Secondary Sarcomas: Biology, Presentation, and Clinical Care

Abstract

Secondary sarcomas are a subset of sarcomas that occur in patients with prior cancer diagnoses and are associated with environmental or genetic factors. Although secondary sarcomas are rare in general, there are predisposing factors that can substantially increase this risk in certain populations. Herein, we review the environmental factors with the strongest association of sarcoma risk, including chemical exposure, certain viruses, cytotoxic and immunosuppressive agents, chronic edema, and radiation exposure. Additionally, the most common genetic disorders that carry a predisposition for sarcoma development will be discussed, including hereditary retinoblastoma (RB), Li-Fraumeni syndrome (LFS), neurofibromatosis type 1 (NF1), and DICER1 syndrome. Although treatment does not generally differ for sporadic versus secondary sarcomas, awareness of the risk factors can alter therapeutic strategies to minimize risk, aid prompt diagnosis by increasing clinical suspicion, and allow for appropriate surveillance and genetic counseling for those patients with cancer predisposition syndromes.

A rare metachronous presentation of periductal stromal sarcoma in a case of recurrent rhabdomyosarcoma – Case report

“…In addition, the most common genetic disorders that carry a predisposition for sarcoma development include hereditary retinoblastoma (RB), Li-Fraumeni syndrome (LFS), neurofibromatosis type 1 (NF1), and DICER1 syndrome. 9 Our case had prior chemoradiotherapy owing to the etiological factor and necessitates the need for further genetic analysis.…”

Ewing Sarcoma as Secondary Malignant Neoplasm—Epidemiological and Clinical Analysis of an International Trial Registry

“…While most EwS as SMN cases are likely due to established clinical risk factors for secondary malignancies, such as irradiation and/or chemotherapy, few cases may have a biological predisposition in the form of underlying mutations. There are several genetic syndromes with links to soft-tissue and bone sarcomas, whereas EwS does not appear to be an associated index tumor, unlike osteosarcoma and embryonal rhabdomyosarcoma [ 37 ]. In EwS, a balanced chromosomal translocation t(11;22)(q12;q24) leading to the specific fusion protein EWSR1–FLI1 appears to be genetically responsible for the tumor [ 38 ].…”

Radiation‐induced osteosarcoma in a patient with DICER1 syndrome

“…6 Although radiotherapy increases the risk of sarcoma, radiationinduced sarcoma is rare and occurs in less than 1% of those who receive radiotherapy. 7 To date, radiation-induced neoplasms or osteosarcoma in patients with DICER1 syndrome have not been reported, which may be attributed to the number of reported cases of DICER1 syndrome being still limited and only a few patients treated with radiotherapy. Whether the presence of DICER1 germline pathogenic variant contributed to the pathogenesis of osteosarcoma in this patient is unclear.…”