NF is a pseudosarcomatous, self-limiting reactive process which was first described by Kornwaler et al. in 1955 as “subcutaneous pseudosarcomatous fibromatosis” . Histologically, NF consists mainly of plump immature fibroblasts that are arranged in short irregular bundles and fascicles, accompanied by a dense reticulin meshwork with small amounts of mature collagen. Extravasated erythrocytes, scattered lymphocytes and osteoclast-like giant cells are often sprinkled between the myofibroblasts. Although mitotic figures are fairly common, atypical mitosis is virtually never seen [2, 15]. Thus, the correct diagnosis of NF mainly depends on tumor size, short duration, red blood cell extravasation, keloid-type collagen, and lack of markedly cellular atypia. In contrast, fibrosarcoma typically occurs in patients older than 50 years and measures more than 3 cm. The cells show more nuclear pleomorphism, atypical mitotic figures. Fibromatosis consists of bland cells arranged in sweeping bundles with dense collagenous stroma and usually lacking inflammatory component, thin-walled vessels and extravasated red blood cells.
Despite this entity has been well described, NF is still often misdiagnosed as a sarcoma or other malignancies because of its rapid growth, rich cellularity, and mitotic activity. So, in addition to histological appearances, some diagnostic markers including proliferative markers should be used for differential diagnosis. Ki67 antigen is a marker of proliferating cells, and is rapidly degraded after mitosis. For the short half-time, it has been suggested that Ki67 staining is more accurate and specific than the counting of mitoses or PCNA staining . Oshiro Y et al. ever reported that NF has higher expression of proliferating cell nuclear antigen than other benign and malignant fibroblastic lesions . However, the utility of the proliferative markers has not been established for distinguishing between these lesions for diagnostic purpose . So far, in addition to Ki67 expression in 3 cases of NF described by Ooe M , there is no deep study on the expression of Ki67 in NF. So, to further detect the diagnostic usefulness of Ki67, we examined the expression of Ki67 in 65 cases of NF, 15 cases of desmoid fibromatosis and 20 cases of fibrosarcoma. The imunohistochemical staining results showed although Ki67 labeling index was variable in NF, there was generally a higher expression level (mean index 23.71±15.01%). Ki67 has been proved to be a useful marker for distinguishing many benign and malignant lesions [6, 7]. Gong et al.  found a significantly higher expression of Ki67 in ghost cell odontogenic carcinoma than in calcifying cystic odontogenic tumor. But, our results revealed that NF could show the higher expression of Ki67. The mean Ki67 index in 15 cases of desmoid fibrosatois is significantly lower than that in nodular fasiitis, however, the mean Ki67 index in 20 cases of fibrosarcoma is not significantly higher than that in NF. This result indicates that usefulness of Ki67 staining in differential diagnosis of NF is limited, and may represent a diagnostic pitfall. And we should not misdiagnose the lesion as a sarcoma because of its higher proliferative index. The higher proliferative index may further indicate it is a lesion which closely mimics a sarcoma. However, in contrast to the average index 5.6 reported by Ooe M et al. , our Ki67 index is much higher. It may be because that the numbers of specimens selected by Ooe M et al. is too small, or the counting method is different.
In addition, we found that the Ki67 labeling index was closely related to duration of lesion, but not to age distribution, lesion size, sites of lesions and gender. This suggests that if the duration was shorter, the myofibroblasts might have the higher proliferative activities, so the cells showed the higher expression of Ki67. That is, in the earlier stage of the lesion, the majority of myofibroblasts might be in immature status, conversely, if the lesion had a long history, only few of the proliferative cells might have high proliferative activities. In contrast, the Ki67 index in fibrosarcoma and fibromatosis was not associated with the duration. This phenomenon may represent self-limiting reactive process of NF. Acording to Allen, nearly all nodules have been effectively treated by local excision, in the series of 895 cases only 9 (1%) reappeared after attempted complete surgical excision . Thompson and colleagues found a local recurrence rate of 9.3% in cases of NF of the external ear, a much higher rate of local recurrence when compared to NF at other sites . Our follow up results reveal a 4.44% recurrence rate, generally similar to the reported previously, indicating the recurrence of NF is rare. Surprisingly, the Ki67 index in two recurred cases was approximately 9% and 15% respectively, relatively not so high. In contrast, Hoos et al.  and Hase-gawa et al.  have reported that analysis of Ki67 can identify tumors with aggressive behavior also among tumors with other high-risk characteristics. That is, the higher Ki-67 index usually means the poorer prognosis and the higher recurrence rate. But our finding indicated that the Ki67 staining may be not suitable for recurrence assessment in NF.