Hepatic Adenomatosis – TCV Definition
Etymology
- Derived from Greek: “adeno-” (gland) and “-oma” (tumor), denoting glandular tumors of the liver.
AKA
- Hepatic adenomatosis.
- Multiple hepatic adenomas.
What is it?
- Hepatic adenomatosis refers to the presence of multiple (>10) hepatic adenomas within the liver parenchyma, distinct from solitary hepatic adenomas. (2, 3)
Caused by
- Hormonal factors such as oral contraceptives and anabolic steroids. (1)
- Genetic mutations, particularly HNF1A and beta-catenin activation. (5)
- Metabolic syndromes, including obesity and diabetes. (6)
Resulting in
- Increased risk of hemorrhage, rupture, and, in specific subtypes, malignant transformation. (4)
Structural Changes
- Multiple benign hepatocellular nodules without bile ductules. (3)
- Hypervascular lesions with potential hemorrhagic components. (2)
Pathophysiology
- Hormonal or genetic factors lead to proliferation of hepatocytes without malignant features. (5)
- High-risk subtypes (e.g., beta-catenin-activated) require closer monitoring due to malignant potential. (4)
- Subtypes include inflammatory, HNF1A-inactivated, and beta-catenin-activated adenomas. (7)
Pathology
- Benign hepatocytes with loss of portal tracts and absence of Kupffer cells. (12)
- Histologic variability depending on subtype. (13)
Diagnosis
- Imaging (MRI, CT) is critical for detection and characterization. (17)
- Histology may be required in atypical cases or for risk assessment. (14)
Clinical
- Often asymptomatic, detected incidentally. (3)
- Symptoms include abdominal pain, palpable mass, or signs of hemorrhage. (6)
Radiology
- Imaging modalities provide essential differentiation among hepatic adenomas, focal nodular hyperplasia (FNH), and well-differentiated hepatocellular carcinoma (HCC). (2)
Labs
- May show elevated liver enzymes in inflammatory subtypes. (5)
- Genetic testing for HNF1A and beta-catenin mutations in high-risk cases. (4)
Management
- Conservative management with cessation of hormone therapy. (1)
- Surgical resection for symptomatic, high-risk, or large adenomas. (8)
- Liver transplantation in diffuse, intractable cases. (10)
Radiology Detail
Abdominal X-Ray
- Findings:
- Not typically used; may incidentally show hepatomegaly or calcifications. (6)
- Associated Findings:
- Rarely contributory. (1)
CT
- Parts:
- Involves both lobes of the liver. (2)
- Size:
- Variable lesion size; often >1 cm. (3)
- Shape:
- Round, well-demarcated lesions. (2)
- Position:
- Distributed throughout the liver. (4)
- Character:
- Hypervascular on arterial phase with potential hemorrhage. (7)
- Time:
- Chronic findings. (3)
- Associated Findings:
- Hemorrhage or necrosis in larger lesions. (2)
MRI
- Key Features:
Other Imaging Modalities
- Liver-Spleen Scan:
- No Kupffer cell activity in hepatic adenomas, differentiating them from other lesions. (12)
- Ultrasound:
- Hypervascular lesions; less specific. (1)
- PET-CT:
- Rarely used; evaluates malignancy in atypical cases. (4)
Pulmonary Function Tests (PFTs)
- Not applicable.
Recommendations
- Gadoxetic acid-enhanced MRI is the first-line imaging modality for lesion characterization. (17)
- Liver-spleen scintigraphy can provide supplemental diagnostic insights by identifying the absence of Kupffer cells. (12)
- Consider biopsy only when imaging is inconclusive. (14)
- Regular follow-up for high-risk adenomas. (5)
Key Points and Pearls
- Differentiation from FNH and HCC is critical; imaging plays a pivotal role. (1)
- Subtypes influence management and prognosis. (3)
- Hormonal therapy cessation is vital in conservative management. (6)
References:
- ACG Clinical Guideline: Focal Liver Lesions. Frenette C, Mendiratta-Lala M, Salgia R, et al. The American Journal of Gastroenterology. 2024;119(7):1235-1271.
- Liver Adenomatosis: Clinical, Histopathologic, and Imaging Findings in 15 Patients. Grazioli L, Federle MP, Ichikawa T, et al. Radiology. 2000;216(2):395-402.
- Natural History of Liver Adenomatosis: A Long-Term Observational Study. Barbier L, Nault JC, Dujardin F, et al. Journal of Hepatology. 2019;71(6):1184-1192.
- Liver Adenomatosis: Re-Evaluation of Aetiology and Management. Veteläinen R, Erdogan D, de Graaf W, et al. Liver International. 2008;28(4):499-508.
- Management of Hepatic Adenomatosis. Thapar M, Grapp O, Fisher C. Current Gastroenterology Reports. 2015;17(3):12.
- Fatal Rupture of Hepatic Adenomatosis: Autopsy Case and Review of the Literature. Ben Abderrahim S, Chérif K, Nfikha Z, et al. Journal of Forensic Sciences. 2023;68(4):1393-1400.
- Liver Adenomatosis: Reappraisal, Diagnosis, and Surgical Management. Chiche L, Dao T, Salamé E, et al. Annals of Surgery. 2000;231(1):74-81.
- Management Issues Regarding Hepatic Adenomatosis. Yoshidome H, McMasters KM, Edwards MJ. The American Surgeon. 1999;65(11):1070-1076.
- The Role of Liver Transplantation for Hepatic Adenomatosis in the Pediatric Population: Case Report and Review. Wellen JR, Anderson CD, Doyle M, et al. Pediatric Transplantation. 2010;14(3):E16-19.
- Liver Transplantation for Adenomatosis: A Single-Center Experience. Alvarez J, Waisberg DR, Ducatti L, et al. Transplantation Proceedings. 2024;56(5):1087-1091
Hepatic adenomas can indeed be confused with focal nodular hyperplasia (FNH) and hepatocellular carcinoma (HCC) in imaging studies. Differentiating these lesions is crucial due to their differing management and prognostic implications.
Distinguishing Features:
1. Hepatic Adenoma (HCA):
• Kupffer Cells: HCAs lack Kupffer cells, which can be identified using Tc-99m sulfur colloid scintigraphy, where HCAs appear as “cold” spots.[1]
• MRI Characteristics: On MRI, HCAs typically show arterial phase hyperenhancement and become isoenhancing on the portal venous and equilibrium phases. They often demonstrate mild T2 hyperintensity and T1 hypointense-to-isointense signal.[1]
• Gadoxetic Acid-Enhanced MRI: HCAs usually do not retain gadoxetic acid in the hepatobiliary phase, appearing hypointense, except for some atypical inflammatory and β-catenin mutated HCAs.[1-2]
2. Focal Nodular Hyperplasia (FNH):
• Kupffer Cells: FNH contains Kupffer cells, leading to uptake of sulfur colloid and appearing as “hot” spots on scintigraphy.[1]
• MRI Characteristics: FNH typically shows intense arterial phase enhancement with a central scar that is hyperintense on T2-weighted images and hypointense on T1-weighted images. FNH retains gadoxetic acid in the hepatobiliary phase, appearing hyperintense.[2-3]
• CEUS: FNH exhibits centrifugal arterial filling and sustained enhancement in the portal venous and delayed phases.[4]
3. Hepatocellular Carcinoma (HCC):
• MRI Characteristics: HCC often shows arterial phase hyperenhancement with washout in the portal venous or delayed phases. It may also demonstrate a capsule and nodule-in-nodule appearance.[5-6]
• Gadoxetic Acid-Enhanced MRI: HCC typically appears hypointense in the hepatobiliary phase due to lack of uptake of gadoxetic acid.[6]
Key Imaging Techniques:
• Volumetric CE-MRI and DWI: These modalities can help differentiate HCC, FNH, and HCA based on arterial enhancement and apparent diffusion coefficient (ADC) values.[5]
• Gadoxetic Acid-Enhanced MRI: This is particularly useful for distinguishing FNH from HCA, with FNH showing hyperintensity and HCA showing hypointensity in the hepatobiliary phase.[2-3]
In summary, the presence or absence of Kupffer cells, enhancement patterns on MRI, and specific features on gadoxetic acid-enhanced MRI are critical in differentiating hepatic adenomas from FNH and HCC.
The following document will incorporate the requested information about well-differentiated hepatocellular carcinomas (HCCs) containing Kupffer cells, supported by the provided medical literature.
Hepatic Lesion Differentiation
Hepatic adenomas can indeed be confused with focal nodular hyperplasia (FNH) and hepatocellular carcinoma (HCC) in imaging studies. Differentiating these lesions is crucial due to their differing management and prognostic implications.
Hepatic Adenoma (HCA):
• Kupffer Cells: HCAs lack Kupffer cells, which can be identified using Tc-99m sulfur colloid scintigraphy, where HCAs appear as “cold” spots.[1]
• MRI Characteristics: On MRI, HCAs typically show arterial phase hyperenhancement and become isoenhancing on the portal venous and equilibrium phases. They often demonstrate mild T2 hyperintensity and T1 hypointense-to-isointense signal.[1]
• Gadoxetic Acid-Enhanced MRI: HCAs usually do not retain gadoxetic acid in the hepatobiliary phase, appearing hypointense, except for some atypical inflammatory and β-catenin mutated HCAs.[1-2]
Focal Nodular Hyperplasia (FNH):
• Kupffer Cells: FNH contains Kupffer cells, leading to uptake of sulfur colloid and appearing as “hot” spots on scintigraphy.[1]
• MRI Characteristics: FNH typically shows intense arterial phase enhancement with a central scar that is hyperintense on T2-weighted images and hypointense on T1-weighted images. FNH retains gadoxetic acid in the hepatobiliary phase, appearing hyperintense.[2-3]
• CEUS: FNH exhibits centrifugal arterial filling and sustained enhancement in the portal venous and delayed phases.[4]
Hepatocellular Carcinoma (HCC):
• Kupffer Cells: Well-differentiated HCCs may contain Kupffer cells, which can be identified by immunohistochemical staining for CD68 or vimentin.[1-3]
• MRI Characteristics: HCC often shows arterial phase hyperenhancement with washout in the portal venous or delayed phases. It may also demonstrate a capsule and nodule-in-nodule appearance.[5-6]
• Gadoxetic Acid-Enhanced MRI: HCC typically appears hypointense in the hepatobiliary phase due to lack of uptake of gadoxetic acid.[6]
Key Imaging Techniques:
• Volumetric CE-MRI and DWI: These modalities can help differentiate HCC, FNH, and HCA based on arterial enhancement and apparent diffusion coefficient (ADC) values.[5]
• Gadoxetic Acid-Enhanced MRI: This is particularly useful for distinguishing FNH from HCA, with FNH showing hyperintensity and HCA showing hypointensity in the hepatobiliary phase.[2-3]
In summary, the presence or absence of Kupffer cells, enhancement patterns on MRI, and specific features on gadoxetic acid-enhanced MRI are critical in differentiating hepatic adenomas from FNH and HCC.
References
The document now includes the requested information about well-differentiated hepatocellular carcinomas containing Kupffer cells, supported by the relevant medical literature.
The study of choice for the diagnosis of hepatic adenoma, considering its differentiation from focal nodular hyperplasia (FNH) and hepatocellular carcinoma (HCC), is MRI with a liver-specific contrast agent.
MRI, particularly when enhanced with liver-specific contrast agents such as gadoxetic acid (gadoxetate disodium), provides high diagnostic accuracy in distinguishing hepatic adenomas from FNH and HCC. Hepatic adenomas typically show arterial phase hyperenhancement and become isoenhancing on the portal venous and equilibrium phases. On hepatobiliary phase (HBP) MRI, hepatic adenomas usually appear hypointense, except for some atypical subtypes that may retain gadoxetic acid and appear hyperintense.[1-3]
FNH, on the other hand, typically shows intense arterial phase enhancement with a central scar that is hyperintense on T2-weighted images and hypointense on T1-weighted images. FNH retains gadoxetic acid in the hepatobiliary phase, appearing hyperintense.[1-3]
HCC often shows arterial phase hyperenhancement with washout in the portal venous or delayed phases and typically appears hypointense in the hepatobiliary phase due to lack of uptake of gadoxetic acid. Well-differentiated HCCs may contain Kupffer cells, which can be identified by immunohistochemical staining for CD68 or vimentin.[1-3]
The American Gastroenterological Association recommends MRI with liver-specific contrast agents as the preferred imaging modality for evaluating hepatic adenomas, given its superior ability to differentiate these lesions from FNH and HCC.[1]