Experience of a Referral Center with Desmoid Tumors, Part 2: A Retrospective Analysis of 109 Cases

Background: Desmoid tumors (DTs) are rare, locally aggressive fibroblastic neoplasms with highly heterogeneous clinical behavior. The present work constitutes the second part of a two-part project, following our previously published multidisciplinary review of the diagnostic and therapeutic landscape of DTs. It provides a comprehensive analysis of our institutional experience as a national reference center for sarcoma. We aim to describe real-world diagnostic pathways, management strategies, and clinical outcomes in a high-volume cohort.

Methods: We conducted a retrospective cohort study that included patients diagnosed with DT at our center between 2014 and 2024. Demographic, clinical, molecular, treatment, and outcome data were collected. Management strategies were analyzed according to tumor location, symptoms, progression patterns, and multidisciplinary decision-making. Outcomes included response rates, event-free survival (EFS), need for active treatment, response to systemic therapy, and recurrence after local treatments.

Results: A total of 109 patients were included (median age 36.8 years; 56.9% women). Somatic CTNNB1 mutations were identified in 23 of 29 tested patients, predominantly T41A, while germline alterations were found in 18 patients, mainly in APC. Initial management was conservative in 40.4% of patients and active in 59.6%, primarily through surgery. After a median follow-up of 41.5 months, 44.9% of patients experienced disease progression. Among patients managed with active surveillance, spontaneous regression occurred in 22.2%, and 58% remained treatment-free. Surgical relapse occurred in 35.8% of patients undergoing upfront resection, with major postoperative complications limited to externally operated cases. Cryoablation achieved radiological responses in most evaluable patients, while systemic therapies showed clinical activity but relevant toxicity, particularly with tyrosine kinase inhibitors. The median EFS for the whole cohort was 57 months. Conservative initial management and R1/2 surgical margins were independently associated with worse EFS.

Conclusions: Our results support a personalized, multidisciplinary management strategy for DTs, prioritizing conservative approaches when appropriate and reserving active treatments for progressive or symptomatic disease. Outcomes achieved in a specialized referral center are comparable to those reported in large international retrospective series, underscoring the value of expert multidisciplinary care in optimizing DT management.

Diagnostic challenges remain in desmoid fibromatosis (DF) due to somewhat frequent β-catenin immunohistochemical negativity, risking misclassification and overtreatment. The present study evaluates the role of CTNNB1 molecular testing in optimizing diagnosis. A single-center, large retrospective analysis of 780 patients with DF was performed. The incidence of DF was higher in females, particularly within the adult demographic. 77.3% of DF cases exhibited nuclear β-catenin positivity.The majority of cases that were β-catenin nuclear negative underwent CTNNB1 exon 3 Sanger sequencing.Molecular analysis revealed that 74.1% of β-catenin negative cases harbored CTNNB1 mutations, primarily at codon 41 (p.T41A). Patients with wild-type CTNNB1 were significantly older. Notably, β-catenin IHC showed higher positivity in resected specimens (79.7%) compared to biopsies (62.0%), whereas CTNNB1 mutational detection was higher in biopsies (93.5%) than resections (76.8%). Codon 41 mutations correlated with higher β-catenin IHC positivity than codon 45 mutations. A subsequent analysis of age demonstrated that DF in the abdominal wall, retroperitoneal cavity, and trunk was more likely to occur in the adult group. Four novel mutations (p.S45_G48del, p.T41V, p.S23N, and p.G34E) were identified. CTNNB1 mutational testing is indispensable for the diagnosis of β-catenin-negative DF, especially in older patients, where IHC limitations are pronounced. Identifying CTNNB1 gene mutations provides an accurate diagnosis in challenging cases without immunohistochemical support, facilitating the development of more effective treatment strategies.

Desmoid-type fibromatosis is a rare soft tissue tumor mimicking typical aggressive childhood malignancies, but with inability to metastasize, and with an essential role for imaging for diagnosis and therapeutic strategies.

Objective: Desmoid tumors (DTs) are rare soft-tissue neoplasms characterized by local invasiveness and high recurrence potential. Due to heterogeneous clinical behavior and unresolved controversies regarding postoperative recurrence risk factors, optimal management remains challenging. This study aimed to identify predictors of recurrence-free survival (RFS) after grossly complete recection.

Methods: We retrospectively analyzed 81 DT patients undergoing resection at our institution (September 2014-December 2024). Clinicopathological variables were assessed using Cox regression for recurrence risk, with RFS compared via Kaplan-Meier analysis.

Results: The median follow-up was 55 months (range: 4-127 months). The 1-year, 3-year, and 5-year RFS rates for the entire cohort were 89.8% (95% CI: 83.1-96.5), 73.8% (95% CI: 63.6-84.0), and 65.5% (95% CI: 53.5-77.5), respectively. Univariate Cox regression analysis showed that larger tumor size (per 1 cm increase: HR = 1.271, p < 0.001), recurrent disease status (HR = 2.741, p = 0.027), and tumor location on an extremity (HR = 2.62, p = 0.021) were significantly associated with poorer prognosis. To mitigate the risk of overfitting, the subsequent multivariate analysis was limited to two variables. This model identified both tumor size (HR = 1.283, p < 0.001) and extremity location (HR = 2.899, p = 0.011) as independent risk factors. The robustness of these findings was further confirmed using a Bonferroni correction (adjusted significance level α = 0.025). Conclusion: In this cohort, tumor size and extremity location were identified as independent predictors of worse recurrence-free survival in patients with desmoid tumors following macroscopic complete resection. These robust factors may aid in postoperative risk stratification and inform patient counseling.

Desmoid-type fibromatosis (DTF) is a rare, locally aggressive myofibroblastic neoplasm. Abdominal wall occurrences are frequently associated with antecedent surgical trauma, such as Cesarean sections, and pregnancy-related hormonal factors. The diagnosis is challenging and requires differentiation from scar endometriosis. We report the case of a 35-year-old woman presenting with a painful infraumbilical mass 4 years after her last Cesarean section. Magnetic Resonance Imaging (MRI) suggested a desmoid tumor, characterized by T2 hypointensity and fascial infiltration. Percutaneous biopsy confirmed the diagnosis, revealing nuclear beta-catenin positivity and negative hormone receptors. Following multidisciplinary assessment and in accordance with the patient’s preference, a conservative management strategy using nonsteroidal anti-inflammatory drugs (NSAIDs) was initiated, resulting in symptomatic relief. This case underscores the importance of MRI in the diagnostic workup and highlights the role of active surveillance and medical management as a viable first-line strategy for symptomatic abdominal wall DTF.

Aims: To identify factors associated with morbidity and local progression-free survival (LPFS) following percutaneous cryoablation (CA) of sporadic extra-abdominal desmoid tumors (EADT).

Methods: All patients undergoing CA for EADT between 2009 and 2024 were included in this retrospective study. Disease progression was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST); morbidity using the Common Terminology Criteria for Adverse Events (CTCAE). Logistic regression analyses were performed to assess associations between patient characteristics, tumor features, procedural parameters, and outcomes related to morbidity and LPFS.

Results: Morbidity analysis included 75 patients. CTCAE grade 1-2 and grade 3-4 events occurred in 38/75 (50.7%) and 8 patients (10.7%), respectively. Oncological outcomes data were available in 64 patients. After a median follow-up of 27.5 months (interquartile range, 13.75-52), disease remained non-progressive in 31 patients (31/64; 48%). Estimated 1-, 3-, and 5-year LPFS rates were 59.6% (95% confidence intervals-CI: 48.2-73.6), 45.6% (95%CI: 33.7-61.7), and 38.5% (95%CI: 26.2-56.5), respectively. Symptom relapse occurred in 27 (27/64; 42.2%) patients, of whom 22 (22/64; 34.4%) showed disease progression. Tyrosine kinase inhibitors (TKIs) were associated with higher morbidity (OR = 53.8; 95%CI: 5.2-2116.1; P < 0.05); complete tumor coverage by the iceball with longer LPFS (OR = 7.14; 95% CI: 1.56-43.2; P < 0.05), symptom recurrence with shorter LPFS (OR = 0.09; 95% CI: 0.02-0.3; P < 0.05). Conclusions: In patients with sporadic EADT treated with CA, prior TKIs are associated with increased morbidity. Complete tumor coverage by the iceball predicts prolonged LPFS, whereas symptom recurrence predicts disease progression.