Study sheet: Malignant Ovarian Tumors

📋 Course Outline

1. Epidemiology and Ovarian Structure
2. WHO Histological Classification
3. Risk Factors and Molecular Pathogenesis
4. Clinical Presentation and Examination
5. Diagnostic Investigations
6. FIGO 2021 Staging
7. Treatment, Prognosis, and Prevention

📖 1. Epidemiology and Ovarian Structure

★ Must-know

• Malignant ovarian tumors are the second most common gynecological malignancies after endometrial cancer and are the most lethal gynecological malignancies.

• Approximately 90% of ovarian malignancies arise from the ovarian surface epithelium, while the ovary also contains germ cells and stromal cells.

• Ovarian cancer is often diagnosed at stages III–IV because malignant cells spread through the peritoneal cavity before clear symptoms appear.

Further detail

• The lifetime risk of ovarian cancer is approximately 1 in 70 women, with peak incidence between 50 and 70 years of age.

💡 Memory Hook

Common after endometrial cancer, but deadliest among gynecologic malignancies

📖 2. WHO Histological Classification

★ Must-know

• The main tumor groups are (WHO, 2020):
  • epithelial tumors
  • germ-cell tumors
  • sex-cord stromal tumors
  • metastatic tumors

📌 High-grade serous carcinoma is common and aggressive and is associated with TP53 and BRCA1/2 mutations, whereas low-grade serous carcinoma grows slowly and is associated with KRAS and BRAF mutations.

• Krukenberg tumor is a bilateral ovarian metastasis containing signet-ring cells, most commonly originating from the stomach.

Further detail

• Mucinous carcinoma is usually a large, multilocular, unilateral tumor, while endometrioid and clear-cell carcinomas are often associated with endometriosis.

📌 Dysgerminoma resembles testicular seminoma, yolk-sac tumor corresponds to an endodermal sinus tumor, and sex-cord stromal tumors include estrogen-secreting granulosa-cell tumors and androgen-secreting Sertoli–Leydig tumors.

💡 Memory Hook

E-G-S-M: epithelial, germ-cell, sex-cord stromal, metastatic

📖 3. Risk Factors and Molecular Pathogenesis

🔑 Key Concepts & Definitions

• STIC : or serous tubal intraepithelial carcinoma, is a proposed precursor lesion from which many high-grade serous carcinomas arise at the fimbrial end of the fallopian tube rather than directly from the ovarian surface

📝 Essential Points

• Reported risk factors include:

  • BRCA1/2 mutations
  • Lynch syndrome
  • family history
  • nulliparity or infertility
  • early menarche
  • late menopause
  • endometriosis
  • obesity
  • hormone replacement therapy

• Protective factors include:

  • oral contraceptives
  • multiparity
  • breastfeeding
  • tubal ligation
  • prophylactic removal of the tubes and ovaries

• High-grade serous carcinoma is associated with TP53 and BRCA1/2 mutations, low-grade serous carcinoma with KRAS and BRAF mutations, and endometrioid or clear-cell carcinoma with ARID1A and PTEN mutations.

💡 Memory Hook

BRCA or Lynch predisposition → earlier or higher-risk ovarian malignancy

📖 4. Clinical Presentation and Examination

★ Must-know

• Early symptoms are vague and include abdominal discomfort, bloating, and early satiety.

• Advanced symptoms include abdominal distension from ascites, a pelvic mass, weight loss, urinary frequency, and constipation.

Further detail

• Paraneoplastic manifestations include irregular or postmenopausal uterine bleeding, precocious puberty from granulosa-cell tumors, and virilization from Sertoli–Leydig tumors.

• Examination findings may include:

  • abdominal distension with ascites
  • a fixed solid or cystic pelvic mass
  • reduced mobility
  • pouch-of-Douglas nodules
  • pleural effusion

💡 Memory Hook

Early vague symptoms → abdominal spread → pelvic mass and ascites

📖 5. Diagnostic Investigations

★ Must-know

• CA-125 is the most useful marker for epithelial ovarian cancer, rises in more than 80% of advanced cases, and is used for follow-up and detection of recurrence rather than general screening.

• CA-125 can also rise in endometriosis, menstruation, pelvic inflammation, pregnancy, and liver disease, so it is not specific for ovarian cancer.

• Transvaginal ultrasound assesses cystic or solid masses, septations, and papillary projections; CT or MRI assesses extension, lymph nodes, and peritoneal implants; and chest radiography assesses pleural effusion and metastases.

📌 When diagnostic uncertainty remains, diagnostic laparoscopy may be performed, but definitive diagnosis requires histopathological examination after surgical removal.

Further detail

• HE4 is an additional marker for epithelial ovarian cancer, while AFP, β-hCG, and LDH are selected mainly according to the suspected germ-cell tumor type.

💡 Memory Hook

CA-125 monitors epithelial cancer but does not screen the general population

📖 6. FIGO 2021 Staging

★ Must-know

📌 FIGO stage I is confined to one or both ovaries or fallopian tubes, stage II extends to other pelvic organs, stage III spreads outside the pelvis or to lymph nodes, and stage IV has distant metastases.

• Stage IIIA is microscopic extra-pelvic or nodal spread, stage IIIB has visible implants measuring 2 cm or less, and stage IIIC has visible implants larger than 2 cm. — FIGO, 2021

• Stage IVA consists of malignant cells in pleural fluid, whereas stage IVB consists of liver or splenic parenchymal metastases or distant metastases such as lung metastases. — FIGO, 2021

Further detail

• Stage IA involves one ovary or fallopian tube with an intact capsule and no malignant cells in the fluid, while stage IB involves both ovaries or tubes with intact capsules and no malignant cells in the fluid. — FIGO, 2021

• Stage IC includes capsular rupture, tumor cells on the ovarian surface, or malignant cells in peritoneal fluid. — FIGO, 2021

💡 Memory Hook

I ovary → II pelvis → III outside pelvis → IV distant metastases

📖 7. Treatment, Prognosis, and Prevention

★ Must-know

• Surgical management includes: total hysterectomy with bilateral salpingo-oophorectomy, staging laparotomy, peritoneal washing, lymph-node sampling, omentectomy, cytoreduction

📌 The first-line chemotherapy regimen for epithelial ovarian cancer is carboplatin plus paclitaxel for six cycles, with neoadjuvant chemotherapy before surgery when the disease is not operable.

📌 Dysgerminoma is treated with BEP chemotherapy and fertility-sparing surgery and is radiosensitive, whereas mucinous carcinoma is usually unilateral and relatively resistant to chemotherapy, making surgery central.

• Five-year survival is approximately 90% in stage I and less than 30% in stages III–IV, and prognosis depends on stage, histological grade, and histological type.

• There is no effective screening test for the general female population; high-risk women may receive genetic counseling and prophylactic removal of the tubes and ovaries after completing childbearing.

Further detail

• Targeted treatment includes PARP inhibitors such as olaparib for patients with BRCA mutations and bevacizumab, an anti-VEGF treatment, as maintenance therapy.

• Fertility-sparing surgery may be considered in young women with unilateral early-stage IA disease and is particularly important for early germ-cell tumors.

• Oral contraceptives reduce ovarian cancer risk by 40–50%, while experimental surveillance for high-risk women includes CA-125 measurement and transvaginal ultrasound every 6–12 months.

💡 Memory Hook

Earlier stage and appropriate surgery plus systemic therapy → better survival

📊 Synthesis Tables

Main Tumor Groups

Group	Approximate proportion	Key examples or feature
Epithelial	90%	Serous, mucinous, endometrioid, clear-cell, Brenner
Germ-cell	5%	Dysgerminoma, yolk-sac tumor, immature teratoma, choriocarcinoma
Sex-cord stromal	5%	Granulosa-cell and Sertoli–Leydig tumors
Metastatic	Not specified	Krukenberg tumor, usually gastric origin