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Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 25 February 2012, last major update February 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.


● 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 Feb 6 [Epub ahead of print]), 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)

Micro images

Adrenal medulla: pheochromocytoma

Ampulla: neuroendocrine carcinoma

Bladder: paraganglioma

Breast: colloid carcinoma (lower left)

Breast: neuroendocrine carcinomas

Breast: small cell carcinoma

Esophagus: carcinoid tumor

Gallbladder: paraganglioma (figure 2a)

Heart: metastatic pheochromocytoma (right side)

Kidney: carcinoid tumor

Lung: primary sclerosing neuroendocrine carcinoma

Nasal cavity: gangliocytic paraganglioma

Neuroblastoma metastatic to bone marrow (figure C)

Pancreas: malignant islet cell tumor with sarcomatous differentiation

Pancreas: pancreatic endocrine neoplasm

Pancreas: solid papillary neoplasm (may be focally positive)

Parathyroid gland: ectopic tissue

Prostate: neuroendocrine carcinomas

Prostate: small cell carcinoma

Rectum and chromogranin A: left-normal mucosa; right-carcinoid

Rectum and chromogranin B: left-normal mucosa; right-carcinoid

Thyroid: medullary 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)
● 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)

End of Stains > Chromogranin

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