Radiation Associated Undifferentiated Pleomorphic Sarcoma of the Neck 2 Decades After External Beam Radiation for Medullary Thyroid Carcinoma: A Case Report and Literature Review.

BACKGROUND Radiation therapy is critical for treating many solid tumors but increases the risk of secondary malignancies due to DNA damage. Radiation-associated sarcomas (RAS) occur in 0.03% to 0.8% of irradiated patients, typically 5 to 20 years after treatment. Undifferentiated pleomorphic sarcoma (UPS) is a common RAS subtype with poor 5-year survival (12%-14%). Risk rises with doses ≥50 Gy and is especially concerning in previously irradiated head and neck regions, where surgery is challenging. Germline mutations in DNA repair genes (eg, ATM) further increase susceptibility. CASE REPORT A 54-year-old man treated in 2003 for multifocal medullary thyroid carcinoma (thyroidectomy, bilateral neck dissection, adjuvant 59.4 Gy radiation) presented 22 years later with a painless neck mass. Imaging showed a 1.9-cm enhancing lesion within the prior radiation field. Excision revealed a 4-cm, FNCLCC grade 3 intramuscular UPS meeting the modified Cahan criteria for RAS. Immunohistochemistry excluded recurrent thyroid carcinoma. Margins were positive, but re-excision and re-irradiation were not feasible. The sarcoma tumor board recommended close surveillance and germline testing. This case involved high-grade UPS arising 2 decades after neck irradiation. Compared with sporadic UPS, RAS-associated UPS has worse disease-specific survival (~52% vs 76%) and higher local recurrence (~55% vs 24%), emphasizing the importance and difficulty of achieving negative margins in previously irradiated fields. CONCLUSIONS As cancer survival improves, lifelong vigilance for RAS remains essential. New masses in irradiated areas require prompt evaluation. Multidisciplinary management and consideration of genetic testing are critical, as treatment options are often limited by prior therapy.