Stains & CD markers
Alpha-1 antitrypsin

Editorial Board Member: Christian M. Schürch, M.D., Ph.D.
Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Monica Abdelmalak, M.D.
Avani Pendse, M.D., Ph.D.

Last author update: 12 September 2023
Last staff update: 12 September 2023

Copyright: 2003-2024,, Inc.

PubMed Search: Alpha-1 antitrypsin

Monica Abdelmalak, M.D.
Avani Pendse, M.D., Ph.D.
Page views in 2023: 2,338
Page views in 2024 to date: 1,487
Cite this page: Abdelmalak M, Pendse A. Alpha-1 antitrypsin. website. Accessed July 13th, 2024.
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 periodic acid-Schiff diastase (PASD) stain
  • Presence of alpha-1 antitrypsin globules does not differentiate between homozygous versus heterozygous deficiency states (J Hepatol 2000;32:406)
  • Expressed in a variety of tumors and pathologic processes, though not commonly used for diagnostic purposes in such entities
  • Sometimes abbreviated AAT or A1AT
Clinical features
  • See Alpha-1 antitrypsin deficiency in Liver & intrahepatic ducts chapter
  • AAT deficiency is highly underdiagnosed
    • Due to overlap of clinical symptoms, testing should be performed in individuals with chronic obstructive pulmonary disease (COPD), liver disease, poorly responsive asthma, cANCA vasculitis, panniculitis or bronchiectasis, in addition to first degree relatives of people with AAT deficiency (N Engl J Med 2020;382:1443)
Uses by pathologists
  • To diagnose alpha-1 antitrypsin deficiency in the appropriate clinical context
    • Initial laboratory test is serum AAT, which is decreased in AAT deficiency (< 1.1 g/L)
    • Correlation with enzyme phenotype (e.g., PiMZ or PiZZ) is recommended to confirm the diagnosis and determine heterozygous versus homozygous deficiency state
    • Note: there is no direct correlation between the serum AAT value, the Pi phenotype and the presence or absence of immunoreactive periportal AAT granules; thus, IHC alone cannot confirm or exclude AAT deficiency (J Clin Pathol 1986;39:58)
  • Can be used to study AAT protein expression within the human liver or exogenous AAT that is delivered through gene therapy (Methods Mol Biol 2017;1639:139)
Prognostic factors
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 (Clin Gastroenterol Hepatol 2012;10:575)
  • Pitfall: globules can sometimes also be seen in cirrhotic livers of any etiology
  • Various tumor types have been shown to have positive AAT staining; however, such immunohistochemistry is currently not used for diagnosis of specific tumor types
Negative staining
Molecular / cytogenetics description
Sample pathology report
  • Liver, random, ultrasound guided needle core biopsy:
    • Alpha-1 antitrypsin deficiency (see comment)
    • Comment: 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 periodic acid-Schiff 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 style answer #1
B. Alpha-1 antitrypsin deficiency; alpha-1 antitrypsin. Answers A, C, D and E are incorrect because 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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