Milea Timbergen

8 General Introduction and Aims of this Thesis Desmoid-type fibromatosis (DTF) is a rare, soft tissue tumour with an incidence in the Dutch population of 5 patients per million people per year 1 . The likelihood that a doctor encounters a desmoid patient in his professional career is low, but early recognition, referral to a specialized centre, and accurate treatment are crucial. This thesis describes desmoid- type fibromatosis in the broadest sense and aims to contribute to the knowledge of this rare disease. Desmoid-type fibromatosis has been given a variety of names since its discovery about 185 years ago 2, 3 . These include: aggressive fibromatosis, desmoid tumour, deep fibromatosis, fibromatosis, and desmoid fibromatosis. Just like the variety of names, DTF displays a wide range of clinical presentations and outcomes. DTF has no metastatic potential and cannot undergo malignant transformation. However, it can display aggressive and invasive growth, and has a tendency towards local recurrence. For this reason DTF is classified as a ‘locally aggressive but non-metastasizing’ tumour by the World Health Organization (D48.1) 4 . It mostly affects females aged between 20 and 40 years 1 . The clinical presentation can vary between a small lump without significant symptoms, to a large infiltrating and debilitating tumour, having a significant impact on the patients’ life. Genetics and Molecular Biology DTF tumours express cell surface markers and genes that are characteristic of mesenchymal stem cells and seem to have a mesenchymal origin 5 . It is a clonal fibroblastic proliferation that arises in connective tissue. Since connective tissues comprises a large part of the body’s musculoskeletal system, DTF can develop anywhere in the body 6 . Roughly two types can be distinguished: hereditary (familiar) and sporadic DTF. The hereditary type occurs more frequent in patients with familial adenomatous polyposis (FAP), and causes intra-abdominal DTF tumours. FAP-related DTF is an autosomal dominant disorder caused by germline mutation of the adenomatous polyposis coli (APC) gene. This hereditary condition predisposes to the development of extra- and intra-intestinal neoplasms, including malignant colorectal carcinoma and DTF tumours 7 . The cumulative rate of DTF in FAP patients is 20.6% at 60 years of age 8 . About 10% of FAP patients die from intra-abdominal DTF tumours. After colorectal carcinoma, DTF is the second most common cause of death in FAP 9 . 1