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Stains

Chromogranin

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

Definition
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● 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)

Terminology
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● 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
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● 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
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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
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● 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
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● 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
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● 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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