Different Shades of Desmoid-Type Fibromatosis (DTF): Detection of Noval Mutations in the Clinicopathologic Analysis of 32 Cases

Background: Desmoid-type fibromatosis (DTF) is a locally aggressive myofibroblastic/fibroblastic neoplasm with a high risk of local recurrence. It has a variety of histologic features that might confuse diagnosis, especially when detected during core needle biopsy. The Wnt/β-catenin pathway is strongly linked to the pathogenesis of DT fibromatosis.

Method: This study examined 33 desmoid-type fibromatoses (DTFs) from 32 patients, analyzing its clinical characteristics, histologic patterns, occurrence rates, relationship with clinical outcomes, immunohistochemical and molecular findings.

Results: The DTFs exhibit a range of 1 to 7 histologic patterns per tumor, including conventional, hypercellular, myxoid, hyalinized/hypocellular, staghorn/hemangiopericytomatous blood vessels pattern, nodular fasciitis-like, and keloid-like morphology. No substantial association was found between the existence of different histologic patterns and the clinical outcome. All thirty-three (100%) samples of DTF had a variable percentage of cells that were nuclear positive for β-catenin. An NGS analysis detected novel non-CTNNB1 mutations in two DTFs, including BCL10, MPL, and RBM10 gene mutations.

Conclusions: This study reveals a diverse morphology of DTFs that could result in misdiagnosis. Therefore, surgical pathologists must comprehend this thoroughly. Also, the importance of the newly identified non-CTNNB1 gene mutations is still unclear. More research and analyses are needed to completely grasp the clinical implications of these mutations.

Desmoid tumor is a rare mesenchymal neoplasm of unknown etiology. Despite rare, the diagnosis of desmoid tumors after bariatric surgery is increased over the last few years. We report a case of a 26-year-old male with complains of abdominal pain and postprandial fullness, diagnosed with a locally advanced large intra-abdominal mass (40 × 21 × 11.7 cm) centered in the mesentery, developed 3 years after sleeve gastrectomy. Percutaneous biopsy was suggestive of a mesenquimatous tumor and the patient underwent surgery. R0 surgical resection was achieved, despite intimal contact and common vascularization with a jejunal loop. Histopathology examination of the surgical specimen revealed fusiform to stellate cells with mild atypia, thin-walled vessels, and diffuse beta-catenin expression (negative for DOG-1, CD117, CD34, S100, desmin, and alpha-actin). The diagnosis of a desmoid tumor was made. The patient remained asymptomatic, and no recurrence occurred over a 4-year follow-up. With the increasing number of bariatric surgeries, owing to the alarming growing incidence of obesity and related conditions, it is expected that desmoid tumors reports will gradually increase over the next few years. Thus, both gastroenterologists and surgeons should be aware of the potential for desmoid tumor development shortly after surgery, to offer a prompt diagnosis and treatment.

Background: Typically, researchers and clinicians determine the agenda in sarcoma research. However, patient involvement can have a meaningful impact on research. Therefore, the Patient-Powered Research Network (PPRN) of the Sarcoma Patient Advocacy Global Network (SPAGN) set up a Priority Setting Partnership (PSP). The primary objective of this partnership is to identify priorities for research and patient advocacy topics.

Methods: In the first phase of this PSP, including 264 sarcoma patients and carers from all over the world, 23 research topics regarding sarcomas and 15 patient advocacy topics were identified using an online survey. In the second phase, participants were asked to fill in a top five and a top three of research and patient advocacy topics, respectively. Additionally, sociodemographic characteristics and sarcoma characteristics were collected. Social media channels, local national patient advocacy groups and the SPAGN website were used to distribute the survey.

Results: In total, 671 patients (75%) and carers (25%) participated in this survey. The five highest ranked research topics were related to causes of sarcoma (43%), prognosis and risk of recurrence (40%), specific subtypes of sarcoma (33%), the role of immunotherapy, targeted therapy and combined therapy (30%), and hereditary aspects (30%). The three highest ranked patient advocacy topics were improving the diagnostic process of sarcoma (39%), access to tumor DNA analysis (37%) and establishing an international sarcoma registry (37%).

Conclusions: This sarcoma PSP has identified priorities for research and patient advocacy, offering guidance for researchers, assisting funding agencies with assessing project relevance and empowering patient advocates to represent the needs of patients and carers.

Background: In recent years, there has been a change in the therapeutic landscape of desmoid-type fibromatosis (DF). Watchful waiting is now preferred over initial local treatments such as surgery and radiotherapy. Systemic treatment is considered for progressive or symptomatic disease. The aim of this study is to review real-life data on the use of sorafenib in DF.

Methods: We established a retrospective dataset of patients treated with sorafenib in our centre, Ghent University Hospital, for progressive DF. Patient demographics, disease characteristics, response to therapy using Response Evaluation Criteria in Solid Tumours 1.1 criteria and toxicity according to CTCAE v5.0 were assessed.

Results: Eleven patients with DF were treated with sorafenib between 2020 and 2024. Median treatment duration was 20.4 months (95% confidence interval [CI], 10.0-NR). 36.4% achieved partial response, 54.5% stable disease and 9.1% progressive disease. For three patients, the treatment is ongoing. The median time to objective response rate is 15.0 months (95% CI, 8.8-NR). The majority (81.8%) experienced grade 2 toxicity, and one third of patients grade 3 toxicity (36.4%). The most common all-grade adverse event was skin toxicity (hand-foot syndrome, pruritus and rash) (90.9%). Nine patients (81.8%) needed dose reduction with a median time to first reduction of 1.1 months (95% CI, 0.5-NR). One patient stopped treatment due to toxicity.

Interpretation: Real-life data on the use of sorafenib in the treatment of DF is consistent with published data in clinical trial setting. Sorafenib is an effective treatment option for progressive DF although associated with significant toxicity and the need for rapid dose reduction.

Purpose: Prognostic biomarkers remain necessary in sporadic desmoid tumor (DT) because the clinical course is unpredictable. DT location along with gene expression between thoracic and abdominal wall locations was analyzed.

Method: Sporadic DT patients (GEIS Registry) diagnosed between 1982 and 2018 who underwent upfront surgery were enrolled retrospectively in this study. The primary endpoint was relapse-free survival (RFS). Additionally, the gene expression profile was analyzed in DT localized in the thoracic or abdominal wall, harboring the most frequent CTNNB1 T41A mutation.

Results: From a total of 454 DT patients, 197 patients with sporadic DT were selected. The median age was 38.2 years (1.8-89.1) with a male/female distribution of 33.5/66.5. Most of them harbored the CTNNB1 T41A mutation (71.6 %), followed by S45F (17.8 %) and S45P (4.1 %). A significant worse median RFS was associated with males (p = 0.019), tumor size ≥ 6 cm (p = 0.001), extra-abdominal DT location (p < 0.001) and the presence of CTNNB1 S45F mutation (p = 0.013). In the multivariate analysis, extra-abdominal DT location, CTNNB1 S45F mutation and tumor size were independent prognostic biomarkers for worse RFS. DTs harboring the CTNNB1 T41A mutation showed overexpression of DUSP1, SOCS1, EGR1, FOS, LIF, MYC, SGK1, SLC2A3, and IER3, and underexpression of BMP4, PMS2, HOXA9, and WISP1 in thoracic versus abdominal wall locations. Conclusion: Sporadic DT location exhibits a different prognosis in terms of RFS favoring the abdominal wall compared to extra-abdominal sites. A differential gene expression profile under the same CTNNB1 T41A mutation is observed in the abdominal wall versus the thoracic wall, mainly affecting the Wnt/β-catenin, TGFβ, IFN, and TNF pathways.

Desmoid tumors (DTs) are rare and locally aggressive with a high rate of local recurrence even with optimal surgical resection. Systemic treatments are often utilized for desmoid cases with high risk of surgical morbidity or for local and symptomatic control of recurrent disease. However, the systemic treatment options for DTs are limited with limited responses. Avapritinib is a tyrosine kinase inhibitor (TKI) approved in 2020 for adults with unresectable or metastatic gastrointestinal (GI) stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (PDGFRA) Exon 18 mutation, including D842V mutations. In this case report, we describe a 55-year-old man with a history of D842V-mutant gastric GIST who presented several years after complete resection of the GIST with an enlarging soft tissue mass in the small intestine. After a nondiagnostic biopsy, the patient was started on avapritinib due to concerns for recurrent D842V-mutant GIST. The tumor had a partial response to treatment by RECIST 1.1 criteria, and the patient underwent surgical resection. The final pathology report revealed a sporadic DT. To our knowledge, this is the first known description of the activity of avapritinib in the treatment of a sporadic mesenteric DT, which is relevant given the limited treatment options for patients with this diagnosis. This clinical finding may be worth exploring in a dedicated clinical trial.