Stains & CD markers
Alpha-1 antitrypsin
Copyright: 2003-2023, PathologyOutlines.com, Inc.
PubMed Search: alpha-1 antitrypsin[TI] pathology[TIAB]
Alpha-1 antitrypsin
Editorial Board Member: Catherine E. Hagen, M.D.
Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Last author update: 1 October 2020
Last staff update: 17 May 2023 (update in progress)
Copyright: 2003-2023, PathologyOutlines.com, Inc.
PubMed Search: alpha-1 antitrypsin[TI] pathology[TIAB]
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Interpretation | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Sample pathology report | Board review style question #1 | Board review style answer #1Cite this page: Abdelmalak M, Pendse A. Alpha-1 antitrypsin. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsa1a.html. Accessed June 2nd, 2023.
Definition / general
- Acute phase plasma protein
- Inhibits neutrophil elastase that causes tissue damage and maintains protease / antiprotease balance in the lung (J Proteome Res 2014;13:3131)
- Most abundant circulating serine protease inhibitor predominantly derived from hepatocytes (J Proteome Res 2014;13:3131)
- Member of serpin superfamily; homologous to alpha-1 antichymotrypsin (Biochem Soc Trans 2002;30:93)
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
- See Alpha-1 antitrypsin deficiency in Metabolic diseases of Liver & intrahepatic ducts chapter
Clinical features
- See Alpha-1 antitrypsin deficiency in Metabolic diseases of Liver & intrahepatic ducts chapter
Interpretation
- Intracytoplasmic globules in hepatocytes (Clin Liver Dis 2018;22:643)
- May be difficult to visualize in neonates, who may show finely granular cytoplasmic staining (Clin Liver Dis 2018;22:643)
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
PASD positive intracytoplasmic globules
Alpha-1 antitrypsin IHC
Positive staining - normal
- In addition to hepatocytes, A1AT is secreted from small intestinal enterocytes, monocytes and macrophages and bronchial epithelial cells (Clin Immunol Immunopathol 1980;16:84, J Clin Invest 1993;92:2022, J Clin Invest 1986;77:1952, J Biol Chem 1997;272:8250)
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?
- Alcohol; glutamine synthetase
- Alpha-1 antitrypsin deficiency; alpha-1 antitrypsin
- Autoimmune hepatitis; CD138
- Steatohepatitis; heat shock protein
- Viral hepatitis; hepatitis B surface antigen
Board review style 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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Reference: Alpha-1 antitrypsin
