What Is Atypical Fibroxanthoma?
Atypical fibroxanthoma (AFX) is a benign lesion in the dermis of sun-exposed skin in elderly or young patients with xeroderma pigmentosum or other diseases characterized by impaired DNA repair. Older people are most likely to develop AFX on sun-exposed skin. AFX is distinguished by its association with ultraviolet radiation, both clinically and molecularly. A diagnosis of AFX can be challenging to make, and it is critical to distinguish it from malignant melanoma and squamous cell carcinoma. A definitive diagnosis requires both immunohistochemical markers and histological characteristics. Helwig suggested the term atypical fibroxanthoma (AFX) for a lesion that was thought to demonstrate a reactive process. This resulted in the identification of the unique clinicopathological characteristics of AFX.
What Signs and Symptoms Can Be Observed in Individuals With Atypical Fibroxanthoma?
Two clinical settings have been used to describe AFX. The tumor appears on sun-exposed skin in elderly people more frequently. The scalp, face, ears, and upper limbs are the most common sites for tumors. In a less frequent variant, the tumor develops on the limbs and trunk when there is no correlation between youngsters and sun exposure. Interestingly, AFX appears in people who have had organ transplants and may be immunosuppressed. Multiple tumor cases have been reported infrequently. A predominance of men (70 percent men, 30 percent women) has also reportedly been noted. The reported age ranges from 29 to 91 years, with 71.9 years being the average.
How Does Atypical Fibroxanthoma Affect the Individuals?
AFX typically affects sun-exposed skin on the head and neck. Because of this, it has long been hypothesized that sun exposure contributes to AFX tumorigenesis. UV (ultraviolet rays) rays from the sunlight are a significant risk factor. Nucleotide excision repair (NER) is the main pathway for repairing UV-induced DNA (deoxyribneuclic acid) damage. The transcriptional activator p53 is a tumor suppressor protein that regulates the cell cycle, apoptosis, and genome instability.
Additionally, p53 directly contributes to NER. UV radiation is considered a significant factor in the development of AFX based on the prevalent mutation trends of C-T (cytosine and thymine) transitions and CC-TT double transitions at pyrimidine sites in the p53 gene. A study found that patients with xeroderma pigmentosum had AFX, and xeroderma pigmentosum is known to be associated with DNA repair defects.
Skin cancer is thought to be caused by the formation of DNA photoproducts caused by UV radiation. Cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone photoproducts (64PPs) are important photoproducts because they are involved in mutagenesis and carcinogenesis. NER removes DNA photoproducts. DNA photoproducts can prevent a number of crucial transcription factors from binding, including those that control the cell cycle and respond to DNA damage. The concentration of DNA photoproducts may influence the pathogenesis of AFX, as reports indicate.
How Does Atypical Fibroxanthoma Differ From Malignant Fibrous Histiocytoma?
Both AFX and MFH (malignant fibrous histofibroma) are myofibroblastic differentiated fibrohistiocytic lesions. In more than half of all AFX cases, the histiocytic or macrophage marker CD68 is positive. But in 86 % of cases of malignant melanoma, CD68 can also be found. AFX exhibits immunoreactivities for a number of myogenic or myofibroblastic markers, including desmin, alpha-smooth muscle actin, and muscle-specific actin, as seen in MFH.
Actin-binding proteins associated with the cytoskeleton include calponin and h-caldesmon. According to reports, they are more precise myogenic markers. To differentiate AFX from leiomyosarcoma, which has smooth muscle differentiation characterized by positive findings for calponin and h-caldesmon, but both AFX and MFH share such expression, it is helpful to determine whether AFX expresses calponin and h-caldesmon positively or negatively.
What Are the Laboratory Findings of Atypical Fibroxanthoma?
AFX is a nodular dermal ulcerative lesion that usually progresses quickly. A light tan to light brown shade describes AFX. The size is typically under 2 cm (centimeter) in diameter, with the reported average preoperative size being 1.7 cm. Ulcers are present in about 50 % of cases. Spindle, plump, epithelioid, and odd cells make up AFX in varying amounts and are arranged in random, hazily fascicular, or storiform patterns. According to reports, spindle cells dominated in 72 % of AFX cases. There are numerous multinucleated giant tumor cells. Hyperchromatic and multilobular nuclei may be present in the lesion.
A wide variety of mitotic figures, including abnormal ones, are visible. Xanthoma-like vacuolated and lipid-rich cytoplasm may be present in some of the lesion's cells. This explained where the term "atypical xanthoma" originated. There has been widespread observation of solar elastosis linked to ultraviolet (UV) radiation. Appendage involvement within the lesion is common, indicating the presence of undestroyed adnexal structures.
The primary differential diagnosis also includes malignant melanoma, the pleomorphic and spindled variant of squamous carcinoma, in addition to MFH and leiomyosarcoma. Other differential diagnoses include keratoacanthoma and basal cell carcinoma.
How Does Atypical Fibroxanthoma Is Treated?
There are no special considerations for the treatment of AFX. However, the recurrence rate for AFX has been estimated to be between 5 % and 10 %, and it is typically treated surgically. Multiple local recurrences are uncommonly reported. Metastases are uncommon, occurring in only about 1% of reported cases. However, in 89 AFX lesions, there was no recurrence or metastasis. Recurrence, vascular invasion, a large tumor, deep tissue invasion, and tumor necrosis are all signs of metastasis. It has been determined that these locally invasive and/or metastasizing lesions may not have been AFX at all but rather MFH, squamous cell carcinoma, or malignant melanoma.
Wide excision with 1 cm margins has previously been advised regarding the surgical margin. However, there have been reports of successful Mohs microsurgery treatments for AFX. Mohs microsurgery removes the tumor with the least amount of normal tissue possible. The surgical area is examined under a microscope throughout the procedure to ensure that all cancerous cells have been removed.
Conclusion:
The relationship between the pathogenesis of AFX and reduced DNA repair capacity remains to be further investigated to establish its validity. The diagnosis of AFX is difficult. The diagnosis should be made only after using a comprehensive panel of immunostains and strict histological criteria. It is believed that AFX is a distinct lesion from MFH. Although AFX and MFH may have different pathways that determine biological activity in a tumor-specific manner, they may share the same pathway that determines morphology.
