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Atypical fibroxanthoma (AFX) is a rare, low-grade superficial sarcoma that typically presents as a red nodule or plaque, most often on the head and neck of older adults, particularly in individuals who are White. This condition is considered a superficial variant of undifferentiated pleomorphic sarcoma, sharing similar histological features but with a less aggressive clinical course. AFX is usually found in sun-exposed areas and can also appear on the trunk, shoulders, upper extremities, and hands. Surgical excision is the preferred treatment for AFX, offering a high rate of cure, though recurrence is possible; metastasis, however, is uncommon. In this educational activity, the participant learns the pathophysiology, presentation, and management of atypical fibroxanthoma. Emphasis is placed on the importance of surgical excision and patient education, particularly regarding sun protection and regular skin examinations for early detection. Collaboration with an interprofessional team, including dermatologists, oncologists, pathologists, and surgeons, enhances patient outcomes by ensuring accurate diagnosis, effective treatment planning, and comprehensive follow-up care. This team-based approach reduces the risk of recurrence and improves the long-term management of AFX. Objectives: Implement appropriate surgical management techniques, ensuring complete excision of the lesion to reduce the risk of recurrence. Assess the histopathological features of biopsied lesions to confirm the diagnosis of atypical fibroxanthoma. Apply evidence-based guidelines for post-surgical care and follow-up, monitoring for any signs of recurrence or complications. Communicate the interprofessional team strategies for improving care coordination regarding managing patients with atypical fibroxanthoma. Access free multiple choice questions on this topic.

Atypical fibroxanthoma is a rare, low-grade superficial sarcoma frequently presenting as a red nodule or plaque. This condition is a superficial variant of undifferentiated pleomorphic sarcoma (formerly malignant fibrous histiocytoma). Although atypical fibroxanthoma has similar histologic features to undifferentiated pleomorphic sarcoma, it behaves less aggressively.[1][2][3][4]

The etiology of atypical fibroxanthomas is poorly understood. Researchers believe it arises from myofibroblasts or fibroblast-like cells. Ultraviolet light appears to play a significant role since most lesions appear on the sun-exposed head and neck of White individuals. Genetic factors also contribute to the development of atypical fibroxanthoma since it shares genetic alterations with undifferentiated pleomorphic sarcomas, including chromosome 9p and 13q deletions. However, undifferentiated pleomorphic sarcoma has a statistically significant larger amount of genomic alterations and a more aggressive clinical course. Other possible risk factors for atypical fibroxanthoma include trauma to the skin, radiation therapy, and immunosuppression (eg, diabetes, human immunodeficiency virus, organ transplant).[5][6][7][8]

Atypical fibroxanthomas are most commonly seen on the head and neck of older White individuals. Other reported sites of atypical fibroxanthoma include the trunk, shoulders, upper extremities, and dorsum of the hands. Trunk and limb lesions appear more commonly in younger patients (mean age 39) than head and neck lesions in the elderly (mean age 69). Results from a review of 171 cases in Western Australia found a patient age range of 41 to 97 years old (median age 74), with 76% of the tumors occurring in men. Atypical fibroxanthoma has also been reported in patients as young as 13 with predisposing disorders such as Li-Fraumeni syndrome and xeroderma pigmentosum. The incidence increases in immunosuppressed populations, with an estimated 78 per 100,000 patients with a transplantation.

The pathophysiology of atypical fibroxanthomas is poorly characterized. Ultra-violet (UV) light has implications for its pathogenesis due to atypical fibroxanthoma predilection for sun-exposed areas of the body and the presence of atypical fibroxanthoma in xeroderma pigmentosum patients who exhibit defective repair of UV-induced cyclobutane pyrimidine dimers. Research results have documented these UV-induced pyrimidine dimers in atypical fibroxanthoma lesions and mutations in the tumor suppressor gene p53. Various rare genetic disorders have correlations with p53-induced atypical fibroxanthomas, including Li-Fraumeni syndrome (with germline p53 mutations) and xeroderma pigmentosum. One study's results showed that mutations of H-Ras and K-Ras genes were present in malignant fibrous histiocytoma but not in atypical fibroxanthoma lesions; this research may prove helpful in establishing the diagnosis of atypical fibroxanthoma.

Hematoxylin and eosin stains of atypical fibroxanthoma lesions show a dermally-based tumor with pleomorphism, atypical mitotic figures, and a spindly architecture. Atypical fibroxanthoma lesions occasionally extend to the subcutaneous tissue. Note that atypical fibroxanthoma is a dermal-based process, while spindle cell squamous cell carcinoma variants (on the differential diagnosis) connect with the epidermis and show signs of keratinization. Multinucleated giant cells and solar elastosis are often present in atypical fibroxanthoma biopsy specimens, while a mixed inflammatory infiltrate may be found at the edge of the tumor. Immunohistochemistry is required to rule out other neoplasms, including spindloid squamous cell carcinoma, melanoma, and undifferentiated pleomorphic sarcoma. Since atypical fibroxanthoma stains are positive for several non-specific stains, including a cluster of differentiation 10 (CD10), p53, S100A6, vimentin, and procollagen-1, it is considered a diagnosis of exclusion histologically. Of note, atypical fibroxanthoma stains negative for HMB-45, p40 (often positive in squamous cell carcinoma), desmin, pan-cytokeratin stains, CD31, and has sparse staining for S100, which may help differentiate it from melanoma. Since poorly differentiated sarcomatoid carcinomas may lose cytokeratin expression, various cytokeratin stains should be used. Severe variants of atypical fibroxanthoma have been described based on various histologic findings, including pigmented atypical fibroxanthoma due to hemosiderin deposit and not actual melanin pigment, granular cell atypical fibroxanthoma, sclerotic atypical fibroxanthoma, spindle cell nonpleomorphic atypical fibroxanthoma, osteoid atypical fibroxanthoma, chondroid atypical fibroxanthoma, myxoid atypical fibroxanthoma, keloidal atypical fibroxanthoma, osteoclast-like giant-cell rich atypical fibroxanthoma, and clear cell atypical fibroxanthoma.

Atypical fibroxanthomas present as well-circumscribed red or pink nodules or plaque that may have ulceration, crust, or scale. Atypical fibroxanthoma lesions are typically small in size, with a median diameter of 1 cm, with less than 5% of the lesions being greater than 2 cm in diameter. They often develop rapidly but lack symptoms such as pain or pruritus. More than 90% of atypical fibroxanthoma tumors occur on the head and neck, while the remaining cases typically present on the extremities and trunk. Dermoscopy of lesions reveals polymorphic vessels (linear, dotted, hairpin, arborescent, and/or highly tortuous vessels) radiating to the center of the lesion with intervening white areas. The differential diagnosis includes basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, amelanotic melanoma, leiomyosarcoma, atypical (pseudosarcomatous) dermatofibroma, pleomorphic dermal sarcomas, and metastasis from internal malignancies. Compared to atypical fibroxanthoma, pleomorphic dermal sarcomas are often clinically larger and are more likely to recur locally and metastasize.

A skin biopsy is the diagnostic gold standard for atypical fibroxanthoma, a rare condition that clinically mimics basal and squamous cell carcinomas, Merkel cell carcinomas, and amelanotic melanomas. Immunohistochemistry is a common test used to make the diagnosis (see "histopathology" above). When atypical fibroxanthoma lesions have metastasized or are poorly accessible (eg, subungual lesions), magnetic resonance imaging (MRI) may be helpful. MRI shows intermediate T1 and T2-weighted signal intensity compared to the high signal intensity of squamous cell carcinoma and melanoma.

Fortunately, atypical fibroxanthoma rarely metastasizes and recurs in only 6% to 10% of cases. Risk factors for metastases include immunocompromised state, tumor depth, vascular or perineural invasion, and the presence of tumor necrosis. The most commonly reported locations for metastases include the parotid gland, lymph nodes, and subcutaneous tissue. Metastases, when present, are typically evident 12 to 24 months after the initial diagnosis of atypical fibroxanthoma. The treatment of choice for atypical fibroxanthoma is surgical excision. Previously, this utilized 1 cm margins, however Mohs micrographic surgery and regular follow-up have become the standard of care, with recurrence rates reported at 0.0% to 6.9%. In patients who are poor surgical candidates, electronic brachytherapy has successfully treated atypical fibroxanthoma and is even more effective if there is tumor debulking before therapy. Another reported treatment modality is electrodesiccation and curettage, which may be appropriate for slow-growing lesions less than 1 cm in diameter.

The differential diagnoses for atypical fibroxanthoma include the following: Amelanotic melanoma Atypical fibroxanthoma Basal cell carcinoma Dermatofibroma with monster cell Leiomyosarcoma Undifferentiated pleomorphic sarcoma Melanoma Merkel cell carcinoma Neurothekeoma Pleomorphic dermal

Atypical fibroxanthoma rates a low-grade sarcoma, usually occurring on sun-exposed head and neck areas in older adult patients. The prognosis is generally excellent when treated with adequate primary tumor excision; recurrence of the tumor occurs in approximately 5% of cases.[9][7][10]

When promptly addressed and treated through adequate excision, atypical fibroxanthoma seldom causes complications. This condition can exhibit significant sclerosis in some instances.[11] There have also been some cases of metastatic involvement, although rare.[12]

Healthcare professionals may frequently encounter abnormal skin growth in patients. Because the differential of dermal growths is large, these patients require a referral to a dermatologist or plastic surgeon for a definitive diagnosis. Atypical fibroxanthoma is 1 such growth that often presents in those who are older and White. Risk factors for metastases include immunocompromised state, tumor depth, vascular or perineural invasion, and the presence of tumor necrosis. The most commonly reported locations for metastases include the parotid gland, lymph nodes, and subcutaneous tissue. The treatment of choice for atypical fibroxanthoma is surgical excision. The key is to educate the patient on avoiding sun exposure and getting regular physical exams for early detection. Recurrence can occur, but metastatic spread is rare.[12][13]