Sporadic mesenteric desmoid-type fibromatosis with “double-hit” T41A and S45P beta-catenin mutation profile: a case report of an extremely rare event—clinically relevant or much ado about nothing?

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Background: Desmoid tumor is a rare non metastasizing neoplasm arising from fascial or deep musculoaponeurotic tissue. Sporadic desmoid tumors are characterized by mutations in the gene-encoding beta-catenin (CTNNB1), in up to 85% of cases. Three major specific mutations of the CTNNB1 gene for sporadic desmoid tumors have been identified, two of which occur at serine 45 (S45F and S45P) and one at threonine 41 (T41A). For the most part, these mutations appear to be mutually exclusive though double-hit mutations have only been rarely reported. Recent studies appear to suggest that CTNNB1-mutated desmoid tumors have a significantly worse recurrence-free survival than wild-type tumors and S45F mutated tumors have been shown to be more aggressive in some series. The therapeutic consequence of these specific mutations is not entirely clear. Case Description: We report herein a 74-year-old female who developed a large mesenteric mass 8 years following gastric bypass (for morbid obesity) and cholecystectomy. Grossly, tumor consisted of a 21.0 cm × 11.0 cm × 7.5 cm fibrous mass located in the mesenteric aspect of the small intestine. Histologic sections show a banal spindle cell proliferation with variable interstitial collagen deposition. By immunohistochemistry, the cells were positive for smooth muscle actin, beta-catenin, focally positive for desmin and negative for S-100, mdm2, DOG1, CD117, MUC4 and CD34, consistent with desmoid type fibromatosis. Furthermore, beta-catenin mutation analysis was positive for c.121A>G resulting in an amino acid change p.T41A (Thr41Ala) as well as DNA change c.133T>C resulting in an amino acid change p.S45P (Ser45Pro). Patient was treated with surgical resection with no systemic therapy and is 18-months post-surgical treatment with no evidence of recurrent disease. Conclusions: We present a unique case of mesenteric desmoid-type fibromatosis (DTF) harboring an extremely rare “double-hit” T41A and S45P beta-catenin mutation profile that so far appears to have a “benign” clinical course following surgical resection alone. While this finding did not appear to impact the treatment strategy or therapeutic outcome in any significant way, the true implication of this mutation profile is unknown. Consequently, routine genotyping of DTF and prospective clinical accrual will help better define molecular subsets with treatment/or prognostic implications.