Definition/General
Introduction:
Hepatic hemangioma is the most common benign liver tumor
It represents 80-90% of benign hepatic lesions
FNAC is typically contraindicated due to bleeding risk
When performed, it shows characteristic vascular cytomorphology with minimal cellularity.
Origin:
Arises from hepatic blood vessels (capillaries and venules)
Represents a developmental vascular malformation rather than true neoplasm
Composed of endothelial-lined vascular channels
Supported by fibrous stroma
May enlarge during pregnancy due to hormonal stimulation.
Classification:
Classified as cavernous hemangioma (most common type)
Capillary hemangioma (rare in adults)
Sclerosed hemangioma (involuted form)
Size classification: small (<4 cm) vs large (>4 cm)
Giant hemangiomas (>10 cm)
Atypical hemangiomas with unusual imaging features.
Epidemiology:
Most common benign liver tumor (prevalence 1-20%)
Female predominance (F:M = 3-5:1)
Peak detection in 4th-5th decades
Often incidental finding on imaging
Congenital lesions may present in infancy
Association with pregnancy and estrogen exposure
Indian population: increasing detection with widespread imaging.
Clinical Features
Presentation:
Usually asymptomatic (>80% cases)
Incidental finding on imaging studies
Large hemangiomas may cause abdominal discomfort
Right upper quadrant pain (stretching liver capsule)
Hepatomegaly (giant hemangiomas)
Rarely: consumptive coagulopathy (Kasabach-Merritt syndrome).
Symptoms:
Most patients completely asymptomatic
Vague abdominal fullness (large lesions)
Nausea (rare, large tumors)
Early satiety (mass effect)
Abdominal pain (atypical, controversial)
Thrombocytopenia (giant hemangiomas, rare)
No constitutional symptoms typically.
Risk Factors:
Female gender (hormonal influence)
Pregnancy (estrogen stimulation causes growth)
Oral contraceptive use
Hormone replacement therapy
Multiple pregnancies
Age >40 years (increased detection)
Familial clustering (rare cases)
No known environmental risk factors.
Screening:
Usually detected incidentally on imaging
Ultrasound: echogenic lesion with posterior enhancement
CT triphasic: peripheral nodular enhancement, centripetal fill-in
MRI (gold standard): T2 hyperintense, characteristic enhancement
Technetium-99m RBC scan: persistent uptake
FNAC generally avoided.
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Gross Description
Appearance:
FNAC (when performed) yields hemorrhagic aspirate
Paucicellular specimen with blood predominance
May show fibrous tissue fragments
Rare endothelial cell clusters
Hemosiderin-laden macrophages may be present
Background shows extensive red blood cells.
Characteristics:
Bloody aspirate with minimal cellular material
Thin consistency due to blood dilution
May contain fibrous connective tissue
Rare smooth muscle fragments
Calcifications in sclerosed areas
Cholesterol clefts (rare)
Background predominantly hemorrhagic.
Size Location:
Variable size: from few mm to >20 cm
Most common location: right hepatic lobe
Subcapsular location frequent
Multiple hemangiomas in 10-15% cases
Giant hemangiomas may occupy entire lobe
Pedunculated forms rarely seen.
Multifocality:
Solitary lesion in 85-90% cases
Multiple hemangiomas (hemangiomatosis) in 10-15%
Bilobar involvement in multiple cases
Associated with cutaneous hemangiomas (rare)
Extrahepatic hemangiomas (spleen, kidney)
Familial multiple hemangiomas (very rare).
Microscopic Description
Histological Features:
Paucicellular aspirate with predominant blood
Rare endothelial cells lining vascular spaces
Flat, bland endothelial cells with oval nuclei
Fibrous tissue fragments with spindle cells
Smooth muscle cells from vessel walls
Hemosiderin deposits in chronic lesions.
Cellular Characteristics:
Endothelial cells: flat, elongated with bland nuclei
Smooth muscle cells: spindle-shaped, eosinophilic cytoplasm
Fibroblasts: spindle cells in fibrous areas
No cellular atypia or pleomorphism
Minimal mitotic activity
Background inflammatory cells rare.
Architectural Patterns:
Vascular pattern with blood-filled spaces
Cavernous pattern: large vascular channels
Capillary pattern: small vessel proliferation (rare)
Sclerotic pattern: fibrous replacement
Thrombosed areas with organization
Calcified areas in old lesions.
Grading Criteria:
No grading system for hemangiomas
Assessment based on vascular pattern
Cavernous type: large blood-filled spaces
Capillary type: small proliferating vessels
Sclerosed type: fibrous replacement
Thrombosed areas: organized thrombi
Calcification degree in chronic lesions.
Immunohistochemistry
Positive Markers:
CD31 (endothelial marker, highlights vascular lining)
CD34 (endothelial and vascular marker)
ERG (endothelial nuclear marker)
Factor VIII (endothelial marker, less specific)
D2-40 (lymphatic endothelium, if present)
Smooth muscle actin (vessel wall smooth muscle).
Negative Markers:
Cytokeratins (negative, excludes carcinoma)
Hepatocyte marker (negative)
CD68 (excludes Kupffer cell tumor)
Desmin (negative in endothelium)
S-100 (negative, excludes neural tumors)
Chromogranin/synaptophysin (negative).
Diagnostic Utility:
Limited utility in FNAC setting due to paucicellular nature
CD31/CD34 can confirm vascular nature
Helps distinguish from other vascular lesions
Excludes malignancy (negative epithelial markers)
Not routinely performed due to bleeding risk
Histology preferred for definitive diagnosis.
Molecular Subtypes:
No specific molecular subtypes recognized
Hormonal receptors (estrogen, progesterone) may be present
VEGF expression in growing lesions
No specific genetic alterations identified
Familial cases: possible genetic predisposition
Research focus on angiogenesis factors.
Molecular/Genetic
Genetic Mutations:
No specific somatic mutations identified
Developmental origin suggests germline factors
Hormonal influence: estrogen receptor pathway
Angiogenesis-related gene expression
Familial clustering: possible genetic predisposition
No tumor suppressor gene involvement.
Molecular Markers:
VEGF (vascular endothelial growth factor) expression
Angiopoietin pathway activation
Endothelial markers: CD31, CD34, ERG expression
Hormonal receptors: ER, PR in some cases
Basic FGF (fibroblast growth factor)
Thrombospondin (anti-angiogenic factor).
Prognostic Significance:
Excellent prognosis (benign lesion)
Size correlation: larger lesions more symptomatic
Pregnancy effect: may enlarge during pregnancy
Malignant transformation extremely rare (not reported)
Complications rare except in giant hemangiomas
Spontaneous regression may occur.
Therapeutic Targets:
Observation for asymptomatic lesions
Propranolol (beta-blocker) for infantile hemangiomas
Corticosteroids (historical use)
Anti-angiogenic therapy (experimental)
Hormonal manipulation (avoiding estrogen)
Surgical resection for symptomatic giant lesions.
Differential Diagnosis
Similar Entities:
Hepatocellular carcinoma (hypervascular HCC)
Focal nodular hyperplasia (FNH with central scar)
Hepatic adenoma (hormonal association)
Metastatic hypervascular tumors (neuroendocrine, RCC)
Angiosarcoma (malignant vascular tumor)
Arteriovenous malformation.
Distinguishing Features:
Hemangioma: centripetal enhancement, T2 hyperintense on MRI
HCC: arterial enhancement with washout, AFP elevation
FNH: central scar, Kupffer cell uptake on sulfur colloid
Adenoma: fat content, oral contraceptive history
Angiosarcoma: rapid growth, irregular enhancement
Metastases: multiple lesions, known primary.
Diagnostic Challenges:
Distinguishing from hypervascular HCC on imaging
Atypical hemangiomas with unusual enhancement
Small hemangiomas vs micrometastases
Flash-filling hemangiomas vs other hypervascular lesions
FNAC interpretation (when performed) challenging
Sclerosed hemangiomas vs fibrotic lesions.
Rare Variants:
Capillary hemangioma (more common in children)
Sclerosed/hyalinized hemangioma
Thrombosed hemangioma with calcification
Giant hemangioma with mass effect
Flash-filling hemangioma
Hemangiomatosis (multiple lesions)
Pedunculated hemangioma.
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 liver lesion on imaging, [clinical presentation]
Procedure Note
FNAC generally contraindicated for suspected hemangioma due to bleeding risk
Specimen Adequacy
Paucicellular specimen, predominantly hemorrhagic
Cytomorphological Features
Shows [blood, rare endothelial cells, fibrous fragments]
Imaging Correlation
Imaging shows [characteristic hemangioma features]
Differential Diagnosis
Differential includes [other vascular lesions, hypervascular tumors]
Final Cytological Diagnosis
Paucicellular vascular lesion, consistent with hemangioma (imaging correlation recommended)
Recommendations
Recommend imaging-based diagnosis, avoid repeat FNAC