Stains & molecular markers
Alpha-1 antitrypsin


Topic Completed: 1 October 2020

Minor changes: 1 October 2020

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PubMed Search: alpha-1 antitrypsin[TI] pathology[TIAB]

Monica Abdelmalak, M.D.
Avani Pendse, M.D., Ph.D.
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Cite this page: Abdelmalak M, Pendse A. Alpha-1 antitrypsin. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsa1a.html. Accessed October 24th, 2020.
Definition / general
Essential features
  • Intracytoplasmic globules in hepatocytes, preferentially in zone 1 near the portal tracts; can be patchy
  • Alpha-1 antitrypsin positive globules will also be highlighted by PAS diastase (PASD) stain
  • Presence of alpha-1 antitrypsin globules does not differentiate between homozygous versus heterozygous deficiency states
  • Expressed in a variety of tumors and pathologic processes, though not commonly used for diagnostic purposes in such entities
Terminology
  • Sometimes abbreviated AAT or A1AT
Pathophysiology
Clinical features
Interpretation
Uses by pathologists
  • To diagnose alpha-1 antitrypsin deficiency in the appropriate clinical context
    • Correlation with enzyme phenotype, e.g. PiMZ or PiZZ, is recommended to confirm the diagnosis and determine heterozygous versus homozygous deficiency state
Microscopic (histologic) images

Contributed by Avani Pendse, M.D., Ph.D.
Eosinophilic intracytoplasmic globules

Eosinophilic intracytoplasmic globules

PASD positive intracytoplasmic globules

PASD positive intracytoplasmic globules

lpha-1-antitrypsin IHC

Alpha-1 antitrypsin IHC

Positive staining - normal
Positive staining - disease
  • A1AT globules seen in the livers of patients with alpha-1 antitrypsin deficiency
  • Pitfall: globules can sometimes also be seen in cirrhotic livers of any etiology
  • Various tumor types have been shown to have positive staining but staining is currently not used for diagnosis of specific tumor types
Sample pathology report
  • Liver, random, ultrasound guided needle core biopsy:
    • Scattered hepatocytes with PAS diastase positive intracytoplasmic globules, highlighted by immunohistochemistry for alpha-1 antitrypsin, suggestive of alpha-1 antitrypsin deficiency.
    • Correlation with laboratory testing for serum levels and alpha-1 antitrypsin phenotype is recommended.
Board review style question #1

A 38 year old man with clinical concern for early onset liver fibrosis has longstanding mild to moderate elevation in transaminases. Viral hepatitis serology is negative and there is no recent history of medication changes or herbal supplement use. A liver biopsy was performed and showed mild portal inflammation with no significant interface activity. A trichrome stain showed bridging fibrosis. Many hepatocytes showed PAS diastase (PASD) positive cytoplasmic globules. What is the likely etiology of the patient's liver disease and the confirmatory immunohistochemistry that would aid with diagnosis?

  1. Alcohol; glutamine synthetase
  2. Alpha-1 antitrypsin deficiency; alpha-1 antitrypsin
  3. Autoimmune hepatitis; CD138
  4. Steatohepatitis; heat shock protein
  5. Viral hepatitis; hepatitis B surface antigen
Board review answer #1
B. Alpha-1 antitrypsin deficiency; alpha-1 antitrypsin. Although liver fibrosis has a variety of etiologies, intracytoplasmic globules that express alpha-1 antitrypsin in hepatocytes are compatible with alpha-1 antitrypsin deficiency.

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Reference: Alpha-1 antitrypsin
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