S100

S100 is the name of a family of proteins found inside certain types of cells in the body. These proteins help cells respond to changes in their environment by regulating processes like growth, movement, and communication. The name “S100” comes from the fact that the proteins are soluble in a solution made with 100% saturated ammonium sulfate. There are many members of the S100 family, but most medical tests focus on a part of the protein called the beta chain.

Because S100 is found in several types of normal cells—especially nerve cells and cells related to the skin and immune system—pathologists use it as a marker to help diagnose various tumors, particularly those that start in or involve the nervous system, melanocytes (pigment cells), or myoepithelial cells (specialized support cells in glands).

What types of normal cells and tissues express S100?

S100 is normally found in both the cytoplasm (the area surrounding the nucleus) and nucleus of certain cells. Some of the main normal cell types that express S100 include:

• Melanocytes (cells that produce pigment in the skin and eyes).

• Schwann cells (which cover and protect nerves).

• Neurons and glial cells in the brain and spinal cord.

• Myoepithelial cells in the breast, salivary glands, and sweat glands.

• Langerhans cells and dendritic cells (types of immune cells).

• Chondrocytes (cartilage cells).

• Adipocytes (fat cells).

Because S100 is found in these cells, it is also found in many benign and malignant tumors that arise from them.

How do pathologists test for S100?

Pathologists test for S100 using a method called immunohistochemistry (IHC). This technique involves applying antibodies that attach to the S100 protein in a tissue sample. If S100 is present, the tissue changes color under the microscope, allowing pathologists to see which cells are positive or negative for S100. A result is considered positive when both the cytoplasm and nucleus of the cell show staining.

The pattern of staining—whether it is strong, weak, widespread, or limited—can help pathologists determine the type of tumor and how it might behave.

What types of tumours express S100?

S100 is commonly expressed in a wide variety of tumors, especially those involving:

Nerve-related tumours:

• Schwannoma

• Neurofibroma

• Malignant peripheral nerve sheath tumor (usually weak or patchy)

• Granular cell tumor

Melanocytic tumours:

• Melanoma (including most subtypes, such as desmoplastic and spindle cell melanoma)
• Benign melanocytic nevi (commonly known as moles)

Brain and spinal cord tumours:

• Astrocytoma

• Oligodendroglioma

• Ependymoma

• Choroid plexus tumors

• Meningioma (especially fibrous type)

Tumours of the immune system:

• Langerhans cell histiocytosis

• Rosai-Dorfman disease

• Interdigitating dendritic cell tumors

Myoepithelial and glandular tumours:

• Myoepithelioma

• Adenoid cystic carcinoma

• Pleomorphic adenoma

• Epithelial-myoepithelial carcinoma

• Metaplastic carcinoma of the breast

Other tumours:

• Clear cell sarcoma of soft tissue

• Chondroid tumors (like chondrosarcoma)

• Chordoma (tumor of the spine)

• Neuroendocrine tumors (subset)

Because S100 can be positive in many tumour types, pathologists often use it alongside other markers to narrow down the diagnosis.

Why is S100 important in a pathology report?

S100 is important because it helps pathologists identify the type of cells that make up a tumor. This can be especially helpful when the tumor has spread (metastasized) and the original site is unclear. For example:

• A tumour that is S100 positive and also positive for other melanocytic markers (like Melan-A) may be diagnosed as melanoma.

• If a tumor is strongly and diffusely S100 positive, it may be a schwannoma.

• A tumour with patchy S100 positivity may be a malignant peripheral nerve sheath tumor.

S100 also helps pathologists identify nerve involvement, Langerhans cell disorders, or tumours with myoepithelial differentiation, which may require different treatments.

Questions to ask your doctor

• What does the S100 result mean in my pathology report?

• Does this result help confirm the type of tumour I have?

• Were any other markers tested along with S100?

• Will this information change the treatment plan or diagnosis?

• Is further testing needed to confirm the tumor type?