Ovarian Neoplasia: MRCOG Part 1 questions and key facts

Ovarian germ cell tumours (OGCTs) are derived from primordial germ cells and predominantly affect young women and adolescents. While CA-125 can be elevated in some OGCTs (as well as epithelial ovarian cancers), specific subtypes produce distinct tumour markers. The essential panel for suspected OGCTs includes AFP (alpha-fetoprotein), HCG (human chorionic gonadotropin), and LDH (lactate dehydrogenase). AFP is typically elevated in yolk sac tumours (endodermal sinus tumours). HCG is produced by syncytiotrophoblastic cells and is elevated in choriocarcinomas and sometimes embryonal carcinomas or mixed OGCTs. LDH is often significantly elevated in dysgerminomas, the most common malignant OGCT.

The other marker panels are associated with different tumour types. CEA, CA 19-9, and CA 15-3 are more commonly associated with gastrointestinal or epithelial malignancies (e.g., mucinous ovarian tumours for CEA/CA 19-9, breast cancer for CA 15-3). PSA is specific for prostate cancer. Inhibin, AMH (Anti-Müllerian Hormone), and Oestradiol are markers primarily associated with sex cord-stromal tumours, such as granulosa cell tumours. HE4 is another marker used alongside CA-125 primarily for epithelial ovarian cancer.

Endometriosis, the presence of endometrial-like tissue outside the uterus, is associated with an increased risk of certain types of epithelial ovarian cancer. The chronic inflammation and cellular changes associated with endometriosis are thought to contribute to malignant transformation in some cases. Histological studies have shown a strong association between endometriosis and both endometrioid and clear cell carcinomas of the ovary. These subtypes can arise directly from endometriotic cysts (endometriomas) or associated pelvic endometriosis.

Serous carcinoma is the most common type of epithelial ovarian cancer overall but is less frequently associated with endometriosis than endometrioid or clear cell types. Mucinous carcinomas typically have a different origin, sometimes associated with mucinous cystadenomas or metastases (e.g., from the gastrointestinal tract). Granulosa cell tumours are sex cord-stromal tumours, not epithelial ovarian cancers, and arise from the granulosa cells of the ovarian follicle; they are not typically associated with endometriosis.

The Risk of Malignancy Index (RMI) is used to estimate the risk of an ovarian mass being malignant, guiding appropriate referral and management. It combines the patient's menopausal status (M), ultrasound findings (U), and serum CA-125 level. The formula is RMI = U x M x CA-125. In this case: U = 3 (complex cyst with solid areas, ascites suggests a score of 3), M = 3 (post-menopausal status scores 3), and CA-125 = 350 U/mL. Therefore, RMI = 3 x 3 x 350 = 3150. An RMI score >250 (or >200 depending on local guidelines) indicates a high risk of malignancy. Such patients require urgent referral for gynae-oncology assessment. This specialist assessment typically includes further imaging, such as a CT scan of the abdomen and pelvis, for staging and surgical planning.

Repeat CA-125 and transvaginal ultrasound in 6 months would be inappropriate given the high suspicion of malignancy; surveillance is reserved for cysts at low risk. Start empirical carboplatin and paclitaxel chemotherapy is not indicated without a histological diagnosis and staging; even when neoadjuvant chemotherapy is chosen, it follows specialist assessment and a tissue biopsy. Perform diagnostic laparoscopy with ovarian cystectomy before specialist assessment risks cyst rupture and spillage, which can upstage an early cancer; a high RMI warrants surgery planned by a gynae-oncologist, usually by laparotomy, to allow full staging and debulking if cancer is confirmed. Offer hormonal therapy and review in 3 months has no role in suspected primary ovarian cancer and would only delay diagnosis.