neonatal liver biopsy
DESCRIPTION
Neonatal Liver Biopsy. Dr Claire Bowen Consultant Paediatric Pathologist. Topics Covered. Neonatal jaundice Indications for biopsy Handling of biopsy in the laboratory Histological assessment of the liver biopsy Patterns of liver disease with examples Biliary atresia A1AT - PowerPoint PPT PresentationTRANSCRIPT
Topics Covered
• Neonatal jaundice• Indications for biopsy• Handling of biopsy in the laboratory• Histological assessment of the liver biopsy• Patterns of liver disease with examples
– Biliary atresia– A1AT– Cystic fibrosis– Neonatal hepatitis– Metabolic
Neonatal Jaundice• Common
– 60% term and 80% of preterm babies develop jaundice in first week of life
– 10% breast fed babies still jaundice at 1 month• Usually harmless
– High concentrations of conjugated hyperbilirubinaemia can cause permanent brain damage (kernicterus)
• Prolonged jaundice can be a sign of underling serious liver disease (conjugated bilirubinaemia >25 umol/L)
• Early recognition and prompt treatment essential– Phototherapy– Kasai portoenterostomy– Metabolic screening– Transplant
Indications
Biopsy indicated• Conjugated
hyperbilirubinaemia– Jaundice persisting
beyond 2 weeks (3 weeks in preterm babies)
– Dark urine– Pale stools
• Total parenteral nutrition in the context of intestinal failure
• Assessment of rejection post-transplant
• Tumour
Biopsy not indicated• Unconjugated
hyperbilirubinaemia – Physiological– Sepsis– Haemolysis
• Liver failure– Coagulopathic– Limited contribution to
aetiology– Usually see explanted
liver
Handling
• Procedure risk - general anaesthetic, bleeding
• Need maximum amount of information from biopsy
• Light microscopy
• Snap frozen tissue for metabolic cases
• Electron microscopy for storage disorders
• Dry tissue for copper
H&E• Number and size of tissue cores• Portal tracts
– Number– Presence/absence of bile ducts– Bile duct proliferation– Inflammation– Fibrosis
• Parenchyma– Giant cell transformation– Rosetting of hepatocytes– Haematopoiesis– Storage cells
• Central veins– Vascular flow abnormalites– Inflammation in rejection
Special stains
• Connective tissue stains to assess fibrosis– EVG – mature fibrosis/pericellular fibrosis
– Reticulin – cell plates, acute collapse
– Trichrome – tends to overestimate fibrosis
• Orcein - Copper associated protein and Hep B
• Perls to assess iron
• PAS/DPAS – glycogen, storage cells and Alpha-1-Antitrypsin globules
1) Biliary Features
• Fibrosis– Fibrous portal tract expansion– Bridging fibrosis– Lobular pattern of cirrhosis
• Ductular proliferation• Ductular bile plugging• Periportal copper-associated protein• Variable giant cell change• Haematopoiesis
Differential diagnosis
• Extrahepatic biliary atresia
• Alpha-1-antitrypsin (mimic)
• Total parenteral nutrition
• Cystic fibrosis – eosinophilic secretions in bile duct and fatty change
Biliary Atresia
• Rare - 1 in 17000 in UK• Presents in first few weeks• 50 cases a year with normal antenatal scans• 20% other anomalies (cardiac, polysplenia)• Lumen of biliary tree obliterated with
obstruction to bile flow• Progressive liver damage – cirrhosis• 5 categories of postulated aetiology –>
Inflammatory, Developmental, Vascular, Environmental and Viral
Alpha-1 Antitrypsin
• Defective A1AT protein• Defective production of A1AT leading to
decreased A1AT activity in the blood and lungs• Deposition of excessive abnormal A1AT protein in
liver cells. • Mimics – Can see biliary pattern or giant cell
pattern• PAS positive globules within hepatocytes – not
identified in first 3 months• Immuno for A1AT
Cystic Fibrosis
• Liver disease 5% in CF patients
• Fibrosis
• Cholestatsis
• Fatty change
• Biliary features
• Mucin in bile ducts characteristic but not always seen
2) Neonatal / giant cell hepatitis
• Largely normal portal tracts• Hepatocyte disarray and collapse• Florid giant cell change• Rosetting of hepatocytes• Cholestasis• Extramedullary haematopoiesis• May see storage cells• Not usually fibrotic
3) Paucity of bile ducts
• Bile duct proper lacking
• Need at least 10 portal tracts (1 in 10 miss bile duct normally)
• Abberent periportal cytokeratin 7 expression– Normally stains biliary epithelium– Stains periportal hepatocytes where there is
duct loss
Differential diagnosis
• Syndromic– Alagilles syndrome
• Non-syndromic– CMV infection– A1AT– Cystic fibrosis– Chronic rejection
Alagille syndrome
• Characteristic facial features – triangular face• Heart problems• Bile ducts seen in early biopsies• Progressive bile duct loss/absence• Fibrosis• Abberant Cytokeratin 7 staining in periportal
hepatocytes
4) Bland cholestasis
• Canalicular cholestasis
• No ductular reaction or bile plugging
• Minimal parenchymal changes
• +/- Fibrosis
Pitfalls in children
• Copper-associated protein present in babies up to 3 months (periportal)
• Small amounts of periportal iron present at birth
• Fat not generally seen, metabolic conditions should be considered
• Hepatocyte plates 2 cells thick until 5/6 years
• Erythropoiesis stops approx. 36 weeks gestation
Neonatal Haemochromatosis• Severe form of iron
overload• Starts to accumulate in
utero - can cause fetal death
• Liver failure• Massive necrosis –
collapse• Iron +++• Usually diagnosed on lip
biopsy – iron storage in salivary glands