They are rare, we are talking about 5-6 cases per million per year, and are caused by the anomalous proliferation of fibroblasts, the connective tissue cells which have the task of supporting the other tissues. They are desmoid tumors which are also called desmoid fibromatosis or aggressive fibromatosis. And they are so-called intermediate tumors, between benign and malignant. To simplify: they do not cause metastases and after 5 years 99 out of 100 patients are alive, however they tend to give relapses and can be very aggressive locally to the point that, if the mass compresses or obstructs an internal organ, the patient can also suffer death (although very rarely).
Where they are formed
Desmoid tumors can grow anywhere in the body. They can be: extra-abdominal, i.e. affecting the neck, shoulders, limbs, buttocks and these are the forms that recur the most after surgical removal; abdominal when the tumor develops from the muscle bands or from the abdominal or thoracic wall; intraabdominal, if the tumor mass is located in depth. The latter are the rarest but are also the most dangerous, because they can put pressure on the internal organs.
Who they hit
Desmoid tumors affect men and women at any period of life, but are more common between the ages of 18 and 35 and among women, and in particular among those who have recently given birth or who have recently undergone surgery. In fact, among the various causes or contributory causes that could explain the disease, surgical trauma has also been hypothesized, as has a role played by hormones in people with a predisposition towards connective tissue diseases.
by Simone Valesini
Speaking of causes, the desmoid tumor in most cases has a sporadic, i.e. unknown, origin. But more than 8 out of 10 patients (approximately 80-85%) have a somatic genetic mutation (which is therefore not inherited and is not passed down to children) in the CTNNB1 gene or beta-catenin gene. Furthermore, in a small percentage of people (around 10%), the desmoid tumor is associated with Gardner’s syndrome (or Fap, familial adenomatous polyposis). In this case the mutation concerns another gene, the APC tumor suppressor gene which controls cell growth and death (this mutation is germinal, i.e. affecting eggs or sperm, and for this reason Gardner’s syndrome can be transmitted to children) .
by Letizia Gabaglio
What are the symptoms
The symptoms and signs of these tumors depend on their site, that is, where they are located. If the masses are superficial, swellings can be seen with the naked eye, which are generally not painful unless they come into contact with nerve fibers. However, when they are found in the abdomen, there can be pain, cramps, nausea, and if they obstruct nearby organs, such as the intestine or one of the large vessels, they can interrupt their functionality and endanger the patient.
by Letizia Gabaglio
How the diagnosis is made
Given their rarity, it happens that misdiagnoses are made, and desmoid tumors are confused with other neoplasms (for example lipomas or liposarcomas) and surgically removed before a biopsy. But surgery, which until a few years ago was the first treatment option, can encourage recurrence. For this reason, the diagnosis must be performed with a CT scan or magnetic resonance imaging and to confirm the suspicion, a biopsy is necessary, followed by histological and immunohistochemical tests. Finally, beta-catenin gene mutation screening is performed.
How they are treated: surveillance, surgery, cryotherapy, drugs
Each desmoid behaves clinically in its own way and in about half of the cases active surveillance (i.e. checks every 3-4 months) is the best option: as long as the tumor does not grow rapidly or does not risk compressing important organs and does not cause inconveniences, side effects of drugs and the risk of relapses related to surgical removal of the tumor can be avoided. “In more than half of cases, desmoid tumors regress spontaneously or stabilize, and do not require treatment – confirms a Oncoline Antonella Brunello, interim director of the Oncology 1 Operating Unit of the Veneto Oncology Institute (Iov) in Padua – Surgery, which in the past was considered the first therapeutic option, is now an option to be carefully evaluated in a multidisciplinary context. A promising local treatment is cryotherapy which freezes the tumor.”
by Irma D’Aria
Furthermore, desmoid tumors are often sensitive to hormone therapy, in particular to hormone therapy with anti-estrogenic activity: “Given that hormones seem to play a role in desmoid tumors and that in fact we are talking about a disease with a high female prevalence – Brunello continues – among the medical treatments there is hormone therapy, even if today it is in fact used. Some chemotherapy drugs also give good responses, for example the methotrexate-vinorelbine combination and tyrosine kinase inhibitors with antiangiogenic action. Both of these treatments are effective, but less specific than other new targeted drugs: gamma-secretase inhibitors, specific for desmoid tumors. The first of this class of molecules has just been approved in the United States by the Food and Drug Administration (FdA), but there will be others, as more Phase III studies are about to be completed.”
New targeted drugs
These new drugs, explains the expert, inhibit a typical mechanism of these tumors, which is called the Notch signaling pathway which is closely correlated with the beta-catenin signaling pathway: or, to simplify, with the mutation which concerns the large part of the desmoids not related to hereditary-familial forms. The first gamma-secretase inhibitor (the one recently approved in the USA) is nirogacestat. “This drug – concludes Brunello – has given very high survival rates free from disease progression, and excellent response rates: around 40%, compared to 8% for the placebo”.