Definition/General
Introduction:
Hepatic adenoma is a benign epithelial tumor composed of hepatocytes
It represents 2-3% of benign liver tumors
FNAC shows monomorphic hepatocytes without portal tracts or bile ducts
Strong association with oral contraceptive use in young women.
Origin:
Arises from clonal proliferation of hepatocytes
Represents a true neoplasm (unlike FNH)
Associated with hormonal stimulation (estrogen, androgens)
Results from genetic alterations in hepatocyte growth pathways
May undergo malignant transformation to HCC (5-10% risk).
Classification:
WHO classification based on molecular alterations
HNF1A-inactivated (35-50%): steatotic, low malignant risk
β-catenin activated (10-15%): high malignant risk
Inflammatory (40-55%): SAA and CRP positive
Unclassified (10%)
Multiple adenomas: adenomatosis (>10 lesions).
Epidemiology:
Rare tumor with female predominance (F:M = 10:1)
Peak incidence in reproductive age (20-40 years)
Strong association with oral contraceptive use (90% cases)
Glycogen storage diseases (type I, III)
Anabolic steroid use in males
Indian women: increasing incidence with OCP use.
Clinical Features
Presentation:
Often asymptomatic (60-70% cases)
Right upper quadrant pain (stretching liver capsule)
Hepatomegaly (large adenomas)
Acute presentation: hemorrhage, rupture (10-15% cases)
Mass effect symptoms (large tumors)
Shock (intraperitoneal bleeding).
Symptoms:
Abdominal pain (most common symptom)
Nausea and vomiting
Acute severe pain (hemorrhage/rupture)
Shoulder pain (diaphragmatic irritation)
Constitutional symptoms rare
Symptoms may worsen during pregnancy
Emergency presentation with bleeding.
Risk Factors:
Oral contraceptive use (strongest risk factor, 90% cases)
High-dose estrogen exposure
Anabolic steroid use (bodybuilders, athletes)
Glycogen storage diseases (GSD I, III)
Tyrosinemia type I
Pregnancy (growth acceleration)
Familial adenomatous polyposis (rare).
Screening:
High-risk patients: long-term OCP users
Imaging surveillance for known adenomas
Ultrasound: hyperechoic mass
CT/MRI: arterial enhancement without washout
Fat content on MRI (HNF1A type)
Normal AFP and other tumor markers.
Master Hepatic Adenoma FNAC Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
FNAC yields highly cellular aspirate with uniform hepatocytes
Monomorphic hepatocytes in sheets and clusters
Absence of bile ducts and portal tracts
Kupffer cells reduced or absent
Background may show blood or necrosis
Fat vacuoles in HNF1A type.
Characteristics:
Cellular aspirate with pure hepatocytic population
Larger hepatocytes than normal (increased cell size)
Abundant cytoplasm (eosinophilic to clear)
Nuclear enlargement with prominent nucleoli
Binucleation common
Steatosis variable (type-dependent).
Size Location:
Variable size: typically 5-15 cm
Any hepatic segment can be affected
Subcapsular location common (bleeding risk)
Well-circumscribed lesion
Multiple adenomas (adenomatosis) >10 lesions
Right lobe predilection.
Multifocality:
Solitary lesion in 80% cases
Multiple adenomas in 20% cases
Adenomatosis: >10 lesions (higher malignant risk)
Bilateral distribution possible
Associated with metabolic disorders
Pregnancy-related growth acceleration.
Microscopic Description
Histological Features:
Monomorphic hepatocytes in thick trabecular pattern
Absence of portal tracts and bile ducts (key feature)
Sinusoidal dilatation with CD34+ endothelial cells
Kupffer cells reduced or absent
Nuclear enlargement with prominent nucleoli
Steatosis variable by subtype.
Cellular Characteristics:
Enlarged hepatocytes (1.5-2x normal size)
Abundant cytoplasm (eosinophilic or clear)
Nuclear enlargement with regular contours
Prominent nucleoli (1-2 per nucleus)
Binucleated cells frequent
Minimal mitotic activity
Glycogen accumulation in some subtypes.
Architectural Patterns:
Thick trabecular pattern (2-3 cells thick)
Loss of normal architecture
Sinusoidal dilatation (peliosis-like)
Absence of bile ducts (diagnostic feature)
Compression of surrounding liver parenchyma
Central necrosis in large tumors.
Grading Criteria:
No standard grading system for adenomas
Assessment based on subtype classification
Nuclear atypia degree
Architectural preservation
Inflammation presence (inflammatory subtype)
β-catenin activation (malignant risk)
Size-related hemorrhage risk.
Immunohistochemistry
Positive Markers:
Hepatocyte marker (positive in hepatocytes)
Arginase-1 (hepatocyte marker)
CD34 (sinusoidal capillarization, key feature)
Glutamine synthetase (homogeneous pattern, unlike FNH)
L-FABP loss (HNF1A-inactivated type)
SAA and CRP (inflammatory type).
Negative Markers:
CK7 (negative, absence of bile ducts)
CK19 (negative, no cholangiocytes)
Glypican-3 (negative, excludes HCC)
AFP (negative)
p53 (negative in benign adenomas)
Reticulin (loss of normal pattern).
Diagnostic Utility:
CD34 positivity confirms sinusoidal capillarization (key feature)
Glutamine synthetase: homogeneous (vs heterogeneous in FNH)
CK7/19 negativity confirms absence of bile ducts
L-FABP status helps subtype classification
β-catenin pattern: nuclear vs membranous
Excludes HCC (Glypican-3-, AFP-).
Molecular Subtypes:
HNF1A-inactivated (35-50%): L-FABP loss, steatotic
β-catenin activated (10-15%): nuclear GS, high malignant risk
Inflammatory (40-55%): SAA/CRP positive, telangiectasia
Sonic hedgehog activated (rare)
Unclassified (10-15%).
Molecular/Genetic
Genetic Mutations:
HNF1A mutations/deletions (35-50% cases)
CTNNB1 mutations (β-catenin, 10-15%)
Inflammatory subtype: IL6ST, FRK, STAT3 alterations
Sonic hedgehog pathway alterations (rare)
GNAS mutations (rare)
Clonal origin confirmed by X-chromosome inactivation.
Molecular Markers:
β-catenin pathway: CTNNB1, AXIN1, APC alterations
HNF1A pathway: transcription factor inactivation
Inflammatory markers: IL6, STAT3, SAA
mTOR pathway activation
Telomerase activity may be present
p53 pathway intact (benign lesions).
Prognostic Significance:
Subtype determines malignant transformation risk
β-catenin activated: highest malignant risk (>10%)
HNF1A-inactivated: low malignant risk (<5%)
Inflammatory type: intermediate risk
Size >5 cm: increased bleeding risk
Male patients: higher malignant risk.
Therapeutic Targets:
Hormonal withdrawal (discontinue OCP/steroids)
mTOR inhibitors (experimental)
Anti-angiogenic therapy (experimental)
Surgical resection for high-risk adenomas
Surveillance vs surgery based on size and subtype
Pregnancy counseling for reproductive-age women.
Differential Diagnosis
Similar Entities:
Focal nodular hyperplasia (bile ducts present, heterogeneous GS)
Well-differentiated hepatocellular carcinoma (malignant features)
Normal liver parenchyma (portal tracts present)
Regenerative nodule (cirrhotic background)
Steatotic liver (diffuse vs focal)
Hepatocellular adenomatosis.
Distinguishing Features:
Adenoma: no bile ducts, CD34+ sinusoids, homogeneous GS staining
FNH: bile ducts present, normal sinusoids, heterogeneous GS
HCC: cellular atypia, Glypican-3+, AFP elevation
Normal liver: portal tracts present
Regenerative nodule: cirrhotic background, reticulin preserved.
Diagnostic Challenges:
Distinguishing from well-differentiated HCC (major concern)
FNH vs adenoma (bile duct presence crucial)
Adenomatosis vs multiple HCCs
Inflammatory adenoma vs HCC with inflammation
β-catenin activated adenoma (pre-malignant)
FNAC limitations in subtype classification.
Rare Variants:
Inflammatory adenoma (SAA+, telangiectatic)
Steatotic adenoma (HNF1A-inactivated)
β-catenin activated adenoma (high malignant risk)
Atypical adenoma (dysplastic changes)
Adenomatosis (>10 lesions)
Pregnancy-associated adenoma growth.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Clinical Information
Patient with [clinical presentation], OCP history: [duration], imaging shows [liver lesion characteristics]
Specimen Adequacy
Adequate for evaluation with high cellularity
Cytomorphological Features
Shows [monomorphic hepatocytes] without bile ducts or portal elements
Key Diagnostic Features
Absence of [bile ducts, portal tracts], presence of [enlarged hepatocytes]
Immunocytochemistry
Hepatocyte marker: [positive]
CK7/19: [negative], Glypican-3: [negative]
CD34: [positive in sinusoids]
Risk Assessment
Risk factors: [size, male gender, β-catenin status]
Final Cytological Diagnosis
Benign hepatocytic neoplasm consistent with Hepatic Adenoma
Recommendations
Recommend [OCP discontinuation, surgical consultation, follow-up imaging]