Topic Completed: 1 February 2012

Revised: 12 June 2019

Copyright: 2003-2019,, Inc.

PubMed Search: Chromogranin[title] stain

Nat Pernick, M.D.
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Cite this page: Pernick N. Chromogranin. website. Accessed September 23rd, 2019.
Definition / general
  • Granin protein located in secretory vesicles of neurons and endocrine cells (Clin Invest Med 1995;18:47, Endocr Rev 2011;32:755)
  • Immunostain is specific but not sensitive for neuroendocrine cells; more sensitive in well differentiated vs. poorly differentiated tumors
  • Antibody binds acidic glycoproteins in the soluble fraction of neurosecretory granules
  • Serum levels may not be useful for diagnosis (Biomarkers 2012;17:186), but changes in levels may reflect response to therapy or recurrence (Folia Biol (Praha) 2011;57:173)
  • Typically refers to Chromogranin A, or parathyroid secretory protein 1 (gene name CHGA)
  • Chromogranin B is not commonly used, and has a different distribution (Mod Pathol 2000;13:140)
Uses by pathologists
  • Commonly used neuroendocrine marker (also synaptophysin and CD56) for normal cells and neuroendocrine tumors
  • Helps differentiate pheochromocytoma (almost always positive) from adrenocortical carcinoma (almost always negative, Am J Surg Pathol 2010;34:423)
Microscopic (histologic) images

Bladder: paraganglioma

Breast: neuroendocrine carcinomas

Kidney: carcinoid tumor

Parathyroid gland: ectopic tissue

Thyroid: medullary carcinoma

Images hosted on other servers:

Adrenal medulla: pheochromocytoma

Ampulla: neuroendocrine carcinoma

Breast: small cell carcinoma

Gallbladder: paraganglioma (figure 2A)

Heart: metastatic pheochromocytoma (right side)

Nasal cavity: gangliocytic paraganglioma

Prostate: neuroendocrine carcinomas

Prostate: small cell carcinoma

Positive staining - normal
  • Neuroendocrine and ganglion cells in adrenal medulla (chromaffin cells), heart AV node, pancreas (islets), parathyroid (chief cells), thyroid (C cells), other tissues
  • Also bile ductules-reactive and pancreatic acinar cells (occasional, Am J Surg Pathol 2009;33:66)
Positive staining - disease
  • Neuroendocrine and ganglion cell tumors (carcinoid, Merkel cell carcinoma-lung, neuroblastoma, neuroendocrine carcinoma, paraganglioma, small cell carcinoma), neuroendocrine hyperplasia
  • Desmoplastic small cell tumor, middle ear adenoma (Mod Pathol 2002;15:543), parathyroid cyst, pituitary adenoma
  • Many fetal-type tumors (hepatoblastoma, lung adenocarcinoma-fetal type)
  • Note: granular cytoplasmic pattern in small cell carcinoma reflects neurosecretory granules
Negative staining
  • Tumors without neuroendocrine components including adrenocortical tumors, chordoma, Ewing's sarcoma/PNET
  • Alveolar rhabdomyosarcoma (may have rare positive cells, Mod Pathol 2008;21:795), pancreatic solid pseudopapillary neoplasm (occasionally focal staining)
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