Mass forming lesions of liver

The evaluation and management of mass-forming lesions in the liver represent a significant and complex aspect of hepatology and oncology. This comprehensive clinical overview aims to shed light on the intricate nature of liver masses, encompassing a range of benign and malignant conditions including hepatic adenomas, cholangiocarcinomas, and liver metastases. With advancements in medical imaging and molecular pathology, the diagnostic accuracy and treatment strategies for these hepatic lesions have evolved, necessitating a thorough understanding among healthcare professionals.

This webpage will delve into various aspects of liver lesions, from their epidemiology and pathogenesis to the intricate details of imaging features, differential diagnosis, and management approaches.

In this detailed comparison, we explore cystic pathologies affecting the liver, shedding light on their origins, etiology, histopathological characteristics, clinical manifestations, laboratory investigations, and imaging findings. We delve into the first-line and medical management strategies, as well as potential surgical and interventional radiology interventions where applicable. A structured overview of the multifaceted approach to diagnosing and characterizing liver mass lesions, incorporating clinical evaluation, laboratory testing, imaging studies, biopsy techniques, and advanced endoscopic and molecular methods is as follows.

Clinical history and Lab investigations

Personal History and Physical Examination
- Chronic hepatitis, liver cirrhosis: Risk for HCC, intrahepatic cholangiocarcinoma.
- Primary sclerosing cholangitis: Risk for cholangiocarcinoma.
- Long-term oral contraceptive use: Risk for hepatic adenoma.
- Family history: E.g., young-onset diabetes mellitus can predispose to hepatic adenomatosis.
- Physical complaints: Non-specific abdominal pain, pruritus, dark urine, pale stools (biliary obstruction).
- Constitutional symptoms: Fever, anorexia, weight loss, fatigue.
- Physical signs: Spider angiomas, caput medusa, hepatomegaly, splenomegaly, jaundice.
Laboratory Tests
- Detect active hepatitis, platelet count (chronic liver disease), hyperbilirubinemia.
- Serum markers: AFP (hepatocellular carcinoma), CA19-9 (cholangiocarcinoma), CEA (colorectal cancer metastasis), Chromogranin A, 5-HIAA (neuroendocrine carcinomas).
- Lymphoma indicators: Elevated LDH, intraabdominal lymphadenopathy.

Radiologic Imaging Studies

Ultrasound (US), Computed Tomography (CT), Magnetic Resonance Imaging (MRI)
- Differentiation of liver masses, detection of metastatic disease.
- Specialized scans: Octreotide (neuroendocrine tumors), PET scans (metastatic disease, cholangiocarcinoma).
Multiphasic Cross-Sectional Imaging (CT/MRI)
- Phases: Arterial, portal venous, equilibrium.
- Hepatobiliary contrast agents for phenotypic characterization (e.g., Gd-EOB-DTPA, Gd-BOPTA).
- MRI characteristics: T2-weighted sequence, In- and Opposed-phase sequence, DWI.
Advanced Techniques
- Perfusion CT, Dual-energy CT, Magnetic Resonance Elastography (MRE), Acoustic Radiation Force Impulse Imaging (ARFI).

Needle Biopsy, Histopathology, and Immunohistochemical Studies

Needle Biopsy
- Important for characterizing suspected malignant masses.
- Considerations of needle tract seeding and false negative rates.
Histopathology and Immunohistochemistry
- Diagnosis and molecular analysis for chemotherapeutic decisions.

Endoscopic, Interventional Radiologic, and Molecular Pathologic Techniques

Endoscopic Techniques
- ERCP, PTC, EUS for biliary system and hepatic hilum imaging.
- Ancillary techniques: Cholangioscopy, bile duct biopsy, lymph node sampling.
Molecular Pathologic Techniques
- FISH examination of cells from pancreatobiliary strictures or lymph nodes.

Comparing Various mass forming lesion effecting Liver:

Feature	Cavernous Hemangioma	Focal Nodular Hyperplasia (FNH)	Hepatic Adenoma	Hepatocellular Carcinoma (HCC)	Liver Metastases	Focal Fat/Fat-Sparing	Biliary tract Carcinomas
Epidemiology	Most common benign liver lesion, up to 7% prevalence, females > males	Common benign mass, 4% prevalence, females > males	1. Uncommon but increasing in men with metabolic syndrome 2. Linked to oral contraceptives, steroids and metabolic syndrome	1. Over 700,000 cases/year, often in cirrhotic livers 2. Most common cause included cirrhosis due to hepatitis virus, alcohol consumption and NASH.	Most common malignant liver masses in non-cirrhotic livers, often originating from colorectal, gastric, pancreatic, or neuroendocrine tumors.	Rising with obesity trends	1. Includes Cholangiocarcinoma and Carcinoma gall bladder 2. Increasing incidence of intrahepatic cholangiocarcinoma; stable rates of extrahepatic cholangiocarcinoma; decreasing gallbladder cancer incidence.
Pathogenesis	Congenital vascular malformations, usually solitary	Hyperplastic growth around pre-existing arterial malformation	1. Inflammatory Hepatic Adenomas: specific genetic deletions affecting the IL-6 signal transduction protein gp130. Highest chance of bleeding. 2. HNF1α-inactivated Hepatic Adenomas: characterised by fatty changes (steatosis) and lack the expression of liver fatty acid binding protein. 3. β-catenin-activated Hepatic Adenomas: They overexpress glutamine synthetase and show abnormal β-catenin expression, which increases the risk of malignant transformation. 4. Indeterminate Subgroup: This category includes adenomas that do not fit into the other classifications. 5. Hepatic Adenomatosis - When a person has a significant number of these adenomas, typically more than five. Associated to various genetic and metabolic conditions, including different types of glycogen storage diseases, Klinefelter syndrome, hereditary diabetes, and genetic predispositions to adenomas.	Hepatocyte senescence from chronic injury, inflammation	Dependent on the primary tumor type.	Macro-vesicular steatosis in specific liver areas	Linked to inflammatory liver and biliary tract conditions (like primary sclerosing cholangitis, liver fluke infestations), diabetes, and smoking.
Morphology	Well-circumscribed, red-brown, blood-filled vascular spaces	Well-circumscribed, non-encapsulated, central scar	1. Round, well-circumscribed, benign hepatocytes 2. Organised in sheets or cords 3. Notably, they lack the normal portal tracts and have naked or unaccompanied arteries	Varied hepatocyte resemblance, naked arteries, absent normal portal tracts	Varies according to the primary tumor type.	Normal portal areas, central veins, steatosis	Well-differentiated adenocarcinomas, often scirrhous, with malignant cells surrounded by dense stroma.
Ultrasound (US)	Homogenous, hyperechoic, sharp margins, acoustic enhancement and generally < 3 cm	1. Slightly hypo-/isoechoic, sometimes only detected by a pseudocapsule or spoke-wheel pattern on color doppler. 2. Central scar may be indistinct. 3. "Spoke-wheel" pattern (central feeding vessel with centrifugal blood flow) in larger lesions.	Variable appearance (due to presence of fat / necrosis / hemorrhage)		1. LM can exhibit a wide range of imaging findings. These characteristics are influenced by factors such as the origin of the primary tumor, its differentiation, histological behavior (e.g., solid or mucinous), potential complications, and the condition of the surrounding liver parenchyma. 2. Hypervascular Metastases: Homogeneous arterial phase enhancement (e.g., from renal cell, breast, thyroid cancers, neuroendocrine tumors (NET), GIST, melanoma, and sarcomas). 3. Hypovascular Metastases: Often from gastrointestinal tract adenocarcinomas, specific delayed phase washout pattern.	US: Hyperechoic (focal fat), hypoechoic (fat sparing).	1. CT/MRI: - Solid masses, hypointense on precontrast images, gradual contrast accumulation across different phases (arterial, portal and venous). - Features of Bile duct obstruction leading to lobar atrophy, compensatory hypertrophy in the contralateral lobe. - Biliary tree dilatation. Characteristic rim enhancement in delayed phase differentiates from HCC.
CT	Hypo-/isodense on unenhanced, peripheral nodular enhancement in arterial phase, progressive centripetal filling in subsequent phases.	Isodense to liver, rapid homogeneous contrast uptake in arterial phase, near normal enhancement in portal and venous phase central scar. (hypodense on CT, T2 bright on MRI) when present is specific of FNH. Delayed phase: Hyperenhancing scar.	1. Homogeneous enhancement in arterial phase, isoechoic/hyperechoic in early portal venous phase 2. Variable appearance (due to presence of fat / necrosis / hemorrhage)	- Arterial phase hyper enhancement, portal venous/delayed phase washout, - LIRADS in patients with cirrhosis and chronic HBV infection.		Hypodense (focal fat), hyperdense region (fat sparing).
MRI (Most specific )	- Hypointense on T1 - Hyperintense on T2 (less hyperintense compared to CSF / simple cyst), - High ADC value, signal drops with increasing b-values - Characteristic centripetal enhancement pattern. - Heterogeneous pattern in large sized hemangioma due to calcification, thrombus and or fibrosis. - Pseudo washout with gadoxetic acid can mimic hypervascular tumors	- T1WI: Isointense or slightly hypointense. - T2WI: Isointense or slightly hyperintense. - Central scar: T1WI hypointense, T2WI hyperintense, hyperintense on delayed phase with extracellular contrast. - Arterial phase: Intense homogenous enhancement, sparing the central scar. - Portal-venous phase: Isointense, hypointense scar. - Delayed phase: Isointense, hyperintense scar. - Gadoxetic acid-enhanced MRI shows high signal in hepatobiliary phase.	1. T1WI and T2WI signal intensities may vary based on fat, hemorrhage, calcification. 2. Early arterial enhancement on contrast-enhanced MRI. Predominantly hypointense on hepatobiliary phase gadoxetic acid imaging (No uptake of hepatobiliary contrast, darker than liver tissue). 3. HNF-1α Inactivated HCA: Homogeneous, variable on T2, diffuse and homogeneous signal dropout on chemical shift T1-weighted sequences 4. Inflammatory HCA: Strong signal (as strong as the spleen) on T2W (atoll sign), persistent enhancement on delayed phase, Iso-/hyperintense on Hepatobiliary MR Phase. 5. β-Catenin Activated HCA: Heterogeneously hyperintense on T2, hypointense on T1, possible central scar, no signal loss on chemical shift sequences 6. Unclassified HCA: Strong arterial enhancement, no delayed enhancement after gadolinium	- T1WI: Isointense to hypointense. - T2WI: Intermediate to high signal. - Arterial phase: Homogenous enhancement for smaller lesions, heterogeneous for larger lesions. - Portal-venous phase: Variable washout. - Delayed phase: Washout with residual enhancement in pseudocapsule. - DWI: Diffusion restriction (hyperintense). - Heptobiliary Phase MRI: Distinct hypo intensity.	1. Hypervascular metastasis: Signal intensity on T1 and T2 images can vary due to factors like melanin, necrosis, or hemorrhage; DWI often shows restricted diffusion. 2. Hypovascular Lesions: Targetoid appearance on T2W images, DWI, and contrast studies.	Signal loss in opposed-phase images.
Differential Diagnosis	Differentiated from malignant lesions by characteristic imaging patterns	Differentiation from adenomas, HCC, especially with atypical features	Differentiation from FNH, HCC, particularly in larger lesions	Differentiating from benign lesions, dysplastic nodules	Determined by primary tumor type and specific imaging characteristics.	Distinguishing from neoplastic lesions	Differentiation from other primary tumors based on clinical and radiological features.
Treatment Indications	1. Symptomatic large lesions (> 10 cm), causing pain, potential for complications like rupture, or liver function compromise. 2. Kasabach-Merrit syndrome - rapidly growing vascular tumour, thrombocytopenia, microangiopathic haemolytic anaemia and consumptive coagulopathy. 3. Progressive enlargement (>2 cm annual growth)	Symptomatic due to size or location, atypical imaging features warranting further evaluation	1. Management of High-Risk Adenomas: Surgical resection is advised for adenomas that are considered high-risk. This includes: - Lesions larger than 5 cm. - Adenomas increasing in size. - Those with signs of internal bleeding. - Adenomas in males, who have a higher risk of malignancy. - Lesions with positive nuclear β-catenin immunohistochemical staining. - Adenomas in older females who have not used oral contraceptives.	1. Based on staging 2. Liver function 3. performance status	Treatment strategy depends on the nature of the primary cancer, size and number of metastases, overall health of the patient; includes systemic chemotherapy, targeted therapy, surgical resection, or ablation techniques for localized disease.	Addressing underlying metabolic issues
Management Approach	1. Observation unless symptomatic. 2. Pregnancy and contraceptive pills are not contraindicated. 3. Image guided biopsy is usually avoided if imaging features are suggestive of hemangioma (high risk of bleeding). 4. Transarterial Embolization, RFA/MWA can be performed. 5. Surgical management - (hepatic resection or enucleation, open, laproscopic or robotic) 6. Monoclonal antibody 7. Radiotherapy 8. Chemotherapy 9. Radiation therapy and TAE 10. Liver transplantation	1. Conservative, no intervention unless symptomatic. 2. Image guided biopsy can be necessary at times to establish the diagnosis 3. Surgical resection for high risk FNH 4. Transarterial Embolization, RFA/MWA can also be performed for non-surgical candidates and patient's refusal for surgery.	1. Surveillance for low-risk 2. Avoid contraceptive pills, hormone-containing IUD, and anabolic steroids. 3. Image guided biopsy can be performed in case of inconclusive imaging features. 4. Surgical resection for symptomatic or high-risk patients. It can also be offered to women planning for pregnancy (high estrogen level). 5. Transarterial Embolization, RFA/MWA can also be performed for non-surgical candidates, pregnant patient with growing hepatocellular adenoma (surgery can be offered < 24 weeks of pregnancy) and patient's refusal for surgery.	1. Ablation, 2. Surgical resection, 3. Liver transplantation, 4. Transarterial chemoembolization / Transarterial radioembolization 5. Tyrosine kinase inhibitor (TKI) - Soralfenib 6. Best supportive Care	Customised to primary tumor type; encompasses systemic therapy, surgical resection, local ablation, or loco-regional treatments like radioembolization, chemoembolization.	Management of underlying steatohepatitis, if present	1. Resectable Tumors: Complete surgical removal. 2. Unresectable / Advanced Tumors: Palliative treatments, including chemoembolization, radioembolization, and systemic chemotherapy. 3. Hilar/Extrahepatic: Multimodal treatment including surgery, radiotherapy, and liver transplantation in select cases.
Surveillance & Follow-Up	1. Stability confirmation on follow-up imaging 2. No specific guidelines	1. Stability monitoring, particularly for atypical FNH. 2. Some guidelines recommend regular follow up	1. CT/MRI - every 6 to 12 months 2. For Pregnant females - by USG every 6-12 weeks	Regular monitoring for treatment response, recurrence	Dependent on primary tumor and treatment; includes regular imaging and monitoring.	Monitoring for progression to steatohepatitis	Regular imaging and monitoring for progression, response to treatment.
Complications & Risks	Benign, stable, very low risk of malignant transformation	Benign, very low risk of complications	1. Hemorrhage (usually the first presentation in lesion > 5cm) 2. Rupture 3. Rare malignant transformation (more common in lesion > 5 cm)	High morbidity and mortality, risk of vascular invasion, metastasis	Dependent on primary tumor; includes spread and progression of disease.	Associated with obesity, metabolic syndrome	Metastasis, unresectability at diagnosis, complications from biliary obstruction.

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