Primary intracranial aggressive fibromatosis arising in sella turcica: illustrative case

Background: Aggressive fibromatosis is a rare histologically benign but locally infiltrative myofibroblastic tumor. Primary intracranial aggressive fibromatosis (IAF) can exhibit a clinically malignant course. Observations: A 22-year-old otherwise healthy woman presented with left painful ophthalmoplegia. Magnetic resonance imaging (MRI) revealed a left sellar tumor with cavernous sinus invasion. Endoscopic transsphenoidal surgery was performed. The lesion could not be totally resected. An inflammatory myofibroblastic tumor was suspected, so steroid pulse therapy was introduced, but it was ineffective. The tumor recurred after a few months, and she complained of visual acuity loss, abducens nerve palsy, trigeminal neuralgia, and panhypopituitarism. The lesion was diagnosed as primary IAF by a pathological review. Gamma Knife radiosurgery was performed, and chemotherapies were introduced but ineffective. Her consciousness was disturbed, and MRI showed hypothalamic invasion of the tumor, occlusion and stenosis of carotid arteries, and cerebral stroke. Palliative care was introduced, and she died 32 months after the onset. The autopsy revealed tumor invasion to the cavernous sinus, optic nerve, hypothalamus, pituitary, and tonsillar herniation due to massive cerebral stroke. Lessons: Radical resection can be impossible in patients with IAF. Radiotherapy and chemotherapy are not always effective for residual lesions. Adjuvant therapy for IAF remains to be explored.

Desmoid fibromatosis is a locally aggressive myofibroblastic neoplasm. In this study, we report a case of desmoid fibromatosis in the paraspinal muscle that was misdiagnosed as intramuscular schwannoma through incisional biopsy at another hospital. We performed total excision of the mass lesion with a clear margin. We found that for an accurate diagnosis, magnetic resonance imaging, incisional biopsy and excisional biopsy were required.

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.