Sporadic desmoid fibromatosis of the neck after dorsal spondylodesis of the cervical spine

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 F.A.P. (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.

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Fibromatosis of the breast is a rare soft tissue lesion that arises from the mammary tissue or the pectoral fascia. We present a case of fibromatosis in a 39-year-old male patient who developed a right lateral breast mass in several weeks without prior trauma or surgery. Ultrasound-guided core needle biopsy findings included differential diagnoses of nodular fasciitis and fibromatosis. The patient was referred to a breast surgeon and underwent excisional biopsy. Final pathology report confirmed fibromatosis. The patient tolerated the surgery well and will continue to follow up post-operatively for recurrence.

Objective: To assess tumour behaviour and the efficacy of active surveillance (AS) in patients with desmoid-type fibromatosis (DTF). Summary background data: AS is recommended as initial management for DTF patients. Prospective data regarding the results of AS are lacking. Methods: In this multicentre prospective cohort study (NTR4714), adult patients with non-intra-abdominal DTF were followed during an initial AS approach for 3 years. Tumour behaviour was evaluated according to RECIST. Cumulative incidence of the start of an active treatment and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Factors predictive for start of active treatment were assessed by Cox regression analyses. Results: A total of 105 patients started with AS. Median tumour size at baseline was 4.1 cm (IQR 3.0-6.6). Fifty-seven patients had a T41A CTNNB1 mutation; 14 patients a S45F CTNNB1 mutation. At 3 years, cumulative incidence of the start of active treatment was 30% (95% CI 21-39) and PFS was 58% (95% CI 49-69). Median time to start active treatment and PFS were not reached at a median follow-up of 33.7 months. During AS, 32% of patients had stable disease, 28% regressed and 40% demonstrated initial progression. Larger tumour size (?5 cm; hazard ratio (HR) = 2.38 [95% CI 1.15-4.90]) and S45F mutation (HR = 6.24 [95% CI 1.92-20.30]) were associated with the start of active treatment. Conclusions: The majority DTF patients undergoing AS do not need an active treatment and experience stable or regressive disease, even after initial progression. Knowledge about the natural behaviour of DTF will help to tailor the follow-up schedule to the individual patient.