Desmoid tumours

What is a desmoid tumour?

A desmoid tumour is a rare mesenchymal neoplasm characterised by monoclonal fibroblastic proliferation. Also known as aggressive fibromatosis or desmoid fibromatosis, desmoid tumours are locally infiltrative and destructive, with no risk of metastasis.

Desmoid tumours may occur in any type of connective tissue that contains fibroblast cells, including muscle, fascia, and aponeurosis. They most commonly arise in the abdominal wall, limbs, and mesentery. Depending on the site, local invasion from desmoid tumours may lead to severe pain, deformity, and functional impairment, necessitating intervention.

Treatment can be challenging due to the rarity, high risk of recurrence, and variability in presentation of this type of tumour.

Who gets desmoid tumours?

Desmoid tumours have an incidence of around 2–4 per million, per year globally. Typically, they affect young adults between the ages of 35–40 years and are more common in women.

Desmoid tumours may develop in 5–10% of patients with known familial adenomatous polyposis (FAP), and in patients with conditions related to adenomatous polyposis coli (APC) gene mutations.

What causes desmoid tumours?

Pathogenesis is multifactorial, although genetics is thought to play a central role, including mutations in the Wnt/APC/beta-catenin pathway.

Broadly, desmoid tumours can be classified into two categories based on their genetics:

• Sporadic — associated with mutations in the CTNNB1 gene which codes for beta-catenin
• Associated with APC mutations — tumours occurring as part of syndromic conditions such as in patients with a family history of desmoid tumours, known FAP, or Gardner syndrome.

Other proposed risk factors for desmoid tumour development include trauma, recent surgery, and high oestrogen states.

What are the clinical features of a desmoid tumour?

Desmoid tumours most commonly present in the abdominal wall; however, can occur in the head, neck, extremities, and pelvis. Depending on the site of proliferation, patients may experience pain and impaired function, or demonstrate no symptoms.

If the tumour is large enough, it can mimic cancer of the affected organ (eg, breast cancer). In these cases, the only way to establish a definitive diagnosis is to perform a biopsy.

What are the complications of desmoid tumours?

The sequelae of desmoid tumours depends on their location, extent, and infiltrative capacity.

• Intra-abdominal — may cause intestinal or ureteral obstruction or involve the mesenteric vessels.
• Pelvis — may infiltrate the urinary bladder or cause hydrosalpinx.
• Extra-abdominal — may invade the pleura if occurring in the chest or may compress nearby vessels and nerves.

Pain management is crucial due to the potential for long-lasting morbidity.

Desmoid tumours can be more complex in pregnancy – a combination of hormonal signalling, trauma, and mechanical constraints may worsen symptoms during this time.

How are desmoid tumours diagnosed?

Desmoid tumours are usually diagnosed through a combination of imaging, including magnetic resonance imaging (MRI), and biopsy.

Histologically, the tumour is usually poorly circumscribed and composed of proliferating stellate to spindle cells. In most patients, staining for nuclear beta-catenin using immunohistochemistry will be positive and help establish a definitive diagnosis.

Given the high rate of misdiagnosis that occurs, guidelines recommend a second opinion by an expert pathologist for confirmation.

What is the differential diagnosis for desmoid tumours?

A broad range of differentials exist, from fibroblastic sarcomas to reactive fibroblastic/myofibroblastic processes.

Differential diagnoses for extra-abdominal desmoid tumours:

• Fibroblastic sarcoma
• Gardner fibroma.

Differential diagnoses for intra-abdominal desmoid tumours:

• Gastrointestinal stromal tumour
• Solitary fibrous tumour
• Inflammatory myofibroblastic tumour
• Sclerosing mesenteritis
• Retroperitoneal fibrosis
• Secondary to certain drugs or an underlying malignancy.

What is the treatment for desmoid tumours?

In asymptomatic patients, the treatment of desmoid tumours relies on active surveillance with multi-disciplinary team (MDT) input, ideally in an experienced centre given the rarity of the condition.

In patients with active symptoms (ie, volumetric progression and compression symptoms), treatment options are primarily surgical with some scope for radiation therapy and systemic therapy.

• Surgery — especially in patients with symptomatic abdominal wall tumours. However, there is a high risk of relapse, particularly at the site of surgical treatment.
• Radiotherapy — a second-line option where surgery is contraindicated, or an adjuvant therapy in post-surgical patients with positive margins on initial resection.
• Systemic therapies — chemotherapy, targeted biologics, and hormonal therapy are reserved for patients with rapidly growing tumours or where surgery would be inappropriate.

Pregnant patients need to be managed in experienced centres with joint care.

What is the outcome for desmoid tumours?

The clinical outcome of desmoid tumours may be unpredictable. Some tumours resolve spontaneously and others frequently recur despite surgical intervention.

Patients can be divided into four main groups based on tumour progression:

• Spontaneously resolves
• Undergoes cycles of progression and resolution
• Remains stable after diagnosis (most common)
• Progresses rapidly.

Intra-abdominal tumours carry the highest risk of morbidity, and patients with syndromic conditions such as familial adenomatous polyposis (FAP) are more likely to have more invasive, symptomatic tumours.

Treatment focuses on preventing symptomatic disease rather than total cure; in 70% of patients, the tumour recurs following definitive management, such as surgery or radiotherapy.