The spectrum of abdominal wall desmoid fibromatosis and the outcomes of its surgical treatment

Background: Desmoid fibromatosis (DF) arises in musculoaponeurotic structures, most commonly the rectus abdominis muscle. It is locally aggressive with no propensity for metastasis. The aim was to describe the spectrum of abdominal wall DF and its surgical treatment and outcome at a tertiary institution. Methods: All abdominal wall DF resected from 2007 to 2019 were retrospectively analysed. The tumours had a fullthickness abdominal wall excision. The defect was reconstructed with biological implants covered by either skin edge undermining or split skin graft. Histological diagnosis was based on characteristic morphological and immunohistochemistry parameters. Parameters analysed were demographics, lesion size, procedure performed and outcomes. Results: Eleven female patients with a median age of 29 years (range 21-61) presented with rapid growth over 6-24 months of anterior abdominal wall tumours with a median maximum resected diameter of 163 mm (range 63-200 mm). There was no specific complication related to the abdominal wall reconstruction. With a median follow-up of 5 years (range 1-11 years), all patients displayed an asymptomatic abdominal wall bulge (eventration). One patient has had a small recurrence currently being observed. Conclusion: Striking features of DF tumours at Chris Hani Baragwanath Academic Hospital (CHBAH) were their location, rapid growth, female gender and large size. Biological implant without complex plastic surgery techniques result in good outcomes, though the rate of progression of eventration to hernia is unknown.

Background: Desmoid fibromatosis (DF) is a locally aggressive rare tumor with high recurrence rate after surgery and unpredictable clinical course. Standard of care for DF patients is active surveillance; 30% of cases undergo disease progression and shift to treatment. Biomarkers discriminating aggressive DF and predicting progressive disease are needed. DF harbors mutations in ?-catenin and a transcriptional ‘inflammatory phenotype’ (PMID: 28627792). Cancer-associated inflammation is fostered by systemic factors and detectable in circulating immune cells. Blood leukocytes thus represent a promising source of prognostic biomarkers for DF patients. In this study we investigate phenotypic and functional features of peripheral blood immune cells to identify DF patients at risk of progression and guide tailored therapeutic approaches. Methods: This is a prospective observational study enrolling DF patients (n=80). Tumor and blood samples collected at diagnosis and during active surveillance will be studied by 1. transcriptomic analysis of DF biopsies; 2. multiparametric flowcytometry and functional profiling of blood cells; 3. RNA profiling of whole blood 4. evaluation of plasma levels of cyto/chemokine and ctDNA of ?-catenin variants. Levels of blood analytes will be correlated with patients’ clinical outcome and integrated with immunological parameters. Results: Peripheral blood immune profile of 40 cases shows that patients display at baseline an altered myeloid profile with respect to healthy donors. An increase in activated granulocytes and granulocytic myeloid-derived suppressor cells, detected by differential co-expression of CD15, CD11b, CD16 and LOX1, is observed, concomitantly, with a boost of monocyte subsets, defined by co-expression of CD33, CD11b, CD14, CD16, HLA-DR and PDL1. These changes are maintained during follow-up in a specific subset of patients. Conclusions: Systemic alterations of immunosuppressive and inflammatory myeloid cell subsets feature the peripheral blood of DF patients and may represent a marker of disease aggressiveness. Transcriptomic data of DF biopsies and of plasma analytes will be also presented.

Desmoid tumors (aggressive fibromatosis) are soft tissue mesenchymal tumors that can be locally invasive and life-threatening. Depending on the location, these tumors are often unresectable or tend to recur after surgery. To date, there are no approved systemic therapies for desmoid tumors. These tumors typically harbor mutations in the ?-catenin oncogene CTNNB1 or the tumor suppressor gene adenomatous polyposis coli, resulting in constitutive activation of the WNT pathway. The Notch pathway is part of the underlying cause for desmoid tumor development, possibly due to crosstalk with the WNT pathway, providing a rationale for Notch inhibition as a therapeutic strategy. The gamma secretase activation of the Notch receptor can be targeted with investigational gamma secretase inhibitors. In this case report, we follow the course of 2 patients with desmoid tumors treated with the highly potent, parenterally administered investigational gamma secretase inhibitor AL101, resulting in long-lasting responses. Case 1 reports on a patient with a mesenteric desmoid tumor who participated in a phase 1 trial and then transitioned into a compassionate use program; Case 2 reports on a patient with recurrent pelvic tumors receiving AL101 through a compassionate use program. After tumor progression on other systemic therapies, Cases 1 and 2 had confirmed partial responses (41% and 60% maximal tumor size decrease from baseline) recorded after 1.0 and 1.6 years of treatment with AL101, with a duration of response of 8.6+ and 2.6+ years, respectively. Also, in a phase 1 study of AL102, a potent orally administered gamma secretase inhibitor that shares structural features with AL101, a patient with a desmoid tumor was noted to have tumor shrinkage. Formal clinical testing of AL102 for the treatment of patients with desmoid tumors that are not amenable to surgery or are refractory to/recurrent from other prior therapies is currently underway.

Introduction: Desmoid tumor is an uncommon tumor with variable spectrum ranged from being a locally lesion to an aggressive and destructive one. The current case aims to report a rare condition of desmoid type fibromatosis of the breast. Presentation of case: A 59-year-old female presented with a right breast mass for 9-months. Mammography showed a small speculated iso-hyper dense mass, just anterior to the pectoralis muscle measuring about 15 mm (M5) in longest axis. Ultrasound examination revealed an irregular mass with internal vascularity and posterior shadowing in the right breast with a single borderline lymph node (25 ? 14 mm of 4 mm cortex). Wide local excision with sentinel axillary lymph nodes biopsy was performed. Histopathological examination of the specimen confirmed the diagnosis of desmoid type fibromatosis of the breast. Discussion: The etiology of this tumor is unknown, however, physical, hormonal and genetic factors have a significant role in the development of desmoid tumor. Conclusion: Desmid type fibromatosis of the breast is an uncommon, benign, locally aggressive fibroblastic tumor with lack of metastatic potential, it may present with features of malignancy.

Intra-abdominal desmoid tumor (IADT) and gastrointestinal stromal tumor (GIST) are both mesenchymal tumors mostly found in gastrointestinal tracts and easily misdiagnosed, which would directly damage the survival prognosis and quality of life of patients. With the advent of the era of precision medicine, the understanding of the above two diseases is more in-depth, and the requirements for accurate diagnosis and individualized precision treatment are more stringent. Moreover, there seems to be some internal relationship between IADT and GIST, and the lack of systematic research and discussion makes clinical decision-making and patient management easy to fall into traps and misunderstandings. Therefore, this paper reviews the clinical characteristics, pathogenesis and treatments of the two, and explore their differences and internal relations, so as to provide research and practical reference for promoting more precise and individualized diagnosis and treatment regimens.

Objective: The mainstay of treatment modality for extra-abdominal desmoid-type fibromatosis (DF) has shifted from surgery, which often impairs ADL/QOL, to conservative treatment including active surveillance. In the present study, we conducted a longitudinal survey on the diagnosis and treatment of DF at facilities belonging to the Japanese Musculoskeletal Oncology Group, which is a research group of facilities specializing in the treatment of bone and soft tissue tumors in Japan to clarify the transition of medical care for extra-abdominal DF. Methods: The same questionnaire was administered in 2015 and 2018, and responses were obtained from 46 (69%) of 67 facilities and 42 (53%) of 80 facilities in 2015 and 2018, respectively. Results: Although immunostaining for ?-catenin was often used for the pathological diagnosis in both 2015 and 2018, CTNNB1 mutation analysis was not performed either in 2015 or in 2018. As for the treatment strategy for resectable cases, surgical treatment including wide resection was selected at 11 facilities (24% of respondents) in 2015, and further decreased to 5 facilities (12%) in 2018. Conservative treatment with active surveillance or medical treatment was the most common treatment for both resectable and difficult-to-resect cases. COX-2 inhibitors and tranilast were often used in the drug treatment of both resectable and difficult-to-resect cases. Few facilities provided radiotherapy, methotrexate and vinblastine, or DOX-based chemotherapy for refractory cases in both 2015 and 2018. Conclusions: A good trend was found in the questionnaire survey. It will be further necessary to disseminate clinical practice guidelines to physicians more widely, and to have them understand and implement the most up-to-date medical practice strategies for this rare disease.