Potential role of the steroid receptor pattern in the response of inoperable intra-abdominal desmoid to toremifene after failure of tamoxifen therapy

Abstract

Dear Editor: Desmoid tumors are rare, non-metastatic soft tissue tumors caused by an abnormal clonal proliferation of fibroblastlike cells with a huge amount of extracellular matrix. Although they can occur sporadically, particularly in the extremities, they typically develop in about 20% of patients with a family history of adenomatous polyposis, in this case, Gardner's syndrome. Desmoid tumors are, in fact, the first cause of death in patients submitted to total proctocolectomy for familial adenomatous polyposis because despite their benign nature, their uncontrolled intra-abdominal growth with mesenteric infiltration usually makes surgical removal impossible. Multiorgan transplantation is usually the final lifesaving option, although the high peri-operative mortality and the risk of further recurrence of the desmoids are grave drawbacks. If feasible, surgical removal is still the most common approach, although the high reported rate of recurrence, up to 30–40%, should discourage this option in favor of other, more conservative treatments. However, this type of tumor usually responds poorly to traditional adjuvant therapy, including radiotherapy and chemotherapy, probably because of the low cellular density. Several other treatments based on non-steroidal antiinflammatory drugs, interferon, imatinib, radio-, and chemotherapy have all been tried with variable success. Recently, increasing attention has been paid to the effect of different anti-estrogen therapies on desmoids, even if the estrogen receptors (ERα and Erβ) issue is controversial. A 32-year-old Caucasian woman underwent total colectomy and ileorectal anastomosis for diffuse colonic polyposis in 1998. The rectum was spared because the polyps, although large, were few and endoscopically removed and in view of the young age of the patient and her desire for future maternity. Histology of the resected specimen revealed multiple adenomatous polyps, some with early cancer foci invading the submucosa. Her family history included several cases with phenotypical evidence of familiar adenomatous polyposis (FAP). Her father died of cancer of the sigmoid colon; one of her sisters died of cerebellar cancer at the age of 8 years (Turcot's syndrome), and another sister was diagnosed with a Gardner's variant of FAP, featuring non-resectable intraabdominal desmoids, at the age of 38 years, and treated with bowel transplantation in 1999. The outcome was very poor, featuring several other operations for desmoids recurrence and death 1 year later. Two other members of the same family (paternal uncles) also died of colonic cancer. Genetic testing revealed a deletion of 5 bp in position 3183 in the APC gene in most of the members of this family, including our patient. One year after the endoscopic removal of the polyps, an abdominal computerized tomography (CT) scan revealed a solid mass in her right iliac fossa measuring 8.5 cm in diameter. Another smaller mass, measuring 6.5 cm, was evident medially, with the same characteristics. Three months There are no sources of support for this article.