Abstract
RATIONALE: Primary vaginal adenocarcinoma (PVA) is an exceptionally rare malignancy, with most cases historically linked to in utero diethylstilbestrol (DES) exposure. Non-DES-associated PVA following definitive chemoradiotherapy for cervical cancer is extremely uncommon, and no standardized management protocol exists. This case illustrates a rare instance of radiation-associated PVA and highlights therapeutic considerations in previously irradiated pelvic fields. PATIENT CONCERNS: A 53-year-old postmenopausal woman presented with intermittent vaginal bleeding occurring 5 years after radical hysterectomy and adjuvant chemoradiotherapy for stage IIA2 cervical squamous cell carcinoma. DIAGNOSES: Colposcopy-guided biopsies of the vaginal anterior wall revealed glandular architecture with cytological atypia. Immunohistochemistry demonstrated CK7(+), CK8/18(+), CEA(+), PAX8(-), ER(-), PR(-), p16 patchy weak negative, and wild-type p53. Systemic workup excluded metastatic disease, supporting the diagnosis of PVA (non-DES-associated, radiation-related). INTERVENTIONS: In view of prior pelvic irradiation, the multidisciplinary team recommended dose-adjusted paclitaxel-cisplatin combination chemotherapy. Six cycles were administered, tailored to minimize cumulative toxicity. OUTCOMES: At 6-month follow-up, imaging studies confirmed complete clinical remission, with no locoregional recurrence or distant metastases. LESSONS: This report underscores the potential for radiation-induced secondary vaginal adenocarcinoma in cervical cancer survivors, even after prolonged remission. Vigilant long-term surveillance, including annual vaginal cytology and targeted biopsies, is critical for early detection. Individualized therapeutic strategies - integrating prior treatment history, immunohistochemical profiling, and consideration of molecular alterations - are essential for optimizing outcomes in this rare patient population.