Nodular fasciitis (NF) is a benign, soft tissue tumor composed of myofibroblasts (i.e. immature cells that contain features of myocytes and fibroblasts) that typically occurs in subcutaneous tissue (i.e. lowermost layer of the skin), fascia (i.e. band  of connective tissue just beneath the skin), and/or muscles. The literature sometimes titles rare NF variants according to their tissue locations. The most frequently used and important of these are: cranial fasciitis (NF variants that occur in the soft and hard tissues of the skull) and intravascular fasciitis (NF variants that involve arteries and/or veins). In 2020, the World Health Organization classified nodular fasciitis as in the category of benign fibroblastic/myofibroblastic tumors. NF is the most common of the benign fibroblastic proliferative tumors of soft tissue and exceeds in frequency any other tumor or tumor-like lesion in this group of tumors.Nodular fasciitis is a rapidly growing, usually self-limiting neoplasm that occurs primarily but not exclusively in adults. Due to its rapid growth, NF has often been misdiagnosed as a malignant tumor, usually a sarcoma. Indeed, NF was originally termed subcutaneous pseudosarcomatous fibromatosis when first described in 1955 by Konwaler et al. The correct diagnosis of a tumor as NF is pivotal to prevent its overtreatment as a more aggressive and/or malignant growth.NF tumors have long been mentioned as local reactions to traumatic injuries in at least some cases. While it still may be precipitated by such injuries, recent studies indicate that NFs are true neoplasms (i.e. abnormal proliferations of cells even after any precipitating event is removed).
Further studies are needed to determine which, if any, of these pathways are overactive in and can be successfully targeted with specific drug therapies to treat NF and its variants.Two cases of NF have tumor cells in which the USP6 gene has fuses with the  PPP6R3 (i.e. protein phosphatase 6 regulatory subunit 3) gene. In both of these cases, the tumors clearly showed malignant behavior. Diagnosis
NF may resemble and therefore be misdiagnosed as dermatofibrosarcoma protuberans, fibrosarcoma, malignant fibrous histiocytoma, spindle-cell melanoma (a rare form of melanoma,) leiomyosarcoma, and inflammatory myofibroblastic tumor. The diagnosis of NF and its variants depends on a combination of findings no single one of which is definitive. These findings are: the tumors: presentation (particularly its location in the cranium, within blood vessels, or outside of these areas); histopathology (particularly analyses of tumor cell mitoses which if atypical strongly suggest the tumor is not NF); presence of myofibroblasts that typically express muscle-specific actin, SMA, and vimentin and may express CD68 but generally do not express S100, desmin, trypsin, factor VIII, F4/80, or CD34 (lack of Cd34-expressing cells indicates that the tumor is not a sarcoma); and presence of typical neoplastic cells expressing an USP6-containing fusion gene. (USP6-containing fusion genes also occur in the tumor cells of aneurysmal bone cysts, fibroma of tendon sheaths, giant cell reparative granuloma, and myositis ossificans/fibro-osseous pseudotumor of digits.)