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INTRODUCTION

ESSENTIALS OF DIAGNOSIS

  • Early-stage ovarian cancer often presents with vague and ill-defined symptoms.

  • Late-stage disease presents with abdominal pain or bloating, early satiety, and/or urinary urgency or frequency.

  • The majority of women present with late-stage disease.

  • Pelvic ultrasound findings show complex adnexal mass(es).

  • The mean age of diagnosis for epithelial ovarian cancer is in the mid-50s, with the majority of patients diagnosed between ages 40 and 65.

  • Patients with hereditary causes of ovarian cancer are diagnosed at earlier age by almost a decade.

  • Nonepithelial ovarian tumors are more common in girls and younger women.

PATHOGENESIS

According to the 2014 World Health Organization (WHO) classification, primary ovarian tumors are subdivided into 3 categories: epithelial, germ cell, and sex cord-stromal tumors. However, the overwhelming majority of adnexal cancers (80–85%) arise from the surface epithelial cells of the ovary (epithelial ovarian cancer [EOC]). Fewer ovarian cancers develop from the remaining cell types (sex cord-stromal, germ cell, or mixed cell type tumors) (Table 52–1), and even fewer adnexal cancers arise from the fallopian tubes, although recent evidence has shown that they account for a greater percentage than previously thought.

Table 52–1.Categories of ovarian cancer.

The specific events leading to the transition of normal tissue to malignancy have not been conclusively established, nor has a definitive precursor lesion been identified. However, much research in recent years has been devoted to advancing our understanding of the precursors and pathogenesis of these tumors. For sporadic tumors, molecular events leading to the inactivation of tumor suppressor genes (PTEN, p16, p53) or the activation of oncogenes (HER2, c-myc, K-ras, Akt) have been described. For the small proportion of genetically heritable cancers, germline mutations in BRCA1, BRCA2, and other genes have been described, but the molecular pathway leading to tumorigenesis has not been elucidated. It is likely that epigenetic events also contribute to the transformation to cancer.

A. Epithelial Ovarian Cancer

The classical theory for the development of EOC associates the repeated trauma and repair to the ovarian epithelium during normal ovulation with subsequent genetic alterations and further progression to malignant transformation. This is supported by evidence that suppression of ovulation (ie, during pregnancy and breastfeeding or while taking oral contraceptive pills) leads to a decreased incidence of EOC. This theory, however, does not account for an increased occurrence ...

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