Intraarticular Nodular Fasciitis of the Elbow Confirmed by USP6-MYH9 Gene Fusion.

doi:10.21203/rs.3.rs-4165855/v1

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Case Report

Intraarticular Nodular Fasciitis of the Elbow Confirmed by USP6-MYH9 Gene Fusion.

https://doi.org/10.21203/rs.3.rs-4165855/v1

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Background: Nodular fasciitis is a benign, usually self-limiting myofibroblastic proliferation with a predilection for the upper extremities, trunk, and head and neck of young adults. Although it usually arises within subcutaneous tissues, it may also occur within skeletal muscle, dermis, vessels, and peripheral nerves. Since nodular fasciitis is not widely recognized to arise within joints, it may therefore cause diagnostic confusion in this uncommon setting. Histology can vary considerably and can, therefore, mimic other benign or low grade malignant neoplasms. Recent molecular analysis revealed that most cases of nodular fasciitis involve USP6-MYH9fusion.

Case presentation: We report an unusual case of an 11-year-old patient who presented with a 6-month history of right elbow swelling and pain. Radiological examinations suggested tenosynovial giant cell tumor. Histology revealed that the tumor was composed solely of proliferating bland spindle cells with osteoclast-like giant cells and scattered foam cells. There was only a focal area of immature granulation-like myxoid change, which suggested nodular fasciitis. Molecular analysis using next-generation sequencing revealed gene rearrangementinvolving USP6 and MYH9, supporting the diagnosis of nodular fasciitis within the elbow joint.

Conclusion: This is the first case of intraarticular nodular fasciitis within the elbow joint in which MYH9-USP6 gene fusion was identified by molecular analysis. Nodular fasciitis should be considered in the differential diagnosis of intraarticular lesions.

Nodular fasciitis

Intraarticular

Elbow

USP6-MYH9

Nodular fasciitis is a self-limiting benign mesenchymal neoplasm of fibroblastic/myofibroblastic origin.[1,2] It typically occurs in subcutaneous tissues of the upper extremities, trunk, or head and neck but can also occur in skeletal muscle or as an intravascular process. Diagnosis can be difficult due to its morphological variety. While recent reports have described nodular fasciitis arising within joints, this is an exceedingly rare occurrence.[3–15] Diagnosing nodular fasciitis in an uncommon location can be challenging for pathologists. It has been shown that the USP6-MYH9 fusion is present in up to 92% of nodular fasciitis patients.[16]

An 11-year-old boy presented with a 6-month history of swelling and pain in the right elbow. Radiological examinations revealed an intraarticular oval mass measuring 2 cm x 2 cm on the anterior aspect of the distal humerus (Fig. 1). Giant cell tumor of tendon sheath was suggested as a possible differential diagnosis, although the possibility of soft tissue sarcoma could not be excluded. The patient underwent excision of a smooth-surfaced white tumor attached to the joint capsule (Fig. 2).

Histological examinations revealed a highly cellular tumor composed of plump spindle-shaped cells arranged in fascicles or in a vague storiform fashion (Fig. 3A and 3B). Mitotic figures were observed, but atypical forms were not present. In a small area, there were numerous osteoclast-like giant cells (Fig. 3C). Although the cellularity was almost entirely high, small foci with myxoid or tissue were found (Fig. 3D). Immunohistochemistry showed only modest expression of SMA in the tumor cells, while β-catenin and CD34 were negative (data not shown). Because the small component with myxoid appearance was reminiscent of nodular fasciitis even though the tumor was located within the joint, we performed molecular analysis using TruSight RNA Pan-Cancer Panel (Illumina) followed by fusion gene detection with DRAGEN RNA app (Illumina) and Arriba. The analysis confirmed a gene arrangement involving USP6 on chromosome 17p13 and MYH9 on chromosome 22q12 (Fig. 4).

Nodular fasciitis usually manifests as a rapidly growing mass in the upper extremities, trunk, or head and neck.[1,2] Its occurrence within joints is not widely recognized, which may lead to misdiagnosis in these unusual anatomical locations. Histologically, the diagnosis of nodular fasciitis can be challenging due to the rich cellularity, high mitotic activity, and rapid growth of the lesion, which can mimic soft tissue sarcoma. In addition, the histological findings are highly variable depending on the age of the lesion. The lack of specific immunohistochemical markers for nodular fasciitis increases the complexity of the differential diagnosis. Nodular fasciitis has been reported in joints, most commonly in the knee joints, and has been diagnosed solely on the basis of morphology.[3–6,8,11,15,17] Only three cases of nodular fasciitis in the elbow joint have been reported to date.[17–19] This case is the first to confirm the diagnosis of nodular fasciitis within the elbow joint by demonstrating gene rearrangement of USP6-MYH9.

The similarity between cellular of fibroma of tendon sheath (CFTS) and nodular fasciitis has been a topic of discussion for more than 40 years.[20] These tumors exhibit identifiable morphologic features of classic fibroma of tendon sheath (FTS) but also contain regions of increased cellularity and nodular fasciitis-like growth patterns. Some argue that such cases should be classified as tenosynovial nodular fasciitis rather than a variant of FTS.[21] Molecular analysis has been conducted to shed light on this discussion. It has been demonstrated that over 90% of nodular fasciitis patients exhibit MYH9-USP6 fusion, which provides reliable sensitivity and specificity for diagnosis.[16] Recent studies by Carter et al. and Mantilla et al. have shown that CFTSs exhibit gene fusions involving USP6 with various partners, including MYH9, while classic FTSs exhibit few cytogenetic alterations.[22,23] Distinguishing between CFTS and nodular fasciitis can be challenging due to their significant morphological overlap and shared gene fusions. It is important to exclude subjective evaluations unless clearly indicated as such. The classification of CFTS as nodular fasciitis may be more appropriate since both lesions appear to exist on a spectrum from morphological and molecular perspectives, and none of the classic FTSs have USP6 rearrangements.

Oliveira et al demonstrated that aneurysmal bone cyst (ABC) and nodular fasciitis, which typically affect younger patients and share morphological similarities, are characterized by structurally similar USP6 fusion genes.[24] They proposed that both lesions belong to the same biologic spectrum of USP-induced tumors. This may explain why an aneurysmal bone cyst developed after the excision of intraarticular nodular fasciitis. USP6 fusion genes are also present in cranial fasciitis,[25] proliferative myositis, and myositis ossificans.[26] The concept of USP6-induced neoplasms based on molecular similarities among them appears to be reasonable for understanding the clinicopathological similarities among those tumors. Additionally, identifying USP6 fusion genes can help avoid overtreatment since the vast majority of neoplasms with USP6 rearrangements behave indolently or benignly.

We present a rare case of intraarticular nodular fasciitis in the elbow joint, which was diagnosed by identifying the MYH9-USP6 fusion. The morphological characteristics of nodular fasciitis can be similar to those of other benign or low-grade malignant lesions, particularly when they occur in unusual locations. Ancillary molecular studies can aid in the identification of USP6 gene rearrangements. Nodular fasciitis should be considered in the differential diagnosis of intraarticular lesions.

1. Ethics approval and consent to participate: Not applicable

2. Consent for publication: Written informed consent was obtained from the patient’s father for publication of this Case Report and any accompanying images.

3. Availability of data and material: Not applicable

4. Competing interests: None

5. Funding: Not applicable

6. Author’s contributions: SAd primarily diagnosed the tumor and is the guarantor of integrity of the entire study. YK was responsible for molecular study. SAb and KK treated the patient. SAd, HN, HT, and RD discussed the present case from histopathological view. All authors read and approved the final manuscript.

7. Author’s details: ¹Department of Pathology, City Hospital of Toyonaka, Osaka, Japan, ²Unit of Cancer Genome, Osaka International Cancer Center, Osaka, Japan, ³Department of Orthopedics, City Hospital of Toyonaka, and ⁴Department of Pathology, Shonan-Kamakura Hospital, Kamakura, Kanagawa, Japan

Acknowledgement: Not applicable

Allen PW. Nodular Fasciitis. Pathology (Phila). 1972;4:9–26.
Price EB Jr, Silliphant WM, Shuman R. Nodular Fasciitis: A Clinicopathologic Analysis of 65 Cases. Am J Clin Pathol. 1961;35:122–36.
Hornick JL, Fletcher CDM. Intraarticular Nodular Fasciitis-A Rare Lesion: Clinicopathologic Analysis of a Series. Am J Surg Pathol. 2006;30:237.
Chan MM, Ong K, Foo SL, Selvarajan S. Intra-articular Nodular Fasciitis: An Unexpected Diagnosis for a Joint Lesion: A Case Report. Malays Orthop J. 2014 ;8:63–5.
Gans I, Morrison MJ, Chikwava KR, Wells L. Intra-articular Nodular Fasciitis of the Knee in a Pediatric Patient. Orthopedics. 2014;37:e313–6.
Hagino T, Ochiai S, Sato E, Watanabe Y, Senga S, Kondo T, et al. Intraarticular nodular fasciitis causing limitation of knee extension: A case report. The Knee. 2010 ;17:424–7.
Harish S, Kuruvilla M, Alowami S, DeNardi F, Ghert M. Intra-articular nodular fasciitis of the shoulder: a case report and review of the literature. Skeletal Radiol. 2011;40:1383–6.
Ko PY, Huang MT, Song HL, Lin MC-J. Intra-articular nodular fasciitis of the knee in a 4-year-old girl: a case report and review of the literature. J Pediatr Orthop B. 2013;22:350.
Lädermann A, Kindynis P, Taylor S, Ceroni D, Hoffmeyer P, Kaelin A, et al. Articular nodular fasciitis in the glenohumeral joint. Skeletal Radiol. 2008];37:663–6.
Matsuzaki T, Akisue T, Kishimoto K, Kishimoto S, Imabori M, Hara H, et al. Intra-articular nodular fasciitis of the knee: a rare cause of recurrent hemarthrosis. Rheumatol Int. 2012;32:1691–4.
Soejima T, Murakami H, Tanaka N, Sato K, Nagata K, Sugita Y. Fasciitis-like proliferation in the knee joint. Arthrosc J Arthrosc Relat Surg. 2003;19:1–4.
Stražar K, Drobnic M, Zupanc O, Jovic V, Pižem J. Intraarticular nodular fasciitis of the hip. Arch Orthop Trauma Surg. 2013;133:537–40.
Tajima S, Zuki T, Koda K. Articular nodular fasciitis of the right shoulder joint: report of an unusual case with focus on immunohistochemical differential diagnosis. Int J Clin Exp Pathol. 2015;8:4242–7.
Van Royen C, Wackens G, Goossens A. Nodular fasciitis in a temporomandibular joint. Int J Oral Maxillofac Surg. 1993;22:168–70.
Yamamoto T, Nagira K, Noda M, Kurosaka M. Intra-articular nodular fasciitis. Arthrosc J Arthrosc Relat Surg. 2001;17:1–4.
Erickson-Johnson MR, Chou MM, Evers BR, Roth CW, Seys AR, Jin L, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011;91:1427–33.
Yamamoto M, Urakawa H, Nishida Y, Hirata H. Secondary aneurysmal bone cyst in the distal humerus after resection of intra-articular nodular fasciitis of the elbow. BMC Res Notes. 2015;8:311.
Nishioka N, Kamishima T, Masuko T, Kubota KC, Komatsu M, Iwasaki N, et al. Intra-articular nodular fasciitis in the elbow joint, with an emphasis on MR imaging findings. Eur J Radiol Extra. 2009;69:e33–6.
Nakamura O, Kaji Y, Yamagami Y, Yamamoto T. A case of intra-articular fasciitis in the elbow joint. Int J Surg Case Rep. 2019;59:156–60.
Chung EB, Enzinger FM. Fibroma of tendon sheath. Cancer. 1979;44:1945–54.
Pulitzer DR, Martin PC, Reed RJ. Fibroma of tendon sheath. A clinicopathologic study of 32 cases. Am J Surg Pathol. 1989;13:472–9.
Carter JM, Wang X, Dong J, Westendorf J, Chou MM, Oliveira AM. USP6 genetic rearrangements in cellular fibroma of tendon sheath. Mod Pathol. 2016;29:865–9. 83
Mantilla JG, Gross JM, Liu YJ, Hoch BL, Ricciotti RW. Characterization of novel USP6 gene rearrangements in a subset of so-called cellular fibroma of tendon sheath. Mod Pathol. 2021;34:13–9.
Oliveira AM, Chou MM. USP6-induced neoplasms: the biologic spectrum of aneurysmal bone cyst and nodular fasciitis. Hum Pathol. 2014;45:1–11.
Paulson VA, Stojanov IA, Wasman JK, Restrepo T, Cano S, Plunkitt J, et al. Recurrent and novel USP6 fusions in cranial fasciitis identified by targeted RNA sequencing. Mod Pathol Off J U S Can Acad Pathol Inc. 2020;33:775–80.
Sukov WR, Franco MF, Erickson-Johnson M, Chou MM, Unni KK, Wenger DE, et al. Frequency of USP6 rearrangements in myositis ossificans, brown tumor, and cherubism: molecular cytogenetic evidence that a subset of “myositis ossificans-like lesions” are the early phases in the formation of soft-tissue aneurysmal bone cyst. Skeletal Radiol. 2008;37:321–7.

No competing interests reported.

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Intraarticular Nodular Fasciitis of the Elbow Confirmed by USP6-MYH9 Gene Fusion.

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