1. Radiation-induced Sarcomas Occurring in Desmoid-type Fibromatosis Are Not Always Derived From the Primary Tumor.
- Author
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Verschoor AJ, Cleton-Jansen AM, Wijers-Koster P, Coffin CM, Lazar AJ, Nout RA, Rubin BP, Gelderblom H, and Bovée JV
- Subjects
- Abdominal Neoplasms chemistry, Abdominal Neoplasms genetics, Abdominal Neoplasms pathology, Adenomatous Polyposis Coli chemistry, Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli pathology, Adolescent, Adult, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Biopsy, Child, DNA Mutational Analysis, Exons, Female, Fibromatosis, Aggressive genetics, Fibromatosis, Aggressive pathology, Humans, Immunohistochemistry, Male, Middle Aged, Mutation, Neoplasms, Radiation-Induced chemistry, Neoplasms, Radiation-Induced genetics, Prognosis, Sarcoma chemistry, Sarcoma genetics, Tertiary Care Centers, Time Factors, United States, Young Adult, beta Catenin genetics, Abdominal Neoplasms radiotherapy, Adenomatous Polyposis Coli radiotherapy, Cell Lineage, Fibromatosis, Aggressive radiotherapy, Neoplasms, Radiation-Induced pathology, Sarcoma pathology
- 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.
- Published
- 2015
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