Radiation-induced Sarcomas Occurring in Desmoid-type Fibromatosis Are Not Always Derived From the Primary Tumor. (December 2015)

• Record Type: Journal Article
• Authors: Verschoor, Arie J.; Cleton-Jansen, Anne-Marie; Wijers-Koster, Pauline; Coffin, Cheryl M.; Lazar, Alexander J.; Nout, Remi A.; Rubin, Brian P.; Gelderblom, Hans; Bovée, Judith V.M.G.
• Is Part Of: American journal of surgical pathology. Volume 39:Number 12(2015)
• Publication Date: 2015-12
• Subjects: desmoid-type fibromatosis -- β-catenin -- CTNNB1 -- radiation-induced sarcoma -- radiotherapy; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000000510
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : Desmoid-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.