A perineurioma is a rare, non-cancerous tumour that arises from perineurial cells, which are part of the protective sheath that surrounds nerves. These tumours belong to a group of tumours called peripheral nerve sheath tumours. Most perineuriomas are found in soft tissue, but they can also occur within nerves (intraneural perineuriomas) or on mucosal surfaces such as the lining of the digestive tract.
Perineuriomas grow slowly and typically do not spread to other parts of the body. A very rare form called malignant perineurioma behaves differently and may spread, but this form is uncommon.
Soft tissue perineuriomas most commonly develop in the lower limbs, followed by the arms and trunk. Less commonly, they are found in the head and neck, or deep within the abdomen or chest cavity. A subtype called sclerosing perineurioma most often occurs on the fingers or palms, especially in young adults.
Most perineuriomas appear as painless, slow-growing lumps just beneath the skin. In some cases, they may be located deeper in the soft tissue. Symptoms depend on the size and location of the tumour. If the tumour grows near a nerve or in a tight space, it may cause discomfort, pressure, or difficulty with movement, but this is uncommon.
Perineuriomas can occur at any age but are most often diagnosed in middle-aged adults. Soft tissue perineuriomas are slightly more common in women, while sclerosing perineuriomas more commonly affect young men. These tumours are rare in children.
In most cases, perineuriomas happen sporadically, meaning there is no known cause or inherited risk. In very rare cases, perineuriomas have been seen in people with neurofibromatosis type 1 (NF1) or neurofibromatosis type 2 (NF2), genetic conditions that increase the risk of nerve sheath tumours.
Changes in specific genes, such as NF2 or NF1, and alterations in chromosomes (especially chromosome 22 and 17) have been found in some perineuriomas. These changes are similar to those seen in other benign nerve sheath tumours, like schwannomas and meningiomas.
The diagnosis of perineurioma usually involves:
Physical examination: A lump is felt under the skin, often during a routine check-up.
Imaging: Tests like ultrasound or MRI may be used to assess the size and location of the tumour.
Biopsy or surgery: A small sample or the entire tumour is removed and examined under a microscope by a pathologist.
Under the microscope, perineuriomas are made up of spindle-shaped cells arranged in patterns that may look whorled, storiform (swirling), or layered (lamellar). These cells have long, thin extensions called bipolar cytoplasmic processes, and their nuclei are usually small, wavy, and uniform.
The surrounding tissue (called the stroma) is often fibrous and may include:
Areas of dense collagen.
Clear or myxoid (gel-like) material in about 20% of cases.
Occasional areas of calcification or fat-like (lipomatous) changes.
Very rare tumours may contain cells with unusual shapes, including multinucleated or pleomorphic cells. These are considered degenerative changes and do not indicate cancer.
Specific subtypes include:
Sclerosing perineurioma: Shows small cords of cells in a densely fibrous background. Most often found on fingers or palms.
Reticular perineurioma: Cells form a lace-like or network pattern.
Malignant perineurioma (rare): These tumours may look similar under the microscope but show features of cancer, such as higher cell density, nuclear abnormalities, and increased mitotic activity (cell division).
Immunohistochemistry is a special test used by pathologists to confirm the diagnosis of perineurioma. This test uses antibodies to detect specific proteins made by the tumour cells.
The tumour cells in perineurioma are usually positive for:
EMA (epithelial membrane antigen): Often seen in perineurial cells.
Claudin-1 and GLUT1: Additional markers that support the diagnosis.
CD34: Present in about 60% of tumours.
The tumour cells in perineurioma are typically negative for:
S100, SOX10, and GFAP: These are seen in other types of nerve sheath tumours, like schwannomas, and help distinguish perineurioma from those tumours.
Calcitonin and CK20: Markers used to rule out other tumours.
In sclerosing perineuriomas, staining for EMA is usually seen, and limited staining for keratin may also be present.
Molecular testing is not routinely used to diagnose perineurioma. While certain gene and chromosome changes have been reported in these tumours, they are not currently needed for diagnosis or treatment decisions in most cases.
Perineuriomas are benign tumours, and in almost all cases, surgical removal is curative. They rarely grow back (recur) after being completely removed.
Even perineuriomas that show degenerative nuclear changes (such as large or oddly shaped nuclei) behave in a benign manner and do not spread.
The very rare malignant perineuriomas may spread to other parts of the body, but they generally behave less aggressively than other malignant nerve sheath tumours. These tumours require closer follow-up and, in some cases, additional treatment.
Is there any chance the tumour will come back?
Should I be monitored with regular follow-up?
Is there any reason to test for genetic conditions like neurofibromatosis?