of oral contraceptives, anabolic steroids, certain storage diseases and some genetic mutations linked to maturity onset diabetes of the young. The coexistence of hepatic adenomatosis and nonalcoholic steatohepatitis has been recently described in two patients suffering from metabolic syndrome. This association is particularly interesting due to the growing prevalence of nonalcoholic fatty liver disease in developed countries and the possibility of a common causal pathway.”
Nonalcoholic steatohepatitis and hepatic adenomatosis: casual or causal relationship?
Pérez-Carreras M et al.
Rev Esp Enferm Dig. 2018 Mar;110(3):204-206 - OBJECTIVE. The objective of our study was to investigate the relationship between hepatic adenoma and liver steatosis.
RESULTS. Hepatic steatosis was present in 14 of 24 patients (58%) with hepatic adenoma versus seven of 24 patients (29%) with hemangioma (p = 0.042). Steatosis was more common in patients with multiple hepatic adenomas (9/11, 82%) than in those with a single hepatic adenoma (5/13, 38%) (p = 0.047).
CONCLUSION. Hepatic adenomas occur in patients with hepatic steatosis.
Multiple Hepatic Adenomas Associated with Liver Steatosis at CT and MRI: A Case-Control Study
Furlan A, Federle MP et al.
AJR 2008; 191:1430–1435 - “The goal of our study was to investigate the association between hepatic adenoma and liver steatosis. According to our results, the presence of liver fat deposition at CT and MRI was more frequently detected among the study group of patients with hepatic adenoma than in the control group of patients with hepatic hemangioma. In addition, in the study group, patients with multiple adenomas more fre- quently had signs of a fatty liver than patients with a single adenoma. These results suggest that liver steatosis may play a role in the development of multiple hepatic adenomas.”
Multiple Hepatic Adenomas Associated with Liver Steatosis at CT and MRI: A Case-Control Study
Furlan A, Federle MP et al.
AJR 2008; 191:1430–1435 - “Investigators have reported that, in patients with diabetes, the accumulation of glycogen within the cells, related to the defect in hepatic catabolism, can play a role in the hyperplastic reaction leading to the genesis of hepatic adenomas. The obesity epidemic has paralleled the rapid increase in the prevalence of type 2 diabetes. In our study, there was a significant increased incidence of diabetes in the adenoma group versus the control group; however, no difference could be found between patients with a single adenoma and those with multiple adenomas.”
Multiple Hepatic Adenomas Associated with Liver Steatosis at CT and MRI: A Case-Control Study
Furlan A, Federle MP et al.
AJR 2008; 191:1430–1435 - “In conclusion, the results of our study show the association of liver steatosis and hepatic adenoma in a case-control setting, which is a suitable study design for uncommon condi- tions such as hepatic adenoma. Multiple ade- nomas were especially correlated with ste- atosis. In view of the increasing incidence of hepatic steatosis and obesity, this group of he- patic adenoma patients might be of growing importance and needs special attention.”
Multiple Hepatic Adenomas Associated with Liver Steatosis at CT and MRI: A Case-Control Study
Furlan A, Federle MP et al.
AJR 2008; 191:1430–1435
- “Hepatocellular adenomas are uncommon benign epithelial liver neoplasms most commonly seen in young women using oral contraceptives or in men using anabolic steroids. The association between adenomas and contraceptive use was rst described by Baum et al. in the early 1970s. Additional risk factors include glycogen storage disease, obesity, and familial polyposis.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “They are often in the right hepatic lobe and typically present as one lesion (70–80% of cases) ranging in size from 1 to 30 cm. Three types of hepatic adenomas have been classi- fied (according to genotype and phenotype), including adenomas with in ammatory features, mutations in the HNF-1α gene, or mutations in β-catenin.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “The inflammatory subtype is the most common (40–50% of cases), mainly seen in young female patients using oral contracep- tives; it is also associated with obesity. The risk of bleeding is the highest in this subtype (approximately 30%), with a low malignancy risk.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “The second most common subtype is the HNF-1α-mutated hepatocellular adenoma (30–35% of cases). This subtype has the lowest complication rate, with essentially no risk for malignancy and minimal risk of bleeding. The third subtype is the β-catenin-mutated hepatocellular adenoma (10–15% of cases) and is more common in men, with an increased association with anabolic steroids, glycogen storage disease, and familial adenomatosis polyposis.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “The malignancy risk to hepatocellular carcinoma (HCC) is 5–10%; this subtype is considered to have the highest association of malignancy, because it is considered a borderline lesion between adenoma and carcinoma. Bleeding can occur, but the frequency is unknown.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “Hepatic adenomatosis occurs when there are 10 or more adenomas along with mutations of the HNF-1α gene. This can be seen in both sexes with or without oral contraceptive usage.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “In general, adenomas are hypo- to isodense at unenhanced CT, with 80% of lesions showing hyperenhancement on arterial contrast- enhanced images. Eighty-five percent of lesions are well-demarcated, and 25% have an enhancing peripheral capsule. Some lesions have a heterogeneous appearance from acute or chronic hemorrhage. Calci cations are dystrophic and typically are eccentric in location found in areas of old hemorrhage or necrosis in 10% of patients. Single or multiple calci cations can be seen.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86
- “This educational review focuses on the epidemiology and radiological evaluation of the various subtypes of hepatic adenomas (HCAs). It includes detailed discussion of the imaging appearances of each HCA subtype and the clinical relevance of the new classification system. Each HCA subtype has a unique biological behaviour. Imaging plays a central role in diagnosis, subtype characterisation, identification of complications, and follow-up assessment. Management of patients should vary according to the specific HCA subtype.”
Hepatocellular adenoma: imaging review of the various molecular subtypes. Dharmana H1, Saravana-Bawan S2, Girgis S3, Low G2. Clin Radiol. 2017 Apr;72(4):276-285 - “The exact mechanism for malignant transformation into HCCs is not well understood. Rapid increase in the size of a previously stable HCA raises the possibility of malignant degeneration or haemorrhage. A recent systematic review by Stoot et al. found that the incidence of malignant transformation was approximately 4.2%. The β-catenin activated subtype has the highest predilection for malignant transformation of all HCAs..”
Hepatocellular adenoma: imaging review of the various molecular subtypes. Dharmana H1, Saravana-Bawan S2, Girgis S3, Low G2. Clin Radiol. 2017 Apr;72(4):276-285 - “HCA has been described in patients with glycogen storage disorders (GSDs), particularly type 1 (Von Gierke's disease) and type 3.GSDs are hereditary disorders with an autosomal recessive transmission. They are characterised by abnormal glycogen accumulation in the liver, which causes chronic inflammation and predisposes to HCA development. HCAs associated with GSDs commonly affect males (male to female ratio of 2:1) and typically develop in patients <20 years of age.These HCAs are more likely to be multiple and have a higher risk of malignant transformation into HCC.”
Hepatocellular adenoma: imaging review of the various molecular subtypes. Dharmana H1, Saravana-Bawan S2, Girgis S3, Low G2. Clin Radiol. 2017 Apr;72(4):276-285 - “Metastatic liver tumor of adenocarcinoma, such as colon cancer or pancreatic cancer, often shows doughnut-like ring enhancement due to its mucinous and fibrous components. As a result, it needs to be differentiated from cholangiocarcinoma. Metastatic liver tumors of renal cell carcinoma, breast cancer, and neuroendocrine tumors, for example, exhibit hypervascularity and have to be differentiated from HCC. When the primary lesion is known, metastatic tumors can be easily diagnosed.”
Hypervascular Benign and Malignant Liver Tumors That Require Differentiation from Hepatocellular Carcinoma: Key Points of Imaging Diagnosis Takamichi Murakami* and Masakatsu Tsurusaki Liver Cancer. 2014 May; 3(2): 85–96.
- Hepatic Adenoma
- Female predominance
- Highly associated with OCP use, steroids, steatosis, and glycogen storage disease
- Can present with hemorrhage in 20%
- Primarily composed of hepatocytes and Kuppfer cells
- Hepatic “adenomatosis” without OCP use
- Malignant degeneration to HCC rare - Hepatic Adenoma
- Hepatic artery vascular supply
- Heterogeneously hypervascular on the arterial phase
- Fat
- Hemorrhage
- Variable appearance on venous and delayed images
- Often encapsulated on venous and delayed images
- Can have a central scar - FNH versus Adenoma
FNH
-Common lesion
-Homogeneously enhancing
-No fat
-No hemorrhage
-No capsule
-No calcification
Adenoma
-Rare lesion
-Heterogeneous (when large)
-Fat
-Hemorrhage
-Capsule
-Can calcify (prior hemorrhage)
- Hepatic Adenoma
- Hepatic artery vascular supply
- Heterogeneously hypervascular on the arterial phase
- Fat
- Hemorrhage
- Variable appearance on venous and delayed images
- Often encapsulated on venous and delayed images
- Can have a central scar
- Hepatic Adenoma
- Female predominance
- Highly associated with OCP use, steroids, steatosis, and glycogen storage disease
- Can present with hemorrhage in 20%
- Primarily composed of hepatocytes and Kuppfer cells
- Hepatic “adenomatosis” without OCP use
- Malignant degeneration to HCC rare
- Hepatic Adenoma
- Female predominance
- Highly associated with OCP use, steroids, steatosis, and glycogen storage disease
- Can present with hemorrhage in 20%
- Primarily composed of hepatocytes and Kuppfer cells
- Hepatic “adenomatosis” without OCP use
- Malignant degeneration to HCC rare - Hepatic Adenoma
1. Hepatic artery vascular supply
2. Heterogeneously hypervascular on the arterial phase
- Fat
- Hemorrhage
3. Variable appearance on venous and delayed images
4. Often encapsulated on venous and delayed images
5. Can have a central scar
- “ Recent advances in pathology and cytogenetics have thrown fresh light on the pathogenesis of hepatic adenomas leading to classification of HCAs into 3 distinct subgroups, each with a characteristic epidemiology, histopathology, oncogenesis and imaging findings.”
Hepatocellular Adenomas: Current Update on Genertics, Taxonomy and Management
Shanbhogue A et al.
J Comput Assist Tomogra March/April 2011; Volume 35:2; pp159-166 - Hepatic Adenomas: 3 Subtypes
- Hepatocyte nuclear factor-1α (HNF-1α)-mutated HCAs (HNF-HCAs)
- β- catenin mutations
- Inflammatory HCAs (I-HCAs) due to mutations involving interleukin-6 signal transducer (IL-6) - Hepatic Adenomas: facts
- More common in woman (1.8-1)
- Mean age of 41 years
- Strong relationship between long term oral contraceptive use and hepatic adenoma (usually greater than 2 years)
- Increased risk with anabolic androgen steroid intake as well as metabolic liver disease such as glycogen storage disease, tyrosinemia, staetohepatits and hemochromatosis - Hepatic Adenomas: facts
- Usually solitary
- May be multiple in adenomatosis (>10 lesion in liver)
- Size range 1-20 cm
- Hepatic Adenoma: Facts
- Predilection to hemorrhage and rupture
- Usually in young woman
- Risk factors include glycogen storage disease (type I) and oral contraceptives/anabolic corticosteroids
- Usually solitary but may be multiple as in adenomatosis (usually greater than 10)
- Increased incidence of malignant degeneration - "Hepatic adenomas occur more frequently and more often are multiple in patients with hepatic steatosis."
Multiple Hepatic Adenomas Associated with Liver Steatosis at CT and MRI: A Case-Control Study
Furlan A et al
AJR 2008;191:1430-1435 - Hepatic Adenoma: CT Findings
- Non contrast CT: hypodense or isodense
- Arterial phase: moderate enhancement
- Portal phase CT: lesions enhance similar to surrounding liver
- Delayed phase CT: lesions enhance similar to surrounding liver - Hepatic Adenoma: CT Findings
- Well defined mass that may contain hemorrhage, necrosis, fat and rarely calcification
- Non contrast CT: hypodense or isodense
- Arterial phase: moderate enhancement
- Portal phase CT: lesions enhance similar to surrounding liver
- Delayed phase CT: lesions enhance similar to surrounding liver - Hepatic Adenoma: Facts
- Majority are solitary (80%)
- Typically in female patients (90%)
- Predisposing factors include
----Oral contraceptive use
----Anabolic steroid use
----Glycogen storage disease (type IA) - "Familiarity with both expected and unexpected imaging appearances of common benign hepatic tumors, less commonly encountered benign hepatic tumors, and iatrogenic abnormalities potentially masquerading as hepatic tumors allows the radiologist to achieve an informed differential diagnosis."
Benign Hepatic tumors and Pseudotumors
Anderson SW, Kruskal JB, Kane RA
RadioGraphics 2009; 29:211-229