• Arie J Verschoor, Anne-Marie Cleton-Jansen, Pauline Wijers-Koster, Cheryl M Coffin, Alexander J Lazar, Remi A Nout, Brian P Rubin, Hans Gelderblom, and Judith V M G Bovée.
• Departments of *Medical Oncology †Pathology ∥Radiation Oncology, Leiden University Medical Centre, Leiden, The Netherlands ‡Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Centre, Nashville, TN §Department of Pathology, Sarcoma Research Center, The University of Texas M.D. Anderson Cancer Center, Houston, TX ¶Robert J. Tomsich Pathology and Laboratory Medicine Institute, and Molecular Genetics, Cleveland Clinic, Taussig Cancer Centre and Lerner Research Institute, Cleveland, OH.
• Am. J. Surg. Pathol. 2015 Dec 1; 39 (12): 1701-7.

AbstractDesmoid-type fibromatosis is a rare, highly infiltrative, locally destructive neoplasm that does not metastasize, but recurs often after primary surgery. Activation of the Wnt/β-catenin pathway is the pathogenic mechanism, caused by an activating mutation in exon 3 of CTNNB1 (85% of the sporadic patients). Radiotherapy is a frequent treatment modality with a local control rate of approximately 80%. In very rare cases, this may result in the development of radiation-induced sarcoma. It is unclear whether these sarcomas develop from the primary tumor or arise de novo in normal tissue. In 4 tertiary referral centers for sarcoma, 6 cases of desmoid-type fibromatosis that subsequently developed sarcoma after radiotherapy were collected. The DNA sequence of CTNNB1 exon 3 in the desmoid-type fibromatosis and the subsequent postradiation sarcoma was determined. Sarcomas developed 5 to 21 years after the diagnosis of desmoid-type fibromatosis and included 2 osteosarcomas, 2 high-grade undifferentiated pleomorphic sarcomas, 1 fibrosarcoma, and 1 undifferentiated spindle cell sarcoma. Three patients showed a CTNNB1 hotspot mutation (T41A, S45F, or S45N) in both the desmoid-type fibromatosis and the radiation-induced sarcoma. The other 3 patients showed a CTNNB1 mutation in the original desmoid-type fibromatosis (2 with a T41A and 1 with an S45F mutation), which was absent in the sarcoma. In conclusion, postradiation sarcomas that occur in the treatment area of desmoid-type fibromatosis are extremely rare and can arise through malignant transformation of CTNNB1-mutated desmoid fibromatosis cells, but may also originate from CTNNB1 wild-type normal cells lying in the radiation field.

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