Proliferative fasciitis and proliferative myositis

PF/PM lesions occur primarily in middle-aged and older adults[6] (peak age of onset 50 to 55 years/old) with no appreciable differences in their incidences between males and females.[1] Only very rare cases have been reported in children and adolescents.[2] In up to 20% to 30% of cases, these lesions are apparently preceded by some sort of mechanical injury.[1] Individuals commonly present within 1–3 weeks[1] or, rarely, longer times (e.g. 3 months)[8] of noticing a rapidly growing, small (<5 cm. in size) mass or swelling in the subcutaneous tissues or muscles[1] of an extremity or, less commonly, the trunk wall, head, or neck areas.[6] Uncommonly, the lesions are ulcerated.[3] In rare cases, the lesions are extensive and highly disruptive, e.g. PF/PM has presented with lockjaw, i.e. a reduced ability to open the jaw due to a PF/PM lesion infiltrating and disrupting the function of the muscles of mastication (i.e. jaw-opening muscles).[1] PF/PM lesions may be associated with tenderness, pain,[6] and/or very rarely fever of unknown cause.[1] The lesions may be regressing at the time of diagnose or, in rare instances, spontaneously regress beginning immediately after being biopsied.[10] Very rarely, these lesions have evolved rapidly, compromised local blood flow,[3] and/or recurred at the site where they were removed by conservative local surgical excision. However, PF/MF lesions do not metastasize to distant tissues.[2]

PF/PM lesions are poorly circumscribed masses[6] which on histopathological microscopic analyses consist of bland fibroblastic and myofibroblastic spindle-shaped cells[3] mixed with variable proportions of giant epithelioid ganglion cell-like cells.[6] These cells are in a myxoid (i.e. a clear, mucus-like substance which when prepared using a standard H&E staining method appears more blue or purple than the red color of normal tissues) to fibrous (i.e. high collagen fiber content) background[6] which may contain areas of necrosis (i.e. sites of dead cells).[2] Overall, the cells in these lesions are amphophilic or basophilic, may have vacuole-laden cytoplasm, are slowly multiplying based on their proliferative index, and lack atypical mitosis figures that might be suggestive of a malignancy. The presence of at least some giant epithelioid ganglion-like cells[10][6] within this histopathological background are necessary and definitive evidence that a swelling or tumor is a PF/PM. Compared to adult cases, pediatric cases of PF/PM lesions are often better delineated from normal tissue, are more cellar, have a greater frequency of necrosis sites,[2] contain diffuse sheets of epitheliod ganglion-like cell cells but lack a spindle-shaped cell component, and are lobulated.[6] The spindle-shaped cells, but not epithelioid ganglion-like cell cells, in proliferative myositis lesions express smooth muscle actin proteins.[8]

A recent study conducted in Japan found that the tumor tissues of 5 of 5 analyzed adult patients with PF/PM lesions expressed a high level of an abnormal c-Fos protein. This protein was a fusion protein formed by a chromosomal translocation between two disparate genes: the c-Fos gene[11] (also termed FOS), a potential cancer-causing oncogene, normally located at chromosome band 24.3 on the long arm (i.e. q arm) of chromosome 14 and the VIM gene,[12] normally located at band 13 on the short arm (i.e. p arm) of chromosome 10. The FOS:VIM fusion gene along with its c-Fos-VIM protein (which possesses uncontrolled c-Fos activity) are associated with the development and/or progression of some other fibroblastic and myofibroblastic tumors as well as malignant sarcomas. The FOS:VIM fusion gene and c-Fos-VIM fusion protein were found primarily in the epithelioid ganglion-like cell cells but mostly absent in the spindle-shaped cells of these lesion. The tumor of the single young person (1 year/old male) analyzed showed no evidence of this fusion gene or fusion protein. While these findings must be confirmed in a larger number of individuals, they do suggest that: 1) the FOS:VIM fusion gene and c-Fos-VIM fusion protein may contribute to the development of PF/PM in adults; 2) this fusion gene and its protein product may not be involved in childhood PF/PM tumors which also differ from adult PF/PM tumors in their histopathology (see the above Pathology section); and 3) the epithelioid ganglion-like cells but not spindle-shaped cells or any other cell types in adult PF/PM tumors may be neoplastic.[6] It is further suggested that spontaneously reversing and self-limiting PF/PM tumors in adults are "transient neoplasms" similar to other theorized transient neoplasms[6] such as nodular fasciitis[13][14] myositis ossificans,[15] aneurysmal bone cyst, and giant cell lesion of small bones.[16] Two other genetic abnormalities have been reported in PF/PM tumors: trisomy 2 (i.e. the presence of an extra chromosome 2) in the tumor cells of two cases[17][18] and a translocation of genetic material between band 23 on the long arm of chromosome 6 and band 32 on the long arm of chromosome 14 in the tumor cells of one case.[19] Neither of these abnormalities have been validated, further characterized, or confirmed in other studies.[6] Finally, 2 of 20 proliferative fasciitis tumors tested positive for the abnormal expression of FOSB protein, a product of the FOSB oncogene.[20][21][22]

The diagnosis of PF/PM lesions depends or their presentation and, most importantly, their histopathology showing the presence of epithelioid ganglion-like cell cells. The presence of at least some of these signature cells in a lesion with an appropriate presentation in either a soft tissue or muscle tissue is considered definitive evidence that the lesion is a PF/PM.[10][6] Analyses of tumor tissues for c-FOS may turn out be another useful marker for PF/PM.[6]

The primary treatment for PF/PM lesions is watchful waiting, i.e. following the lesions for spontaneous regression or any possible complications that require surgical intervention. Symptomatic therapy such as analgesics, e.g. nonsteroidal anti-inflammatory drugs, may be required to treat pain or rare cases of fever.[1] Rare PF/PM lesions may require surgical excision when, for example, they interfere with blood flow[23] or produce a painful, poorly functional hand due to the tumor inducing a trigger finger,[24] Surgical resections in these cases are generally curative.[25]