Molecular Pathogenesis of Sporadic Desmoid Tumours and Its Implications for Novel Therapies: A Systematised Narrative Review

Sporadic desmoid-type fibromatosis is a rare, fibroblastic soft-tissue neoplasm with local aggressiveness but no metastatic potential. Aberrant Wnt/β-catenin signalling has been extensively linked to desmoid pathogenesis, although little is known about other molecular drivers and no established treatment approach exists. We aimed to summarise the current literature regarding the molecular pathogenesis of sporadic desmoid-type fibromatosis and to discuss the effects of both current and emerging novel therapies targeting these mechanisms. A literature search was conducted of MEDLINE® ALL and EMBASE databases for published studies (2000-August 2021) using keywords related to ‘fibromatosis aggressive’, ‘immunohistochemistry’, ‘polymerase chain reaction’ and ‘mutation’. Articles were included if they examined the role of proteins in sporadic or extra-abdominal human desmoid-type fibromatosis pathogenesis. Searching identified 1684 articles. Following duplicate removal and eligibility screening, 36 were identified. After a full-text screen, 22 were included in the final review. At least 47% of desmoid-type fibromatosis cases displayed aberrant β-catenin immunoreactivity amongst ten studies. Cyclin D1 overexpression occurred in at least 40% of cases across five studies. Six studies reported oestrogen receptor-β expression with a range of 7.4-90%. Three studies implicated matrix metalloproteinases, with one study demonstrating vascular endothelial growth factor overexpression. One study explored the positive relationship between cyclooxygenase-2 and platelet-derived growth factor receptor-β. Aberrant Wnt/β-catenin signalling is a well-established pathogenic driver that may be targeted via downstream modulation. Growth factor signalling is best appreciated through the clinical trial effects of multi-targeted tyrosine kinase inhibitors, whilst oestrogen receptor expression data may only offer a superficial insight into oestrogen signalling. Finally, the tumour microenvironment presents multiple potential novel therapeutic targets.

Introduction and importance: Desmoid Fibromatosis (DF) represents a rare neoplasm developing from fascial and musculoaponeurotic structures. Preoperative diagnosis of DF is a challenge because of its rarity and nonspecific presentation. Imaging may be helpful for determining the correct diagnosis. Currently there are different clinical treatments of DF including surgical treatment, drug treatment and radiotherapy. Case presentation: A 43-year-old Caucasian male presented to the Emergency Department with a 6-month history of recurrence of post-traumatic chest wall hematoma. Physical examination revealed a partially solid, painless mass on the right anterior chest wall. Laboratory tests reported and neutrophilic leukocytosis. Thoracic contrast-enhanced computed tomography showed a smooth contour, heterogeneous and hypodense subcutaneous soft tissue mass anterior to the right pectoral muscles and to the right 4th-7th rib. The patient underwent surgery: a solid suprafascial neoplasm was completely excised. The postoperative course of the patient was uneventful. Clinical discussion: DF is a soft tissue neoplasm with a tendency for local invasion and recurrence. The course of DF cannot be predicted, being fatal if DF infiltrates vital structures. Diagnosis of DF is difficult and imaging may be helpful for determining the correct diagnosis. Currently the treatment for DF has shifted from surgery (post-operative recurrence rates of 20%-70%) to conservative therapy including watchful waiting. Conclusion: DF is a myofibroblastic proliferative soft tissue tumor and classified as an intermediate malignancy. Preoperative diagnosis of DF needs a high index of suspicion and is facilitated by imaging. Surgery, among different treatments, represents a potentially curative treatment of DF.

No Abstract

Breast fibromatosis is a benign breast tumor of mesenchymal origin, accounting for 0.2% of breast tumors. This study reports two cases of breast fibromatosis highlighting its diagnostic, morphological, therapeutic and evolutionary features. In both cases, this tumor clinically and radiologically mimicked a cancer. Diagnostic confirmation was based on histological examination. Breast fibromatosis was characterized by local progression and a tendency to recurrence, hence the role of surgical excision with free surgical margins in our patients. The role of locoregional treatments (radiotherapy and cryotherapy) and medical treatments, in particular anti-estrogen therapy, is not clearly defined. In conclusion, breast fibromatosis must be known as it mimicks breast cancer and is characterized by a very high recurrence rate, without ever developing metastases.

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.

Introduction. Aggressive fibromatosis, also known as desmoid type fibromatosis (DF) is a locally aggressive fibroblastic neoplasm that can arise anywhere in the body with no potential for metastasis and a high recurrence rate after surgical resection. Mesenteric fibromatosis are locally aggressive DF of the mesentery with a high propensity for bowel involvement. The real etiology of these tumors remains unknown, occurring sporadically or in association with familial adenomatous polyposis (F.A.P.), as Gardnerʼs syndrome. Case report. A 34-year-old female patient presented with a palpable solid tumefactive mass in the left hemiabdomen. Contrast enhanced computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple massive solid tumefactions in the mesentery and in between the small bowel loops. Colonoscopy confirmed the presence of multiple sessile polyps characteristic of FAP. Tissue samples of the mesenteric mass were acquired via ultrasound guided biopsy with histopathologic confirmation of desmoid fibromatosis with imunohistochemical analysis. The risk of surgery was deemed too high at the time due to the size of the mass and proximity to mesenteric vascular structures, therefore the patient was planned for chemotherapy with a potential for further surgical reevaluation. Conclusion. Mesenteric fibromatosis is a rare neoplasm that presents with a wide range of histologic and imaging features. CT and MRI play a crucial role in evaluation and planning an optimal treatment model for patients with mesenteric fibromatosis.