Genetic profile, risk factors and therapeutic approach of desmoid tumors in familial adenomatous polyposis

Abstract

Introduction Desmoid tumors are the main extraintestinal manifestation of FAP, presenting high morbidity and mortality. It is a neoplasia without metastasis capacity, but with infiltrative growth and with a high rate of recurrence. In familial forms, these tumors are associated with a germinal mutation in the APC gene, with a genotype–phenotype correlation influenced by other risk factors. Materials and methods A review of articles published since the year 2000 in Portuguese, English or Spanish on desmoid tumors in patients with FAP was carried out. A total of 49 publications were included. Results The site of the mutation in the APC gene is related to the severity of FAP and to the frequency of desmoid tumor. Mutations located distally to codon 1309 are associated with a more attenuated polyposis, but with higher frequency of desmoid tumors. Clinically, these tumors may or may not be symptomatic, depending on their size and location. In their treatment, priority should be given to medical therapy, especially in intra-abdominal tumors, with surgery being the last option if there are no other complications. Discussion These tumors are associated with certain risk factors: genetic (mutation site), hormonal (estrogenic environment) and physical (surgical trauma) ones. In young women, a later prophylactic colectomy is suggested. Moreover, the laparoscopic approach to prophylactic surgery seems to be an option that reduces surgical trauma and consequently the appearance of desmoid tumors. Conclusion The step-up medical approach has been shown to be valid in the treatment of intra-abdominal desmoid tumors, and medical treatment should be the first therapeutic option.

Large desmoid tumors in familial adenomatous polyposis: a successful outcome

“…DT may arise sporadically or in the context of an extra-colic manifestation of FAP, and may be intra-abdominal, located in the abdominal wall, or extra-abdominal 5 , 10 , 11. They comprise only 0.03% of all neoplasms and 3% of all soft tissue tumors.…”

“…Therefore, surgical trauma may be implicated as one of the factors capable of leading to the development of DT, and appears unrelated to a specific type of surgery 8. Nevertheless, some authors observed a lower incidence of DT in laparoscopic versus open procedures, so minimally invasive approaches might presumably reduce the risk of the occurrence of DT after prophylactic colectomy in patients with FAP 10 , 19…”

“…In the case of intra-abdominal DT, the approach should be progressive,10 initially with observation,4 followed by medical treatment, as the first line, with non-steroidal anti-inflammatory drugs (NSAIDs; e.g. sulindac or celecoxib, with an efficacy rate close to 50%), or an anti-hormonal agent (tamoxifen or toremifene),14 , 22 , 23 even in estrogen receptor-free DT, because this therapy may still induce a response in that setting 24 , 25.…”

“…The familial form of this neoplasm may occur between 10% and 25% of FAP patients and is attributed to a germline mutation in the adenomatous polyposis coli (APC) gene 8 , 9. The carriers of these mutations have “850 times greater risk than the general population.”2 , 10 The sporadic forms of DT result from somatic mutations in the APC or the beta-catenin genes5 , 11 and are relatively rare, affecting approximately two to five individuals per million per year in the general population 12 , 13…”

“…FAP is an inherited condition “that results from the autosomal dominant transmission of a germline mutation in the APC tumor suppressor gene,” which is located on the long arm of chromosome 5 10. This pathology is characterized by the development of several (hundreds to thousands) of adenomatous polyps in the colon and rectum, with a subsequent risk of developing colorectal carcinoma 14.…”