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 Strategies
8. Prognosis Prevention and Follow-up

📖 1. Epidemiology and Ovarian Structure

📝 Essential Points

• Malignant ovarian tumors are the second most common gynecologic malignancy after endometrial cancer and are the deadliest gynecologic malignancies.

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

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

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

💡 Memory Hook

Common after endometrial cancer, but deadliest among gynecologic malignancies

📖 2. WHO Histological Classification

🔑 Key Concepts & Definitions

• Epithelial tumors : include serous, mucinous, endometrioid, clear-cell, and Brenner tumors

★ Must-know

• The main categories are:
  • epithelial tumors at 90%
  • germ-cell tumors at 5%
  • sex-cord stromal tumors at 5%
  • metastatic tumors

📌 High-grade serous carcinoma is common and aggressive with TP53 mutation, whereas low-grade serous carcinoma grows slowly and is associated with KRAS or BRAF mutation.

📌 Granulosa-cell tumors secrete estrogen and may cause endometrial hyperplasia, whereas Sertoli–Leydig tumors secrete androgens and may cause virilization.

Further detail

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

• The listed germ-cell tumors are:

  • dysgerminoma
  • yolk-sac tumor
  • immature teratoma
  • choriocarcinoma

💡 Memory Hook

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

📖 3. Risk Factors and Molecular Pathogenesis

🔑 Key Concepts & Definitions

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

📝 Essential Points

• Important risk factors include:

  • BRCA1 or BRCA2 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/Lynch and reproductive risks increase susceptibility; STIC can precede high-grade serous cancer

📖 4. Clinical Presentation and Examination

★ Must-know

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

• Late manifestations include abdominal distension from ascites, a pelvic mass, weight loss, frequent urination, and constipation.

Further detail

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

• Examination may reveal abdominal distension with ascites, a fixed solid or cystic pelvic mass, rectovaginal Douglas-pouch nodules, and pleural effusion in advanced disease.

💡 Memory Hook

Early vague symptoms → late mass, ascites, and systemic or paraneoplastic signs

📖 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 monitoring and detecting recurrence rather than general screening.

• 🔄 Diagnostic imaging proceeds through: transvaginal ultrasound for cystic or solid masses, septations, and papillary projections, CT or MRI for extension, lymph nodes, and peritoneal implants, chest radiography for pleural effusion and metastases

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

Further detail

• CA-125 is not specific because it can rise with endometriosis, menstruation, pelvic inflammation, pregnancy, and liver disease.

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

💡 Memory Hook

CA-125 supports monitoring, whereas histopathology establishes diagnosis

📖 6. FIGO 2021 Staging

🔑 Key Concepts & Definitions

• FIGO stage I : is limited to one or both ovaries or fallopian tubes
• FIGO stage II : FIGO stage II ovarian cancer involves extension to pelvic organs or tissues, including the uterus, the other ovary or tube, bladder, bowel, or other pelvic tissues.

📝 Essential Points

• Stage IA involves one ovary or tube with an intact capsule and no malignant cells in the fluid, stage IB involves both ovaries or tubes with intact capsules, and stage IC includes capsular rupture, surface tumor, or malignant cells in peritoneal fluid.

• Stage III includes microscopic extrapelvic or lymph-node spread in IIIA, visible peritoneal implants of 2 cm or less in IIIB, and visible implants larger than 2 cm in IIIC.

• Stage IVA consists of malignant pleural effusion, whereas stage IVB consists of parenchymal liver or spleen metastases or distant metastases such as lung metastases.

💡 Memory Hook

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

📖 7. Treatment Strategies

★ Must-know

• The surgical procedure includes: total abdominal hysterectomy with bilateral salpingo-oophorectomy, staging laparotomy, omentectomy, peritoneal washing, lymph-node sampling, removal of all visible tumor

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

📌 High-grade serous carcinoma is treated with surgery and chemotherapy, mucinous carcinoma mainly with surgery because it is relatively chemoresistant, and dysgerminoma with BEP chemotherapy plus fertility-preserving surgery.

Further detail

• Targeted treatment includes PARP inhibitors such as olaparib for patients carrying BRCA mutations and the anti-VEGF drug bevacizumab as maintenance therapy.

📌 Fertility-preserving surgery may be considered in young women with early unilateral stage IA disease and is especially relevant for early germ-cell tumors.

💡 Memory Hook

Surgery → platinum chemotherapy → targeted maintenance → fertility preservation when appropriate

📖 8. Prognosis Prevention and Follow-up

★ Must-know

• Prognosis depends on stage, histological grade, and histological type.

• Five-year survival is about 90% in stage I and less than 30% in stages III–IV.

📌 There is no effective screening test for the general female population.

📌 High-risk women with BRCA mutations may receive genetic counseling and risk-reducing removal of the tubes and ovaries after completing childbearing.

Further detail

• Oral contraceptives reduce ovarian-cancer risk by approximately 40–50%.

• Experimental surveillance in high-risk women consists of CA-125 testing and transvaginal ultrasound every six to twelve months, while follow-up also includes periodic clinical review, tumor markers, and imaging.

💡 Memory Hook

Stage I has about 90% five-year survival, whereas stages III–IV have less than 30%

📊 Synthesis Tables

WHO Tumor Categories

Category	Approximate proportion	Key examples or features
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; commonly gastric origin