Ultrasound features and differential diagnosis for superficial nodular fasciitis

Nodular fasciitis (NF) has nonspecific clinical manifestations and is often misdiagnosed as sarcoma. The investigations of imaging methods for NF were limited.

misdiagnosed as sarcoma due to its rapid growth, rich cellularity, and increased mitotic activity. 2Hence, it is important to make correct diagnosis to avoid unnecessary resection.
The literatures about the imaging features of NF are limited and not thoroughly evaluated.The magnetic resonance imaging (MRI) and musculoskeletal US are the most common imaging modalities for diagnosing NF.The MRI findings of NF are nonspecific, with only a few certain features that might suggest NF. 3 US is more convenient and cost-effectiveness compared with MRI.However, only a few former studies with limited cases described ultrasonic features of NF. 4,5 According to the previous studies, NF was manifested as an oval or lobulated hypoechoic mass in echogenicity, which is difficult to differentiate other soft tissue tumors. 5Hence, it is necessary to further investigate the ultrasonic features of NF and explore the potential value of US in diagnosing NF.
NF can be classified as the superficial, intermuscular, intramuscular types according to its location.The NF was most frequently found in the superficial site.Thus, in this study, We undertook a retrospectively research on a series of superficial NF cases to conclude the sonography types.The other soft tissue tumors that confused with NF were also included for making comparisons with NF.The study aims to improve the diagnostic capacity of US in identifying NF.

| Patients
The study was approved by the institutional ethics committee of Peking University Shen Zhen Hospital.Written consent forms were obtained from the patients.First, we defined the superficial-type NF as the lesion located in the subcutaneous fat layer or the deep fascia between the subcutaneous fat layer and the muscle, including subcutaneous NF and the fascial NF.The patients from January 2013 to March 2021 with pathologically confirmed superficial NF were recruited retrospectively.All the patients had the tumor removal via surgery to receive the histological diagnosis, and before surgery, they underwent the musculoskeletal US examination.The patients with the interval between the US scanning and pathological examination of more than 1 month were excluded.

| Imaging examinations
The patients were scanned using the Philips IU22 and LOGIC E9 US scanners equipped with 5-15 MHz linear array transducer.
F I G U R E 1 Three types of the superficial NF on musculoskeletal ultrasound.Type 1: Hypoechoic area in the center of the mass, surrounded by the hyperechoic nodule or halo.Type 2: A hypoechoic mass with parallel strip-like hyperechoic structure inside, no surrounding with hyperechoic nodule or halo.Type 3: A hypoechoic mass neither has the parallel strip-like hyperechoic structure inside nor the hyperechoic nodule or halo surrounded.
For gray-scale US, the following imaging settings were adopted: the depth for visualizing the lesions was set at 2-3 cm, and the maximum gain was 85%-90%.The longitudinal and transverse sections showing the maximal diameter of the lesions were recorded.
For the color Doppler examination, the PRF was set at 3-8 cm/s.The color Doppler gain was set just below the color noise threshold to visualize the low-velocity flow.The vascular pattern of the NF was assessed according to the Adler grade classifications which were determined to be four grades, including absent, minimal, moderate, and marked.Grades 1 and 2 were subjectively defined as the minimal vascularity, and the Grades 3 and 4 were abundant.
The imaging examinations were conducted by a senior radiologist with 10 years of experience in musculoskeletal US.

| Images analysis
Two musculoskeletal radiologists with more than 5 years of experience retrospectively reviewed all of the images.The following sonographic features were analyzed: echogenicity (hypoechoic, isoechoic, or hyperechoic compared with the subcutaneous fat layer), the strip-like hyperechoic structure inside the mass, the hyperechoic halo or nodule in the rim of mass, and the blood flow signal in the mass.All of the interpretation was decided by consensus.
According to the previous literature review 6 and the clinical experience, the NF can be divided into three types.(1) Type 1, hypoechoic area in the center of the mass, surrounded by the hyperechoic nodule or halo.(2) Type 2, a hypoechoic mass with parallel strip-like hyperechoic structure inside, no surrounding with hyperechoic nodule or halo.
(3) Type 3, a hypoechoic mass neither has the parallel strip-like hyperechoic structure inside nor the hyperechoic nodule or halo surrounded (Figure 1).All the tests were two-sided, and p < 0.05 was considered a significant difference.

| Basic clinical and demographic features of the NF patients
A total of 74 patients with NF were initially identified.Three patients were excluded because of the interval between pathological and ultrasound examination was more than 1 month.And 10 patients with the lesions located in the muscle layer were excluded.A total of 61 patients were finally recruited for further analysis, including 28 males and 33 females aging 12-63 years old.
Regarding the comparison of other US features, we identified consecutive 6406 tumors in subcutaneous fat layer.A total of 2158 lymph nodes disease and 942 cystic lesions were excluded, and 3306 tumors were included.In order to reduce the imbalance of samples, 1/6 cases, a total of 551 lesions, including 538 benign and 13 malignant tumors, were randomly selected.Details about the other soft tissue masses in the subcutaneous fat layer were shown in Table 1.For the anatomical sites of the NF lesions, 65.6%  2).Type 1 and type 2 NF more likely had the minimal vascularity, and type 3 NF had abundant vascularity.

| Comparisons of clinical features among the three sonographic NF types
The information obtained from NF and other soft tissue tumors was shown in Tables 1 and 3.There was no statistically significant  difference in gender between the groups.The average age of NF patients was 34 years old, which was much lower than that of patients with other soft tissue tumors (p = 0.002).For the anatomical sites, NF were significantly more likely located in the upper extremities than the other soft tissue tumors (p < 0.001).Among the three types, type 1 and type 2 of sonographic features were significantly more commonly observed in NF than in other soft tissue tumors (p < 0.001).There were no significant differences in type 3 distributions between the two groups (p = 0.109).The type 1 and type 2 sonographic feature distributions in the other soft tissue tumors were shown in Table 3 (Figure 2).
Among the other soft tissue tumors, two malignant cases manifested as type 1 and no cases manifested as type 2.

| DISCUSSION
In this study, we investigated the distinctive features visualized by musculoskeletal US that can contribute to the NF diagnosis.The different types of sonography imaging were based on the pathology of NF.The proportion of type 1 in our study was 57.4%, which was slightly lower than the 66.7% reported in the literature. 2 The pathological feature of type 1 has been described in the literature previously. 6The hypoechoic area constitutes main body of the lesion, and is composed of the collagen bundles mixed with fibrohistocytic spindle cell.And the peripheral hyperechoic halo or nodule is regarded as the fibrohistocytic spindle cell infiltrating into the adjacent adipocytes. 6In our research, 16 cases of other soft tissue masses in the subcutaneous fat layer also manifested as type 1 (Table 4).For the metastasis tumor, the hyperechoic and irregular edge is associated with displacement of surrounding tissue, reactive hyperplasia of inflammatory cells and fibrous tissue, tumor infiltration, neovascularization, or lymphangioinvasion. 7For the endometrial implantation lesion originating from deep fascia, the cyclic bleeding leads to the marked fibroblastic proliferation with fibrosis, adherence of endometrial cells, and distortion of adjacent fat layer. 8en lymphedema arises in the patients with panniculitis and cellulitis, fluids progressively dilate the lymphatic collectors leading to disappearance of the hyperechoic fibrous scaffold of the subcutaneous tissue and increase in its thickness with multiple hypoechoic tubular structures. 9Thus, we can see the thin hypoechoic strip between the hyperechoic fat lobules of the subcutaneous layer.The medical history and symptoms can distinguish these soft tissue tumors from NF. 24.6% of cases in our study were manifested as type 2, which have not been reported in the previous literature.It is speculated that the hyperechoic strip-like structure was related to the uneven tissues in NF and the increased acoustic impedance between the tissues.In addition, if the lesion originating from the deep fascia, a multilayers structure composed of collagen fibers oriented parallel to each other in a wave-like arrangement, the histological feature may also explain the hyperechoic strip sign. 10The venous malformation in subcutaneous soft tissue was also presented as type 2. High vessel density and high peak arterial Doppler shift can be used to distinguish hemangiomas from other soft-tissue masses. 11pe 3 composed 18% of our study, for which the pathological feature was described as the smooth tumor border surrounded by the fibrotic collagenous stroma without adjacent adipose infiltration. 6e typical manifestations of type 3, even or uneven hypoechoic mass, can be detected in various kinds of subcutaneous soft tumors including giant cell tumor and angioleiomyoma. 12,13e relationship between NF types and vascularity has not been investigated.In our study, the type 1 and type 2 NF were lacked of vascularity, while type 3 NF was abundant.This characteristic will contribute to the diagnosis of NF.
Accurate diagnosis of NF is important in deciding treatment strategies.The type 1 and type 2 sonography features were more frequently observed in NF than the other soft tissue tumors, which might help us in identifying NF.Additionally, the biological features of NF are similar to sarcoma, which are rare but lethal.The musculoskeletal US is recommended as the first-line assessment to recognize and differentiate sarcoma, thus reducing the overdiagnosis. 14The US plays a key role in the diagnosis of these soft tissue tumors and can guide the percutaneous biopsy of the lesions.
This study has a few limitations.First, the one-to-one correspondence between US images and the pathological specimens was not verified.Second, the ultrasound imaging was acquired via different equipments and settings, potentially introducing bias to the imaging judgment.Third, the number of NF cases included was relatively small.
It still needs to be further explored by multicenter prospective studies with larger samples.

| CONCLUSION
US is a suitable imaging method for diagnosing NF, enabling the detailed assessment of NF.The sonographic features, especially type SPSS 25.0 (IBM, New York, NY) was used for statistical analysis.Qualitative variables are presented as frequencies (%).Quantitative variables are presented as means ± standard deviations.Chi-square test or Fisher exact test were conducted to detect the potential difference in the distributions of three types in the patients with NF and the other soft tissue tumors in the subcutaneous fat layer.

1 2 3. 2 |
lesions were located in the upper extremities (n = 40), 16.4% were in the lower extremities (n = 10), 6.5% were in the head-and-neck region (n = 4), and 11.5% were in the trunk (n = 7).The average diameters of the lesions were 11.44 ± 5.35 mm, ranging from 4 to 38 mm.T A B L E 2The vascularity pattern of the three types of NF.The pathology of the other soft tissue tumors in the subcutaneous fat layer.The sonographic features of NF All the NF cases were solitary and hypoechoic.The parallel hyperechoic strip-like structure could be seen in 20 (32.8%) cases, and 41 (67.2%) cases were absent.The surrounding hyperechoic nodule or halo could be detected in 35 (57.4%) cases, and 26 (42.6%) cases were absent.The vascularity of 15 (24.5%) cases was abundant, while 46(75.5%)cases were minimal.The distribution of the vascularity pattern among the three types of NF has the significant difference (Table

F I G U R E 2
The tumors in the subcutaneous fat layer that manifested as type 1 and type 2. (A) The metastasis of melanoma in the thigh manifested as type 1. (B) The endometrial implantation lesion in the abdomen manifested as type 1. (C) The epidermoid cyst in the lower back manifested as type 1. (D) The panniculitis in the lower leg manifested as type 1. (E) The cellulitis in the thigh manifested as type 1. (F) The vascular malformations in the acrotarsium manifested as type 2.

1 and 2 ,
have potential to improve the diagnostic accuracy and reduce the unnecessary surgery for THE NF lesions.FUNDING INFORMATION This research was funded by (1) the General Program for Clinical Research at Peking University Shenzhen Hospital (grant number: LCYJ2021003), (2) the Science Technology and Innovation Commission of Shenzhen Municipality in China (grant number: JCYJ20210324110015040), (3) the Research Foundation of Peking T A B L E 4 The type 1 and type 2 sonographic feature distributions in the other soft tissue tumors.
Comparison between NF and the other soft tissue tumors in the subcutaneous fat layer.