Retroperitoneal sarcoma (RPS) is a rare disease accounting for 0.1%–0.2% of all malignancies. Management of RPS is complex and requires multidisciplinary, tailored treatment strategies at all stages, but especially in the context of metastatic or multifocal recurrent disease. Due to the rarity and heterogeneity of this family of diseases, the literature to guide management is limited. The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaboration of sarcoma experts from all disciplines convened in an effort to overcome these limitations. The TARPSWG has compiled the available evidence surrounding metastatic and multifocally recurrent RPS along with expert opinion in an iterative process to generate a consensus document regarding the complex management of this disease. The objective of this document is to guide sarcoma specialists from all disciplines in the diagnosis and treatment of multifocal recurrent or metastatic RPS. All aspects of patient assessment, diagnostic processes, local and systemic treatments, and palliation are reviewed in this document, and consensus recommendations provided accordingly. Recommendations were guided by available evidence, in conjunction with expert opinion where evidence was lacking. This consensus document combines the available literature regarding the management of multifocally recurrent or metastastic RPS with the practical expertise of high-volume sarcoma centers from multiple countries. It is designed as a tool for decision making in the complex multidisciplinary management of this condition and is expected to standardize management across centers, thereby ensuring that patients receive the highest quality care.

The canonical Wnt signaling pathway is involved in a variety of biological processes like cell proliferation, cell polarity, and cell fate determination. This pathway has been extensively investigated as its deregulation is linked to different diseases, including various types of cancer, skeletal defects, birth defect disorders (including neural tube defects), metabolic diseases, neurodegenerative disorders and several fibrotic diseases like desmoid tumors. In the "on state", beta-catenin, the key effector of Wnt signaling, enters the nucleus where it binds to the members of the TCF-LEF family of transcription factors and exerts its effect on gene transcription. Disease development can be caused by direct or indirect alterations of the Wnt/β-catenin signaling. In the first case germline or somatic mutations of the Wnt components are associated to several diseases such as the familial adenomatous polyposis (FAP) - caused by germline mutations of the tumor suppressor adenomatous polyposis coli gene (APC) - and the desmoid-like fibromatosis, a sporadic tumor associated with somatic mutations of the β-catenin gene (CTNNB1). In the second case, epigenetic modifications and microenvironmental factors have been demonstrated to play a key role in Wnt pathway activation. The natural autocrine Wnt signaling acts through agonists and antagonists competing for the Wnt receptors. Anomalies in this regulation, whichever is their etiology, are an important part in the pathogenesis of Wnt pathway linked diseases. An example is promoter hypermethylation of Wnt antagonists, such as SFRPs, that causes gene silencing preventing their function and consequently leading to the activation of the Wnt pathway. Microenvironmental factors, such as the extracellular matrix, growth factors and inflammatory mediators, represent another type of indirect mechanism that influence Wnt pathway activation. A favorable microenvironment can lead to aberrant fibroblasts activation and accumulation of ECM proteins with subsequent tissue fibrosis that can evolve in fibrotic disease or tumor. Since the development and progression of several diseases is the outcome of the Wnt pathway cross-talk with other signaling pathways and inflammatory factors, it is important to consider not only direct inhibitors of the Wnt signaling pathway but also inhibitors of microenvironmental factors as promising therapeutic approaches for several tumors of fibrotic origin.

Aim: To establish the accuracy of magnetic resonance imaging (MRI) in distinguishing between benign and malignant lipomatous tumors; to evaluate the reproducibility of the MRI interpretation assessing the agreement between judgments of two radiologists with the same experience in soft-tissue sarcomas; to identify an association among MRI findings (size, depth, septa, nodules, signal homogeneity) and nature of the lesion. Materials and Methods: A total of 54 patients (28 men and 26 women), with a mean age of 56 (range=27-84) were included years. All subjects followed-up by the Multidisciplinary Sarcoma Group. The following MRI findings were judged in a blind study by two radiologists: size, localization, septa, nodules and signal homogeneity. A diagnostic indication was then given from among lipoma, atypical lipomatous tumour (ALT) and liposarcoma. Accuracy in distinguishing between benign and malignant lesions, and between lipoma and ALT (Fisher's exact test), inter-operator agreement (Cohen's kappa), association of MRI findings and malignancy of the lesion (Fisher's exact test and odds ratio) were evaluated. Results: The inter-operator agreement was complete (100%). The agreement between diagnostic hypothesis and histological diagnosis was statistically significant (p<0.05). Among the radiological findings taken into account, only septa and signal homogeneity were significantly associated with the malignancy of the lesion (p<0.05). Conclusion: MRI could be helpful in distinguishing lipomatous tumors, allowing biopsy to be avoided in some cases (negative predictive value=100%).