Benign fibrous tumors can grow in all organs and also in the extremities. The term benign fibrous tumors classically has included a range of rare tumors that are morphologically distinguished as spindle cell tumors. More recently, nonmalignant tumors of fibrous origin have been grouped as either intermediate grade or benign. Intermediate-grade tumors (desmoid tumors, solitary fibrous tumor, fibromatosis) are distinguished by a propensity to invade nearby tissues and organs with greater propensity for local recurrence and, in some cases of solitary fibrous tumor, even metastasis. Those that are considered to be benign (with low invasive potential) include fibromas, nodular fasciitis, and fibrous histiocytomas.^1,2 It is important to describe the main features of the benign fibrous tumors, including clinical presentation, diagnostic strategies, and treatment options.

Desmoid tumors are locally aggressive neoplasms that most commonly occur in men in proximal areas about the shoulder and buttock, followed by the posterior thigh (Figure 1), popliteal space, arm, and forearm. They are benign, enlarging tumors without metastatic potential. Despite their benign nature, they can infiltrate and/or engulf surrounding vessels and nerves, causing dysfunction. Desmoid tumor is also referred to as extra-abdominal desmoid tumor, aggressive fibromatosis, or simple desmoid tumor and is distinct from abdominal desmoid tumors, which are usually seen in young women following pregnancy. Desmoid tumors most commonly occur in older children or young adults. In most patients, a solitary tumor is present, in which mutation of the beta-catenin gene is common. Multicentric involvement can occur in association with the familial adenomatous polyposis variant known as Gardner syndrome. Gardner syndrome is now considered a phenotypic variant of familial adenomatous polyposis and is characterized by polyposis of the large bowel and craniofacial osteomas. It is caused by a mutation in the adenomatous polyposis coli gene located at chromosome band 5q21 and is inherited in an autosomal dominant manner. Intra-abdominal (rather than extra-abdominal or abdominal) desmoid tumors are the most common in patients with familial adenomatous polyposis.^1,2 Both adenomatous polyposis coli and beta-catenin are important components of the Wnt signaling pathway, which has relevance to current strategies for medical treatment.

Desmoid tumors originate from muscle fascial planes and can also occur in tendon sheaths, in joint capsules, and inside bone. Clinically and histologically, they resemble low-grade fibrosarcomas, but they are locally aggressive and tend to recur even after complete resection. Compared with sarcomas, desmoid tumors are poorly encapsulated, making them difficult to resect with negative margins.^1,3

Clinically, desmoid tumors are firm to palpation and frequently cause pain. They tend to grow along muscle planes and often reach considerable size, leading to restricted joint motion about the shoulder, hip, or knee. Diagnosis requires a biopsy, and microscopically the tumor is heavily collagenized but has a low mitotic index, with an appearance similar to plantar fibromatosis. Longitudinally oriented sheaths of fibroblasts and myofibroblasts are surrounded by a collagenous background. For desmoid tumors that do not calcify, imaging is best achieved with MRI, where the tumor will be low signal intensity on T1-weighted images, and intermediate to high signal intensity on T2-weighted images (Figure 1).

In some patients, particularly when the tumor is asymptomatic and found incidentally, observation is a reasonable form of management. Published data suggest that the disease may stabilize in some patients over time.⁴ However, many patients report pain and an enlarging mass. Until recently, in patients with resectable disease, surgical resection with negative margins was used. Currently, surgical resection is more selectively used because of the high recurrence rates following resection. Alternative modalities that are commonly used include cryoablation, high-intensity focused ultrasonography, and medical treatment. In addition, some publications indicate that observational or symptomatic management may be more indicated than previously thought.^5,6,7

Without additional treatment, recurrence following resection is reported in the range of 25% to 50%.³ Radiation therapy is an effective adjuvant, albeit with potential morbidity and complications and could be considered as part of a multidisciplinary treatment approach.⁵ Radiation usually starts 2 weeks postoperatively, to the extent of 50 Gy to the surgical site. Radiation therapy reduces the chance of local recurrence to zero to 40%. In patients for whom surgery would be significantly disfiguring or result in increased morbidity, irradiation can be used as the sole treatment. Irradiation doses of 60 to 65 Gy for gross residual disease and 50 to 60 Gy for microscopic residual disease are recommended. Radiation appears to be less effective in younger patients, and a 2019 study found that the 5-year local control rate was 43% for patients age 30 years or younger compared with 75% for patients older than 30 years.⁵ Amputation may be necessary in rare cases, usually when the patient has multiple recurrences following radiation therapy. Spontaneous involution of desmoid tumors is rare, but has been reported in patients older than 40 years.

Estrogen may play a role in the development of desmoid tumors. Antiestrogenic agents such as tamoxifen are being used in some centers with some reported clinical benefit. Other adjuvant therapies include NSAIDs. In selected patients with progressive disease, chemotherapeutic agents including tyrosine kinase inhibitors,
low-dose vinblastine, and methotrexate can also be used.^2,8 In a double-blind study on the tyrosine kinase inhibitor sorafenib, the 2-year progression-free survival was 81% for sorafenib compared with 36% for the placebo control group.⁹ In 2023, a double-blind randomized phase 3 study on nirogacestat, a gamma-secretase inhibitor of the Wnt signaling pathway, found a 2-year event-free survival of 76% versus 44% for placebo.¹⁰

Fibromatoses are benign, fibrous, clinically aggressive, proliferative processes that occur in the palmar fascia (Dupuytren disease), plantar fascia (Ledderhose syndrome), and penile fascia (Peyronie disease). Palmar fibromatosis is typically seen in older patients and can result in contracture of a finger. Plantar fibromatosis is more common in children and young adults and usually occurs on the medial portion of the arch of the foot (Figure 2). There can be a familial association (in Scandinavians), with a greater incidence in males.^11,12 The etiology is a nodular proliferation of fibrous tissue. On histology, both palmar and plantar fibromas are typically cellular and can be misdiagnosed as a malignant sarcoma. If the lesions are asymptomatic, observation is warranted. However, if pain results, a simple surgical resection can be performed and can be curative. In the most severe cases, complete fasciectomy may be indicated; partial or subtotal fasciectomy frequently results in local recurrence. Most recently, clinical trials have shown that injections of collagenase clostridium histolyticum are an effective, minimally invasive option for treatment of Dupuytren disease. In a prospective randomized trial, collagenase clostridium histolyticum injection followed by joint manipulation improved outcomes compared with placebo.¹³