Ovarian cancer: Clinical sciences

Chapters:

Watch video only

Introduction0:00–0:58

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.

Focused H&P0:58–1:59

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.

Suspect benign adnexal mass1:59–2:29

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.

Suspect ovarian malignancy2:29–2:53

There might also be evidence of pelvic free fluid. These findings are suggestive of an ovarian malignancy.

Malignant germ cell tumor of the ovary2:53–6:13

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.Here’s another clinical pearl! The surgical stage of the disease helps to predict prognosis and plan treatment.
Surgical staging for ovarian cancer involves exploration of the abdomen and pelvis, aspiration of ascites or obtaining pelvic washings, taking biopsies of any suspicious areas, and performing an omentectomy and lymph node dissection.
The surgery also involves the removal of the primary tumor with its associated ovary and fallopian tube. If the tumor appears to be confined to the ovary and the patient desires fertility preservation, the uterus and contralateral ovary may be left in place.
However, if there is evidence of widespread or metastatic disease, or there is no desire for future fertility; the uterus, cervix, ovaries, and fallopian tubes are removed.

Malignant sex cord or stromal tumor of the ovary6:13–8:20

Now let’s consider malignant sex cord or stromal tumors of the ovary. In this case, patients are usually reproductive-aged and might have a family history of ovarian cancer.
They may report abnormal vaginal bleeding or symptoms of hirsutism or virilization. These symptoms are suggestive of a malignant sex cord or stromal tumor of the ovary.
Next, obtain tumor markers such as Inhibin A and B; AFP; as well as estradiol and testosterone levels. Different tumors produce different combinations of biochemical markers.
For example, granulosa cell tumors may secrete Inhibin A and B, estradiol and testosterone. Sertoli-Leydig cell tumors may secrete Inhibin A and B, AFP, estradiol, and testosterone, while sex cord tumors with annular tubules may produce estradiol.
After obtaining tumor markers, perform a surgical staging procedure to establish the diagnosis. The surgical findings will include a complex adnexal mass, possibly with hemorrhagic or necrotic components.
Additionally, you might find abdominal or pelvic adhesions or ascites. Again, the diagnosis is made by pathologic findings.
Three common types of sex cord or stromal tumors are granulosa cell tumors, Sertoli-Leydig cell tumors, and sex cord tumors with annular tubules.
Granulosa cell tumors are the most common of the group. They have a microscopic appearance that demonstrates coffee bean nuclei and cells arranged in rosettes, called Call-Exner bodies.
Post-operative treatment involves platinum-based chemotherapy and monitoring with tumor markers and physical examination.
If there’s a recurrence, management involves surgical debulking, chemotherapy, and radiation.Finally, let’s discuss the most common type of ovarian cancer, epithelial ovarian carcinoma.

Epithelial ovarian carcinoma8:20–10:44

These patients are usually older than 55 years of age and may report a family history of ovarian cancer or a family cancer syndrome.
When you suspect epithelial ovarian cancer, obtain tumor markers, such as cancer antigen 125 or CA-125, carcinoembryonic antigen or CEA, and cancer antigen 19-9 or CA 19-9.
These tumor markers might be elevated. In addition, a CT scan or MRI can be useful for assessment of metastatic disease or surgical planning.
The next step is a surgical exploration with a staging procedure. Surgical findings include a solid adnexal mass with cystic components, and possibly abdominal or pelvic adhesions and ascites.
Since epithelial ovarian cancers are usually found at a more advanced stage, other likely findings include omental caking or tumor studding on the peritoneal and subdiaphragmatic surfaces.
Pathology will help to delineate the specific type of epithelial ovarian cancer including serous, endometrioid, mucinous, and clear-cell carcinomas.
Serous epithelial cell carcinoma is the most common type. In these tumors, the key histologic finding is atypical nuclei with variation in size and the presence of tumor giant cells.
Once the diagnosis of an epithelial ovarian carcinoma is made, treatment includes platinum-based chemotherapy and monitoring for recurrence with tumor markers and physical examination, and sometimes imaging such as CT scans.
If there’s a recurrence, management includes surgical debulking, chemotherapy, and angiogenesis inhibitors such as bevacizumab.
Let’s wrap this up with a high-yield fact! Factors that may reduce the risk of epithelial ovarian carcinoma include breastfeeding, pregnancy, oral contraceptive use, later age of menarche, and earlier age of menopause.
There’s also risk reduction surgery, like bilateral salpingo-oophorectomy, for high-risk patients like those with mutations in the breast cancer or BRCA gene.
Alright, as a quick recap… The three main types of ovarian cancer are germ cell tumors, sex cord or stromal cell tumors, and epithelial cell tumors.

Review10:44–11:25

History, physical exam, ultrasound, and tumor markers are used to make an initial diagnosis. The definitive diagnosis is made with surgical staging and histologic findings.
Stage at presentation is a key factor in overall prognosis and further treatment, which usually involves platinum-based chemotherapy.
Recurrence is monitored with tumor markers and physical exam and is generally managed with surgery and chemotherapy.