The published literature describes NF as a benign myofibroblastic proliferation, which was initially reported in 1955 as a pseudosarcomatous fibromatosis or fasciitis[1]. The exact etiology of this proliferative lesion is not known, although local injury or inflammation have been postulated as triggers[10]. The NF lesion typically develops in the subcutaneous superficial fascia of the upper limbs (46%), especially over the volar aspect of the forearm, followed by the head and neck (20%), trunk (18%), and lower extremities (16%)[11].There are no gender differences in NF incidence, and all reported lesions measure less than 5 cm in diameter.
Periosteal fasciitis, a subtype of NF, is characterized by periosteal overgrowth and reactive new bone formation. There are only a few case reports (10 cases) of periosteal fasciitis in the literature, most of which were reported in the 1970s and 1980s, although one case was recently reported in 2017. Among those10 cases (four males; six females), four occurred in the jaw (one in the maxilla, three in the mandible) and six in the hand.The largest reported tumor diameter was approximately 5 cm. Most of the cases were diagnosed by histomorphological features, and FISH was undertaken in only one case in the recent literature and showedUSP6 gene-related heterotopia. All patients were followed up, and there are no reports of recurrence (Table 1). In our case, NF was initially diagnosed by histomorphology and immunohistochemistry; however, because of the unusually large tumor and its periosteal origin, we undertook aUSP6 FISH examination. The results showed USP6-related ectopia, which further confirmed a diagnosis of NF. The patient has shown no recurrence on follow-up for 10 months. This report presents a rare case of clinical NF of the humeral periosteum with a tumor diameter of 7.5 cm.
Table 1
Published studies reporting periosteal fasciitis
References | Published time | Number of cases | Sex | Age (years) | Symptom presence and duration | Location | Treatment | Size (cm) | USP6 gene | Follow-up (month) | Recurrence | Injury |
Laaveri M [16] | 2017 | 1 | Female | 7 | No | Mandible | Local resection | 3 | Yes | 36 | No | No |
Rankin G [17] | 1991 | 1 | Female | 39 | No | Hand | Local resection | 5 | NA | 10 | No | No |
Mostofi RS [18] | 1987 | 1 | Male | 46 | No | Mandible | Local resection | 3 | NA | 30 | No | No |
Sato M [19] | 1981 | 1 | Male | 31 | Pain for 2 mos. | Maxillary | Local resection | 4 | NA | 8 | No | No |
McCarthy EF [20] | 1976 | 1 | Male | 40 | No | Ring finger. | Amputation | NA | NA | 12 | No | No |
Johnson MK [21] | 1975 | 1 | Male | 38 | Pain and swelling for 3 mos. | Metacarpal & ring finger | Local resection | NA | NA | 12 | No | No |
Goncalves D [22] | 1974 | 1 | Female | 23 | Pain and swelling for 2 wks. | Index finger | Amputation | NA | NA | 60 | No | No |
Lumerman H [23] | 1972 | 1 | Female | 31 | Pain for 3 days | Mandible | Local resection | 2 | NA | 30 | No | No |
Carpenter EB, Lublin B [24] | 1967 | 1 | Female | 32 | Pain and swelling for 7 mos. | Proximal and middle phalanges, ring finger | Amputation | NA | NA | 12 | No | No |
Mallory TB[25] | 1933 | 1 | Female | 28 | Pain, swelling for 4 wks. | 4th & 5th metacarpals | Incomplete local resection | NA | NA | 12 | No | No |
Note: mos., months; wks., weeks. |
Due to its fast and infiltrative growth pattern, NFremains one of the most commonly misdiagnosed benign spindle cell neoplasms[5]. A common differential diagnosis of NF is low-grade malignant myofibroblastic tumors because, despite their large size, the tumor cells are characterized by mild atypia;positive staining foractin, desmin,calponin,and CD34 (focal),and negative staining for S100 and nuclear β-catenin[12–14]. However, FISH shows no USP6 gene-related ectopia, and myofibroblastic tumors have a high recurrence after surgical resection.
Sometimes, it may be difficult to distinguish low-grade myxofibrosarcoma from NF, especially in cases with small tumor volume and without specific immunohistochemical markers. Nonetheless, curvilinear thin-walled blood vessels andpseudolipoblasts suggest the possibility of a myxofibrosarcoma, and FISH examination shows no USP6 gene-related ectopia.
Low-grade malignant fibromyxoid sarcoma is another differential diagnosis of NF. The identification can be comprehensively evaluated by immunohistochemical staining and molecular detection. Immunohistochemistry shows EMA positivity from focally to 80%, and MUC4 positivity has high sensitivity and specificity for the detection of fibromyxoidsarcoma[15].Molecular genetics showFUS-CREB3L2 or FUS-CREB3L1 gene fusion (Table 2).
Table 2
Primary differential diagnosis
Tumor types | Epidemiology | Clinical features | Size | Histopathology | Immunophenotype | Genetics |
Nodular fasciitis | Young adults, no gender difference | Grows rapidly, painless, recurrence is rare | Median size, ≤ 2 cm (always < 5 cm) | Spindle-shaped fibroblasts, growth in S- or C- shaped, interstitium is loose and myxoid, visible exosmosis of erythrocytes | Positive: SMA, Calponin, CD10; negative: S100, CD34, nuclear β-catenin[26–27] | MYH9–USP6 gene fusion |
Low-grade fibromyxoid sarcoma | Typically affect young adults, no gender difference | Slow growth, no pain, easy recurrence | Median size, 5 cm (1–20 cm) | Original glue and myxoid region are mixed, spindle cell, small blood vessels, early formation of collagen rosettes | EMA positive from focally to 80%, MUC4 positive has high sensitivity and specificity[15] | FUS–CREB3L2 or FUS–CREB3L1 gene fusion |
Low-grade myofibroblastic sarcoma | Predominantly in adults, 40–50 year see more, slight predominance in males | Enlarging mass, Painless, easy recurrence | Median size, 4 cm (1.4–17 cm) | Diffusely infiltrative growth, spindle cells arranged in a storiform pattern or fascicles | Positive: actin, desmin, calponin, CD34(focal); negative: S100, nuclear β-catenin[12–14] | Only one showed a circular chromosome |
Low-grade myxofibrosarcoma | Elderly patients, over 60 years, slight predominance in males | Slowly enlarging, painless, easy recurrence | Larger volume (range variable) | Spindle cells, mild atypia, curvilinear thin-walled blood vessels, pseudolipoblasts | Positive: SMA, negative: desmin and histiocyte-specific markers[28] | No specific aberration |
Immunohistochemical staining has no specific significance in the identification of NF; however, it can be used as an auxiliary and differential diagnostic tool because spindle cells in NF often diffusely express SMA, and are negative for desmin[6]. Recent studies have shown that USP6 in situ hybridization has higher specificity and sensitivity in the diagnosis of NF[9], particularly in cases with uncharacteristic morphology.
Furthermore, NF can be accurately diagnosed by combining tumor morphological characteristics,immunohistochemical findings, and USP6 detection, thereby avoiding misdiagnosis and overtreatment of patients.
NF poses a diagnostic challenge as it is often mistaken for a sarcoma, or easily misdiagnosed as a sarcomatous lesion such as malignant fibrous histiocytoma or fibrosarcoma, because of its rapid growth, rich cellularity, and poorly circumscribed nature. NF should be considered in a rapidly growing nodule with a relatively clear border in the upper limb, despite an atypical site and large tumor volume, because arelatively conservative diagnosis, especially during the surgery, could reduce overtreatment. Postoperative histopathological examination of whole sectionscan be combined with immunohistochemical staining and, if necessary, the diagnosis can be confirmed by molecular detection.