Aggressive fibromatosis in the submandibular region of a child

Aggressive fibromatosis is proliferation of well-differentiated fibroblasts. Submandibular region is rare location for fibromatosis. We report a case of a rapidly growing mass in submandibular region of 5-year-old girl, excised surgically and ascertained to be aggressive fibromatosis on histological examination. Recovery was uneventful, and she was disease-free in 6-month follow-up.

Desmoid tumors are rare soft tissue tumors that can have aggressive infiltrative growth and relapse locally. Desmoid tumors can impact functionality and cause treatment-related morbidity and mortality. Here, the authors review current management strategies and avenues for further investigation. As part of the evolution of therapy away from primary surgical approaches to less invasive options, image-guided ablation has been accepted as less morbid and include cryoablation and high-intensity focused ultrasound. Systemic therapy options currently include hormonal agents, nonsteroidal anti-inflammatory drugs, tyrosine kinase inhibitors, and anthracycline-based regimens. Hormonal agents and nonsteroidal anti-inflammatory drugs have benign side effect profiles but generally limited efficacy. Anthracycline-based therapies are limited by the risk of secondary malignancies and cardiomyopathy. Tyrosine kinase inhibitors are well studied, and sorafenib is now one of the most utilized therapies, though limited by its side effect profile. Nirogacestat (PF-0308401) is an investigational small molecule gamma-secretase (GS) inhibitor that has demonstrated efficacy in phase 1 and II trials. A phase III trial investigating patients with desmoid tumors or aggressive fibromatosis is estimated to be completed December 2021 (NCT03785964). In addition to nirogacestat, the gamma-secretase inhibitor AL102 is being investigated for the treatment of patients with progressing desmoid tumors in the phase II/III RINGSIDE trial. Finally, the beta-catenin inhibitor Tegavivint (BC2059) is being investigated in a phase 1 open-label trial in patients with a proven primary or recurrent desmoid tumor that is unresectable and symptomatic or progressive.

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.

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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.