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Review Article - (2024) Volume 15, Issue 5

Intradermal Nodular Fasciitis: A Review of the Current Genetic Analysis
Kazumi Fujioka*
 
Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
 
*Correspondence: Kazumi Fujioka, Department of Radiology, Nihon University School of Medicine, Tokyo, Japan, Email:

Received: 27-Aug-2024, Manuscript No. JCM-24-26801; Editor assigned: 29-Aug-2024, Pre QC No. JCM-24-26801 (PQ); Reviewed: 12-Sep-2024, QC No. JCM-24-26801; Revised: 19-Sep-2024, Manuscript No. JCM-24-26801 (R); Published: 27-Sep-2024, DOI: 10.35248/2157-2518.24.15.456

Abstract

Erickson-Johnson suggested that USP6 transcriptional upregulation may be the driving force behind the high proliferative activity and growth and the consistent involution nature of Nodular Fasciitis (NF). The author previously reported the case series of NF and strongly suggested that proliferative findings of the margin of the nodule on US and pathological features are caused by the driving force of USP6 transcriptional upregulation from an established cytogenetic nature. Recently molecular analysis of USP6 gene rearrangements have been detected in the most of NF cases, while MYH9 gene has been identified as the most common USP6 partner. It is suggested that the identification of USP6 fusion partners for NF may contribute to understand the biological effect. As intradermal NF is a rare lesion, few cases with molecular genetics have been shown until now. This review outlines the current knowledge and trends of the rare intradermal nodular fasciitis focusing on the genetic analysis. The result showed USP6 rearrangement in all cases and two cases of MYH9, one case of EIF5A, and one case of TPM4 as a fusion partner with USP6 have been exhibited. The detection of USP6 gene rearrangement using FISH may be the very useful and important genetic analysis for accurate diagnosis in even intradermal NF. Further study is needed to verify the pathogenesis of development and biological effect of fusion partner for this entity.

Keywords

Intradermal nodular fasciitis; USP6-associated neoplasia; USP6 rearrangement; MYH9 gene; Genetic analysis

Introduction

Erickson-Johnson et al., suggested that USP6 transcriptional upregulation may be the driving force behind the high proliferative activity and growth and the consistent involutional nature of Nodular Fasciitis (NF) [1]. When the lesion showed the proliferative findings of the margin on both US and pathology, accompanied by clinically rapid growth, self-limited and/or regress course, NF could be strongly suggested as previously described [2]. Recently genetic analysis of USP6 gene rearrangements have been detected in the most of NF cases. Though several fusion partners for ordinary NF have been identified, the most of NF cases commonly showed a MYH9-USP6 gene fusion [3]. Because intradermal NF is a rare lesion, there are few reports of this entity with molecular analyses until now. In this review, the author outlined the current knowledge of the rare intradermal nodular fasciitis focusing on the recent molecular genetics.

Nodular fasciitis as USP6-related neoplasia through multiple pathways

Nodular fasciitis is a benign soft tissue tumor of fibroblastic/ myofibroblastic differentiation that was first described in 1955 by Konwaler et al., and the first case of rare intradermal nodular fasciitis has been documented in 1990 [4,5]. The author previously has reported an ordinary type of NF and a rare intradermal NF [6,7]. Though this entity has rarely occurred, intradermal nodular fasciitis as a rare lesion analyzed in a series of 24 cases, seven cases of cutaneous NF with molecular analysis, and a few reports including dermatologic field have been studied [8-13]. Regarding clinical manifestations, NF presents most typically in the upper extremities, the trunk, and the head and neck between the ages of 20 and 40 years, often accompanying with tenderness. The subcutaneous, fascial, intramuscular, and rarely intradermal type have been reported with a peculiar clinical manifestation characterized by rapid, self-limited growth and spontaneous regression after a few weeks. With regards to pathological appearances, NF is typically characterized by uniform spindled cells arranged in irregularity intersecting short fascicles, and occasional storiform patterns. The cells contained plump, spindled to stellate nuclei with fine to open chromatin and small nucleoli accompanied with the background stroma ranged from myxoid to collagenous. It is well known that the characteristic tissue culture-like, feathery myxoid appearance is observed at least focally [14]. Immunohistochemical findings show that spindle cells in NF contain Muscle-Specific Actin (SMA), vimentin, and smooth muscle-specific actin [15], while NF is negative for several markers such as desmin, keratin, or S-100 protein in contrast with sarcoma [16]. Due to the aggressive clinical manifestation, malignant ultrasonograpic features, and its high cellularity and high mitotic activity in histopathology, NF can be misdiagnosed as a malignant soft tissue tumor such as fibrosarcoma and low-grade myxo- fibrosarcoma, often leading to unnecessary aggressive treatment [17].

Literature Review

USP6 fusion partners in nodular fasciitis

A clear association between NF and a recurrent genetic abnormality has been established by using FISH analysis [1,14,18,19]. USP6 oncogenes was also detected in Aneurysmal Bone Cyst (ABC), suggesting that these histological manifestations in ABC and NF may have a common pathogenic denominator mediated by USP6 transcription upregulation [1]. Shin et al., reported that FISH analysis for USP6 had a sensitivity of 86% and specificity of 100% for a diagnosis of NF [14], whereas another study reported that the sensitivity and specificity of USP6 in FISH for NF was 74.4% and 100%, respectively [18]. These studies indicate a clear relationship between NF and a recurrent genetic abnormalities in FISH analysis. Previous study described that the level of USP6 was associated with the cellularity and age of NF [20]. The author previously described a review of the literature on NF as USP6- associated neoplasia through multiple pathways [21]. In addition to the presentations of clinical, ulrtrasonographic, and pathological appearances of NF, the evaluation of percentage of USP6 break-apart FISH signals reflecting lifetime and mitotic counts in NF may be a potential procedure for accurate diagnosis in particularly young NF (preoperative duration <1 month) [2,21]. Wang et al., described that MYH9-USP6 gene fusion has been observed in most of NF cases [22]. Molecular analysis of USP6 gene rearrangements has been detected in the most of NF cases, while MYH9 gene has been identified as the most common USP6 partner. Furthermore, the detection of the USP6 gene rearrangement has also been recognized as a diagnostic procedure in cases with morphological uncertainty [3].

The detection of other fusion partners with USP6 includes TPM4, EIF5A, PPP6R3, CTNNB, SPARC, THBS2, COL6A2, TNC, SEC31A, COL1A1, COL1A2, COL3A1, CALU, NACA, SLFN11, LDHA, SERP1NH1, PDLIM7, MYL12A, PAFAH1B1 and MIR22HG as previously reported [3,23,24]. The recent study provided the new and rare fusion patterns with USP6 in NF including one novel KIF1A and five rare types (TMP4, SPARC, EIF5A, MIR22HG, COL1A2) of fusion partners with USP6. A novel partner, KIF1A gene which is a member of 1A kinesin family has been identified in patient with superficial lesion of the arm [3].

Five rare partners including TMP4, SPARC, EIF5A, MIR22HG, and COL1A2 of fusion partners with USP6 have been reported [3]. TPM4 gene which is an actin binding protein has been previously reported in a patient with cheek lesion and has been recently demonstrated in a patient with deep tibial lesion [3,13]. MIR22HG which is a gene connected closely to miRNA class has been previously reported in a patient with subscapular lesion and has been also identified in a man patient with superficial lesion of corner of the mouth [3,19]. SPARC gene that encodes cysteine-rich acidic matrix- associated protein has been shown in a patient with a mass of tendons and is recently demonstrated in a female patient with superficial lesion of temporal area [3,19]. COL1A2 gene which encoded one chain of collagen type 1 has been reported in a patient with cervical lesion and is recently shown in a female patient with superficial lesion of the arm [3,22]. EIF5A gene that encodes transcription initiation factor 5A-1 involved in maintenance. In addition to the previous dermatologic report, the recent study described that EIF5A is identified in a female patient with subcutaneous region of forearm [3,11]. Regarding NF with malignant behavior, PPP6R3- USP6 gene fusion has been shown in two cases of NF accompanied with malignant manifestation [25,26]. Guo et al., reported a case of NF with traditional histologic findings accompanying with multiple recurrences and metastatic manifestation showing the novel PPPR6-USP6 gene fusion by molecular analysis [25]. Recently, the detection of several fusion partners with USP6 in NF has been popular, suggesting that the identification of USP6 fusion partner of NF may contribute to understand the biological effects leading to accurate diagnosis and the prevention for the unnecessary aggressive therapy [3].

Intradermal nodular fasciitis as a rare lesion

Kumar et al., reported USP6 rearrangement in all cases by FISH; in two of three cases, the characteristic MYH9-USP6 fusion was shown by RT-PCR suggesting that the presence of the USP6 rearrangement and MYH9-USP6 gene fusion in cutaneous NF cases mirrors what has been reported in typical subcutaneous NF [9]. This review outlined the rare intradermal NF including clinical and pathologic presentations and molecular genetics (Tables 1 and 2). Pathological features revealed the involvement of the dermis location in all eleven cases (Table 1).

Study Case Age/Sex Location Pathology
Kumar et al. [9] 1 15/m Brow Dermis and superficial subcutis
2 34/m Chin Dermis and superficial subcutis
3 19/m Back Dermis and superficial subcutis
4 60/m Back Dermis and superficial subcutis
5 46/m Palm Dermis and superficial subcutis
6 34/w Nasolabial fold Dermis and superficial subcutis
7 65/m Tragus Dermis and cartilage involvement
Maloney et al. [10] 39/f Glabella Dermis and subcutis
Lenz et al. [11] 41/f Forearm Predominantly dermal location
Sennett et al. [12] 9/f Chin Deep dermis and subcutis
Rodriguez et al. [13] 34/m Cheek Deep dermis and subcutis

Table 1: Intradermal nodular fasciitis (clinical and pathologic manifestations).

Study Case Age/sex FISH RT-PCR USP6 fusion partner
Kumar et al. [9] 1 15/m USP6 rearrangement NA NA
2 34/m USP6 rearrangement NA NA
3 19/m USP6 rearrangement NA NA
4 60/m USP6 rearrangement NA NA
5 46/m USP6 rearrangement Positive MYH9
6 34/f USP6 rearrangement Positive MYH9
7 65/m USP6 rearrangement Negative NA
Maloney et al. [10] 39/f USP6 rearrangement NA NA
Lenz et al. [11] 41/f USP6 rearrangement Negative EIF5A
Sennett et al. [12] 9/f USP6 rearrangement NA NA
Podriguez et al. [13] 34/m USP6 rearrangement NA TPM4

Table 2: Intradermal nodular fasciitis (molecular analysis).

Intradermal NF may tend to occur in the region with thin subcutaneous fat layer such as face, head, and neck as previously described [27]. Seven of eleven cases were shown in the face and head regions including brow, chin, nasolabial fold, tragus, glabella, and cheek suggesting the tendency of the occurrence of intradermal NF in the location of the thin subcutaneous fat layer (Table 1). All cases including dermatologic and pediatric cases revealed the USP6 rearrangement by FISH (Table 2). Lenz et al., reported a novel EIF5A-USP6 gene fusion of NF associated with predominantly dermal location and epidermal ulceration [11]. USP6 gene rearrangement by FISH was shown and a novel EIF5A-USP6 gene fusion was identified using the Archer fusionPlex Sarcoma kit suggesting that the detection of USP6 gene rearrangement is extremely useful molecular analysis for diagnosis of NF [11]. Recent study provided the cutaneous NF in the cheek region with rare TPM4-USP6 gene fusion by using a comprehensive sarcoma fusion panel analysis [13]. The detection of USP6 rearrangement was shown in all eleven cases and two cases of MYH9, one case of EIF5A, and one case of TPM4 as a fusion partner with USP6 were identified (Table 2).

Based on the evidence, the author will suggest that the identification of USP6 gene rearrangement using FISH is very useful and important tool of accurate diagnosis for even rare intradermal NF with the reduced risk of misdiagnosis such as sarcoma and overtreatment. Though several fusion partners have been identified for typical NF, it is well known that most of NF cases commonly exhibits a MYH9-USP6 gene fusion. While, as intradermal NF is a rare lesion, therefore few cases with genetic analyses have been investigated until now. The differential diagnosis of intradermal nodular fasciitis includes malignant cutaneous entities such as low-grade fibromyxoid sarcoma and low-grade myofibroblastic sarcoma [9]. Previous report suggested the detection of MYH9-USP6 rearrangement by FISH may assist the differential diagnosis of cutaneous spindle cell tumors [9]. Further investigation is significant to elucidate the pathogenesis and biological effect of fusion partner for intradermal NF.

Discussion

In this article, the author described a review of the literature on the rare intradermal NF including clinical and pathologic manifestations and molecular genetics (Tables 1 and 2). Seven of eleven cases were shown in the face and head region suggesting the tendency of the development of this entity in the location of the thin subcutaneous fat layer (Table 1). It is well known that USP6 gene rearrangement by FISH is a very useful procedure for the accurate diagnosis of typical NF [3]. As several fusion partners for ordinary NF have been identified, the most of NF cases commonly showed a MYH9-USP6 gene fusion. The recent study investigated the new and rare fusion partners with USP6 in NF including one novel KIF1A and five rare types (TMP4, SPARC, EIF5A, MIR22HG, COL1A2) of fusion partners with USP6 [3]. It is suggested that the identification of USP6 fusion partners for NF may contribute to understand the biological effect [3]. While few cases with molecular analyses have been shown until now, because intradermal NF is a rare lesion [27]. The result showed USP6 rearrangement in all cases and two cases of MYH9, one case of EIF5A, and one case of TPM4 as a fusion partner with USP6 have been exhibited (Table 2). Based on the evidence, the author will suggest that the detection of USP6 gene rearrangement using FISH may be the very useful and significant molecular genetics for accurate diagnosis in even intradermal NF to avoid the misdiagnosis such as fibro sarcoma and low-grade myxofibrosarcoma and unnecessary aggressive therapy. Further investigation is significant to elucidate the pathogenesis of development and biological effect of fusion partner for rare intradermal NF.

Conclusion

The result provided that intradermal nodular fasciitis tended to occur in the face and head regions of the thin subcutaneous fat layer. The detection of USP6 gene rearrangement using FISH may be the very useful and important molecular findings for even intradermal nodular fasciitis. lt has been suggested that the identification of USP6 fusion partners for ordinary NF may contribute to understand the biological effect. MYH9, EIFSA, and TPM4 genes as a fusion partner with USP6 gene have been identified in rare intradermal nodular fasciitis. Further study is needed to verify the pathogenesis and biobgical spectrum of fusion partner for even this entity.

Conflict of Interest

Author declares that there are no conflicts of interest.

References

Citation: Fujioka K (2024). Intradermal Nodular Fasciitis: A Review of the Current Genetic Analysis. J Carcinog Mutagen. 15:456.

Copyright: © 2024 Fujioka K. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.