Definitive diagnosis of infantile fibrosarcoma (IFS) and related kinase-altered spindle cell neoplasms (SCN) requires immunohistochemistry (IHC) or molecular assays that are variable in performance or not widely available. Recent transcriptomic studies identified differential gene expression in IFS with ETV6::NTRK3 fusions, prompting investigation of SOX11 expression pattern by IHC in IFS/IFS-like SCN and morphologic mimics. SOX11 staining (MRQ-58) was performed on 201 spindle cell tumors, including 28 IFS and congenital mesoblastic nephroma (CMN) with ETV6::NTRK3 fusion, 44 IFS/IFS-like SCN with alternative kinase fusions, 15 inflammatory myofibroblastic tumor, 4 dermatofibrosarcoma protuberans, 6 myofibroma, and 104 mimics comprising 38 malignant peripheral nerve sheath tumor (MPNST), 24 synovial sarcoma, 19 desmoid fibromatosis, 7 neurofibroma, 4 schwannoma, 4 fibrous hamartoma of infancy, 4 spindle cell/sclerosing rhabdomyosarcoma (SRMS), and 4 clear cell sarcoma of kidney (CCSK). SOX11 was positive in 18/28 (64%) ETV6::NTRK3-rearranged IFS/CMN (21% with diffuse strong nuclear expression and 43% with multifocal moderate to strong positivity) and 3/69 (4%) other kinase-altered tumors, including one EGFR-altered tumor and two cellular myofibromas. SOX11 was positive in 5/24 (21%) synovial sarcoma, 6/38 (16%) MPNST, 2/4 (50%) SRMS, and all 4 CCSK. Overall, SOX11 was 64% sensitive for ETV6::NTRK3-fused IFS/CMN and 96% specific compared to kinase-altered tumors, with 88% specificity compared to all mimics. SOX11 is moderately sensitive but highly specific for IFS/CMN with ETV6::NTRK3 fusion. In the correct context, SOX11 shows utility as a screening adjunct for focused molecular testing.

Desmoid fibromatosis (DF) is a refractory tumor with a high recurrence rate, resulting in severe organ's deformity, morbidity, and mortality. The cellular characteristics of DF remain elusive. Herein, we performed single-cell RNA sequencing (scRNA-seq) to reveal the cell landscape of DF. To uncover the exclusive characteristics of DF, we compared the transcriptional profile of DF with that of keloid fibroblast (KF) and normal fibroblast (NF) in the public data (GSE163973). When compared with KF and NF, mesenchymal fibroblasts were significantly expanded in DF. The mesenchymal fibroblasts were further divided into two subtypes according to the differentiation states, among which LAMP5+ SULF1+ fibroblasts may account for the hard property of DF by promoting tumor ossification. ADAM12 and CREB3L1 were identified as the specific marker and transcription factor for DF, respectively. Both the quiescent and proliferative COL11A1+ neural cells exerted dominant rolesin the maintenance of the profibrotic microenvironment in DF through modulating extracellular matrix. This study revealed the heterogeneity of fibroblasts in DF for the first time. The novel gene markers and transcription factor identified in DF and the significance of neural cells in the tumor microenvironment may point to new directions for the targeted therapy of DF in the future.

Aggressive fibromatosis (desmoid tumour) of the breast is a rare tumour thataccounts only for 0.2% of primary breast tumours. This is a benign mesenchymal tumour that develops from muscular fasciae and aponeuroses. It is characterized by its local evolution and its tendency to relapse without metastasizing. Wide radical resection should be attempted whenever possible. Positive margins at resection and reoperation are associated with a high risk of local recurrence. The role of radiotherapy and of medical treatments especially antiestrogens remains unclear.

DICER1-related tumor predisposition is an inherited disorder, generally pediatric in onset, featuring a characteristic array of mainly mesenchymal tumors. We report a chest wall desmoid fibromatosis, occurring in a child who uniquely carries a germline "hotspot" DICER1 variant that likely leads to impaired miRNA biogenesis in all cells. This lesion contained a hotspot CTNNB1 c.134C > T, (p.S45F) exon 3 somatic mutation and immunohistochemistry showed nuclear accumulation of β-catenin. Desmoid fibromatosis is known to be associated with dysregulation of β-catenin, resulting from altered APC or CTNNB1, leading to increased WNT pathway signaling. In fetal lung tumors linked to DICER1 hotspot variants, APC and/or CTNNB1 somatic mutations are found in most cases, suggesting a synergistic effect with DICER1 hotspot mutation to increase WNT pathway signaling. We postulate a similar mechanism is involved in this case and that desmoid fibromatosis is a rare mesenchymal lesion that could be part of DICER1-related tumor predisposition.

Desmoid tumors are rare mesenchymal neoplasms characterized by a clonal proliferation of fibroblasts and myofibroblasts. Using the novel contrast-enhanced susceptibility-weighted imaging (CE-SWI) for characterizing desmoid tumors can enhance the separation between fibrous T2-hypointense and cellular T1-enhancing components. We aim to evaluate the effectiveness of the CE-SWI signal, volumetric, and radiomics-derived features in assessing desmoid treatment response. This IRB-approved study included 17 single-lesion extremity desmoid fibromatosis patients who underwent standard-of-care MRI, including CE-SWI, from March 2021 to February 2024. Measurements of maximum diameter, volume, and the modified Choi (m-Choi: tumor/muscle T2 ratio) were computed based on CE-SWI and T2-STIR volumetric tumor segmentations. 107 shape, first-order, and textural radiomic features were calculated. Patient response was assessed using conventional RECIST as a reference standard and compared against T2-STIR and CE-SWI volumetric, m-Choi, and radiomics features. RECIST-progression (n = 3): In two patients, CE-SWI volume detected progression 10 months earlier than T2-STIR-based RECIST. Only 33% were characterized as progression by the routine radiologic report (RRR). RECIST-stability (n = 14): 5% exhibited at least one expected first-order response/progression-related change in the mean, skewness, 10th percentile, or 90th percentile, with all four changes present in 33% of cases. In RECIST-progression, CE-SWI showed an average of 15% more voxels at the 90th percentile than T2-STIR. Volume and CE-SWI/T2-STIR shape-derived size dimensional features demonstrated the highest separation between progressive and responding patients. CE-SWI has a higher sensitivity than T2-WI in detecting the active/progressive enhancing component. Volume and Shape-derived and, to a lesser extent, textural radiomic features and m-Choi effectively distinguish between progressive and responding cases, outperforming first-order radiomics, RRR, and RECIST. Particularly, progression prediction by CE-SWI/T2-STIR-volume and response prediction by CE-SWI-m-Choi outperform and precede RRR and RECIST. The novel CE-SWI enhances tumor insight and desmoid treatment-response prediction by effectively separating responding T2-hypointense-collagenized-mature components from potentially progressive T1-shortened/enhancing T2-hyperintense-immature components.

The article presents a rare form of pathological neoplasms — breast desmoid type fibromatosis. There are etiology and pathogenesis of the disease, clinical and morphological features, diagnostics and tactics of treatment of the disease. Widely covered clinical examples from the practice of a surgeon-oncologist. Desmoid fibromatosis (DF) is an aggressive non-metastatic mesenchymal formation that arises from musculoponeurotic structures. DF accounts for 0.03 % to 0.1 % of solid tumors and 3 % of mesenchymal tumors. Among breast pathology, this neoplasm is even rarer (0.2 %). Due to the rarity of such pathology, clinicians are not always able to correctly interpret the diagnostic picture and recognize the disease. The etiology and pathogenesis of the disease are also not fully understood, and therefore there are no standards for the treatment of desmoid fibromatosis. Surgical treatment remains the main one. To reduce the frequency of recurrence of the disease, the surgeon needs to achieve clean edges of the resection. Radiation therapy, hormone therapy, targeted therapy, and chemotherapy may additionally be considered as an alternative type of treatment. When the clean edges of the resection are reached, strict dynamic monitoring of pa is considered as further treatment.

Impact and safety of pregnancy on desmoid fibromatosis management in the era of active surveillance. An international multicenter retrospective observational study.

11547 Background: Recently, first-in-class FDA approval was granted in the U.S. for use of the gamma secretase inhibitor (GSI), nirogacestat, for adults with progressive desmoid fibromatosis. In tandem, the unpredictable clinical behavior of desmoids, which ranges from local aggression to regression, raises consideration of whether diagnostic and molecular variability underlie their varying biological potential. With an aim to understand both, and to explore the potential for biomarkers for GSI therapy selection, prediction, and prognosis, we performed a retrospective review of comprehensive genomic profiling and histology of desmoids and other soft tissue tumors harboring CTNNB1 or APC mutations. Methods: Using real-world reference laboratory database of tumors submitted for clinical genomic assessment (Caris Life Sciences), we queried for samples with a diagnosis of desmoid fibromatosis, or for other neoplasms of soft tissue origin harboring CTNNB1 or APC mutations. Samples underwent next-gen sequencing of (whole exome) to identify gene variants/copy number alterations and of RNA (whole transcriptome) for expression and fusion profiling. Findings were correlated with available clinical data and whole slide image histologic review. Results: We identified 74 tumors submitted as desmoid fibromatosis, of which 80% harbored CTNNB1 and 15% harbored APC pathogenic or likely pathogenic variants. CTNNB1 variants included codon 41 (58%), codon 45 (41%), and ubiquitin motif codon 36 (1%), while 91% of APC variants detected were in exon 16. Recurrent co-alterations were rare, involving MUTYH (heterozygous G396D) in 2 samples, and TMB-High (≥10 mutations/Mb) present in 3 . Notably, 4 “desmoids” (5%) lacked characteristic mutations, one of which harbored COL1A1::USP6 fusion, reclassified as nodular fasciitis. Among 76 soft tissue tumors diagnosed as other entities at analysis but found to harbor CTNNB1/APC mutations, 6 (all limited core biopsies), could be confidently reclassified as desmoids. The remaining 70 CTNNB1/APC mutant neoplasms were diverse, including synovial sarcoma (11%) and rhabdomyosarcoma (10%). Conclusions: Correlation of genomics and histopathology may allow identification of other tumor types misclassified as desmoid fibromatosis. Conversely, genomic correlation facilitated recognition of additional desmoids among tumors submitted with other diagnoses. The striking lack of secondary mutations seen in this large cohort with comprehensive DNA sequencing implies that other mechanisms explain and could predict their variable behavior, for which we are exploring paired transcriptome profiling data. Finally, subsets of diverse, other soft tissue neoplasms harbor CTNNB1 or APC mutations, which may have implications for the design of future biomarker-selected Phase II basket trials.

Contrast enhanced ultrasound versus MRI for response assessment of extra-abdominal desmoid Fibromatosis- A feasibility study.

Background: Desmoid fibromatosis (DF) is a rare, locally aggressive soft tissue tumour with unpredictable clinical behaviour. Historically, treatment has involved surgery; however, contemporary guidelines, such as those from the Desmoid Tumour Working Group, advocate active surveillance. This article reviews current perspectives on DF, focusing on epidemiology, pathogenesis, treatment strategies, emerging research directions and cost effectiveness based on our experience at the West of Scotland Musculoskeletal Oncology Service, Glasgow Royal Infirmary (GRI). Methodology: We reviewed 101 patients diagnosed with desmoid fibromatosis between 2010 and 2024. A review of patient records was conducted to gather information on demographics, date of diagnosis, prior treatment, treatment initiation, intervention types, imaging intervals, follow-up duration, recurrence rate for surgery and other intervention, and discharge timelines. All data was systematically organized and analyzed to assess our outcomes. Results: Out of 101 patients with DF in the study, 66% were females. The most common site of primary tumour was lower extremity (39.6%) followed by near equal distribution in upper extremity and trunk. Out of the total cases, 72 (71.2%) were successfully managed with active surveillance involving serial imaging and clinical reviews in accordance with European guidelines. A total of 22 patients (21%) received treatment: 10 underwent surgery alone, 2 had surgery combined with radiotherapy, 8 received only radiotherapy, 1 was treated with hormonal therapy and 1 participated in a trial with Nirogacestat. Of the seven remaining patients, six had unplanned surgery outside followed by active surveillance at GRI. One patient was on alternative treatment modality, homeopathy. The average number of MRI scans per patient was 3.11, with many patients requiring significantly more imaging. MRI surveillance varies significantly in desmoid tumours due to their heterogeneous behaviour. Active or symptomatic tumours often require more frequent scans (every 3–6 months), while stable cases may need only imaging annually or just clinical monitoring. Recurrence was noted in eight patients, all of which were related to prior surgery. The total combined cost of imaging and appointments exceeds £6500 per patient in active surveillance. Conclusions: We conclude that most patients with desmoid fibromatosis in our cohort were effectively treated with active surveillance, consistent with current European guidelines. Surgical management of desmoid fibromatosis in our cohort is historic and has shown a significant recurrence risk. Our study proposes a revised follow-up protocol that significantly reduces costs without compromising on patient care. We suggest a two-year surveillance period for stable disease with patient-initiated return to reduce unnecessary clinic visits, imaging and healthcare costs.

Desmoid-type fibromatosis is a locally aggressive tumor characterized by a well-differentiated proliferation and a high risk of recurrence. It is classified into extra-abdominal, abdominal, and intra-abdominal subtypes based on its location. Although rare, cervical desmoid fibromatosis is an even less common manifestation. Furthermore, its radiological features are seldom reported in the literature, making differentiation from other cervical masses particularly challenging. We report an unusual case of a 16-year-old female patient, who presented with a progressively enlarging, painless mass on the left side of her neck over the past six months. Further imaging and histopathological evaluation were performed, leading to the diagnosis of cervical desmoid fibromatosis.

Desmoid tumor (DT), also known as desmoid fibromatosis, is a rare, locally proliferative tumor characterized by an overgrowth of myofibroblastic cells. Due to the varied clinical presentation of DT, there are a multitude of treatment options. This study provides our institutional experience in characterizing and treating DT as well as patient outcomes. A retrospective review was performed for 49 patients diagnosed with DT. Patient demographics, tumor characteristics, treatment characteristics, and tumor recurrence were reported. We reported our institution’s treatment trends over time, relative risk analysis for surgery, as well as univariate analysis for recurrence. Thirty-seven patients received surgery with an overall recurrence rate of 29.7% (11/37). In total, ten patients received medical therapy including tamoxifen/sulindac (n = 7), nirogacestat (n = 1), and sorafenib (n = 2). One patient has been followed with active surveillance. Relative risk for surgery and tumor recurrence was not significantly correlated with race, gender, location, or large tumor size > 5 cm. Four patients treated with medical therapy experienced tumor reduction and symptomatic improvement. Management of DT includes many surgical and non-surgical options. We noted a similar recurrence rate in patients who received surgical treatment to what has been reported in the literature roughly 33%. We also noted effective tumor control in patients receiving medical therapy. As such, surgery can be utilized in situations with well-demarcated DT which can be removed en bloc, while utilizing medical therapy for highly invasive tumors.

Desmoid fibromatosis with CTNNB1 exon 3 deletion-inversion complex mutation: report of a case

Chest wall desmoid fibromatosis involving the pedicle of a microvascular free flap breast reconstruction: a case report

Desmoid fibromatosis (DF) is a rare low-grade benign myofibroblastic neoplasm that originates from fascia and muscle striae. For giant chest wall DF, surgical resection offer a radical form of treatment and the causing defects usually need repair and reconstruction, which can restore the structural integrity and rigidity of the thoracic cage. The past decade witnessed rapid advances in the application of various prosthetic material in thoracic surgery. However, three-dimensional (3D)-printed custom-made titanium ribs have never been reported for chest wall reconstruction post-DF resection. Here, we report a successful implantation of individualized 3D–printed titanium ribs to repair the chest wall defect in a patient with DF.

ObjectiveTo identify MRI features of desmoid tumors (DTs) that predict the growth of residual disease following ablation.MethodsPatients who underwent MRI-guided ablation for DTs between February 2013 and April 2021 were included in this single-center IRB-approved retrospective study. MRI scans assessed three suspicious tissue features: intermediate T2 signal [+iT2], nodular appearance [+NOD], and contrast enhancement [+ENH]. Percent-monthly change in diameter (PMCD) of suspicious foci determined growth (PMCD > 1%), unchanged (PMCD between −1% and +1%), or regression (PMCD < −1%). Statistical tests compared mean PMCD between groups and evaluated sensitivity and specificity.ResultsThirty-three patients (32 years ± 13.3; 22 females) with 34 DTs underwent 47 MRI-guided ablations, with a median follow-up of 269 days (IQR 147). Of 93 suspicious foci, 62 (67%) grew (PMCD: +5.6% IQR: 5.8), 13 (14%) remained unchanged (PMCD: −0.1% IQR: 0.6), and 18 (19%) regressed (PMCD: −3.9% IQR: 4.2). Features [+iT2], [+ENH], and [+NOD] were associated with PMCDs of +5.2% IQR: 6.0, +3.4% IQR: 6.0, and +3.4% IQR: 6.5, respectively, compared to −1.5% IQR: 4.7 (p < 0.0001), −0.5% IQR: 0.8 (p = 0.003), and +0.4% IQR: 7.5 (p = 0.0056) for their respective negative counterparts. Sensitivity, specificity, and accuracy for distinguishing growth were [+iT2]: 0.95, 0.71, 0.87, [+ENH]: 1.00, 0.32, 0.77, and [+NOD]: 0.84, 0.42, 0.70. Combining [+iT2 + NOD + ENH] yielded PMCD +5.9% IQR: 6.2 and the best performance for distinguishing growth (sensitivity 0.81, specificity 0.94, accuracy 0.85).DiscussionMRI features reliably predict the growth of residual or recurrent DTs post-ablation, with [+iT2] being the most accurate. Adding nodular enhancement to [+iT2] improved specificity without sacrificing accuracy.Key PointsQuestionPost-ablation imaging of desmoids is challenging due to tumor heterogeneity and treatment-related inflammation. This study evaluates MRI features for assessing future tumor growth.FindingsFoci of intermediate T2 signal post-ablation predicted desmoid growth with high sensitivity (0.95), while T2 signal, nodularity, and enhancement combined offer high specificity (0.94).Clinical relevanceIntermediate T2 signal predicts desmoid tumor growth post-ablation with high sensitivity and accuracy but moderate specificity. Combining nodularity and enhancement improves specificity and predictive value, helping clinicians in managing desmoid tumor patients post-ablation.

Pediatric desmoid fibromatosis – Experience from a tertiary care cancer hospital

Background: Desmoplastic fibroma is a very rare bone tumour that is commonly recognised by its striking resemblance to desmoid fibromatosis, commonly seen in soft tissues. Case Presentation: A 3-year-old girl presented to the Oral and Maxillofacial Department with swelling on the lower jaw for 4 months duration. Extra-oral examination revealed: Facial asymmetry due to the discrete swelling on the right mandible measuring 14 x 12cm in widest diameter below the right pre-auricular region to the right mental region. The Craniofacial CT scan showed an expansile jaw mass with destruction of the mandible. There was no evidence of bone formation. Histopathology diagnosis was desmoplastic fibroma of the bone. The tumour cells were weakly positive for MyoD1. Conclusion: Pathologists must know that cells of desmoplastic fibroma may sometimes be weakly positive for MyoD1, as in rhabdomyosarcoma.

Background: Desmoid fibromatosis is a locally aggressive benign fibroblastic soft tissue tumor representing nearly 0.03% of all neoplasms. They can be sporadic or may be associated with Familial Adenomatous Polyposis (FAP). Around 50% of fibromatosis are intrabdominal or arise in the abdominal wall. Rarely, these tumors can arise from the intestinal wall. Appendix and mesoappendix are extremely rare sites of presentation with only 3 reported cases. Case Presentation: A healthy 43-year-old male presented with abdomen distension. CECT scan showed a well-defined enhancing mass in the lower abdomen attached to the appendix with no surrounding infiltration, fat stranding, or evidence of distant metastasis. A wide resection was performed, and gross examination showed a well-circumscribed mass measuring 8 cm attached to the appendix. Histological examination revealed a well-circumscribed cellular spindle cell neoplasm with focal infiltrative borders. The tumor cells showed nuclear immunoreactivity for Beta-catenin and focally for Desmin, while they were negative for DOG1, CD117, CD34, STAT6, S100 &amp; Pan Cytokeratin. The morphology and immunohistochemistry were compatible with Desmoid fibromatosis. CT scans were negative for recurrence or distant metastases after 8 months of follow-up. Conclusion: Appendix and mesoappendix desmoid fibromatosis are extremely rare and can present as an abdominal mass or features of acute appendicitis. Gastrointestinal stromal tumor (GIST) is an important differential diagnosis at this site and is crucial to differentiate from fibromatosis for patient management and follow-up. Identifying beta-Catenin (CTNNB1) mutation is a diagnostic criterion to differentiate from other spindle cell tumors, especially on small biopsies. Multi-disciplinary treatment approach is crucial for management.

S4810 Obstructive Conundrum: Desmoid Fibromatosis as a Rare Cause of Small Bowel Obstruction