Desmoid Tumors: Symptoms, Types, Causes and Treatment

Desmoid tumors are rare, locally aggressive growths that can have a profound impact on the lives of those affected. Despite being non-metastatic, these tumors can cause significant pain, functional limitations, and anxiety due to their unpredictable nature and tendency to recur. In this article, we'll explore the symptoms, types, causes, and modern treatment approaches for desmoid tumors—synthesizing the latest research to provide a clear, human-centered overview.

Symptoms of Desmoid Tumors

Desmoid tumors can present with a wide variety of symptoms, making diagnosis challenging. Because their presentation depends greatly on tumor location and size, individuals may experience anything from vague discomfort to severe pain and functional impairment. Many patients experience a high burden of symptoms that can significantly impact daily life and emotional wellbeing.

Symptom	Description	Impact	Source(s)
Pain	Chronic, often severe	Sleep, mood, daily function	1, 2
Swelling	Localized mass or swelling	May limit movement	1, 3
Functional loss	Limited mobility or function	Affects daily activities	1, 2
Fatigue	Persistent tiredness	Reduces life quality	1
Muscle weakness	Reduced strength	May hinder movement	1
Anxiety/depression	Emotional distress	Mental health impact	1, 2

Table 1: Key Symptoms of Desmoid Tumors

Pain and Functional Limitation

Pain is the most common and burdensome symptom, experienced by up to 63% of patients. This pain can be chronic and severe, leading to sleep disturbances (reported by 73% of sufferers), irritability, and mood disorders such as anxiety and depression. In some cases, pain may be the first and only symptom—leading to delays in diagnosis, as patients consult multiple healthcare providers before a correct conclusion is reached 1, 2.

Swelling, Fatigue, and Weakness

Desmoid tumors often cause visible or palpable swelling in the affected area, which can be mistaken for other conditions. As tumors grow, they may interfere with nearby muscles or organs, leading to reduced strength and persistent fatigue 1, 3. When tumors are located in the abdomen, symptoms can include abdominal fullness, early satiety, or gastrointestinal disturbances 3.

Emotional and Psychological Impact

The unpredictable clinical course of desmoid tumors and their frequent recurrences can lead to significant psychological distress. Patients often report irritability, anxiety, and depression resulting from chronic pain, loss of function, and uncertainty about the future 1, 2.

Quality of Life

Overall, individuals with desmoid tumors tend to have a lower quality of life compared to healthy individuals, primarily due to persistent pain, restricted mobility, and emotional challenges. Tools like the GODDESS© symptom/impact scale have been developed to better assess and monitor these impacts during both clinical care and research 2.

Types of Desmoid Tumors

Desmoid tumors are not a single disease but a group of related conditions that differ based on where they arise, whom they affect, and their biological behavior. Understanding these types is critical for both diagnosis and treatment planning.

Type	Common Location	Typical Patient Group	Source(s)
Extra-abdominal	Limbs, chest wall	Young girls, elderly	4, 5
Abdominal	Abdominal wall, mesentery	Fertile & menopausal women, elderly	4, 5
Intra-abdominal	Gastrointestinal tract	FAP patients, post-abdominal surgery	3, 10
Sporadic	Any site	No familial link	8, 13
FAP-associated	Abdominal/mesenteric	Familial adenomatous polyposis patients	8, 10

Table 2: Major Types of Desmoid Tumors

Extra-abdominal Desmoid Tumors

These tumors arise outside the abdominal cavity, most commonly in the limbs, chest wall, shoulder girdle, or head and neck. They are more frequently seen in young females (the "juvenile" group) and in the elderly ("senescent" group), but can occur at any age 4, 5.

Abdominal Wall Tumors

Abdominal desmoid tumors typically affect women of childbearing age ("fertile" group) or those in the menopausal period. They often develop in the abdominal musculature and are sometimes associated with pregnancy or prior surgery 4, 5, 9.

Intra-abdominal Tumors

These occur within the abdominal cavity, often originating from the mesentery or connective tissue around the intestines. Intra-abdominal desmoid tumors are frequently associated with familial adenomatous polyposis (FAP) and can be life-threatening due to the risk of bowel obstruction or compression of vital organs 3, 10.

Sporadic vs. FAP-associated Desmoid Tumors

• Sporadic desmoid tumors arise without a known hereditary pattern and can occur at any anatomical location. They are most often linked to mutations in the beta-catenin gene (CTNNB1) 8, 13.
• FAP-associated desmoid tumors occur in patients with familial adenomatous polyposis, a hereditary cancer syndrome caused by mutations in the APC gene. These tumors are more likely to develop in the abdomen or mesentery and tend to be more aggressive 8, 10.

Age and Sex Distribution

Research has defined four major age-related groups:

• Juvenile (extra-abdominal, predominantly in girls)
• Fertile (abdominal, mostly in women of childbearing age)
• Menopausal (abdominal, sex ratio approaches 1:1)
• Senescent (abdominal and extra-abdominal, equal sex ratio) 4, 5

Each group has distinct biological properties, growth rates, and hormonal associations.

Causes of Desmoid Tumors

The development of desmoid tumors is complex and multifactorial, involving genetic, hormonal, and environmental influences. While the exact cause remains incompletely understood, several key factors have been identified.

Cause/Factor	Description	Contribution	Source(s)
Genetic Mutations	CTNNB1, APC gene mutations	Tumor initiation	6, 8, 10, 11
Hormonal	Estrogen dominance	Promotes growth, esp. in women	5, 9
Trauma/Surgery	Prior injury or surgery	Local tumor development	3, 5, 9, 13
Inherited Syndromes	Familial adenomatous polyposis (FAP)	Higher risk, aggressive course	8, 10, 11
Wound Healing	Aberrant fibroblast proliferation	Tumor origin	11, 13

Table 3: Key Causes and Risk Factors for Desmoid Tumors

Genetic Mutations

The majority of sporadic desmoid tumors are driven by mutations in the CTNNB1 gene, which encodes beta-catenin, a key protein in the Wnt signaling pathway. This pathway controls cell growth and differentiation. In familial cases—particularly those associated with FAP—mutations in the APC gene are responsible 6, 8, 10, 11.

• APC gene mutations: Cause both FAP and FAP-associated desmoid tumors. These mutations lead to deregulated cell growth and a predisposition to both colon polyps and desmoid tumors 10.
• CTNNB1 mutations: Predominate in non-familial (sporadic) cases and can be detected in tumor tissue 6, 8.

Hormonal Influences

Desmoid tumors, particularly those in women of childbearing age, show a distinct relationship with estrogen levels. Fertile women with desmoid tumors often have a hormonal imbalance favoring estrogen, and the tumors themselves frequently contain estrogen receptors. This supports a role for hormones—especially estrogen—in tumor growth and recurrence 5, 9.

Trauma and Surgical History

A significant number of desmoid tumors develop at sites of previous surgery or trauma. For example, up to one-third of patients with abdominal desmoid tumors report prior surgery in the same region. Wound-healing fibroblasts may undergo abnormal growth, triggering tumor formation 3, 5, 9, 13.

Inherited Syndromes

Familial adenomatous polyposis (FAP) is a hereditary syndrome that dramatically increases the risk of desmoid tumors, particularly intra-abdominal ones. In families with FAP, desmoid tumors may have more aggressive behavior and a higher risk of recurrence 8, 10, 11.

Other Contributing Factors

• Pregnancy: Increases the risk and growth rate of desmoid tumors in some women, likely due to hormonal changes 5, 9.
• Bone Malformations: Up to 80% of affected patients have minor bone anomalies, suggesting a shared defect in connective tissue regulation 9.

Treatment of Desmoid Tumors

Because desmoid tumors have an unpredictable clinical course—sometimes growing rapidly, sometimes remaining stable or even regressing—treatment must be individualized. There is no single "best" treatment; instead, a range of options is available, and a multidisciplinary approach is recommended.

Treatment	Approach	Indication/Notes	Source(s)
Active Surveillance	Watchful waiting	Asymptomatic, stable cases	1, 6, 13, 14, 15
Surgery	Tumor removal	Symptomatic, accessible, or progressing tumors	6, 12, 14
Systemic Therapy	NSAIDs, hormonal agents, chemotherapy, targeted therapy	Unresectable, recurrent, or progressing disease	1, 6, 8, 13, 14
Radiation Therapy	Local control	Incomplete resection, select cases	6, 12, 13, 14
Locoregional Therapy	Ablation, cryotherapy	Select cases, clinical trials	1, 14

Table 4: Treatment Options for Desmoid Tumors

Active Surveillance ("Watchful Waiting")

Many desmoid tumors, especially those that are asymptomatic or stable, may not require immediate treatment. Studies show that over half of patients can be managed with observation alone, as some tumors may remain unchanged or even regress 1, 13, 14, 15. Regular imaging and symptom monitoring are essential to ensure timely intervention if the tumor progresses.

Surgery

Surgical removal was traditionally considered the main treatment. However, surgery is now reserved for tumors causing significant symptoms, functional impairment, or life-threatening complications, particularly when the tumor can be removed without excessive morbidity 6, 12, 14. Even with complete removal, recurrence rates remain significant.

Systemic Therapy

For patients with unresectable, recurrent, or progressing tumors, systemic therapies are increasingly used:

• Nonsteroidal anti-inflammatory drugs (NSAIDs): May slow tumor growth.
• Hormonal agents: Such as tamoxifen, particularly given the role of estrogen in some cases.
• Chemotherapy: Used for aggressive or symptomatic disease.
• Targeted therapy: Agents like tyrosine kinase inhibitors (e.g., nirogacestat), targeting molecular pathways involved in tumor growth, are under investigation and showing promise 1, 8, 13, 14.

Radiation Therapy

Radiation can be considered in select cases—such as after incomplete surgical removal or for tumors in locations where surgery is not feasible. The benefit must be weighed against potential long-term side effects, especially in younger patients 6, 12, 13, 14.

Locoregional Therapy

Experimental approaches, such as radiofrequency ablation or cryotherapy, are being explored in clinical trials for select patients 1, 14.

Multidisciplinary and Personalized Care

Given the complexity and variability of desmoid tumors, optimal care involves a team of specialists—including surgeons, oncologists, radiologists, and patient advocates—to tailor therapy to each individual's needs and preferences 6, 12, 14, 15.

Conclusion

Desmoid tumors are rare, locally aggressive growths that present unique challenges in diagnosis and management. Their unpredictable behavior, diverse causes, and profound impact on quality of life require a nuanced and patient-centered approach.

Key points:

• Symptoms are varied but most commonly include pain, swelling, loss of function, fatigue, and emotional distress 1, 2, 3.
• Types of desmoid tumors are defined by their location, patient age, and association with genetic syndromes like FAP 4, 5, 8, 10.
• Causes include genetic mutations (CTNNB1, APC), hormonal influences, trauma, and inherited syndromes 5, 6, 8, 9, 10, 11.
• Treatment is increasingly conservative, favoring active surveillance for many cases, with surgery, systemic therapy, and radiation reserved for progressive, symptomatic, or life-threatening disease 1, 6, 12, 13, 14, 15.
• Multidisciplinary care and individualized treatment planning are essential for optimizing outcomes and preserving quality of life.

For patients and families affected by desmoid tumors, continued research and collaboration promise more effective, less burdensome therapies in the future.