Unraveling the Mystery of Desmoid Tumors: Insights From a Moroccan Tertiary Center.

Desmoid tumors (DTs) are rare, aggressive malignancies developing from clonal fibroblastic proliferation originating from soft tissues. Despite their low metastatic potential, their invasiveness towards neighboring organs and a high recurrence rate contribute significantly to morbidity and mortality, thereby impacting the quality of life of patients. Several therapeutic options are available, but standardized protocols are lacking. In this study, we reviewed 14 cases of DT retrospectively over a period of 15 years, from September 2008 to December 2023. The most prevalent tumor locations were in the extremities, and the majority of patients were female. We identified risk factors in two patients, those being surgical trauma and familial adenomatous polyposis (FAP). Half of the patients underwent surgery for DT, and two received salvage radiotherapy. Systemic therapy was used in the first and second lines and comprised of chemotherapy, endocrine therapy, and non-steroidal anti-inflammatory drugs (NSAI). Active surveillance was proposed in three patients. This is the first retrospective study to assess the characteristics of DT in Moroccan patients in a tertiary care setting. It aims to shed light on the challenges faced in treating these rare tumors in the context of a lack of therapeutic standardization.

Favorable clinical efficacy of cytotoxic chemotherapy in patients with progressive desmoid tumors: a retrospective real-world study.

BACKGROUND: The real-world evidence about the efficacy of cytotoxic chemotherapy in desmoid tumors is still limited. We investigated the efficacy of chemotherapy in the treatment of recurrent or progressive desmoid tumors. METHODS: The patients with desmoid tumors who had received cytotoxic chemotherapy between November 2007 and June 2020 in two tertiary hospitals in Korea were reviewed. RESULTS: A total of 25 patients were included in the analysis. The most common primary tumor site was the intra-abdominal or pelvic cavity (56%), followed by the trunk and abdominal wall (24%), extremities (16%), and head and neck (4%). Sixty percent of the patients had familial adenomatous polyposis and 76% received doxorubicin plus dacarbazine. The objective response rate and disease control rate was 64% (95% confidence interval [CI]: 40.7-82.8) and 96% (95% CI: 77.2-99.9), respectively. With the median follow-up time of 55 months (95% CI: 41.0-68.2), the 3-year PFS rate was 65% (95% CI: 41.1-80.5), and the 3-year OS rate was 89% (95% CI: 63.8-97.3). Grade 3 or 4 hematologic adverse events were reported in 14 patients, all of which were manageable. CONCLUSION: Our real-world evidence suggests that doxorubicin-based cytotoxic chemotherapy can be an effective treatment option for recurrent and progressive desmoid tumors with respect to favorable clinical outcomes.

Giant Intrathoracic Desmoid Tumor - a Case Report.

Desmoid tumors are soft tissue neoplasms arising from fascial and muscle-aponeurotic structure. These tumors are locally aggressive and have a high recurrence rate, even after complete resection. We present the case of a female with a giant intrathoracic desmoid tumor. She underwent complete surgical resection with no disease recurrence. Desmoid tumors' natural history is not well defined and is often enigmatic, making these tumors difficult to manage. Currently, for intrathoracic desmoid tumors, medical treatment is the recommended approach, nevertheless, surgery can be considered in selected patients.

Desmoid Tumors: Current Perspective and Treatment.

OPINION STATEMENT: Desmoid tumors are rare tumors with a tendency to infiltrate locally. The lack of a standard treatment approach makes choosing the most appropriate treatment for patients challenging. Most experts recommend watchful observation for asymptomatic patients as spontaneous regression of tumor is observed in up to 20% of patients. Upfront resection of the desmoid tumor has fallen out of favor due to high morbidity and high relapse rates associated with the tumor. Systemic therapy has evolved over several decades. Where chemotherapy, hormonal therapy, and non-steroidal anti-inflammatory drugs were used over the last several decades, tyrosine kinase inhibitors came to the forefront within the last decade. Most recently, gamma-secretase inhibitors have shown significant clinical benefit in patients with desmoid tumors, bringing forth an entirely new mechanistic approach. Several Wnt pathway inhibitors are also under development. Invasive approaches like cryoablation have also shown clinical benefit in patients with extra-abdominal desmoid tumors in recent years. The recent approval of nirogacestat has ushered in a new era of treatment for patients diagnosed with desmoid tumors. Several new molecules are expected to be approved over the coming years.

TGF-ß signaling promotes desmoid tumor formation via CSRP2 upregulation.

Desmoid tumors (DTs), also called desmoid-type fibromatoses, are locally aggressive tumors of mesenchymal origin. In the present study, we developed a novel mouse model of DTs by inducing a local mutation in the Ctnnb1 gene, encoding ß-catenin in PDGFRA-positive stromal cells, by subcutaneous injection of 4-hydroxy-tamoxifen. Tumors in this model resembled histologically clinical samples from DT patients and showed strong phosphorylation of nuclear SMAD2. Knockout of SMAD4 in the model significantly suppressed tumor growth. Proteomic analysis revealed that SMAD4 knockout reduced the level of Cysteine-and-Glycine-Rich Protein 2 (CSRP2) in DTs, and treatment of DT-derived cells with a TGF-ß receptor inhibitor reduced CSRP2 RNA levels. Knockdown of CSRP2 in DT cells significantly suppressed their proliferation. These results indicate that the TGF-ß/CSRP2 axis is a potential therapeutic target for DTs downstream of TGF-ß signaling.

Update on Familial Adenomatous Polyposis-Associated Desmoid Tumors.

Desmoid tumors (DT) represent the second high risk of tumor in familial adenomatous polyposis (FAP) patients. Although FAP-associated DTs (FAP-DT) are caused by germline mutations in the adenomatous polyposis coli (APC) gene, extracolonic manifestations, sex, family history, genotype, and the ileal pouch anal anastomosis procedure are all linked to the development of DTs in FAP patients. Multidisciplinary management has replaced aggressive surgery as the preferred treatment of DTs. There is growing evidence to support the use of active surveillance strategy as first-line treatment for FAP-DT patients. Radiotherapy for intra-abdominal desmoids is now rarely used because of severe late toxicity. Pharmacotherapy, however, represents a promising future with the improvement of traditional cytotoxic drugs and the investigation of targeted drugs. Although nonsurgery treatment has been used widely nowadays, surgery remains the mainstay when symptomatic or life-threatening DTs are present. Further research will be needed for more optimal clinical practice.

Desmoid Tumors: A Comprehensive Review.

Desmoid tumors (DT) are rare, locally aggressive, fibroblastic soft-tissue tumors that are characterized by infiltrative growth and can affect organs and adjacent structures, resulting in substantial clinical burden impacting patients' health-related quality of life. Searches of PubMed, Embase, Cochrane, and key conferences were conducted in November 2021 and updated periodically through March 2023 to identify articles describing the burden of DT. Of 651 publications identified, 96 relevant ones were retained. Diagnosis of DT is challenging because of its morphologic heterogeneity and variable clinical presentation. Patients visit multiple healthcare providers, often facing delays in correct diagnosis. The low incidence of DT (estimated 3-5 cases per million person-years) limits disease awareness. Patients with DT experience a high symptom burden: up to 63% of patients experience chronic pain, which leads to sleep disturbance (73% of cases), irritability (46% of cases), and anxiety/depression (15% of cases). Frequently mentioned symptoms are pain, limited function and mobility, fatigue, muscle weakness, and swelling around the tumor. Overall, quality of life in patients with DT is lower than in healthy controls. There is no treatment approved by the US Food and Drug Administration for DT; however, treatment guidelines reference available options, such as active surveillance, surgery, systemic therapy, and locoregional therapy. Choice of active treatment may depend on tumor location, symptoms, and risk of morbidity. The substantial burden of illness of DT is related to difficulties in timely and accurate diagnosis, high symptom burden (pain and functional limitations), and decreased quality of life. There is a high unmet need for treatments that specifically target DT and improve quality of life.

Disease and economic burden of surgery in desmoid tumors: a review.

INTRODUCTION: Desmoid tumors (DT) are soft-tissue tumors that infiltrate into surrounding structures with ill-defined margins. Although surgery is a potential treatment option, complete excision with negative margins is not often possible, the postsurgery recurrence rate is high, and surgery can result in disfigurement and/or loss of function. AREAS COVERED: We conducted a literature review to assess the burden of surgery in patients with DT, focusing on recurrence rates and functional deficits resulting from surgeries. Since economic data related to DT surgery is lacking, reviews of surgery costs in soft-tissue sarcomas and of general costs of amputations were conducted. Risk factors for DT recurrence after surgery are young age (<30 years), tumor location (extremities), tumor size (>5 cm in greatest diameter), positive resection margins, and history of trauma in the area of the primary tumor. Tumors in the extremities have the highest risk of recurrence (30%-90%). Lower rates of recurrences have been reported when radiotherapy was used after surgery (14%-38%). EXPERT OPINION: Although effective in specific cases, surgery may be associated with poor long-term functional outcomes and higher economic costs. Therefore, it is imperative to find alternative treatments with acceptable efficacy and safety profiles that do not adversely affect functional aspects in patients.

Osteoma of the Jaw as First Clinical Sign of Gardner's Syndrome: The Experience of Two Italian Centers and Review.

Gardner's syndrome (GS) is a combination of polyposis, osteomas, fibromas, and sebaceous cysts. The aim of the study is to highlight whether maxillofacial osteoma could represent an early detection symptom of GS. Patients with suspected osteoma of the jaw underwent genetic and radiographical examinations. The database gathered 19 patients with oral osteoma that was histologically diagnosed; the whole sample was positive for APC gene mutation. Other cranial and peripheral locations were reported. Osteoma of the jaw is a crucial predictive factor of GS, and dentists and oral and maxillofacial surgeons must be aware of the importance of a timely diagnosis.

Exploring the CXCR4/CXCR7/CXCL12 Axis in Primary Desmoid Tumors.

BACKGROUND: Desmoid tumors have an extremely variable natural history. The uncertainty behind desmoid behavior reflects the complexity, which subtends its development and non-linear advancement. Apart from Wnt- ßcatenin mutation, estrogen receptors, and COX-2 overexpression, little is known about the ability of desmoids to grow and recur while being unable to metastasize. Several tumors have been shown to express the CXCR4/CXCR7/CXCL12 axis, whose functions are essential for tumoral development. AIMS: This study aimed to investigate the expression of the CXCR4/CXCR7/CXCL12 axis in primary desmoid tumors and discuss the potential role of this key-signaling as an antiangiogenic therapeutic strategy. METHODS: In this study, 3 µm-thick consecutive sections from each formalin-fixed and paraffin-embedded tissue block were treated with mouse monoclonal antibodies developed against CD34, CXCR4, CXCR7, and CXCL12. RESULTS: Two distinct vessel populations: CXCR4+ and CXCR4- vessels, have been found. Similarly, chemokine receptor CXCR7 expression in the entire desmoid tumor series positively stained a portion of tumor-associated vessels, identifying two distinct subpopulations of vessels: CXCR7+ and CXCR7- vessels. All 8 neoplastic tissue samples expressed CXCL12. Immunohistochemical positivity was identified in both stromal and endothelial vascular cells. Compared to CXCR4 and CXCR7, the vast majority of tumor-associated vessels were found to express this chemokine. CONCLUSION: It is the first time, as per our knowledge, that CXCR4/CXCR7/CXCL12 axis expression has been identified in a desmoid type-fibromatosis series. CXCL12 expression by neoplastic cells, together with CXCR4 and CXCR7 expression by a subgroup of tumor-associated vessels, was detected in all desmoid tumor tissue samples examined. Since chemokines are known contributors to neovascularization, CXCR4/CXCR7/CXCL12 axis may play a role in angiogenesis in this soft-tissue tumor histotype, thereby supporting its growth.

Intra-abdominal desmoid tumors in familial adenomatous polyposis: How much do clinical and surgical variables interfere with their development?

OBJECTIVE: Familial Adenomatous Polyposis is a complex hereditary disease that exposes the carrier to a great risk of Colorectal Cancer (CRC). After prophylactic surgery, intra-abdominal desmoid tumors are known to be one the most important cause of death. Therefore, recognition of increased-risk patients and modification of operative strategy may be crucial. AIM: The objective of this study was to estimate the desmoid tumor risk in relation to various surgical and clinical variables. METHODS: Patients who had undergone polyposis since 1958 were included in the study. After exclusion criteria were met, those who had developed desmoid tumors were selected to undergo further evaluation. RESULTS: The study revealed that the risk of developing desmoid tumors was associated with various factors such as sex ratio, colectomy, and reoperations. On the other hand, the type of surgery, family history, and surgical approach did not affect the risk of developing desmoid tumors. The data collected from 146 polyposis patients revealed that 16% had desmoid polyps. The sex ratio was 7:1, and the median age at colectomy was 28.6 years. Family history, multiple abdominal operations, and reoperations were some of the characteristics that were common in desmoid patients. CONCLUSION: Recognition of clinical (female sex) and surgical (timing of surgery and previous reoperations) data as unfavorable variables associated with greater risk may be useful during the decision-making process.

Intra-abdominal desmoid tumors in familial adenomatous polyposis: How much do clinical and surgical variables interfere with their development?

Abstract Objective: Familial Adenomatous Polyposis is a complex hereditary disease that exposes the carrier to a great risk of Colorectal Cancer (CRC). After prophylactic surgery, intra-abdominal desmoid tumors are known to be one the most important cause of death. Therefore, recognition of increased-risk patients and modification of operative strategy may be crucial. Aim: The objective of this study was to estimate the desmoid tumor risk in relation to various surgical and clinical variables. Methods: Patients who had undergone polyposis since 1958 were included in the study. After exclusion criteria were met, those who had developed desmoid tumors were selected to undergo further evaluation. Results: The study revealed that the risk of developing desmoid tumors was associated with various factors such as sex ratio, colectomy, and reoperations. On the other hand, the type of surgery, family history, and surgical approach did not affect the risk of developing desmoid tumors. The data collected from 146 polyposis patients revealed that 16% had desmoid polyps. The sex ratio was 7:1, and the median age at colectomy was 28.6 years. Family history, multiple abdominal operations, and reoperations were some of the characteristics that were common in desmoid patients. Conclusion: Recognition of clinical (female sex) and surgical (timing of surgery and previous reoperations) data as unfavorable variables associated with greater risk may be useful during the decision-making process.

Current clinical practice for familial adenomatous polyposis in Japan: A nationwide multicenter study.

Introduction: In Japanese patients with familial adenomatous polyposis (FAP), colectomy tends to be postponed or avoided. Aim: This study aimed to clarify the current clinical practice from a Japanese multicenter cohort study database. Methods: We analyzed the records of 250 patients with non-dense FAP who did not require colorectal cancer removal. The clinical outcomes were compared between patients who received colectomy (n = 142) (Group A) and those who did not receive colectomy (n = 108) (Group B). Results: The colectomy rate based on the age at the final follow-up examination was 46%, 60%, 54%, 65%, at ≤29, 30-39, 40-49, and ≥ 50 years, respectively (P = .11). The development of colorectal cancer did not differ between Groups A and B (25% vs 22% P = .67); however, colorectal cancer was diagnosed at the Tis stage in 88% of the patients with colorectal cancer in Group B, and 34% of the patients with colorectal cancer in Group A (P < .01). Regarding survival, all patients in Group B were alive at the final follow-up examination. In contrast, six patients in Group A died, including three patients with desmoid tumors and one with colon cancer. Conclusion: Over one-third of patients with non-dense FAP (polyps ≤ 1000) in Japan did not receive colectomy at >30 years of age, and patients who managed without colectomy showed acceptable survival with the early diagnosis of colorectal cancer, and a very low incidence of desmoid tumor development, indicating that this approach represents a potential option for the management of selected non-dense FAP patients.

A desmoid tumor with fluorodeoxyglucose accumulation arising from the anastomotic site of postoperative gastric cancer: a case report.

BACKGROUND: Desmoid tumors are extremely rare borderline benign and malignant tumors that do not exhibit accumulation on fluorodeoxyglucose positron emission tomography-computed tomography. In the present study, we report a rare case of a desmoid tumor with fluorodeoxyglucose accumulation at the anastomotic postoperative gastric cancer site. CASE PRESENTATION: A 68-year-old Japanese man underwent robot-assisted laparoscopic distal gastrectomy for early-stage gastric cancer in 2019. The pathological diagnosis was stage IA cancer, and no adjuvant chemotherapy was administered. Two years after surgery, a soft mass appeared on the greater curvature side of the anastomosis on computed tomography. Fluorodeoxyglucose positron emission tomography-computed tomography revealed fluorodeoxyglucose accumulation, which suggested a malignancy; therefore, surgery was performed for diagnostic treatment. The histopathological findings led to the diagnosis of a desmoid tumor. The patient has not experienced recurrence to date. CONCLUSIONS: In the present study, we encountered a desmoid tumor arising from the anastomotic site of a postoperative gastric cancer. This case is rare as fluorodeoxyglucose positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in the desmoid tumor, and a preoperative diagnosis could not be reached. We hope that further studies will improve the accuracy of preoperative diagnosis.

A Giant Sporadic Intra-abdominal Desmoid Tumor in a Male Patient: A Case Report.

Desmoid tumors (DTs) are rare locally aggressive benign soft tissue tumors with an estimated annual incidence of two to four new cases per million people. The giant intra-abdominal mass presents a diagnostic challenge that includes a broad differential diagnosis of gastrointestinal stromal tumor (GIST), fibrosarcoma, retroperitoneal fibrosis, and other malignancies from adjacent organs. We report a case of a 38-year-old male patient with a giant intra­abdominal mass. Magnetic resonance imaging (MRI) of the abdomen and pelvis indicated mucinous cystic neoplasm or gastrointestinal stromal tumor (GIST), but histopathology confirmed it to be a desmoid tumor. The patient was discharged, and on follow-up five months until now, there is no recurrence. This case highlighted the importance of including DT in the differential diagnosis of very large intra­abdominal masses.

Multimodality Imaging Assessment of Desmoid Tumors: The Great Mime in the Era of Multidisciplinary Teams.

Desmoid tumors (DTs), also known as desmoid fibromatosis or aggressive fibromatosis, are rare, locally invasive, non-metastatic soft tissue tumors. Although histological results represent the gold standard diagnosis, imaging represents the fundamental tool for the diagnosis of these tumors. Although histological analysis represents the gold standard for diagnosis, imaging represents the fundamental tool for the diagnosis of these tumors. DTs represent a challenge for the radiologist, being able to mimic different pathological conditions. A proper diagnosis is required to establish an adequate therapeutic approach. Multimodality imaging, including ultrasound (US), computed tomography (CT) and Magnetic Resonance Imaging (MRI), should be preferred. Different imaging techniques can also guide minimally invasive treatments and monitor their effectiveness. The purpose of this review is to describe the state-of-the-art multidisciplinary imaging of DTs; and its role in patient management.

Management of Desmoid Tumors.

The management of desmoid tumors (DT) is shifting toward conservative and patient-tailored strategies. Active surveillance is currently considered the first line of treatment for most DT patients, according to international guidelines. When active treatment is required, several systemic and local treatments are considered. The choice of the first-line systemic therapy and the management of recurrence still represent a therapeutic challenge, for which well-defined and shared guidelines are lacking. Such issues represent the next challenge for The Desmoid Tumor Working Group.

Desmoid tumors located in the abdomen or associated with adenomatous polyposis: French intergroup clinical practice guidelines for diagnosis, treatment, and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFR).

INTRODUCTION: Desmoid tumor (DT) of the abdomen is a challenging and rare disease. The level of evidence available to document their treatment is relatively low, however, recent publications of prospective studies have allowed to precise their management. METHODS: This document is a summary of the French intergroup guidelines realized by all French medical and surgical societies involved in the management of DT located in the abdomen or associated with adenomatous polyposis. Recommendations are graded in four categories (A, B, C and D), according to the level of evidence found in the literature until January 2021. RESULTS: When the diagnosis of DT is suspected a percutaneous biopsy should be performed when possible. A molecular analysis looking for pathogenic mutations of the CTNNB1 and APC genes should be systematically performed. When a somatic pathogenic variant of the APC gene is present, an intestinal polyposis should be searched. Due to a high rate of spontaneous regression, non-complicated DT should first benefit from an active surveillance with MRI within 2 months after diagnosis to assess the dynamic of tumor growth. The treatment decision must be discussed in an expert center, favoring the less toxic treatments which can include broad spectrum tyrosine kinase inhibitor or conventional chemotherapy (methotrexate-vinblastine). Surgery, outside the context of emergency, should only be considered for favorable location in an expert center. CONCLUSION: French guidelines for DT management were elaborated to help offering the best personalized therapeutic strategy in daily clinical practice as the DT therapeutic landscape is complexifying. Each individual case must be discussed within a multidisciplinary expert team.

Huge mesenteric desmoid-type fibromatosis with unusual presentation: A case report.

Introduction: Desmoid-type fibromatosis, also known as desmoid tumors, are rare fibroblastic neoplasms that account for less than 3% of all soft tissue tumors. Although they are benign neoplasms without metastatic potential, they are known to be locally aggressive and may invade adjacent structures leading to fatal complications. Case presentation: We describe the case of a 26-year-old woman who presenting with the clinical picture of acute peritonitis. Emergency surgery was performed and a large poorly-circumscribed heterogeneous tumor was found, occupying the jejunum mesentery and infiltrating the jejunal wall causing its perforation into the abdominal cavity. En bloc resection of the tumor and the involved jejunum was performed. Histology and immunohistochemistry confirmed it to be mesenteric desmoid-type fibromatosis. The postoperative course was uneventful and the patient had no evidence of recurrence 18 months after tumor resection. Conclusions: Mesenteric desmoid-type fibromatosis is a rare condition with insidious growth and locally aggressive behavior. Serious complications such as bowel perforation are rare but possible, as shown in our presentation. Complete surgical resection is the first-line treatment bur high recurrence rates remain problematic.

Case Report: Tyrosine Kinase Inhibitors Induced Lymphadenopathy in Desmoid Tumor Patients.

Tyrosine kinase inhibitors (TKIs) are nowadays a valuable treatment of desmoid tumors, a rare mesenchymal neoplasm. Although many side effects of imatinib and pazopanib, commonly or rarely occurring, have been described, reactional lymphadenopathy has not yet been reported. In this publication, we report two cases of patients with desmoid tumors, treated with pazopanib and imatinib, who developed reactional lymphadenopathy. As this side effect is presented as a newly formed mass, it can result in new diagnostic questions and added imaging tests and can even lead to discontinuation of the treatment. This report may help the clinicians facing similar problems adopt a "watch and wait" approach.