Alkaline phosphatase

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

Revised: 22 September 2015, last major update November 2013

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

PubMed Search: alkaline phosphatase[title]
  • Membrane bound glycoprotein with hepatic, osseous, renal and placental isoenzymes
  • See also PLAP-placental alkaline phosphatase
  • Tissue-nonspecific alkaline phosphatase (TNAP) plays a key role in bone mineralization by degrading inorganic pyrophosphate and providing free inorganic phosphate
  • TNAP gene defect causes hypophosphatasia, characteristic of systemic skeletal hypomineralization
  • Surgical pathology applications discussed below
Clinical Features
Uses by Pathologists
  • Component of an alternative method in immunohistochemistry, click here
  • Muscle biopsies uses an enzymatic technique
    • Use frozen tissue (protocol from IHC World)
    • In inflammatory myopathies, appears to “spill out” from capillaries into interstitium due to increased vascular permeability
    • Also a marker for regenerating myofibers
  • Osteoblasts (active)
    • Often labeled using naphthol phosphate and the diazonium dye fast blue to demonstrate alkaline phosphatase enzyme activity directly, present on apical (secretory) cell membrane
    • Confirms diagnosis of giant cell tumor of bone (Virchows Arch A Pathol Anat Histol 1978;378:287)
Micro Images

Muscle: various images

Muscle: regenerating fibers and
proliferative connective tissues

Muscle: immature small fibers
have cytoplasmic staining

Positive Staining - Normal
  • Cardiac muscle, smooth muscle
  • Endothelial cells: sites of alkaline phophatase activity appear red, nuclei stain blue
  • Osteoblasts
Positive Staining - Disease
  • Giant cell tumor of bone and soft tissue, mononuclear stromal cells (Hum Pathol 2005;36:945)
  • Muscle: regenerating fibers, immature muscle fibers, proliferative connective tissues