Nodular fasciitis

Nodular fasciitis (NF) is a benign, soft tissue tumor composed of myofibroblasts that typically occurs in subcutaneous tissue, fascia, 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 and intravascular fasciitis. 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. 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 or malignant growth. They are located in the upper limbs (39–54% of cases), trunk (15–20% of cases), lower limbs (16–18% of cases), and head or neck area (20% of cases). Involvement of the head or neck area is more commonly observed in children. or nerves are rare, but do occur. Individual cases of NF have been reported to occur in the bladder, prostate, tongue, lower female genital tract, and parotid gland. In some cases, NF tumors have regressed after incisional biopsy. In a review of 50 cases, the intravascular fasciitis variant of NF occurred in individuals aged 6 months to 66 years (median age 27 years), with males and females being equally affected (52%:48%). Individuals with this variant commonly present with a blood vessel localized tumor in the head and neck area (34% of cases), lower extremities (32% of cases), upper extremities (20% of cases), or trunk (14% of cases). The tumors originate in the small blood vessels of the oral mucosa, eyes, lips, cheeks, tongues, and subcutaneous tissue of the extremities (78% of all cases). About 18% of cases involve major veins. The presenting symptoms of these tumors are strictly dependent on their locations and impacts on the involved vasculature. Most cases involving superficial sites present with a small (mean diameter of 1.5 cm), painless, slowly growing mass. However, tumors growing in deep tissues can go unnoticed until they became large enough (e. g. 15 cm) to obstruct blood flow. Cases involving the ascending aorta can present with the signs and symptoms of acute aortic dissection (e. g. severe pain, heart failure, cardiac arrest, fainting , stroke, ischemic peripheral neuropathy, and/or paraplegia), while cases involving large veins may present with acute swelling, pain, and tissue/organ dysfunctions in the areas drained by the involved veins. Immunohistochemical analyses indicate that the cells in NF usually express smooth muscle actin, muscle specific actin, and vimentin proteins but generally do not express CD34, S 100 protein, desmin, trypsin, factor VIII, F4/80, or HLA DR1 proteins. However, recent findings indicate that up to 92% of NF tumors involve the self limiting growth of a clone of neoplastic cells that contain a fusion gene. Fusion genes are abnormal genes consisting of parts from two different genes that form as a result of large scale gene mutations such as chromosomal translocations, interstitial deletions, or inversions. The fusion gene found in NF tumor cells consists of a part of the USP6 gene combined with any one of numerous other genes. Its most common partner gene in NF is the MYH9 (myosin 9) gene. with part of the MYH9 gene at band 13.2 on the short (or "p") arm of chromosome 22. Other genes that partner with the USP6 gene to form a fusion gene found in NF include: RRBP1 (ribosome binding protein 1), CALU (calumenin), CTNNB1 (catenin beta 1), MIR22HG, SPARC (secreted protein acidic and cysteine rich), THBS2 (thrombospondin 2), COL6A2 (collagen type VI alpha 2 chain), SEC31A, EIF5A (eukaryotic translation initiation factor 5A), COL1A1 (collagen type I alpha 1 chain), COL1A2 (collagen type I alpha 2 chain), COL3A1 (collagen type III alpha 1 chain), PAFAH1B1 (platelet activating factor acetylhydrolase 1b regulatory subunit 1), SERPINH1 (serpin family H member 1), While very few cases have been analyzed to date, USP6 containing fusion genes have been found in the tumor cells of 7 of 15 tested cases of cranial fasciitis and six of six tested cases of intravascular fasciitis. All of the USP6 containing fusion genes in NF and variants overproduce a chimeric protein containing a part of the USP6 gene's product, ubiquitin carboxyl terminal hydrolase 6a, that has uncontrolled deubiquitinating enzyme activity. This may result in the inappropriate stimulation of multiple cell signaling pathways, including the Wnt signaling pathway, one of the JAK STAT signaling pathways, the c Jun signaling pathway, Each of these pathways, when inappropriately activated, has been implicated in promoting the development of various tumors and cancers. gene. In both of these cases, the tumors clearly showed malignant behavior.

NF may resemble and therefore be misdiagnosed as dermatofibrosarcoma protuberans, fibrosarcoma, malignant fibrous histiocytoma, spindle cell melanoma, leiomyosarcoma, Some studies, however, have suggested reevaluating the diagnosis in recurrent NF tumors to ensure the diagnosis is correct. Surgical and corticosteroid interventions may need to be performed promptly in order to a cranial tumor from expanding into the skull's interior or an intravascular tumor from compromising blood flood flow.

Two cases of NF in which tumor cells expressed a USP6 PPP6R3 fusion gene had highly aggressive, locally invasive, repeatedly recurrent, and progressively enlarging tumors over 2 and ten years. One case developed multiple metastases that were partially controlled with radiation therapy. The other case was treated by wide surgical resection of the tumor; this case did not have metastatic disease and one year after the wide resection had no recurrences.