Review

Desmoid disease in the context of familial adenomatous polyposis (FAP) consists of a spectrum of lesions, ranging from 3-dimensional tumors to 2-dimensional plaques. Even these plaques can cause symptoms, as they are commonly found in the retroperitoneum or small-bowel mesentery, where they pucker and distort tissues, leading to bowel and ureteric obstruction or ischemia. In the case reported by Venkat and associates,¹ a desmoid tumor distorted the colon of their patient and caused obstruction. Studies have shown that 30% of FAP patients will develop desmoid disease, with intra-abdominal desmoids comprising approximately 50% of cases and abdominal wall desmoids comprising 45% of cases.² Sporadic intraabdominal desmoid tumors are rare, and in patients such as the one presented by Venkat and associates, FAP must be excluded.¹

Excluding Familial Adenomatous Polyposis

Desmoid disease in FAP is associated with 3' mutations in the adenomatous polyposis coli (APC) gene, though the genotype/phenotype correlation is neither universal nor exact. Risk factors for desmoid disease in FAP include female gender, a family history of desmoid disease, the presence of extracolonic manifestations of a germline APC mutation, and the presence of a 3' APC mutation.³ A 3' APC mutation is also associated with increasingly attenuated polyposis; thus, patients carrying germline mutations at the extreme 3' end of APC may have desmoids but few colorectal adenomas.⁴ Therefore, when patients present with an apparently isolated intra-abdominal desmoid tumor, colonoscopy is mandatory. Even if no adenomas are seen, both esophagogastroduodenoscopy and genetic testing for an APC and MYH germline mutation are recommended.⁵ In patients without genetic or phenotypic evidence for FAP, colonoscopic surveillance every 5 years is recommended.

Staging Abdominal Desmoids

The literature concerning abdominal desmoids is full of small series and isolated case reports that often combine FAP-associated cases with sporadic cases. This reporting makes comparison and aggregation of studies and cases difficult. My colleagues and I have developed a system of staging abdominal desmoid disease that makes treatment planning more logical and potentially facilitates analysis of outcomes.⁶ Stage I tumors are small (<10 cm), asymptomatic, and stable. Stage II tumors are also small (<10 cm) but cause moderate symptoms (eg, pain or nausea) and are slowly growing. Stage III tumors are 10–20 cm in diameter and cause severe symptoms (eg, bowel or ureteric obstruction), whereas stage IV tumors are large (>20 cm), rapidly growing, or life threatening (eg, sepsis, fistula, necrosis with hemorrhage). The case presented by Venkat and associates¹ fits stage II. In our experience, the most severely symptomatic desmoid tumors are found in young women with FAP.⁷

Treating Desmoid Tumors

Medical Therapy

There is no predictably effective medical treatment for desmoid disease. The most commonly used options have been discussed in the case report by Venkat and associates¹ and include nonsteroidal anti-inflammatory drugs (NSAIDs; particularly sulindac 150–200 mg bid), estrogen-blocking drugs (tamoxifen up to 120 mg daily; raloxifene 120 mg daily), chemotherapy (methotrexate and vinorelbine, doxorubicin), and imatinib (Gleevec, Novartis).¹ Physicians tend to treat these patients according to the stage of their disease. Patients with stage I disease receive sulindac or no treatment. Patients with stage II disease are treated with sulindac and raloxifene, stage III disease with methotrexate and vinorelbine, and stage IV disease with doxorubicin (most recently, liposomal doxorubicin or doxorubicin hydrochloride [Doxil, Ortho Biotech]).^6,8 The endpoint of treatment is not tumor disappearance but, rather, tumor stabilization and disappearance of symptoms.

Surgery

Surgery is the preferred treatment for abdominal wall desmoid tumors in FAP, as a margin-free resection (R0) is almost always possible. Recurrence rates are high, but morbidity is low.^9,10

Most intra-abdominal desmoids related to FAP are found in the root of the small-bowel mesentery, where they surround the superior mesenteric artery, making them unresectable (unless extensive enterectomy is contemplated).¹¹ In the case presented by Venkat and associates, as with some FAP-associated desmoids, the tumor is more distal in the mesentery.¹ This, plus the location in the mesocolon, allows for the possibility of resection. If an obstructing desmoid is unresectable, other surgical options include bypass or diversion. The risk of recurrence after desmoid excision ranges from 50% to 80%^9–11; thus, surgery should be followed by prophylactic sulindac.

Resectability of intra-abdominal desmoid tumors can be determined by clinical examination (mobility of the mass) and by CT scan. Symptomatic intra-abdominal desmoids should be resected if possible.

Radiation

Desmoid tumors are sensitive to radiation, which is often used for extra-abdominal tumors. For intra-abdominal lesions, the proximity of the intestine makes radiation therapy a dangerous choice and generally a last resort.

Natural History of Desmoid Disease

Two of the challenges posed by desmoid disease are its unpredictability and its clinical heterogeneity. It is difficult to predict the clinical course of desmoid disease in any particular patient. However, in the context of FAP, it has been found that desmoids behave the worst in young nulliparous women⁷ and that pregnancy ameliorates symptoms.¹² In over 100 FAP patients with desmoid disease, 10% experienced complete regression of their tumor and 7% died from aggressive, unresponsive disease; the remaining 83% experienced variable growth and were never desmoid-free, though they were not severely affected.⁷ The patient treated by Venkat and associates¹ was a 46-year-old woman, who might thus have been expected to have a relatively benign course of desmoid disease. Her birth history would have been helpful in further defining the likelihood of symptomatic recurrence. Finally, there was no mention of the presence of plaquelike lesions elsewhere in the mesentery of the bowel during laparotomy.

Summary

An intra-abdominal desmoid tumor has a typical appearance on computed tomography scan and, in the absence of FAP, should be biopsied to exclude low-grade sarcoma or tumors of other histologies. Treatment is based upon resectability and symptomatology. Symptomatic resectable lesions should be removed, whereas asymptomatic lesions may be observed. Nonresectable tumors are treated with NSAIDs, estrogen blockers, or chemotherapy, depending upon the stage of the tumor and the response to therapy. The patient treated by Venkat and associates¹ should undergo esophagogastroduodenoscopy, colonoscopy, and testing for a germline mutation in APC. Abdominal magnetic resonance scan or computed tomography scan should be performed in 6 months, but, thereafter, the interval may be extended, as long as the patient is asymptomatic and previous scans show no recurrence. If APC testing is negative for mutations, and all other tests are normal, colonoscopy every 5 years is reasonable.