A 28-year-old woman presents to the emergency department with six months of increased abdominal distention, fatigue, and bloating. She has had nausea, early satiety, orthopnea, and a 15-pound unintentional weight loss.
She has a history of “abnormal periods,” and is not pregnant. The photo shows her abdominal CT scan.
What diagnosis concerns you? See p. 12.
Diagnosis: Ovarian Cancer
Ovarian cancer is the second most common gynecological malignancy after cervical cancer, but causes more deaths than any other cancer of the female reproductive tract. It is the eighth most common cancer in women in the United States but the fifth leading cause of death in this population. (www.cdc.org.) The lifetime risk for developing invasive ovarian cancer is approximately one in 71. (www.cancer.gov.)
The ovary is an ovum- and hormone-producing (estrogen and progesterone) organ found in female vertebrates. It is covered with cuboidal surface epithelial cells. Inside the layer is a fibrous connective tissue (Tunica albuginea). Below this, inside the ovary, is the inner and outer cortex of the stroma, which contains the imbedded sac-like follicles. The stroma contains the progesterone- and estrogen-producing cells.
The very center of the ovary is the medulla, which contains the nerve fibers and lymphatic and blood vessels. Most ovarian cancer tumors are derived from epithelial cell (95%) (e.g., serous, mucinous, endometrioid, clear cell, transitional cell) with the rest derived from germ cell (e.g., dysgerminoma, yolk sac, choriocarcinoma, teratoma) and sex cord-stromal (e.g., granulose, thecoma, Sertoli, Sertoli-Leydig) tumors (<1 %). (Gynecol Oncol 2005;97:519.)
The exact etiology is unknown, but the primary risk factor for developing ovarian cancer is a positive family history. (Obstet Gynecol 1992;80:700.) The risk of developing ovarian cancer has been specifically associated with the BRCA 1 and 2 gene mutations, hereditary nonpolyposis colorectal cancer (Lynch syndrome), and a family history in either a first- or second-generation relative.
Ovarian cancer tends to be a disease of older women, with 90 percent of affected women over 40 and most 60 or older. Other than increasing age, risk factors include a personal history of endometriosis, infertility, and personal history of estrogen replacement therapy. Synchronous endometrial cancer is also a risk factor, with 10 percent of women with ovarian cancer also reported to have endometrial cancer. (Gynecol Oncol 2001;83:355.) Studies have demonstrated, however, that the risk appears to be mitigated by an early age of first pregnancy, older age of last pregnancy, multiparity, breastfeeding, the use of combined oral contraceptives, and having had a tubal ligation.
Symptoms of ovarian cancer are often nonspecific initially and therefore go unrecognized; these include abdominal bloating and or swelling (ascites), pelvic pain and pressure, anorexia, nausea, early satiety, urinary frequency and urgency, unintentional weight loss, fatigue, back pain, constipation, and abnormal vaginal bleeding. An incidental adnexal mass can also be the initial finding in some cases. (Cancer 2007;109:221.)
Advanced disease patients can present with acute findings of bowel obstruction, malignant pleural effusions, respiratory distress, and venous thromboembolism (rarely). (Arch Intern Med 2005;165:1782.) Patients also present rarely with a variety of paraneoplastic syndromes, including nephritic syndrome, hemolytic anemia, and polyneuritis. (Radiographics 2010;30:903.)
The evaluation of a suspected ovarian mass starts with imaging, initially by ultrasound. Some cases of advanced disease with abdominal pain and swelling from severe ascites or bowel obstruction may require initial imaging to be abdominal or pelvic CT scan or MRI (more common as outpatient and less common as primary imaging in the emergency department). Patients with pulmonary symptoms should receive imaging to rule out pleural effusion (most common finding of stage 4 disease; Cancer 1987;60:1561), mediastinal lymphadenopathy, and if clinically indicated, pulmonary embolism.
Confirmatory tissue diagnosis is typically made surgically because diagnosis by fine-needle aspiration is not typically recommended because violation of the mass can lead to a more advanced staging, worse prognosis, and peritoneal cytological contamination. Surgical exploration is reserved for patients with a relatively high index of suspicion based on the patient's clinical presentation, identification of metastasis, exclusion of alternative primary malignancy (breast and gastrointestinal malignancies are the most common to metastasize to the ovary), initial evaluation of ovarian mass identified on imaging, and tumor markers.
There are many different types of ovarian germ cell (e.g., dysgerminoma, immature teratoma, choriocarcinoma, gonadoblastoma, mixed germ cell, embryonal) and sex cod-stromal tumors (Sertoli-Leydig, granulosa cell, thecoma-fibroma). Tumor markers are helpful for diagnostic consideration, staging, and treatment monitoring after a confirmatory diagnosis is made and treatment is initiated. Depending on the type of ovarian malignancy suspected or confirmed, different tumor markers are elevated but can include CA 125, alpha-fetoprotein, human chorionic gonadotropin, lactate dehydrogenase, estradiol, testosterone, and androstenedione, and dehydroepiandrostenedione (DHEA).
Ovarian tumors are staged according to the International Federation of Gynecology and Obstetrics (FIGO) or TNM categories. Disposition of a patient in the emergency department depends on the clinical presentation, the level of concern for a diagnosis of previously undiagnosed ovarian cancer, and resource and follow-up considerations. Any woman with a mass concerning for ovarian malignancy requires close gynecology follow-up for further evaluation and definitive diagnostic testing and care.
Unfortunately, ovarian cancer typically purports a poor prognosis; the five-year survival rate is less than 50 percent. A malignancy identified early (stage 1) has a cure rate more than 90 percent. (Am J Obstet Gynecol 2003;189:1120.) Unfortunately, as many as 75 percent of women have stage 3 or 4 disease at diagnosis because there are no good screening studies. The disease also has nonspecific early symptoms and tends to be more advanced when initially diagnosed. (Clin Obstet Gynecol 2012;55:43.) Ovarian cancer tends to spread locally to peritoneal structures including the uterus, bladder, bowel, and omentum via the lymphatic and vascular dissemination.
This patient had an abdominal CT scan that demonstrated retroperitoneal lymphadenopathy, large ascites, and a high-grade small bowel obstruction caused by a large left-side ovarian mass. She was admitted to the hospital for management of her small bowel obstruction and workup of the left ovarian mass concerning for metastatic ovarian cancer. Unfortunately, she refused further evaluation and left against medical advice without a tissue diagnosis being made, and has since been lost to follow-up.
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