Until recently, nodular fasciitis has been considered to be a reactive process of uncertain cause (1). The recent identification of genomic rearrangements indicates that nodular fasciitis is a self-limiting clonal neoplastic process (2). Nodular fasciitis is most commonly found in adults of 20 to 50 years of age and is rarely seen on the hands (3). Differentiating between nodular fasciitis and sarcomas is often clinically and pathologically challenging as nodular fasciitis exhibits rapid growth, high cellularity, and mitotic activity (3). In addition, a recent report suggested that nodular fasciitis displays malignant behavior such as multiple recurrent lesions and metastasis (4).

We report a case in which a locally aggressive nodular fasciitis lesion grew rapidly on the patient's palm, and discuss the surgical management of the lesion. Our case suggests that fusion gene analysis was useful for differentiating nodular fasciitis from sarcomas. In addition, marginal excision was sufficient even though the tumor was extremely aggressive and grew fast, since our patient did not develop local recurrence or metastasis in two years.

A 53-year-old female presented with a four-month history of a painful mass on her left palm. Her medical history included hyperthyroidism and uterine myomas, but she did not recall any trauma involving her left hand. On physical examination, a 2-cm mass was found around the hypothenar eminence. It was elastic, slightly mobile, and tender. The associated pain and numbness radiated towards the patient's ring and little fingers. On magnetic resonance imaging, a lesion measuring 20x15x30 mm was located between the palmar aponeurosis and flexor tendons (Fig. 1). It was well delineated and exhibited low intensity on T1-weighted imaging, whereas it was isointense on T2-weighted imaging and displayed inhomogeneous contrast enhancement. An open biopsy showed a lesion composed of spindle-shaped cells, which was consistent with nodular fasciitis. After the biopsy, the patient's pain and numbness were unchanged, and a marginal excision was planned.

Two weeks after the initial biopsy, the wound opened, and the tumor protruding from the palm had reached the size of a golf ball (Fig. 2). The numbness affecting the patient's left ring and little fingers disappeared after the wound dehiscence, possibly because the pressure on the ulnar nerve had been reduced. Another incisional biopsy was carried out to exclude malignancies, as the tumor had grown extremely fast, and we suspected that it was a sarcoma. The lesion outside the skin, which measured 47x35x40 mm, was excised for histological examination. The cut surface of the lesion was gelatinous and hemorrhagic. Histologically, it consisted of spindle-shaped cells proliferating in a myxoid stroma (Fig. 3). The lesion demonstrated low cellularity. There were some mitotic figures without atypical mitoses, and slight pleomorphism was seen among the proliferating spindle-shaped cells. Some of the cells exhibited slightly hyperchromatic nuclei, but no bizarre nuclei were seen. These are typical histological findings of nodular fasciitis. On immunohistochemistry, the tumor was found to be positive for smooth muscle actin, vimentin, and p16, but negative for epithelial membrane antigen, bcl-2, CD34, CD56, cytokeratin AE1/AE3, desmin, mic2 (CD99), anaplastic lymphoma kinase, S-100, mucin 4, and signal transducer and activator of transcription 6. RNA was extracted from the frozen specimen and subjected to reverse transcription polymerase chain reaction (RT-PCR) using the primers myosin-9 (MYH9) 75F: 5'-AGGGCACGGAAGGCTAAGC-3' and ubiquitin carboxyl-terminal hydrolase 6 (USP6) 1630R: 5'-TGTGGATGTGAACTGCGGTC-3'. This revealed the presence of the MYH9-USP6 fusion gene, which supported a diagnosis of nodular fasciitis (Fig. 4). Fluorescence in situ hybridization (FISH) also confirmed the chromosomal translocation (Fig. 5).

Since the histological examination did not suggest that the lesion was a sarcoma or other type of malignancy, the tumor was marginally excised. A spindle-shaped incision was employed, and the palmar aponeurosis was excised en bloc (Fig. 6). The palmaris brevis was partially resected together with the tumor, as it was very close to the lesion. The ulnar nerve, which was located under the tumor, was released and kept intact. The median nerve was not exposed, as it was sufficiently far away from the tumor. The superficial palmar artery and venous arches had adhered to the tumor; therefore, they were ligated and sacrificed. After the excision of the tumor, the skin was closed directly without flaps or skin grafts. The patient had not suffered any local recurrence or metastasis at 24 months post-operation.

We reported a rare case of aggressive nodular fasciitis of the hand. A strong point of this study is the confirmation of the MYH9-USP6 fusion gene by both RT-PCR and FISH. In addition, the tumor was biopsied twice to confirm the diagnosis. The patient was already followed up for two years without local recurrence of metastasis. A limitation of the study is that this is a case report and we do not have similar cases to compare the outcomes. Some nodular fasciitis may behave differently and require different treatment strategies. Although we believe that our case is sufficiently informative because the size and speed of tumor growth were aggressive, the tumor was locally controlled by surgical excision only.

Nodular fasciitis of the palm is rare and may exhibit very rapid growth, mimicking that of sarcomas. Such aggressive growth can cause nerve palsy, especially when the tumor is located in the hand, as it is rich in nerves. Kanaya et al reported a case in which intraneural nodular fasciitis caused median nerve palsy and eventually required the resection of the median nerve (5). Sevilla et al reported a case in which a large nodular fasciitis lesion on the palm grew to 9 cm in five months (6). According to the latter report, the patient stated that the lesion had grown faster in the few weeks before their initial visit. The location and size of the tumor were similar to those of our case; thus, nodular fasciitis of the palm may have the potential to grow rapidly and to be of considerable size.

The relationship between the malignant potential of nodular fasciitis and its oncogenic mechanism is currently being intensively investigated (4). In contrast, some nodular fasciitis lesions are self-limiting and spontaneously regress (7,8). Guo et al reported a case of ‘malignant nodular fasciitis’, which recurred several times and even metastasized to soft tissues (4). In the latter case, molecular analyses revealed the presence and amplification of the serine/threonine-protein phosphatase 6 catalytic subunit (PPP6)-USP6 fusion gene, which resulted in upregulated transcription of USP6 mRNA. In addition, Guo et al suggested that USP6 amplification may underlie the biology of many unclassifiable low-grade spindle-shaped cell/myofibroblastic sarcomas.

Nodular fasciitis often poses a diagnostic challenge to pathologists, as it does not express any specific immunohistochemical markers, and until recently, the diagnosis of such lesions was based on histological features alone. In 2011, rearrangement of the USP6 gene was reported as a recurrent and specific finding of nodular fasciitis (2). USP6 gene rearrangement was found in 92% of cases of nodular fasciitis, and the sensitivity and specificity of FISH for detecting USP6 were reported to be 86 and 100%, respectively (2,9). The detection of USP6 fusion genes may be useful for diagnosing nodular fasciitis lesions.

As for the treatment of nodular fasciitis lesions, surgical excision is usually curative. Some clinicians recommend that nodular fasciitis lesions should initially be observed because of the self-limiting nature of the disease (8). We recommend excising such lesions, especially when they are symptomatic, and marginal resection seems to be sufficient for achieving local control. Intralesional or piecemeal resection may be employed when the lesion is located adjacent to nerves, although it may increase the risk of tumor growth (5).

In conclusion, we reported a rare case of aggressive nodular fasciitis of the hand. The lesion increased rapidly in size, and obtainment of a histological diagnosis was challenging, as the lesion exhibited non-specific immunohistochemical findings. The detection of the MYH9-USP6 fusion gene supported a diagnosis of nodular fasciitis. In spite of its aggressive characteristics, the tumor was locally controlled via marginal excision, and no metastasis was detected postoperatively.