Gardner syndrome is characterized not only by typical syndrome including family adenomatous polyposis and extra-intestinal tissue tumor but also by a rare presentation with giant abdominal desmoid tumors during pregnancy [1]. The desmoid tumor can be as large as a fetus and the tumor can be locally aggressive, so it is hard to decide for the available treatment options. In our case, although the celiac desmoid tumor was huge, the fetus was in good condition without intrauterine distress or hypoxia and the fetus development was normal. Therefore, after the natural delivery of the fetus, an operation to remove the desmoid tumor is an appropriate treatment option to avoid fetal dyspnea, dysplasia, and increased maternal mortality. Early operation to prevent local desmoid infiltration and mesenteric desmoid tumors, which is the second leading cause of mortality in FAP patients [2], would have increased the maternal mortality risk. The localization of desmoid tumors is generally classified as intra-abdominal in the abdominal wall or extra-abdominal [3]. Desmoid tumors most commonly involve the extra-abdominal locations in the general population, whereas patients with FAP mostly present with intraabdominal disease. Only 5% of sporadic desmoid tumors are intra-abdominal, but 80% of patients with familial adenomatous polyposis (FAP)-associated desmoid tumors develop intra-abdominal disease [4]. The incidence is 3% for soft tissue sarcomas and about 0.03% for all malignancies [5].
Gardner's syndrome is associated with familial adenomatous polyposis (FAP), involving a mutation in anaphase promoting complex gene and several extra-digestive manifestations: osteomas, epidermal cysts and desmoid tumors [6]. Approximately 7.5% of desmoid tumors are associated with familial adenomatous polyposis (FAP) in the general population. There is a special relationship between desmoids and FAP (Gardner syndrome), with an incidence of 3.5–32% [7]. The usual presentation is a slowly growing mass without associated pain or discomfort. Depending on the location of the tumor, it may present with symptoms such as neurological deficit, joint stiffness or abdominal complaints. In our case, the patient complained of abdominal pain during pregnancy. Despite the significant size of the mass, the abdominal pain was not so severe, hence, the patient presented for delayed consultation. As a result, the fetal growth during pregnancy can be overlooked with the presence of abdominal masses. Moreover, failure to recognize Gardner syndrome combined with familial intestinal polyps resulted in the growth of desmoid tumors in the abdominal cavity. Therefore, we suggested that when a patient with an age of below 30 with FAP and the history of extra-abdominal desmoid tumors, the possibility of intraperitoneal desmoid tumor growth should be taken into consideration. If the patient desire to conceive again, they should go to the hospital for a regular review at least once every 3 months.
Although the mechanism of desmoid tumors remains largely unknown, desmoid tumors might be driven by alterations of the Wnt/APC/β-catenin pathway [8], e.g., sporadic desmoid tumors are associated with somatic mutations of CTNNB1, and germline mutations of APC and somatic mutations of CTNNB1 are probably mutually exclusive. The rate of cases diagnosed with core-needle biopsies and CTNNB1 mutational analysis increased from 30.6 to 40.7% and from 87.8 to 94.1%, respectively. The mean delayed for pathological diagnosis confirmation constantly decreased from 107 to 47 days [9]. In addition, hormonal, genetic and physical factors all play a role in the development and growth of desmoid tumors. Desmoids occur between the age of 15 and 60 years, but particularly during early adolescence and with a peak age of about 30 years. Women during pregnancy have an increased risk for the development of desmoid tumors [3, 10, 11], likely with the sex hormone to be one of the triggers.
Regarding the treatment of desmoid tumors, new alternatives emerged especially in primary non-resectable locations in recent years. Initially, local surgery is the first chosen treatment for desmoid tumors. With advanced techniques, large en bloc surgery is no longer regarded as a cornerstone treatment for desmoid tumors, given that the relapse rate after surgery exceeds 60% in larger series, and that spontaneous regression is documented to be approximately 25% of the cases [12]. Therefore, there is a current shift to a more conservative approach, namely the ‘wait-and-see policy’ [13], which is currently recommended as the first approach in Desmoid-type fibromatosis (DTF) [14]. However, a nationwide prospective cohort [15] showed that there was no difference between patients undergoing an operation and those managed by the wait-and-see policy in terms of two years of event-free survival (EFS). Among the patients with favorable locations (abdominal wall, breast, intra-abdominal and lower limb), the 2-year EFS was similar in patients treated by either surgery or the wait-and-see approach. Among patients with unfavorable locations (chest wall, head and neck and upper limb), the 2-year EFS was significantly enhanced in patients initially managed with the wait-and-see approach compared with those who underwent initial surgery. Nevertheless, systematic therapy is an option in unresectable or recurrent diseases. Available options include hormonal therapies, non-steroidal anti-inflammatory drugs (NSAIDs), interferon, and chemotherapy. The use of hormonal therapy for the treatment of these tumors is based on the association of these tumors with pregnancy or contraceptives pills and reports of regression after menopause or oophorectomy. Success rates of around 50% have been obtained with hormonal treatments and other agents such as NSAIDs, Vitamin C and warfarin. The most common regimen uses high dose tamoxifen at 120 mg per day along with sulindac and chemotherapy (imatinib and doxorubicin) [16]. In our case, we selected surgery to remove the intra-abdominal desmoid tumor after the natural delivery of the fetus and no abnormalities were observed during the 6 months follow-up. Women during pregnancy have an increased risk for the development of desmoid tumors, likely with the sex hormone to be one of the triggers. Therefore, we suggested that when a patient with Gardner syndrome desire to conceive again, they should go to the hospital for a regular review at least once every 3 months.