Diagnosis
Diagnosis
Desmoid fibromatosis (DF)/Desmoid-type fibromatosis
Discussion
DF is a rare myofibroblastic neoplasm characterized by infiltrative growth, a tendency for local recurrence, and lack of metastatic potential. It accounts for less than 3% of all soft tissue tumors. Although histologically bland and lacking metastatic capability, desmoid-type fibromatosis can demonstrate a relentlessly progressive clinical course, leading to significant morbidity due to local invasion of adjacent structures.
DF most frequently arises in the extremities but may also occur in the abdominal wall, intra-abdominal cavity, retroperitoneum, and chest wall. Abdominal wall lesions are particularly common in women of reproductive age and have been associated with prior trauma, surgical procedures, and pregnancy. DF may occur sporadically or in association with familial adenomatous polyposis (FAP), especially Gardner syndrome. In the syndromic setting, germline APC mutations are implicated, whereas sporadic cases most commonly harbor activating mutations in the CTNNB1 gene encoding β-catenin. Recognition of this association is clinically important, as identification of DF—particularly in intra-abdominal or abdominal wall locations—should prompt consideration of underlying APC-associated polyposis and appropriate genetic counseling and surveillance.
Histologically, DF is composed of long, sweeping fascicles of uniform, bland spindle cells that often extend across an entire low-power (10× objective) field. The lesional cells resemble fibroblasts or myofibroblasts and exhibit pale eosinophilic or amphophilic cytoplasm, elongated nuclei with fine chromatin, and inconspicuous nucleoli. Cytologic atypia is minimal or absent, and mitotic figures are rare. The stroma is variably collagenous, and thin-walled blood vessels with perivascular edema are frequently observed. An infiltrative growth pattern with entrapment of adjacent skeletal muscle or adipose tissue is characteristic, and lymphoid aggregates may be seen at the advancing edge of the lesion. Immunohistochemically, tumor cells typically express smooth muscle actin (SMA) reflecting myofibroblastic differentiation. Approximately 80% of cases demonstrate nuclear β-catenin expression, which serves as a valuable diagnostic marker. In small biopsies or in cases with negative or equivocal β-catenin staining, molecular testing for CTNNB1 mutations may be helpful for confirmation.
The differential diagnosis DF includes several benign and low-grade spindle cell lesions:
Low-grade fibromyxoid sarcoma (LGFMS): may mimic fibromatosis due to its deceptively bland cytology. However, LGFMS typically shows alternating fibrous and myxoid areas, whorled growth, and characteristic curvilinear vasculature. MUC4 immunohistochemistry is strongly and diffusely positive in LGFMS and serves as a sensitive and specific marker. In contrast, desmoid-type fibromatosis lacks MUC4 expression and demonstrates nuclear β-catenin positivity.
Scar tissue (reactive fibrosis): can closely resemble fibromatosis, particularly in patients with prior trauma or surgery. However, scars generally lack a mass-forming growth pattern, display zonation with more cellular areas in early lesions and dense, hyalinized collagen in more mature regions. In addition they do not show diffuse nuclear β-catenin staining or CTNNB1 mutations.
Gardner fibroma: is a hypocellular, collagen-rich lesion associated with FAP and may precede the development of desmoid-type fibromatosis. It is typically more collagenized and less cellular than DF and lacks the long sweeping fascicles and infiltrative myofibroblastic proliferation characteristic of desmoid tumors.
Additional considerations may include nodular fasciitis, although it is usually more cellular, demonstrates tissue culture–like growth and harbors USP6 rearrangement. However, focal, nodular fasciitis-like areas can also be seen in desmoid fibromatosis.
Management of DF has evolved significantly. Active surveillance is now an increasingly accepted initial approach for asymptomatic or stable disease, as some tumors may remain indolent or even regress spontaneously. Surgical resection is generally reserved for symptomatic or progressive lesions, with the goal of achieving negative margins when feasible; however, margin status alone does not fully predict recurrence risk. Recurrence rates vary widely and are influenced by tumor location, size, and mutation subtype. Notably, CTNNB1 S45F mutations might be associated with a higher risk of recurrence compared with other mutation types. In patients with FAP, lifelong surveillance is essential due to the risk of gastrointestinal and extracolonic manifestations.
In summary, DF is a locally aggressive myofibroblastic neoplasm with distinct morphologic and molecular features. Accurate diagnosis is essential not only for appropriate local management but also for identifying patients who may require genetic evaluation and long-term surveillance for associated syndromic conditions.
References
- Fallen T, Wilson M, Morlan B, Lindor NM. Desmoid tumors -- a characterization of patients seen at Mayo Clinic 1976-1999. Fam Cancer. 2006;5(2):191-4. doi: 10.1007/s10689-005-5959-5. PMID: 16736290.).
- (Salas S, Chibon F, Noguchi T, et al. Molecular characterization by array comparative genomic hybridization and DNA sequencing of 194 desmoid tumors. Genes Chromosomes Cancer. 2010;49(6):560-568. doi:10.1002/gcc.20766)
- DE Marchis ML, Tonelli F, Quaresmini D, et al. Desmoid Tumors in Familial Adenomatous Polyposis. Anticancer Res. 2017;37(7):3357-3366. doi:10.21873/anticanres.11702
- (Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F (Eds). WHO Classification of Tumours of Soft Tissue and Bone. 5th ed. IARC; 2020)
- (Huss S, Nehles J, Binot E, et al. β-catenin (CTNNB1) mutations and clinicopathological features of mesenteric desmoid-type fibromatosis. Histopathology. 2013;62(2):294-304. doi:10.1111/j.1365-2559.2012.04355.x)
- Bonvalot S, Ternès N, Fiore M, et al. Spontaneous regression of primary abdominal wall desmoid tumors: more common than previously thought. Ann Surg Oncol. 2013;20(13):4096-4102. doi:10.1245/s10434-013-3197-x).