Chromogranin: Definition

Chromogranin is a family of proteins primarily found in neuroendocrine cells—specialized cells that release hormones into the blood in response to signals from the nervous system. The main types are chromogranin A, B, and C. These proteins play a crucial role in the storage and release of hormones.​

Why do pathologists test for chromogranin?

Pathologists test for chromogranin to help identify and diagnose neuroendocrine tumors—growths originating from neuroendocrine cells. Detecting chromogranin in tissue samples can confirm the presence of these tumors and assist in determining their type and origin.​

How do pathologists test for chromogranin?

Pathologists use immunohistochemistry to test for chromogranin. In this process, they apply specific antibodies to a thin tissue slice on a microscope slide. If chromogranin is present, the antibodies bind to it, causing the cells to change color. Cells that change color are described as “positive,” indicating they contain chromogranin. Cells without color change are “negative.”​

What types of normal cells and tissues will be positive for chromogranin?

Normal cells that typically test positive for chromogranin include:​

• Neuroendocrine cells in the gastrointestinal tract: Cells in the stomach, small intestine, and large intestine that secrete hormones like serotonin and gastrin.​

• Pancreatic islet cells: Cells in the pancreas, particularly beta cells, which produce insulin.​

• Adrenal medulla cells: Cells in the inner part of the adrenal gland that release adrenaline and noradrenaline.​

• Pituitary gland cells: Various hormone-producing cells in the pituitary gland.​

• Thyroid C cells: Cells in the thyroid gland that produce calcitonin, a hormone involved in calcium regulation.

What types of tumors will be positive for chromogranin?

All tumours that arise from neuroendocrine cells can express chromogranin because these cells naturally contain chromogranin as part of their normal function in storing and releasing hormones.

Tumors commonly positive for chromogranin include:

• Carcinoid tumor: These slow-growing neuroendocrine tumors are commonly found in the lungs or gastrointestinal (GI) tract.

• Well differentiated neuroendocrine tumor: Tumors that closely resemble normal neuroendocrine cells and typically grow slowly.

• Poorly differentiated neuroendocrine carcinoma: Aggressive cancers made up of cells that no longer closely resemble normal neuroendocrine cells.

• Small cell carcinoma: Highly aggressive cancers often originating in the lung.

• Large cell neuroendocrine carcinoma: Aggressive tumors commonly found in the lung, although they can arise anywhere in the body.

• Medullary thyroid carcinoma: A type of thyroid cancer originating from thyroid C cells, which produce the hormone calcitonin.

• Merkel cell carcinoma: A rare and aggressive form of skin cancer arising from neuroendocrine cells.

• Pheochromocytomas and paragangliomas: Tumors arising from neuroendocrine cells associated with nerve tissues.

Identifying chromogranin in these tumors helps pathologists confirm their neuroendocrine origin, ensuring accurate diagnosis and appropriate treatment.