Chapter 12: High-Grade Serous Carcinomas of the Ovary, Fallopian Tube, and Peritoneum

INTRODUCTION

Epithelial ovarian, fallopian tube, and primary peritoneal cancers remain the most lethal of all the gynecologic malignancies. In 2010, approximately 21,880 women will be diagnosed with ovarian cancer in the United States; of these, 13,850 will be expected to die from this disease.¹ Cancers arising from the fallopian tube and peritoneum are significantly less common that those arising from the ovarian epithelium, but share several similarities in their epidemiology, diagnosis, treatment, and associated outcomes. Because the vast majority of fallopian tube and primary peritoneal cancers exhibit a high-grade papillary serous histology, comparisons to similar disease in primary ovarian cancers suggest common molecular pathways that may promote carcinogenesis within the serous classification of these tumors. Several recent hypotheses also propose a fallopian tube origin for metastatic disease that would traditionally be considered as primary ovarian or peritoneal. Given the recent advances surrounding these diseases, this chapter considers this subset of high-grade serous reproductive cancers as a group, with specific differences highlighted.

EPIDEMIOLOGY

Key Points

1. Women with an inherited ovarian cancer syndrome, particularly those with mutations in the BRCA1 and BRCA2 genes, have the highest lifetime risk of develop-ing high-grade, papillary serous epithelial ovarian, primary peritoneal, and fallopian tube cancer.

2. For ovarian cancer, epidemiologic factors that are associated with an increase in lifetime ovulatory cycles confer an increased risk.

3. Bilateral salpingo-oophorectomy, oral contraceptives, tubal ligation, and hysterectomy are all well established risk modifiers of epithelial ovarian, fallopian tube, and primary peritoneal cancer.

Epidemiologic data indicate that ovarian cancer is the ninth most common malignancy affecting women in the United States, with 21,880 cases predicted for 2010; unfortunately, it is the fifth most common cause of cancer-related deaths, with 13,850 women estimated to die of this disease in the same time period.¹ The incidence of ovarian cancer increases with age and is most prevalent in the eighth decade of life, with a rate of 57 per 100,000 women. The median age at diagnosis is 63 years, and 70% of patients present with advanced disease.²

The true incidence of fallopian tube and primary peritoneal malignancies is more difficult to quantify. Despite criteria established by the Gynecologic Onco-logy Group to define primary peritoneal cancers, uniform application by pathologists remains unclear, which clouds identification of the true incidence of this disease. High-grade serous carcinomas of the fallopian tube are rare entities, with 3479 new cases expected to be diagnosed yearly.³ However, incomplete pathologic sectioning and evaluation of the tubes in women with presumed metastatic ovarian cancer may preclude identification of a true tubal origin. Recent evidence suggests that nearly 60% of all high-grade, non-uterine serous cancers initially classified as primary ovarian or peritoneal in origin demonstrate serous tubal intraepithelial carcinoma (STIC), suggesting that the fallopian tube may be the organ of origin.^4,5

One of the strongest risk factors ...