Desmoid Tumour

Original Editor - Rishab Mishra Top Contributors - Rishab Mishra, Lucinda hampton, Khloud Shreif, Vidya Acharya and Ewa Jaraczewska

Introduction

Desmoid tumors are rare mesenchymal neoplasms that are locally invasive but do not metastasize. They are also referred to as aggressive fibromatosis, deep fibromatosis, or musculoaponeurotic fibromatosis. Despite their non-metastatic nature, these tumors can cause significant morbidity and mortality due to their invasive behavior. The management of desmoid tumors remains complex, with no standardized treatment approach currently available. Effective treatment often requires thorough evaluation and discussion within a multidisciplinary tumor board.

The World Health Organization (WHO) defines desmoid tumors as a "clonal fibroblastic proliferation arising in the deep soft tissues, characterized by infiltrative growth and a tendency for local recurrence without metastatic potential." Although they do not spread to distant sites, these tumors can present as multifocal lesions within the same limb or anatomical region.

Etiology

The exact cause of desmoid tumors remains unknown. Most cases occur sporadically, with approximately 85% linked to mutations in the CTNNB1 gene, which encodes the β-catenin pathway. Three specific mutations have been identified: 41A, 45F, and 45. Among these, the 45F mutation is associated with a higher risk of recurrence. Studies have reported that the 5-year recurrence-free survival rates are 23% for patients with the 45F mutation, 57% for those with the 41A mutation, and 65% for individuals without any identified mutations.

Epidemiology

Desmoid tumors are rare, with an incidence of approximately 2 to 4 cases per million individuals, accounting for just 0.03% of all neoplasms. These tumors most commonly occur in individuals aged 30 to 40 years, with a higher prevalence in women than in men. While desmoid tumors can develop at any age, they are most frequently observed between 15 and 60 years. They may arise in various locations, including abdominal, intra-abdominal, and extra-abdominal regions. Additionally, about 5% to 10% of cases are associated with familial adenomatous polyposis (FAP).

Pathophysiology

The pathophysiology of desmoid tumors is rooted in the dysregulation of the Wnt signaling pathway. Mutations in the CTNNB1 gene, which encodes β-catenin, or germline mutations in the adenomatous polyposis coli (APC) gene, result in the accumulation of β-catenin protein. This accumulated β-catenin translocates to the nucleus, where it activates the expression of Wnt target genes. This activation leads to the production of various proteins, including cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), which contribute to tumor growth. Notably, these proteins are also therapeutic targets for certain medications used in the treatment of desmoid tumors.

Evaluation

MRI

Imaging Studies: Imaging plays a critical role in diagnosing and evaluating desmoid tumors. Techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) are commonly used to determine tumor size, location, and extent of invasion into surrounding tissues. MRI, in particular, is preferred due to its superior soft tissue contrast.

Histological Evaluation: Histopathological analysis remains essential for confirming the diagnosis of desmoid tumors. Tissue biopsy typically reveals spindle-shaped fibroblastic cells arranged in a collagenous stroma. The absence of nuclear atypia and mitotic activity helps distinguish desmoid tumors from other sarcomas.

Immunostaining: Immunohistochemistry is a valuable tool for further characterizing desmoid tumors. Tumor cells typically show positive staining for markers such as β-catenin and vimentin. Nuclear β-catenin staining, in particular, is considered a key diagnostic feature and is frequently used to confirm CTNNB1 mutations.

Next-Generation Sequencing (NGS): Advances in genomic technologies, such as NGS, have enhanced the understanding of desmoid tumor biology. NGS can identify mutations in the CTNNB1 or APC genes, which are implicated in the development of desmoid tumors. This information can help tailor treatment strategies and assess the risk of recurrence.

Colonoscopy and Genetic Assessment: In cases associated with familial adenomatous polyposis (FAP), colonoscopy and genetic testing are essential. These assessments help identify germline mutations in the APC gene and evaluate the risk of other FAP-related complications. Screening family members for APC mutations is also crucial in these cases.

Treatment/Management

Surgical Treatment:

The primary goal of surgery for desmoid tumors is to preserve limb function and protect critical structures. Unlike other soft-tissue sarcomas, where achieving microscopic negative margins (R0 resection) is a priority, an R0 resection in desmoid tumor surgery is considered desirable but not mandatory. Functional preservation often takes precedence over extensive resections.

Radiation Therapy:

Radiation therapy is typically employed as an adjuvant treatment in cases where surgical margins are positive or when surgical resection is not feasible. It can help control tumor growth and reduce the risk of local recurrence.

Systemic Therapy:

Systemic therapy is generally reserved for patients experiencing rapid tumor growth or when the tumor poses a threat to critical structures. This approach may include the use of targeted therapies, chemotherapy, or other systemic agents to manage tumor progression effectively.

Hormonal Therapy:

Hormonal therapy may be considered in certain cases, particularly when the tumor is hormone-sensitive. Agents such as tamoxifen have been explored for their potential to inhibit tumor growth by targeting hormonal pathways.

When evaluating a desmoid tumor, it is crucial to consider other conditions that may present with similar clinical or radiological features. The differential diagnoses include:

• Breast Cancer: Particularly in cases where the tumor is located in the chest wall or breast region.
• Dermatological Manifestations of Gardner’s Syndrome: Skin lesions associated with Gardner’s syndrome may mimic desmoid tumors.
• Familial Adenomatous Polyposis (FAP): Desmoid tumors can arise in the context of FAP, but other associated conditions should be ruled out.
• Fibrosarcoma: A malignant tumor of fibroblastic origin that can resemble desmoid tumors histologically.
• Gastrointestinal Stromal Tumor (GIST): A mesenchymal tumor of the gastrointestinal tract that can present with overlapping features.
• Inflammatory Myofibroblastic Tumor: A rare tumor with fibroblastic and myofibroblastic proliferation, often requiring differentiation from desmoid tumors.
• Retroperitoneal Fibrosis: A fibrotic condition that may mimic desmoid tumors in retroperitoneal locations.
• Sclerosing Mesenteritis: Chronic inflammation and fibrosis of the mesentery, potentially confused with desmoid tumors in intra-abdominal regions.
• Solitary Fibrous Tumor: A fibroblastic tumor that can occur in similar anatomical locations.

Physiotherapy

A personalized rehabilitation program was meticulously designed to address pain management, restore range of motion (ROM), improve muscle strength, and enhance overall functional capabilities. The rehabilitation process commenced on the third day after surgery, ensuring early intervention to promote recovery.

The treatment strategy adopted a phased approach, beginning with gentle passive and active-assisted movements. These exercises aimed to prevent joint stiffness and promote mobility. Gradually, the plan advanced to include scar management techniques, targeted strength-building activities, and functional training. Each stage was carefully structured to support the patient's journey toward regaining full functional independence and improving their quality of life.

Complications

SITES

Complications associated with desmoid tumors primarily result from their tendency to compress neurovascular structures or invade adjacent organs, bones, or soft tissues. The symptoms vary depending on the tumor's location and the structures affected. Patients may experience significant pain, functional impairment, or deformities, while tumors encroaching on neurovascular structures can lead to compromised blood flow or nerve function. In cases where symptoms are severe or rapidly progressing, early intervention and initiation of treatment are often necessary to prevent further complications.