A 59-year-old postmenopausal woman comes to the office for evaluation of breast tenderness. The patient first noticed intermittent breast tenderness 4 months ago, which at first was relieved with ibuprofen, but for the past several weeks the tenderness has occurred daily. She has had no breast masses or nipple discharge. The patient has also noticed an increase in her weight, particularly around the abdomen, despite not being able to eat as much. She went through menopause 5 years ago. Mammogram history is normal, including one performed earlier this year. The patient has no chronic medical conditions and has had no previous surgeries. There is no family history of breast, ovarian, or endometrial cancer. Vital signs are normal. BMI is 24 kg/m². Breast examination shows bilateral, diffuse fibrocystic changes. The abdomen is distended, and a large right lower quadrant mass is palpable. Pelvic ultrasound reveals a 12-cm complex right ovarian mass with solid components and multiple septations, a slightly enlarged uterus, and a 9-mm endometrial stripe. Which of the following tumor markers is most likely to be elevated in this patient?

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11ec25c8_d9d5_8a3c_bc81_c327673c9e64_MD0003_00 This patient's bilateral breast tenderness and fibrocystic changes (due to increased breast tissue proliferation) are suggestive of estrogen exposure. The additional symptoms of increasing abdominal girth, early satiety, and a complex ovarian mass are concerning for an ovarian malignancy-specifically, a granulosa cell tumor, a type of ovarian sex cord-stromal tumor. Granulosa cells are the primary components of the ovarian stroma and function in converting testosterone to estradiol via aromatase. They secrete both estradiol (via aromatization of testosterone) and inhibin (which suppresses pituitary FSH release via negative feedback). Malignant proliferation of granulosa cells can cause high estradiol levels that affect the breast (eg, tenderness) and endometrium (eg, unopposed proliferation). Therefore, patients can have concomitant endometrial hyperplasia/cancer that presents in postmenopausal women as an enlarged uterus with abnormal uterine bleeding or a thickened (>4 mm) endometrial stripe on ultrasound. Patients are managed surgically and require monitoring for disease progression or recurrence with serum inhibin levels. (Choice A) Alpha-fetoprotein is secreted by yolk sac tumors, an aggressive germ cell tumor. Because these tumors are rapidly-growing, patients typically present with abdominal pain. There is no associated breast tenderness. (Choice C) Elevated hCG levels occur in embryonal carcinomas (an ovarian germ cell tumor) and gestational trophoblastic disease (eg, hydatidiform mole). Patients with an embryonal carcinoma have rapid-onset pelvic pain. Those with a hydatidiform mole can have uterine enlargement, bilateral ovarian masses (ie, theca lutein cysts), hyperemesis gravidarum, or hyperthyroid symptoms. The breast tenderness that occurs with elevated hCG (eg, during early pregnancy) is due to elevated estrogen. (Choice D) Lactate dehydrogenase is secreted by dysgerminomas, malignant germ cell tumors that typically present as rapidly enlarging, painful masses. There is no associated breast tenderness or thickened endometrium. (Choice E) Sertoli-Leydig cell tumors, a sex cord-stromal ovarian tumor, secrete testosterone; therefore, patients have virilization (eg, acne, clitoromegaly) and hypoestrogenism (eg, breast atrophy, thin endometrium). (Choice F) Mature teratomas are benign ovarian germ cell tumors that occasionally secrete thyroxine (eg, struma ovarii). Most patients are asymptomatic; however, symptomatic patients typically have weight loss despite an increased appetite due to the increased metabolic rate associated with elevated thyroxine levels. Educational objective: Granulosa cells are the primary component of the ovarian stroma and convert testosterone to estradiol via aromatase. Malignant proliferation of these cells (ie, granulosa cell tumor) results in high estradiol levels that affect breast tissue (eg, tenderness, fibrocytic changes) and the uterine lining (eg, postmenopausal thickened endometrium). References: Recent advances in granulosa cell tumor ovary: a review. (http://www.ncbi.nlm.nih.gov/pubmed/24426698) Ovarian sex-cord stromal tumours and small cell tumours: pathological, genetic and management aspects. (http://www.ncbi.nlm.nih.gov/pubmed/29198337) Granulosa cell tumor of the ovary: tumor review. (http://www.ncbi.nlm.nih.gov/pubmed/18815151)

A 59-Year-Old Postmenopausal Woman Comes to the Office for Evaluation