Ovarian cancer

Summary

Ovarian tumors, benign in 80% and malignant in 20% of cases, arise from surface epithelium, germ cells, or sex cord–stromal tissue and are the deadliest gynecologic cancers. Risk increases with factors that raise lifetime ovulations (e.g., nulliparity, BRCA mutations) and decreases with pregnancy or OCP use. Symptoms are often late and nonspecific, such as abdominal distension, GI or urinary complaints, and ascites. Diagnosis uses imaging, tumor markers, and surgical biopsy, with treatment based on surgery and chemotherapy. Prognosis depends on stage, with prevention targeting high-risk women through genetic testing and risk-reducing surgery.

Definition

Ovarian tumors are neoplastic growths arising from the ovary, which may be benign (80%) or malignant (20%), and can be solid or cystic in nature (cystic forms are more common). They originate from one of three embryonic tissue types:

1. Surface (coelomic) epithelium – most common (≈90% of malignant cases)

2. Germ cells (ova)

3. Sex cord–stromal/mesenchymal cells

Epidemiology

• Second most common gynecologic malignancy after endometrial cancer.

• Highest mortality rate among gynecologic cancers.

• Mean age at diagnosis for epithelial ovarian carcinoma: 69 years; peak incidence: 55–64 years.

• Lifetime risk: 1% in the general population, up to 65% in BRCA1 carriers.

Risk and Protective Factors

Risk Factors (conditions increasing ovulatory cycles):

• Nulliparity, infertility, first pregnancy after age 30

• Early menarche, late menopause

• Ovulation-inducing drugs

• BRCA1/BRCA2 or Lynch syndrome mutations

• Obesity, endometriosis, PCOS

• Family history of breast, ovarian, or endometrial cancer

• Personal history of breast cancer

• Increasing age, radiotherapy exposure

Protective Factors (conditions decreasing ovulatory cycles):

• Oral contraceptive use

• Pregnancy and lactation

• Early first pregnancy, multiparity

• Late menarche, early menopause

• Tubal ligation, hysterectomy

Pathology and Classification

1. Epithelial Tumors (≈90% of malignant ovarian tumors)

• Examples: Serous cystadenocarcinoma (most common), mucinous, endometrioid, clear cell, Brenner tumors.

• Often bilateral (60–70%), slow-growing but poor prognosis.

• Tumor marker: CA-125 (used for monitoring).

• Spread: primarily peritoneal dissemination; can also spread lymphatically or hematogenously.

2. Germ Cell Tumors (most common ovarian cancer in young females)

• Usually benign (95%), but malignant types grow rapidly.

• Common types:

• Dermoid cyst (mature teratoma) – benign, may contain hair, teeth, skin; risk of torsion; 10% contain thyroid tissue → thyrotoxicosis. Rupture: chemical peritonitis. 

• Dysgerminoma – most common malignant germ cell tumor.

• Endodermal sinus tumor (yolk sac tumor), embryonal carcinoma, choriocarcinoma.

• Tumor markers: AFP, β-hCG, LDH.

3. Sex Cord–Stromal Tumors

• Granulosa-theca cell tumors – estrogen-secreting; may cause precocious puberty, menstrual irregularities, or postmenopausal bleeding; associated with endometrial hyperplasia or carcinoma.

• Sertoli–Leydig cell tumors – androgen-secreting; cause virilization (hirsutism, deep voice, clitoromegaly, breast atrophy).

• Ovarian fibroma – benign, nonfunctional, have long pedicle (label to torsion); may be part of Meigs’ syndrome (ovarian tumor + ascites + pleural effusion).

Secondary (Metastatic) Ovarian Tumors

• Common primaries: stomach (Krukenberg tumor – signet ring cells), breast, colon, endometrium.

Clinical Features

• Early stages: often asymptomatic.
•  Advanced stages:

  • Abdominal distension, bloating, pelvic or back pain

  • GI symptoms: early satiety, constipation, nausea

  • Urinary symptoms: frequency, urgency

  • Ascites, pleural effusion (Meigs’ syndrome)

  • Sister Mary Joseph nodule (umbilical metastasis)

  • Menstrual changes, abnormal bleeding (rare)
    

Diagnosis

1. Imaging:

• Transvaginal ultrasound (Doppler) – assess septations, solid components, ascites.

• CT/MRI – staging, metastasis detection.

2. Laboratory:

• CA-125, AFP/β-hCG/LDH, inhibin A/B, estrogen, testosterone.

3. Definitive:

• Surgical biopsy (preferred) – avoid needle aspiration to prevent tumor seeding.

Staging

• Based on FIGO/TNM systems.

• Surgical staging: total abdominal hysterectomy, bilateral salpingo-oophorectomy (TAH-BSO), omentectomy, peritoneal washings, lymph node sampling

Management

• Surgery:

• Early stage: unilateral salpingo-oophorectomy (fertility-preserving) if benign; TAH-BSO if completed childbearing.

• Malignant: cytoreductive (debulking) surgery – aim for <1 cm residual tumor.

• Chemotherapy:

• Standard: carboplatin + paclitaxel ± bevacizumab.

• Neoadjuvant chemotherapy for high-risk advanced disease.

• Targeted therapy:

• PARP inhibitors (olaparib, niraparib) for BRCA-positive or platinum-sensitive disease.

• Follow-up: CA-125 levels, imaging.

Prognosis

• Overall 5-year survival: ≈51% (all stages).

• Poor prognosis with advanced stage, older age, and suboptimal debulking.

• Early-stage disease has much higher survival rates.

Prevention

• No effective screening for average-risk women.

• High-risk women: genetic counseling, BRCA/Lynch testing.

• Risk-reducing bilateral salpingo-oophorectomy after childbearing completion in mutation carriers.

• OCP use and surgical sterilization reduce risk.