Ovarian cancer: Clinical sciences

Ovarian cancer is the second most common gynecologic cancer after endometrial cancer, and the leading cause of gynecologic cancer death. The three main types of ovarian cancer are germ cell tumors which arise from primordial germ cells; sex cord or stromal cell tumors that arise from supporting tissues of the ovary; and epithelial cell tumors, which come from the mesothelium that covers the ovary.

The majority of ovarian malignancies are epithelial cell tumors, which primarily occur in older patients. Due to their vague symptoms, they are usually diagnosed at a later stage. Germ cell and sex cord or stromal cell tumors commonly occur among younger patients. They might produce hormones that cause symptoms of pregnancy, precocious puberty, abnormal bleeding, or virilization; and are therefore diagnosed at an earlier stage.

When a patient presents with a chief concern suggesting ovarian cancer, the first step is to perform a focused history and physical examination. Patients often report a history of abdominal or pelvic pain or bloating, and possibly a decrease in appetite, early satiety, or a change in bowel habits. The physical examination reveals an abdominal, pelvic, or adnexal mass and sometimes abdominal or pelvic tenderness, or abdominal distension. With these findings, suspect an adnexal mass and obtain a pelvic ultrasound.

Here’s a clinical pearl! When reproductive-age patients present with abdominal or pelvic symptoms, be sure to assess for pregnancy with an hCG. Keep in mind that some germ cell tumors produce hCG which may result in a false positive pregnancy test. Also, a diagnosis of pregnancy does not exclude malignancy.

Okay, if the ultrasound reveals a thin, anechoic, smooth walled cyst that is less than 10 centimeters without septations, internal blood flow, or solid components, the probable diagnosis is a benign adnexal mass. In this case, manage the patient expectantly with serial ultrasounds. However, if the patient has severe or persistent pain or if the mass increases in size, consider surgical intervention.

On the other hand, the ultrasound may demonstrate a complex mass, possibly greater than 10 centimeters in diameter. The mass may contain septations or loculations and solid components such as mural nodules, as well as increased internal doppler flow. There might also be evidence of pelvic free fluid. These findings are suggestive of an ovarian malignancy.

At this point, the patient’s age, risk factors, and symptoms will help to differentiate among the three main types of ovarian malignancy. If your patient is less than thirty years old with possible family history of ovarian cancer and symptoms of precocious puberty, pregnancy, or abnormal vaginal bleeding, suspect a malignant germ cell tumor of the ovary.

Next, obtain tumor markers including alpha-fetoprotein or AFP, human chorionic gonadotropin or hCG, and lactate dehydrogenase or LDH. Germ cell tumors produce different combinations of these markers. For example, dysgerminomas may secrete hCG and LDH, yolk sac tumors and immature teratomas may produce AFP and LDH, and mixed germ cell tumors may secrete all three of these markers.

Here’s another clinical pearl! Keep in mind that the presence of tumor markers is not required to diagnose any specific ovarian cancer diagnosis. Tumor markers are additional supportive tests with value in monitoring response to treatment. If surgery and chemotherapy are successful, tumor markers will decline. If treatment is not successful or there’s recurrence, tumor markers will plateau or increase.

After checking tumor markers, the next step is to perform a surgical exploration with a staging procedure. Surgical findings will include a solid adnexal mass and possibly abdominal or pelvic adhesions, with or without ascites. The diagnosis is made by pathology. The types of malignant germ cell tumors are dysgerminomas, yolk sac tumors, mixed germ cell tumors, and immature teratomas. Dysgerminomas are one of the most common malignant germ cell tumors. Upon microscopic examination, their cells often have clear cytoplasm and a centrally placed nucleus, with a “fried egg” appearance. Once you have the definitive diagnosis of a malignant germ cell tumor, the treatment typically involves platinum-based chemotherapy and monitoring for recurrence with tumor markers and physical examinations. If there is a recurrence, management involves surgical tumor debulking and chemotherapy.