Desmoid tumour (desmoid fibromatosis, agressive fibromatosis) is rare but locally aggressive. It is a benign proliferation of myofibroblasts that can cause significant morbidity or even mortality due to local invasion, but it does not have the ability to metastasize. Women are affected twice more than men, at ages comprise between 25-35yo. Abdominal wall and small bowel mesentery are the most frequent locations, but desmoid tumour can occur on the chest wall and extremities.
Desmoid tumour is locally aggressive.
Most of them occur sporadically, but there are cases associated with familial adenomatous polyposis (linked to APC gene mutations). Desmoid tumours are associated with genetic predisposition, pregnancy (common presentation is a post-partum woman with abdominal mass, however it is not contraindication for futures pregnancies), hormonal exposure, trauma and/or surgery. Patients with familial adenomatous polyposis (FAP) have 850-fold increased risk of having a desmoid tumour. Additionally, desmoid tumour has become the main cause of death among FAP population who have had a previous prophylactic colectomy.
Signs and symptoms depend on the tumour location, tumour size, and growing rate. Pain can arise due to increasing size, and because of local growth it can invade or push adjacent organs and cause organ malfunction. Hydronephrosis, bowel obstruction, fistulas, bowel perforation and peritonitis are possible complications. Recurrence rate can be as high as 77%/year. Recurrence risk is associated with younger ages, larger tumours, and anatomic location (extra-abdominal and extremities have higher risk). Natural history can vary: 10% spontaneously disappear; 30% have a cyclic pattern of regression and recurrence; 50% are stable; 10% rapidly grow.
Signs and symptoms depend on the tumour location, tumour size, and growing rate.
This is a rare disease and there is a lack of studies. So... What shall you do?
Surgery with negative-margins is traditionally the preferred approach. However there has been a shift in the treatment towards a "wait and see" strategy, limiting surgery for selective cases. Margin status after surgery is controversial. Some studies concluded that microscopically positive-margin is a risk factor for recurrence, while others concluded that microscopically positive-margin does not affect recurrence and has no impact in survival. I think negative-margins must be our goal, but knowing that microscopically positive-margins may not affect survival can make us think twice if patient's life or body function are in risk if a negative-margin resection is to be achieve. Do not forget that there are other treatment options (keep reading). In this setting, abdominal wall and intra-abdominal desmoid tumours may pose a significant challenge due to their anatomical location. In the latter situation, a mesenteric desmoid tumour may lead to a significant amount of bowel resection causing small bowel syndrome.
To achieve a negative-margin resection, severe complications can arise. In that setting, a microscopically positive-margin may be accepted for some difficult cases.
Abdominal desmoid tumours are unpredictable. Patients submitted to no treatment may see no progression or even regression. Patients submitted to surgery with negative-margins may have a recurrence while others with positive-margins do not. From these data emerged the "wait and see" strategy, which is gaining worldwide acceptance. An initial period of observation following diagnosis may help us identify more indolent tumours and avoid aggressive treatments. Those treatments are indicated for aggressive behaviour tumours that can be identified by means of serial physical evaluations and CT scans. Interestingly, some authors found that patients not treated surgically had similar outcomes as patients submitted to R0 resection and better than those with R1 resection. The question is how to distinguish tumours that need immediate treatment from those that can be kept in observation. It is impossible to answer in the present time. Although no predictive factors for progression have been found, some authors concluded that the majority of patients progress in the first two years. Based on this, a very close surveillance program has been suggested for the first two years following the diagnosis. It is clear to me that this shift in the treatment strategy towards "wait and see" will avoid unnecessary surgeries, which can lead to severe complications. However, more studies are necessary to help us decide between observation and immediate treatment.
"Wait and see" strategy can avoid unnecessary and aggressive surgeries.
Radiation in also a possibility as both adjuvant and definitive treatment. However, its role is still unclear. Why? Most patient treated with radiation are those who have either a recurrence or a positive-margin resection. Additionally, radiation as the unique treatment is only offered to patients with unresectable disease. Even though, there are studies advising the use of radiation with or without surgery, instead of surgery alone. But we must not forget possible bowel complications from radiation, and that there are patients who do not benefit from radiation. Radiation may be freely used for desmoid tumours of the extremities but not for abdominal ones, I think. Decision is not easy and must be multidisciplinary.
Systemic therapy is frequently used for mesenteric desmoid tumours because other treatments are difficult to use in this setting. High morbidity from resection of mesenteric tumours is due to major vessel involvement or potential need for significant amount of bowel resection. Systemic treatments include: hormonal therapy (tamoxifen or raloxifen as anti-estrogen drugs) and non-steroid anti-inflammatory drugs (sulindac); chemotherapy (response up to 79%); targeted therapy (tyrosine kinase inhibitors). Once again, significant bias exists because patients submitted to systemic therapy are those who failed surgical treatment or have unresectable disease. (See references bellow for more information about these treatments).
Decision to offer radiation and systemic therapy must be multidisciplinary.
Nowadays there is a lack of randomised prospective studies comparing therapies. This gap comes from the rarity of this disease. The small number of patients treated does not allow for valid and solid conclusions about which is the best treatment strategy. In several authors' opinion, as well in mine, "wait and see" strategy can be offered to asymptomatic patients with small tumours not invading or pushing adjacent organs. Surgical resection should be offered to symptomatic patients, and negative-margins should be our goal assuring life or body function is not going to be put in risk. A multidisciplinary team is crucial to decide whether both radiation and systemic therapy are indicated, and this decision must be made for each individual patient.
Rare diseases do exist, so learn about them.
References (with links):
Dr. Carlos Eduardo Costa Almeida
General Surgeon