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Table of Contents
Definition / general | Clinical features | Laboratory | Diagrams / tables | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - diseaseCite this page: Alpha-1-antitrypsin. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsa1a.html. Accessed July 12th, 2017.
Definition / general
- 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
- Common genetic deficiency, see Liver nontumor chapter
- Occurs in 1 per 2,500-5,000 newborns in Western Europe / USA
- Incidence is highly dependent on Scandinavian descent within the population
- Disorder due to folding errors (IUBMB Life 2009;61:1)
- Causes emphysema (Orphanet J Rare Dis 2008;3:16), chronic hepatitis (Hum Pathol 2012;43:753) or cirrhosis (Am J Gastroenterol 2008;103:2136, Clin Gastroenterol Hepatol 2012;10:575)
- In liver, mutant Z gene synthesizes mutant Z protein, which folds abnormally and accumulates, rather than being secreted; accumulated protein causes liver injury, cirrhosis, hepatocellular carcinoma (Curr Gastroenterol Rep 2014;16:367)
- Also associated with bronchiectasis, vasculitis (including Wegener's granulomatosis-Rheumatol Int 2014;34:553), panniculitis (Dermatol Clin 2008;26:447, Respir Med 2014;108:338
- Treatment include intravenous augmentation therapy (Orphanet J Rare Dis 2013;8:149) including Proliastin® (BMC Clin Pharmacol 2010;10:13), liver transplant (Liver Transpl 2013;19:1370)
Laboratory
- Screening tests use dried blood spots (J Bras Pneumol 2013;39:547)
- Evaluation for genetic deficiency involves quantitation of serum A1A protein and characterization of genetic polymorphisms (Am J Clin Pathol 2012;138:398)
Diagrams / tables
Structure
Polymer of AAT molecules
Uses by pathologists
- Immunohistochemistry marker of alpha-1-antitrypsin genetic disease in hepatocytes
- Also marker of normal histiocytes and hepatocytes
Microscopic (histologic) images
Images hosted on Pathout server:
Liver-alpha-1-antitrypsin deficiency-
Pancreas-solid pseudopapillary tumor is A1A+
Images hosted on other servers:
Liver-H&E
PAS+ diastase resistant inclusions
Pancreatoblastoma (fig B)
Images hosted on Nature.com:
Z alpha 1 antitrypsin in hepatocytes
Pancreas-solid pseudopapillary tumor is A1A+
Positive staining - normal
- Histiocytes, reticulum cells, gallbladder, hepatocytes, small intestinal enterocytes (J Clin Invest 1993;92:2022)
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)
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