Primary Clear Cell Adenocarcinoma of the Cervix: A Series of 12 Cases Without Exposure to Diethylstilbestrol

Background and objective Clear cell adenocarcinoma of the uterine cervix (CCAUC) is a rare malignancy, historically linked to in utero diethylstilbestrol (DES) exposure. However, several cases have been reported in non-DES-exposed populations, particularly in Asia. This study aimed to evaluate the clinicopathological features, treatment modalities, and outcomes in patients with CCAUC unassociated with DES exposure. Methods We conducted a retrospective analysis of 12 patients diagnosed with CCAUC between 2015 and 2022 at Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan. All diagnoses were confirmed by central pathology review. Patient data included demographics, clinical presentation, staging (FIGO: International Federation of Gynecology and Obstetrics), treatment details, and outcomes. Treatment approaches varied by disease stage and included surgery, chemotherapy, and concurrent chemoradiotherapy (CCRT). Results The mean age at diagnosis was 46.25 years, with most patients being premenopausal. Tumor size exceeded 4 cm in 83.3% of cases, with 50% cases being either stage FIGO IIB or IIIA. A majority (91.7%) received CCRT. The five-year overall survival was 64.3%, and disease recurrence occurred in 25% of patients, with distant metastases being the most common. Conclusions CCAUC in non-DES-exposed women tends to manifest in older age groups with bulky disease. Although treatment strategies are not standardized, primary surgery remains favorable for early-stage disease, while CCRT is appropriate for advanced stages. Given the rarity and poor prognosis of CCAUC, larger prospective studies are warranted to refine treatment guidelines and improve outcomes.