Dermatofibroma (DF), also known as benign fibrous histiocytoma (BFH), is a common benign mesenchymal tumor composed of fibroblastic and histiocytic cells1. DF occurs anywhere on the body surface but has a propensity for the extremities. To our knowledge, DF arising in the oral cavity or perioral region is quite rare, and its long-term clinical behavior has yet to be elucidated. Herein we reported the clinical, microscopic, and immunohistochemical aspects of a case of DF of the upper lip.

A 41-year-old female came to our department for evaluation of a hard nodule on her upper lip that had been noted 4 months earlier. Her medical and family histories were noncontributory. She denied any history of trauma to the lesion. Clinical examination revealed a rubbery, firm, non-mobile nodule, 1.0 cm in diameter, on the upper lip (Fig. 1). The appearance of the overlying labial mucosa and skin was normal. There was no pain or tenderness. Excision biopsy was performed, and the specimen was stained with hematoxylin-eosin.

Microscopically, a poorly defined, non-encapsulated, nodular tumor was observed throughout the depth of the dermis. Histological findings showed acanthosis of the epidermis and a poorly defined, non-encapsulated deep dermal tumor (Fig. 2A) composed of fibroblastic spindle cells without atypia and pleomorphism in a storiform pattern, separating the dermal collagen, with a few histiocytes in both the superficial (Fig. 2B) and deep portions of the tumor (Fig. 2C). Immunohistochemical stains for CD34, factor XIIIa, CD68 and smooth muscle actin (SMA) were then performed on sections of the tumor. CD34 was negative in fibroblastic spindle tumor cells and positive in vessels (Fig. 3A), factor XIIIa was positive in only a few dendritic cells and negative in fibroblastic cells (Fig. 3B), CD68 was weak in spindle cells and strong in histiocytes (Fig. 3C), and SMA was strong in fibroblastic spindle cells (Fig. 3D). As a result of clinical and pathologic findings, the diagnosis was interpreted as DF.

DF is a common benign dermal fibrohistiocytic tumor that presents as a firm, red-brown nodule. There has been controversy about the pathogenesis of DF. Whether DF is a true neoplasm or reactive hyperplasia induced by mechanical stimuli is still unclear2. Prolonged sun exposure, traumatic injury and chronic infection have been suggested as possible causative agents. DF occurs anywhere on the body surface, most commonly on the extremities, and usually on the lower legs. Involvement of the oral mucosa is quite rare. There have been a few published reports of DF that involved the oral and maxillofacial regions3-7. Gray et al.6 reviewed the literature on oral and perioral DF and reported that the buccal mucosa/vestibular region was the most commonly affected site. Also, cases of DF/BFH of the tongue, gingiva, mandible, maxilla, lower and upper lip have been described. Yamada et al.7 reported a case of BFH of the upper lip in an infant. Five cases of DF of the lip have been reported in the literature (Table 1)3,5-7.

Histologically, the epidermis demonstrates hyperplasia, hyperpigmentation of the basal layer, and elongation of the rete ridges ("dirty fingernail" sign), which are separated by a clear (Grenz) zone from the tumor in the dermis. The tumor itself is composed of fibroblast-like spindle cells, histiocytes, and blood vessels in varying portions.

DF has a variable immunohistochemical profile. Early lesions are highly reactive for macrophage markers such as CD688. Most cells in early phase DFs have been found to react with factor XIIIa, a marker of normal dermal dendrocytes. This reactivity is mostly seen at the periphery of the tumor, continuously diminishes with aging of the lesion, and is completely absent in atrophic variants9. Other variably expressed markers include smooth muscle actin, CD56, and NSE. Labeling for SMA is most prominently seen in myofibroblastic DF10. Variable reactivity is seen with vascular markers such as factor VIII or CD31. Exceptional cases with characteristic histologic features of DF show diffuse reactivity for CD3411; other rare cases express S-100 protein. Mentzel et al.12 reported that tumor cells of facial DF showed immunoreactivity for factor XIIIa in 13 out of 17 cases and a focal immunepositivity for CD68 in 6 out of 10 cases; Mentzel et al.12 also showed that spindle-shaped tumor cells in 16 out of 19 neoplasms stained at least focally positive for SMA. The more cellular forms of DF tend to express SMA, whereas the lesions with more epithelioid cells and giant cells tend to express histiocytic markers.

The main differential diagnoses of spindle cell neoplasms arising on the face, especially the oral cavity, include nodular fasciitis, low-grade myofibroblastic sarcoma, and neurofibroma. Nodular fasciitis may also present as spindle cells ordered in a storiform configuration, similar to that seen in DF, but the fascicles are separated by a myxoid stroma, mitoses are frequent and immunohistochemical staining for S-100 antigen is reactive13. Low-grade myofibroblastic sarcoma is characterized morphologically by ill-defined fascicles of atypical, spindle-shaped myofibroblastic tumor cells that infiltrate preexisting structures in a diffuse pattern. Spindle-shaped tumor cells of DF do not stain positively for desmin, a marker that is frequently expressed in cases of low-grade myofibroblastic sarcoma14. Neurofibroma is composed of elongated spindle-shaped S-100 protein-positive tumor cells containing fusiform nuclei15. Cellular fibrous histiocytoma, the cellular variant of DF, must be especially distinguished from dermatofibrosarcoma protuberans (DFSP). DFSP is generally characterized by more uniform spindle cells and a more prominent storiform pattern than that seen in DF. CD34 staining is usually diffusely positive in DFSP and negative in most forms of DF. However, some DFs may express CD34, and some DFSP may express factor XIIIa16. Paradoxically, cellular atypia is often more pronounced in cellular fibrous histiocytoma than in DFSP, and factor XIIIa staining is often negative.

DFs arising on the face, including the oral cavity, are more often of the cellular type, extend into the subcutaneous fat or muscle, and frequently recur12. Therefore, a wider initial excision is recommended, and local excision is the definitive treatment for DF of the head and neck region. Because oral DFs are rare and the long-term clinical behavior has yet to be elucidated, regular clinical follow-up is recommended.