Perineurioma: Understanding Your Pathology Report

Section Editor: Bibianna Purgina MD FRCPC
September 25, 2026

A perineurioma is a rare noncancerous tumor that develops from perineurial cells. These cells form the thin protective layer that wraps around bundles of nerve fibers. Perineurioma belongs to a group of tumors called peripheral nerve sheath tumors.

Perineuriomas grow slowly and do not spread to other parts of the body. Most form a lump in the soft tissue, and a separate form grows inside a nerve. The two behave differently and are managed differently, so your report will state which one you have.

This article explains how a perineurioma is diagnosed and what the type, immunohistochemistry results, and other findings in your pathology report mean.

What are the types of perineurioma?

Soft tissue perineurioma. Also called extraneural perineurioma, this type forms a lump in the soft tissue, usually in a leg. Less often, it develops in an arm, the trunk, the head and neck, or deep in the abdomen or chest. It is the most common type and is usually found in middle-aged adults, slightly more often in women.
Intraneural perineurioma. This type grows inside a nerve and thickens it rather than forming a separate lump. It usually affects teenagers and young adults.
Sclerosing perineurioma. This type occurs mainly on the fingers and palms, most often in young men. It contains small cords of cells in a dense, fibrous background.
Reticular perineurioma. This uncommon type forms a lace-like network of cells.

What are the symptoms of a perineurioma?

A soft tissue perineurioma usually appears as a painless, slow-growing lump beneath the skin. Larger or deeper tumors may cause pressure or discomfort, particularly in a tight space, but this is uncommon.

An intraneural perineurioma causes different symptoms because it affects the nerve from within. The usual pattern is slowly progressive weakness in the muscles supplied by that nerve, sometimes with numbness. At first, it is often mistaken for a nerve injury or nerve entrapment, such as a pinched nerve.

What causes a perineurioma?

Most perineuriomas occur by chance, and no cause is identified. They are not inherited.

The tumor cells carry genetic changes that differ by type. Many intraneural perineuriomas have a change in a gene called TRAF7. Soft tissue perineuriomas often show changes involving chromosome 22, including the NF2 gene, which is the same region altered in several other nerve sheath tumors.

Rarely, a perineurioma occurs in a person with an inherited condition affecting nerve sheath tumors, such as neurofibromatosis type 1 or NF2-related schwannomatosis. That second condition was previously called neurofibromatosis type 2, and an international group changed the name in 2022.

How is the diagnosis made?

The diagnosis of a perineurioma is made after a pathologist examines tumor tissue under the microscope. For a soft tissue perineurioma, the tissue usually comes from surgery that removes the lump. For an intraneural perineurioma, MRI often shows a thickened nerve, and a small targeted sample of the affected nerve bundle may be taken to confirm the diagnosis.

Under the microscope, a perineurioma is made of spindle cells with very long, thin extensions and small, uniform, wavy nuclei. The cells are arranged in whorls, swirls, or layers. In an intraneural perineurioma, the cells wrap around individual nerve fibers in rings that reports describe as pseudo-onion bulbs.

The surrounding supporting tissue is often fibrous and may contain dense collagen, gel-like myxoid material, calcification, or fat-like areas. A few tumors contain multinucleated or pleomorphic cells, meaning cells of unusual size and shape. These are degenerative changes and are not a sign of cancer.

Immunohistochemistry

Immunohistochemistry uses antibodies to show which proteins tumor cells make. It is important for this diagnosis because a perineurioma can resemble other spindle cell tumors under the microscope.

EMA. Epithelial membrane antigen is the main marker of perineurial cells and is positive in a perineurioma.
Claudin-1 and GLUT1. These proteins are also found in perineurial cells and support the diagnosis.
CD34. This protein is positive in roughly 6 in 10 perineuriomas.
S100 and SOX10. These are negative. They are positive in schwannoma and other Schwann cell tumors, so a negative result helps separate a perineurioma from those tumors.

Molecular testing is not routinely needed. The genetic changes described above are not currently used to make the diagnosis or to guide treatment.

What about malignant perineurioma?

You may come across the term malignant perineurioma. It does not describe a perineurioma that turned into a cancer.

The term is used for a small subset of malignant peripheral nerve sheath tumor in which the tumor cells show perineurial features rather than the usual Schwann cell features. These tumors are classified and treated as a cancer from the start. A diagnosis of perineurioma, without the word malignant, means a noncancerous tumor.

Margins

A margin is the edge of tissue cut by the surgeon. Your report may note whether the tumor reaches the cut edge.

For a perineurioma, a positive margin does not carry the meaning it does for cancer. It means only that a small amount of tumor may remain, which slightly raises the chance the lump comes back. For a tumor inside a nerve, surgeons deliberately leave tumor behind to protect movement and sensation.

What is the prognosis?

The outlook is excellent. A perineurioma is noncancerous and does not spread. For a soft tissue perineurioma, removal is almost always curative, and these tumors rarely come back.

Degenerative changes such as large or oddly shaped nuclei do not change this. They look concerning under the microscope but do not affect behavior.

For an intraneural perineurioma, the tumor itself is harmless, but the weakness it causes may persist. The goal of treatment is to preserve or restore function rather than to remove every tumor cell.

What happens after the diagnosis?

Soft tissue perineurioma. Removing the lump is usually all that is needed, and no further treatment or long-term imaging is typically required.
Intraneural perineurioma. Treatment focuses on function. Options include monitoring, surgery to relieve pressure on the affected nerve, physiotherapy and bracing, and reconstructive procedures such as tendon transfer when weakness is significant. Removing the affected nerve segment would cause permanent loss of function, so doctors avoid it when possible.
Follow-up. Symptoms guide follow-up. A specialist usually sees people with an intraneural tumor in nerve disorders or nerve surgery.

Questions to ask your doctor

Which type of perineurioma does my report describe?
Was the whole tumor removed, or was some left to protect the nerve?
Is there a chance the tumor will come back?
If I have weakness or numbness, is it likely to improve?
Would physiotherapy or a brace help?
Do I need follow-up appointments or imaging?
Is there any reason to be assessed for an inherited condition?