Atypical fibroxanthoma (AFX)

by Jason Wasserman MD PhD FRCPC
July 5, 2025

Atypical fibroxanthoma (AFX) is a rare skin tumour that typically affects older adults with sun-damaged skin. It most often develops in areas exposed to long-term ultraviolet (UV) light, such as the scalp, face, or ears. Although AFX can appear concerning under the microscope, it typically behaves in a non-aggressive (low-grade) manner when strict diagnostic criteria are applied.

AFX is related to a more aggressive tumour called pleomorphic dermal sarcoma (PDS). The main difference is that AFX is confined to the upper layers of the skin (the dermis) and does not invade deeper tissue, nerves, or blood vessels. If these features are seen, the tumour is diagnosed as PDS instead.

Is atypical fibroxanthoma cancerous?

Although atypical fibroxanthoma (AFX) can look aggressive under the microscope, when strict diagnostic criteria are used, it behaves like a noncancerous (benign) tumour. This means that it does not typically spread to lymph nodes or other parts of the body. Most patients are cured with surgery alone, and the tumour does not come back if it has been completely removed.

Where does atypical fibroxanthoma occur?

AFX most commonly arises in sun-exposed areas of the skin, particularly in the head and neck region. The ears are a frequent site. Lesions that appear on the arms or legs, especially in younger people, may be misdiagnosed as AFX and could represent other, similar-looking tumours.

What are the symptoms of atypical fibroxanthoma?

AFX typically presents as a solitary, rapidly growing nodule on sun-damaged skin. The nodule may appear pink, red, or flesh-colored, and often has a central ulceration. The tumour is generally painless and measures up to 2 cm in diameter. Because it can grow quickly and may ulcerate, it is sometimes mistaken for more common skin cancers, such as squamous cell carcinoma.

Who gets atypical fibroxanthoma?

AFX primarily affects older white adults, especially men and those living in regions with high sun exposure. It is rare in young people but has been reported in patients with certain inherited conditions, including:

• Li-Fraumeni syndrome, which involves mutations in the TP53 gene

• Xeroderma pigmentosum, a disorder that makes the skin highly sensitive to UV damage

AFX has also been seen in patients with a history of radiation therapy, organ transplantation, or weakened immune systems.

What causes atypical fibroxanthoma?

Long-term exposure to ultraviolet (UV) radiation is the leading risk factor for AFX. UV light causes genetic damage to skin cells over time, leading to mutations in genes that control cell growth and repair. Commonly mutated genes in AFX include:

• TP53, a tumour suppressor gene

• TERT promoter, which affects how cells divide and age

• CDKN2A/CDKN2B, which regulate the cell cycle

These mutations are similar to those seen in pleomorphic dermal sarcoma and other UV-related skin cancers.

How is atypical fibroxanthoma diagnosed?

AFX is diagnosed after the tumour is removed and examined under the microscope. A small sample may first be taken using a biopsy, but a full diagnosis usually requires removing the entire tumour.

To confirm the diagnosis, pathologists look at both the microscopic appearance of the tumour and the results of immunohistochemistry, a test that checks for specific proteins made by the tumour cells. This helps rule out other skin cancers, especially melanoma, squamous cell carcinoma, and soft tissue sarcomas.

What does atypical fibroxanthoma look like under the microscope?

Under the microscope, AFX is a highly cellular tumour that is confined to the dermis (the layer beneath the outer skin). The tumour does not invade the underlying fat, nerves, or blood vessels.

Key features include:

• Pleomorphic tumour cells: Cells vary in size and shape, often with large, irregular nuclei.

• Spindle-shaped or epithelioid cells: These may be arranged in short bundles (fascicles).

• Brisk mitotic activity: The cells divide frequently, sometimes in abnormal ways.

• No tumour necrosis.

• No deep tissue invasion.

Variants of AFX include:

• Spindle cell AFX: Made up entirely of spindle-shaped cells.

• Clear cell AFX: Contains tumour cells with clear or foamy cytoplasm.

• Other rare forms include granular cell, keloidal, myxoid, and sclerotic AFX.

Occasionally, tumours may show regression (spontaneous reduction in size) or haemosiderin (iron from old bleeding). These features can make diagnosis more difficult, especially on small or partial biopsies.

Immunohistochemistry

Immunohistochemistry plays a crucial role in the diagnosis of atypical fibroxanthoma (AFX). This test uses antibodies to detect specific proteins produced by tumour cells, helping pathologists distinguish between other types of skin cancer that may appear similar under the microscope. In particular, immunohistochemistry helps distinguish AFX from melanoma, squamous cell carcinoma, and soft tissue sarcomas.

AFX is typically negative for melanocytic markers such as S100, SOX10, and Melan-A, which helps rule out melanoma. It is also negative for epithelial markers such as cytokeratins, p63, and p40, which are commonly seen in squamous cell carcinoma. Muscle markers, such as desmin and h-caldesmon, are usually negative as well. If any of these markers are strongly positive, the diagnosis may need to be reconsidered.

AFX almost always exhibits strong, diffuse staining for CD10, a nonspecific marker that supports the diagnosis. Many tumours also express CD68 and CD163, which are markers found in both tumour cells and surrounding immune cells. AFX may show staining for MiTF and occasionally for SMA or EMA, although these results are not specific. In some cases, pathologists may perform additional stains such as CD31 and ERG to rule out vascular tumours like angiosarcoma.

Ultimately, AFX is diagnosed when the tumour shows negative staining for at least two melanocytic and epithelial markers, in combination with its microscopic appearance and confinement to the upper layer of the skin (dermis). A broad panel of immunostains is typically used to ensure the diagnosis is accurate and to exclude other, more aggressive tumours.

What is the difference between atypical fibroxanthoma and pleomorphic dermal sarcoma?

AFX and pleomorphic dermal sarcoma (PDS) look very similar under the microscope, but they behave differently.

The key differences are:

• AFX is limited to the dermis and does not invade blood vessels, nerves, or fat.

• PDS shows invasion into deeper tissues and may spread to lymph nodes or other parts of the body.

If any deep invasion, tumour necrosis, or perineural or vascular invasion is observed, the diagnosis is changed from AFX to PDS, which carries a higher risk of recurrence and metastasis.

What is the treatment for atypical fibroxanthoma?

The main treatment is complete surgical removal of the tumour.

This may be done by:

• Wide local excision with a clear margin.

• Mohs micrographic surgery is particularly useful in cosmetically sensitive areas, such as the face or scalp.

Because AFX is typically a low-grade tumour, no additional treatment is usually required after surgery if the tumour has been completely removed.

What is the prognosis for atypical fibroxanthoma?

AFX has an excellent prognosis when diagnosed correctly and completely removed. In most cases, the tumour does not come back.

• Recurrence occurs in up to 5% of cases, typically when the tumour was not fully excised.

• Metastasis (spread to other parts of the body) is very rare, and deaths from AFX are extremely uncommon.

If the tumour shows features that suggest a higher risk of recurrence or spread (such as deep invasion), it may be reclassified as pleomorphic dermal sarcoma, which requires closer follow-up.

Questions to ask your doctor

• Was the tumour completely removed?

• Was this definitely atypical fibroxanthoma, or are there features of pleomorphic dermal sarcoma?

• Do I need any additional treatment?

• How often should I have follow-up skin checks?

• What can I do to protect my skin from further sun damage?