Desmoplastic fibroma of the pediatric cranium with CTNNB1 mutation: case report and literature review.

PURPOSE: Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature. CASE PRESENTATION: A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22 months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg). CONCLUSION: Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF.

Recurrent FOSL1 rearrangements in desmoplastic fibroblastoma.

The FOS gene family has been implicated in tumourigenesis across several tumour types, particularly mesenchymal tumours. The rare fibrous tumour desmoplastic fibroblastoma is characterised by overexpression of FOSL1. However, previous studies using cytogenetic and molecular techniques did not identify an underlying somatic change involving the FOSL1 gene to explain this finding. Prompted by an unusual index case, we report the discovery of a novel FOSL1 rearrangement in desmoplastic fibroblastoma using whole-genome and targeted RNA sequencing. We investigated 15 desmoplastic fibroblastomas and 15 fibromas of tendon sheath using immunohistochemistry, in situ hybridisation and targeted RNA sequencing. Rearrangements in FOSL1 and FOS were identified in 10/15 and 2/15 desmoplastic fibroblastomas respectively, which mirrors the pattern of FOS rearrangements observed in benign bone and vascular tumours. Fibroma of tendon sheath, which shares histological features with desmoplastic fibroblastoma, harboured USP6 rearrangements in 9/15 cases and did not demonstrate rearrangements in any of the four FOS genes. The overall concordance between FOSL1 immunohistochemistry and RNA sequencing results was 90%. These findings illustrate that FOSL1 and FOS rearrangements are a recurrent event in desmoplastic fibroblastoma, establishing this finding as a useful diagnostic adjunct and expanding the spectrum of tumours driven by FOS gene family alterations. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

An Update on Clinicopathological, Imaging and Genetic Features of Desmoplastic Fibroblastoma (Collagenous Fibroma).

Desmoplastic fibroblastoma (also known as collagenous fibroma) is an uncommon benign fibroblastic/myofibroblastic neoplasm that primarily arises in the subcutaneous tissue of upper extremity. Magnetic resonance imaging reveals a well-defined mass in intimate association with dense connective tissue and prominent low signal intensity on all pulse sequences. Peripheral and septal enhancement is usually seen after intravenous contrast. Histologically, the lesion is paucicellular and consists of spindle to stellate-shaped cells embedded in a collagenous or myxocollagenous stroma with low vascularity. Diffuse and strong nuclear immunoreactivity for FOS-like antigen 1 seems to be characteristic of desmoplastic fibroblastoma. Cytogenetic studies have demonstrated the presence of 11q12 rearrangements and an identical t(2;11)(q31;q12) translocation. This review provides an updated overview of the clinical, radiological, histological, cytogenetic and molecular genetic features of desmoplastic fibroblastoma and discusses the relationship to fibroma of tendon sheath.

Next-Generation Sequencing in the Diagnosis of Rare Pediatric Sinonasal Tumors.

The diagnosis of desmoid fibromatosis or other spindle cell tumors in the sinonasal region is very rare in children and needs to be thoroughly confirmed with immunohistochemical and/or molecular tests. We report 2 patients with such rare tumors and describe the use of next-generation sequencing in their evaluation. A 3-year-old female had a 4.4-cm midline nasal cavity mass involving the bony septum and extending into the base of the skull bilaterally. The moderate cellular fibroblastic proliferation revealed areas of thick keloid-like collagen bands and other areas with myxoid edematous stroma. Deep targeted sequencing identified a novel G34V mutation in the CTNNB1 gene consistent with desmoid fibromatosis. An 11-month-old male infant presented with a right nasal mass that extended through the cribriform plate into the anterior cranial fossa and involved the right ethmoid sinus and adjacent right orbit. Histology revealed an infiltrative atypical fibrous proliferation with focal calcifications that was negative for CTNNB1 and GNAS mutations. A novel RET E511K variant was identified in the tumor and later was also found in the germline and hence rendered of unknown significance. Both cases highlight the utility of next-generation sequencing in the evaluation of pediatric sinonasal spindle cell tumors that may have overlapping pathologic features. Reporting of rare or novel variants in tumor-only sequencing should be cautiously evaluated in children and pairing with germline sequencing may be needed to avoid the pitfall of assigning uncommon variants.

Desmoid-type fibromatosis of the head and neck region in the paediatric population: a clinicopathological and genetic study of seven cases.

AIMS: Desmoid-type fibromatosis (desmoid) is a locally aggressive (myo)fibroblastic lesion. It represents one of the more common fibrous tumours in children and adolescents. The head and neck region is more often involved than in adults. METHODS AND RESULTS: We investigated the clinicopathological and genetic characteristics of seven paediatric desmoids at this anatomical site, including two cases of desmoplastic fibroma located in the mandible. There were two females and five males with an age range of 1.5-8 years. The sites of the soft tissue lesions were sinonasal (n = 4) and paramandibular (n = 1). All cases showed typical morphology and nuclear ß-catenin expression. CTNNB1 gene sequencing, performed successfully in five cases, revealed mutations in three cases with one p.T41A (bone lesion), one p.S37A and one novel mutation, p.D32V (sinonasal soft tissue lesions). Six patients were treated by excision with positive margins in five cases. Follow-up, available for six patients (median 4 years), showed no evidence of disease in four cases, slow progression in one case, and recurrence with stable disease in the last case. CONCLUSIONS: Our study provides evidence of genetic similarities in desmoid and desmoplastic fibroma. Additionally, we expanded the spectrum of mutations in CTNNB1 with one novel desmoid mutation.

Collagenous fibroma (desmoplastic fibroblastoma) with trisomy 8 as the sole cytogenetic abnormality.

Collagenous fibroma (desmoplastic fibroblastoma) is a benign fibrous soft tissue tumor that usually occurs in the subcutaneous tissue or skeletal muscle of adults. Recent cytogenetic studies have revealed clonal rearrangements of the chromosomal band 11q12. We present a unique case of collagenous fibroma arising in the right shoulder of a 63-year-old female. Magnetic resonance imaging showed a solid soft tissue mass deeply relative to the deltoid muscle, with low-to-intermediate signal intensity on T1-weighted sequences and low-to-slightly high signal intensity on T2-weighted sequences. Contrast-enhanced fat-suppressed T1-weighted sequences demonstrated heterogenous internal enhancement with rim enhancement. Following an open biopsy, marginal excision of the tumor was performed. Histological examination confirmed the diagnosis of collagenous fibroma. Cytogenetic analysis displayed a simple karyotypic change with trisomy 8. The postoperative course was uneventful, and the patient is doing well without local recurrence two months after the surgery. To the best of our knowledge, this is the first case of collagenous fibroma with trisomy 8 as the sole cytogenetic abnormality.

Molecular genetic characterization of the 11q13 breakpoint in a desmoplastic fibroma of bone.

Desmoplastic fibroma (DFB) is a benign primary bone tumor that usually occurs in adolescents and young adults. The genetic information on DFB is very limited. We here present cytogenetic, fluorescence in situ hybridization and single nucleotide polymorphism array findings in a case that had a rearrangement involving chromosomes 11 and 19 at G-banding analysis. The results showed that the breakpoint in 11q was different from that in desmoplastic fibroblastomas, and a segment containing five genes was hemizygously deleted from 11q13.

Translocation t(2;11) is characteristic of collagenous fibroma (desmoplastic fibroblastoma).

Collagenous fibroma (desmoplastic fibroblastoma) is a rare, benign soft-tissue tumor composed of spindled and stellate-shaped cells embedded in a dense collagenous stroma. Recently, a translocation between chromosomes 2 and 11 or a rearrangement involving the chromosome 11q12 breakpoint was reported to be recurrent and unique in collagenous fibroma. Herein, we describe a case of collagenous fibroma arising in the left thigh of a 57-year-old man. Magnetic resonance imaging revealed a 5.5 cm soft-tissue mass deep relative to the vastus medialis with low signal intensity on both T1- and T2-weighted sequences. A marginal excision of the tumor was performed, and histopathologic features were consistent with collagenous fibroma. Cytogenetic analysis exhibited a reciprocal translocation involving the long arms of chromosomes 2 and 11. This finding suggests that the t(2;11) is likely to be of pathogenetic significance in a subset of collagenous fibromas.

Desmoplastic fibroma with malignant transformation.

Desmoplastic fibroma (DF) is a rare neoplasm of bone, showing infiltrative and locally aggressive nature. Here, we report a case of DF with an unusual histology arising in a 41-year-old female in the left distal femur, which was detected by plain x-ray as an osteolytic lesion and by magnetic resonance imaging as a well-demarcated mass with endosteal scalloping. Pathologically, the tumor was composed mainly of bland-looking spindle cells in abundant collagenous stroma, accompanied with areas of myxofibrosarcomatous and malignant fibrous histiocytomatous components. These histologically different areas were admixed with each other. The array-based comparative genomic hybridization study on the histologically different areas showed some specific gained or lost loci according to their histologic features. The specific genetic events and the histologic features of this case might represent the malignant transformation of DF.

Translocation (2;11)(q31;q12) is recurrent in collagenous fibroma (desmoplastic fibroblastoma).

Collagenous fibroma (desmoplastic fibroblastoma) is a rare, benign tumor composed of spindle and stellate-shaped fibroblasts and myofibroblasts in a densely collagenous background. A t(2;11)(q31;q12) has been reported in one case of collagenous fibroma and a rearrangement of the 11q12 breakpoint in a second case. In the present study, we detected a t(2;11) identical to that previously described in a collagenous fibroma arising in the supraclavicular fossa of a 55-year-old man. This finding confirms the nonrandom association of t(2;11)(q31;q12) with collagenous fibroma.

Collagenous fibroma (desmoplastic fibroblastoma): genetic link with fibroma of tendon sheath?

We observed clonal chromosome abnormalities in two fibrous soft tissue tumors diagnosed as collagenous fibroma (desmoplastic fibroblastoma). The involvement of the same band of the long arm of chromosome 11, 11q12, was observed in both tumors. The presence of hitherto unreported similar chromosomal abnormalities in this tumor supports the neoplastic nature of this lesion. In addition, a possible relationship with fibroma of tendon sheath, which also shows rearrangement of 11q12, is suggested. 11q12 might be a common genetic denominator of benign fibroblastic lesions, such as collagenous fibroma and fibroma of tendon sheath.

Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor.

We report two cases of desmoplastic small round cell tumor (DSRCT) with novel molecular variants of the specific EWS-WT1 gene fusion. This fusion usually encodes a chimeric RNA with an in-frame junction of exon 7 of EWS to exon 8 of WT1. In one variant patient, the EWS-WT1 fusion transcript contained an in-frame junction of exon 9 of EWS to exon 8 of WT1. Moreover, in this patient the tumor arose in the hand, an extremely unusual site for DSRCT. In the second patient, an in-frame junction of exon 10 of EWS to exon 8 of WT1 was present. These two cases of DSRCT show that the molecular variability in the EWS breakpoint observed in the EWS-FLI1 fusion of Ewing's sarcoma can occur in DSRCT as well. This type of heterogeneity is relevant to the interpretation of molecular diagnostic assays and could also affect the functional properties of the encoded chimeric transcription factors.

Desmoplastic fibroma of the bone. A report of two patients, review of the literature, and therapeutic implications.

BACKGROUND: Desmoplastic fibroma (DF) is an extremely rare bone tumor. The recommendations for therapy are often based on limited personal experience, and the rate of local recurrence in the published cases is very high. Therefore, an analysis of treatment results of published cases was performed. Furthermore, DNA analysis of the tumors from two patients was also performed. METHODS: The clinical, radiologic, and histologic data of two patients with DF of the long bones are presented. DNA flow cytometry was performed on both DFs, three cases of abdominal fibromatosis, and three cases of extraabdominal fibromatosis. One hundred eighty-nine patients analyzed in the literature and our own 2 patients were evaluated with regard to epidemiologic, clinical, and histologic data, with particular emphasis on treatment results. RESULTS: DNA analysis of the locally infiltrating tumors revealed indices of proliferation between 21.5% and 24%, noticeably elevated values in comparison with extraosseous desmoid tumors (8.04%). Magnetic resonance imaging (MRI) was most valuable for imaging the intraosseous and extraosseous extent of DF. The evaluation of 191 patients (189 from the literature, 2 of the authors) showed the numbers of males and females to be equivalent, with a mean age of 23 years. DF has been reported in almost all bones, with a tendency to occur in the mandible and the long bones. Approximately 12% of patients presented with a pathologic fracture (20 of 161 patients). Infiltrative growth in the soft tissue was documented in 48% of patients. Three patients developed metastases after local recurrence. Analyzing the treatment results, the authors found a recurrence rate of 55-72% after nonresection procedures, and 17% after resection. No recurrences are reported after resection with wide surgical margins. The recurrence rate of tumors of the extremities was 55%, and 25% of these patients eventually required an amputation. CONCLUSIONS: Considering the "semimalignant" character of this entity and the poor treatment results in patients with recurrent tumors, marginal or wide resection for primary treatment is recommended. The superior imaging quality of MRI greatly facilitates preoperative planning.