Synaptophysin

Synaptophysin is a protein found in certain types of cells, particularly those in the nervous system and in neuroendocrine cells, which are specialized cells that release hormones in response to nerve signals. Synaptophysin is located on small storage sacs called synaptic vesicles, which are used to send messages between nerve cells or to release hormones. Because it is found in specific cells, synaptophysin is used by pathologists as a marker to help identify neuroendocrine tumours and tumours that develop from nerve tissue.

What types of normal cells and tissues express synaptophysin?

Synaptophysin is normally found in the cytoplasm (the area outside the nucleus) of:

• Nerve cells in the brain and spinal cord.

• Neuroendocrine cells in the pancreas, adrenal glands, thyroid, and parathyroid.

• Cells of the pineal gland and other hormone-producing tissues.

In these normal tissues, synaptophysin helps package and release chemical signals that allow cells to communicate.

How do pathologists test for synaptophysin?

Pathologists test for synaptophysin using a method called immunohistochemistry (IHC). A small tissue sample is treated with special antibodies that stick to the synaptophysin protein. If the protein is present, it causes a cytoplasmic stain (colour change in the body of the cell) that is visible under a microscope. A positive result means that synaptophysin is being made by the cells, which suggests that the tumour may have neuroendocrine or nerve-related features. A negative result means that synaptophysin is not detected.

Pathologists often test for synaptophysin alongside other markers, such as chromogranin A, INSM1, and CD56, to confirm a diagnosis of a neuroendocrine tumour.

What types of tumours express synaptophysin?

Synaptophysin is found in many types of tumours that come from neuroendocrine or nerve-related cells.

Neuroendocrine tumours:

• Well-differentiated neuroendocrine tumour (carcinoid tumour) – A slow-growing tumour found in the lungs, intestines, or pancreas.

• Small cell neuroendocrine carcinoma – An aggressive cancer most often found in the lung.

• Large cell neuroendocrine carcinoma – A high-grade cancer that behaves aggressively.

• Medullary thyroid carcinoma – A rare thyroid cancer that starts in neuroendocrine cells.

• Merkel cell carcinoma – A rare and aggressive skin cancer that arises from neuroendocrine cells in the skin.

• Paraganglioma and pheochromocytoma – Rare tumours that develop from nerve cells in the adrenal glands or elsewhere in the body.

• Neuroblastoma – A tumour that develops from immature nerve cells, usually in children.

Brain and spinal cord tumours:

• Ganglioglioma and gangliocytoma – Tumours made up of nerve cells and supporting cells.

• Medulloblastoma – A fast-growing brain tumour seen in children.

• Pilocytic astrocytoma – A slow-growing brain tumour.

• Central neurocytoma and pineocytoma – Rare tumours of the central nervous system.

• Choroid plexus tumours – Tumours that arise in the brain’s fluid-producing tissue.

Other tumours:

• Adrenal cortical tumours.

• Parathyroid tumours.

• Desmoplastic small round cell tumour.

• Ewing sarcoma.

• Glomus tumour.

Synaptophysin may also show normal expression in some cancers not typically associated with neuroendocrine cells. These cancers are often described as showing neuroendocrine differentiation. In these cases, it may be linked to differences in tumour behaviour or prognosis.

Why is synaptophysin important in a pathology report?

Synaptophysin is important because it helps pathologists determine whether a tumour is of neuroendocrine origin or related to the nervous system. This is especially helpful when:

• The tumour could be a neuroendocrine tumour or neuroblastoma.

• The tumour shows features seen in both neuroendocrine and non-neuroendocrine cancers.

• The diagnosis is uncertain, and other markers are needed to clarify the type of tumour.

Synaptophysin testing also provides helpful information about how the tumour might behave and what treatments may be most effective. In some cancers, synaptophysin expression has been associated with variations in patient outcomes.

Questions to ask your doctor

• What does the synaptophysin result in my pathology report mean?

• Does this result suggest that my tumour is a neuroendocrine tumour?

• Were other neuroendocrine markers, like chromogranin or CD56, also tested?

• How does this result affect my diagnosis and treatment plan?

• Do I need any additional tests to better understand my tumour?