Definitive Radiotherapy in Serous Carcinoma of Unknown Primary With Isolated Nodal Disease: A Case Review

High-grade serous carcinoma (HGSC) is an aggressive malignancy that may arise from the endometrium, ovary, fallopian tube, or peritoneum, but in rare cases, the primary site remains unknown. Isolated nodal presentation is particularly uncommon, and in such cases, it is inferred to be metastasis. Serous carcinoma of unknown primary (SCUP) lacks management guidelines, with treatment often extrapolated from other gynecologic cancers. We describe the case of a woman with isolated inguinal and pelvic nodal SCUP who achieved durable disease control with definitive radiotherapy after progression on endocrine therapy. An 88-year-old woman presented with a large left inguinal mass. Biopsy demonstrated HGSC of Müllerian origin. She was initiated on tamoxifen 20 mg twice a day; however, after seven months, the inguinal mass enlarged, and CA-125 levels increased from 2,691 U/mL to 4,191 U/mL. Given her frailty and the morbidity associated with resecting nodes with clinical extracapsular extension, the patient underwent definitive external beam radiotherapy (55 Gy/25 fractions to involved nodes; 45 Gy/25 fractions to the ipsilateral groin and hemipelvis). Six months after radiotherapy, CT showed a reduction of the inguinal mass and pelvic sidewall lymph node, with CA-125 levels declining to 19 U/mL. The patient has remained without disease progression by imaging and CA-125 for 30 months following completion of radiotherapy. This case describes an uncommon presentation of HGSC of Mullerian origin with isolated inguinal nodes in the absence of identifiable uterine, adnexal, or peritoneal primary. In the absence of established guidelines, it demonstrates the feasibility of definitive radiotherapy in achieving durable disease control.