An unusual presentation of atypical fibroxanthoma
Department of Pathology, Department of Dermatology, Baylor College of Medicine
Atypical fibroxanthoma (AFX) is a rare cutaneous spindle-cell neoplasm. The tumor occurs most commonly in sun-damaged skin of the head and neck in elderly patients. A small subset of patients (approximately one in five cases) is middle-aged and presents with AFX of the trunk or extremities in areas without evidence of actinic damage. We report an unusual case of AFX of the lower leg in an 81-year-old woman with extensive actinic damage.
An 81-year-old woman with a history of basal cell carcinomas of the face and extremities, numerous actinic keratoses, and melanoma in situ presented to the dermatologist for a total body skin examination. She was found to have a 6-mm dome-shaped nodule on the posterior aspect of the left lower leg. The nodule was firm and pink without ulceration, and the surrounding skin was erythematous. The patient had never noticed the nodule; she denied pain, pruritus, and bleeding. The nodule was biopsied and sent for histopathologic and immunohistochemical assessment. The biopsy showed a tumor that filled and expanded the dermis producing a nodular lesion. The tumor cells had either a spindle-shaped or larger epithelioid appearance. Many of the larger epithelioid cells were multinucleated (Fig. 1), and atypical mitotic forms were easily found. Neither keratin-pearl formation nor cytoplasmic melanin was observed. The larger epithelioid and multinucleated cells expressed CD68; the smaller spindle-shaped cells expressed Factor XIIIa (Fig. 2). Both cell populations were negative for smooth muscle actin, desmin, S100 protein, and cytokeratins. This immunophenotype is consistent with a lesion of fibrohistiocytic differentiation. The tumor was diagnosed as atypical fibroxanthoma (AFX). Mohs micrographic surgery was performed in May 2006 and no recurrence was noted in one year of followup.
Generally considered to be part of the fibrohistiocytic family of tumors, AFX is a dermal nodule comprised of pleomorphic and atypical spindle cells with frequent mitoses, multinucleated giant cells, and a fibrous stroma [1, 2, 3, 4]. Despite its ominous and malignant-appearing profile on histology, AFX tends to follow a benign clinical course. The tumor was initially termed by one investigator as paradoxical fibrosarcoma because of the inconsistency between its histologic findings and clinical behavior .
Atypical fibroxanthoma classically presents as a relatively nondescript, erythematous nodule less than 2 cm in diameter; the tumor may ulcerate and bleed, but pain and pruritus are uncommon . Atypical fibroxanthoma is an acquired nodule and is capable of rapid growth. Fretzin and Helwig report a median interval of 4 months between the time of onset and the time of diagnosis . Based on clinical findings, the differential diagnosis of AFX includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma, Merkel-cell carcinoma, and pyogenic granuloma.
Several large case series have revealed a bimodal distribution of age and anatomic location of AFX [5,7,9]. The vast majority of patients is elderly (in the seventh and eighth decade) and presents with AFX of the cheek, nose or ear. These patients are almost exclusively light skinned and have evidence of actinic damage to adjacent skin . A second, smaller group of patients presents in the fourth or fifth decade with AFX on the trunk or extremities in areas without sun exposure [2, 9]. The patient in our present case is unusual in two respects. First, she is elderly and has extensive sun exposure but developed an AFX on the lower leg, an uncharacteristic location for her demographic group. Second, AFX of the extremities tends to occur in skin without actinic damage; our patient has widespread actinic damage, including the skin of the extremities.
Because of the frequent occurrence of AFX on sun-damaged skin, exposure to ultraviolet radiation has long been considered a risk factor for development of AFX [2, 3]. In fact, most patients with AFX have other previously diagnosed skin cancers, including BCC and SCC . Furthermore, genetic analysis of AFX tumor cells has revealed mutations of the p53 tumor-suppressor gene known to be specifically induced by ultraviolet radiation .
Despite its ominous genetic and histologic profile, AFX tends to follow a benign clinical course. Although these tumors may be locally aggressive, metastasis is reported in fewer than one percent of cases  and is typically preceded by local recurrence if surgically excised . The recurrence rate of AFX after wide local excision has been reported to range from 16 to 20 percent [7,12]. Mohs micrographic surgery has emerged as a valid alternative to local excision for the treatment of AFX. Positive tumor marginscharacterized by pleomorphic spindle cells and frequent mitotic figuresare readily identified on frozen sections [3,11]. The recurrence rate after Mohs micrographic surgery has been reported to range from 0 to 6.9 percent .
Atypical fibroxanthoma is a rare cutaneous neoplasm occurring most commonly on the head and neck in elderly light-skinned patients with actinically damaged skin. A minority of patients is middle-aged and presents with AFX on the extremities without actinic damage. We present the unusual case of an elderly woman with extensive sun exposure who developed an AFX of the leg. This case is illustrative of the principle that AFX should be considered when differentiating cutaneous nodules even in uncharacteristic demographic and anatomic distributions.
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