Author: Nat Pernick, M.D. (see Authors page)

Revised: 24 September 2015, last major update January 2014

Copyright: (c) 2003-2015,, Inc.

PubMed Search: Alpha-1-antitrypsin[title]
  • Acute phase plasma protein predominantly derived from liver which inhibits neutrophil elastase
  • Most abundant circulating serine protease inhibitor
  • Elastase digests lung tissue and is secreted by neutrophils during inflammation (Wikipedia)
  • Member of serpin superfamily; homologous to alpha-1-antichymotrypsin
Clinical Features


Polymer of AAT molecules

Uses by Pathologists
  • Immunohistochemistry marker of alpha-1-antitrypsin genetic disease in hepatocytes
  • Also marker of normal histiocytes and hepatocytes
Micro Images
Liver-alpha-1-antitrypsin deficiency


PAS+ diastase resistant inclusions

Z alpha 1 antitrypsin in hepatocytes

Pancreas-solid pseudopapillary tumor is A1A+

Pancreatoblastoma (fig B)

Positive Staining - Normal
Positive Staining - Disease
  • Various sites: angiosarcoma (hyaline globules), granular cell tumor (J Oral Pathol Med 2000;29:284, Mod Pathol 1996;9:888), histiocytic lymphoma, MFH, pleomorphic adenoma (epithelium), Rosai-Dorfman disease (focal)
  • Bile duct: adenoma - (cytoplasmic inclusions, Int J Surg Pathol 2008;16:218)
  • Bladder: yolk sac tumor of urachus
  • Bone: giant cell tumor
  • Cervix: decidual reaction
  • Eye: oncocytoma of conjunctiiva
  • Kidney: renal cell carcinoma-clear cell type
  • Liver: alpha-1-antitrypsin deficiency (cytoplasmic inclusions), focal nodular hyperplasia, hepatoblastoma (40%, Appl Immunohistochem Mol Morphol 2008;16:140), hepatocellular adenoma (cytoplasmic globules), hepatocellular carcinoma, undifferentiated embryonal sarcoma
  • Lung: bronchioloalveolar carcinoma (Clara cells in non-mucinous types)
  • Ovary: endodermal teratoma, MMMT and yolk sac tumor (hyaline droplets, Hum Pathol 1982;13:930)
  • Pancreas: cystic fibrosis (mucous globules), neuroendocrine tumor, solid pseudopapillary tumor (not specific, Am J Surg Pathol 2000;24:1361, Case of Week #121)
  • Skin: atypical fibroxanthoma
  • Testis: papillary cystadenoma, Sertoli cell tumor and yolk sac tumor (hyaline globules)
  • Thyroid: papillary thyroid carcinoma (Am J Surg Pathol 1996;20:956)