Large desmoid tumour of the small bowel mesentery

A 74-year-old man was being investigated for a pancreatic insulinoma when an incidental mesenteric mass measuring 2.6 cm x 2.5 cm was noticed on CT imaging. A wait-and-see approach was decided on. Thirty-nine months later, the patient presented with symptoms of abdominal obstruction. CT images revealed the mesenteric mass filled majority of the abdominal cavity and measured 29 cm x 26 cm x 16 cm. The patient underwent an open bypass gastrojejunostomy which stopped working a few weeks later due to further compression by the tumour. A debulking surgery was performed: a right hemicolectomy and small bowel resection with excision of the desmoid tumour and bypass gastrojejunostomy. The tumour measured 12.6 kg and was macroscopically visualised to have a white cut surface with a focal translucent area. Microscopic analysis revealed bland spindle cells with pale eosinophilic cytoplasm showing no cytological atypia, in keeping with a mesenteric desmoid tumour. Currently, two and a half years from the debulking surgery, the patient remains well and in remission with planned surveillance.

*Article is in Japanese* An 84-year-old man underwent laparoscopic descending colon resection for colon cancer with stage â… . Follow-up computed tomography(CT), 18 months after surgery showed a soft tissue density nodular mass, 30 mm in size, in the small intestinal mesentery. The surgical resection of the tumor was performed after a thorough examination. Histopathological examination showed spindle-shaped fibroblasts and abundant collagen fibers. Immunohistochemical staining was negative for c-kit and CD34 and positive for α-SMA and β-catenin. From the above, this tumor was diagnosed as intra-abdominal desmoid tumor.

Aggressive fibromatosis (AF) is a rare, benign neoplasm originating from musculoaponeurotic stromal structures characterized by aggressive growth and infiltration of local tissues. To date, only six previous cases of AF involving the larynx have been reported. The present case was that of a 70-year-old female patient with a 5-year history of hoarseness and an enlarging neck mass consistent with aggressive recurrent fibromatosis. MRI displayed a large, solid mass arising from the left anterior cervical space displacing the trachea and upper airway to the right. At one year after the initial radical resection, the patient presented with recurrence. A second radical excision was performed not including a laryngectomy. Radiation therapy was considered for possible local treatment to prevent subsequent tumor recurrence. According to the literature, AF has recurrence rates of up to 40-70% within 18 months. There is only sparse literature to guide treatment. Using the mutations detected in the patient’s AF tissue, an Ingenuity Pathway Analysis (IPA) was used to guide treatment of the recurrence. In the present case, the IPA analysis indicated the use of pazopanib to treat the patient’s cancer. In general, surgery appears to be the treatment of choice for head and neck AF, but the management of recurrence is controversial.

Background: Rare soft-tissue tumors, termed desmoid fibromatosis (DF), are comprised proliferated spindle cell fibroblasts and myofibroblasts embedded in a prominent collagenous stroma. They can occur either sporadically, due to prior trauma or surgery, or may have a genetic component. Clinically, DF has a high infiltrative growth/ local recurrence rate, but does not metastasize. Case description: A 58-year-old male underwent a C5-C7 laminectomy/instrumented fusion. Two years later, he presented with a large gross swelling on the right side of the neck. The lesion was removed and proved to histologically consist of DF. Within the first postoperative 12 months, tumor did not recur. Conclusion: Sporadic DF may follow trauma or prior surgery. Symptomatic tumors are treated by surgical en bloc resection (preferably R0). If lesions are inoperable, partially resected, or recur, different hormonal/ chemotherapeutic systematic treatment options are available (e.g., tamoxifen or tyrosine kinase inhibitors). In the future, better molecular understanding of DF likely offers additional therapeutic approaches (e.g., immune checkpoint inhibitors).

Introduction: Desmoid-type fibromatosis (DTF) is a rare, soft tissue tumour. Sorafenib, a multikinase inhibitor, has demonstrated antitumour efficacy in DTF patients. Little is known about the underlying molecular mechanisms, which are crucial to know to further optimize systemic treatments. Here we investigated the molecular effects of sorafenib exposure on DTF and stromal cells, with an emphasis on cell death mechanisms. Material and methods: DTF primary cell cultures, with known CTNNB1 status, and primary stromal cell cultures, derived from DTF tissue, were exposed to clinically relevant concentrations of sorafenib in the presence or absence of inhibitors of ferroptosis, apoptosis and autophagy. Cell viability was determined after 24 and 48 h using MTT assays. Annexin V/PI staining, lipid peroxidation analysis and immunoblotting were performed to assess apoptosis, ferroptosis and autophagy. Results: Exposure to sorafenib caused a significant, concentration- and time-dependent decrease in cell viability in all primary DTF and stromal cell cultures. Inhibitors of ferroptosis and apoptosis protected against sorafenib-mediated cytotoxicity implicating that both cell death mechanisms are activated. Annexin V/PI stainings and lipid peroxidation analyses confirmed induction of apoptosis and ferroptosis, respectively. Autophagy inhibition enhanced the cytotoxic effect of sorafenib and led to a stronger induction of apoptosis and ferroptosis. Conclusion: This study identified ferroptosis and apoptosis as mechanisms for the sorafenib induced cell death in DTF cells as well as stromal cells. Furthermore, autophagy inhibition enhanced the cytotoxic effects of sorafenib. Knowledge of the mechanisms by which sorafenib affects DTF at a cellular level may help to optimize its clinical efficacy and mitigate toxic effects.

Desmoid-type fibromatosis (DF) is a distinctly rare condition, mostly of younger adults, characterized by the development of locally aggressive tumors of mesenchymal origin. Desmoid tumors (DT) arise either sporadically or in association with FAP (familial adenomatous polyposis), although certain risk factors have also been identified, including pregnancy and antecedent surgical trauma. They can emerge from any connective tissue including muscle, fascia and aponeurosis and are therefore classified, according to location, as intra-abdominal, of the abdominal wall and extra-abdominal. Despite the lack of metastasizing potential, the course can be unpredictable. Various mutations of APC and ?-catenin genes, among others, play a catalytic role in the pathogenesis of this neoplastic entity. Surgery has lost its traditional role as first line treatment of the disease and several other treatment methods are being considered. Cytotoxic chemotherapy, non-cytotoxic systemic therapy and targeted therapy have been revealed as part of different treatment regimens. Recent progress regarding DT biology and molecular pathways has led to the development of promising novel biological agents. In any case, a multidisciplinary approach is required and is gradually employed, espe-cially in intra-abdominal DTs. In this review, we aim to present current knowledge on DF and summarize current treatment regimens as well as their effectiveness, with emphasis on the intraperitoneal type of DT.