What Is a Desmoid Tumor? What Are Its Symptoms and How Is It Treated?

Desmoid tumors (aggressive fibromatosis) are slow-growing soft tissue tumors that tend to grow locally and do not metastasize , meaning spread to distant organs. Although the disease usually causes no symptoms, some patients may lose organ function depending on tumor location. The term “desmoid” comes from the Greek word “desmos,” meaning band- or tendon-like, and describes tumors with a tendon-like structure ; it was first used in the 1800s.

How common are desmoid tumors?

They have highly heterogeneous subtypes and are extremely rare. They account for %0.03 of all cancers and %3 of soft tissue sarcomas.

Desmoid tumors are very rare tumors. Their annual incidence is 2.4 - 4.3 per million.

How do desmoid tumors progress, and who develops them?

Local recurrence rates are high even after extensive surgery. In patients with Gardner syndrome, a condition associated with familial colon polyps (FAP), they may cause death through loss of vital organ function. This group accounts for %5-15 of all desmoid tumors, usually located within the abdomen or abdominal wall.

Beta-catenin, a CTNNB1 gene mutation, is frequently encountered in desmoid tumors associated with familial colon polyps and in the group called sporadic, of unknown cause, which accounts for most desmoid tumors. CTNNB1, AKT1 E17K, BRAF V600E and TP53 R273H mutations may also accompany them.

Because some cases occur during and after pregnancy, they are associated with the female hormone estrogen. Physical trauma and scar tissue formed during healing after surgery may also be triggering factors.

Where in the body are desmoid tumors most commonly located?

Common sites are the trunk, arms and legs, inside the abdomen and the abdominal wall.

Which imaging methods are used to diagnose desmoid tumors?

We use methods such as CT, MRI and ultrasonography. There are no tumor-specific findings on these imaging methods.

For a patient with a soft tissue mass detected on investigations and suspected to be a desmoid tumor, a thick-needle tumor biopsy (core or trucut biopsy) is usually sufficient for diagnosis. Special pathology stains distinguish it from other possible diagnoses. An experienced pathologist readily recognizes the tumor. Under the microscope, the tissue does not show aggressive features or a high mitotic rate. It usually stains positively for vimentin, smooth muscle actin and nuclear beta-catenin, but negatively for desmin, cytokeratins and S-100. These findings may appear in the pathology report.

How are desmoid tumors staged?

Staging (extent of disease) is graded according to tumor size and whether the patient has symptoms. A tumor smaller than 10 cm is stage 1; smaller than 10 cm but symptomatic is stage 2; larger than 10 cm is stage 3; and a size above 20 cm leads to classification as stage 4.

What should be done after a desmoid tumor diagnosis?

If the tumor is small and asymptomatic, it can be observed without intervention; some tumors shrink spontaneously during follow-up. However, considering the difficulties of treating advanced disease, our practical approach in most cases is wide surgical removal without leaving tumor cells behind.

What should be done after desmoid tumor surgery?

Recurrence is not uncommon despite successful surgery. Research shows that recurrence may occur even when pathology demonstrates negative surgical margins, evidence that no tumor remains.

For patients whose tumor is too large to operate on, preoperative radiotherapy may contribute to surgical success by making surgery possible. For patients whose tumors can never be operated on or whose disease has recurred, radiotherapy and certain drugs—hormonal drugs, NSAID painkillers, smart drugs and chemotherapy—can help shrink and control the disease.

Which drugs are appropriate for newly diagnosed inoperable tumors or recurrent disease that cannot be operated on?

Because desmoid tumors are influenced by estrogen, a female hormone, tamoxifen, the hormonal treatment used in breast cancer, may help. Patients may also benefit from medications described as antirheumatic drugs and painkillers, namely NSAIDs.

One of the first smart drugs identified in cancer treatment, containing the active ingredient imatinib, is Glivec , which may provide substantial benefit in this cancer type. Although certain specific tests are performed before using it in other cancers, they are not particularly mandatory in desmoid tumors. Patients may benefit from Glivec even when tumor tissue tests specific to this drug, called C Kyt and PDGFR, are negative. Some may also benefit from Nexavar, containing sorafenib, a smart drug proven effective in kidney and liver cancers. However, these medications are not reimbursed by the social security institution. If your physician wishes to use them, an off-label application to the Ministry of Health is required.

Chemotherapy can be used when none of the drugs above helps and the tumor grows and causes symptoms. Adriamycin, one of the oldest drugs, and vinca alkaloids such as vinblastine and vinorelbine can be used in uncontrolled desmoid tumors. Other options include dacarbazine and temozolomide, drugs used in soft tissue cancers.

A Drug Receives FDA Approval for Desmoid Tumors for the First Time

For adults with progressing desmoid tumors requiring systemic treatment, nirogacestat (Ogsiveo, SpringWorks Therapeutics, Inc.) was approved on 27 November 2023 by the United States Food and Drug Administration (FDA).

Nirogacestat inhibits the activity of an enzyme called gamma-secretase.

Gamma-secretase plays a critical role in the maturation of proteins regulating intracellular signaling pathways and affecting important functions such as cell growth, differentiation and programmed cell death. This enzyme,  Notch signaling pathway  among other signaling pathways, is necessary for activating the proteins involved.

Table: Studies in desmoid tumors and the effects of the drugs used

Progression-free survival: Progression-free survival: the time after treatment during which tumors do not grow.

* Median progression-free survival has not yet been reached for these patients.

Is immunotherapy effective in desmoid tumors?

An older immunotherapy drug, interferon (IFN), did not achieve the desired success with INF treatment in a study of 13 patients. There are currently no studies of the more specific, newly developed immunotherapies. Studies in desmoid tumors are being planned for these agents, which have been successful in many cancers.

Summary

Desmoid tumors are rare, slow-growing soft tissue tumors that grow locally and do not metastasize. Usually asymptomatic, they can sometimes cause loss of organ function. Their annual incidence is very low, and they may arise particularly in association with genetic conditions such as Gardner syndrome and under the influence of the female hormone estrogen. Diagnosis uses imaging and biopsy, while treatment generally involves surgery. Observation and follow-up may also be preferred when tumor size and symptoms are absent. In advanced or recurrent disease, radiotherapy and various drug treatments may be used. Newly developed drugs and immunotherapies are promising developments in desmoid tumor treatment. Indeed, on 27 November 2023, FDA approval of nirogacestat for adults with advanced desmoid tumors requiring systemic treatment was one such innovation. In light of these developments, the effectiveness of drugs used for desmoid tumors and continuous improvement of treatment methods remain important.