Gynecology Topic 30. Etiology, clinical picture and screening of ovarian tumors

I. Ovarian Tumors

General

• Ovarian tumors include benign, borderline and malignant tumors.
• Main groups:

1. Epithelial ovarian tumors → Most common ovarian cancers.
2. Germ cell tumors → More common in young patients.
3. Sex cord-stromal tumors → May produce hormones.
4. Metastatic tumors → Example: Krukenberg tumor from gastric cancer.

• Ovarian cancer has high mortality because early disease is usually silent.

II. Etiology and Risk Factors

Risk Factors

• Multiple lifetime ovulations → Repeated ovulatory epithelial trauma/repair.

• Increasing age.
• Early menarche.
• Late menopause.
• Nulliparity/low parity, delayed childbearing.
• Infertility.

• Genetic/familial:

• BRCA1 mutation → High risk of ovarian/fallopian tube/primary peritoneal cancer.
• BRCA2 mutation → Increased risk, generally lower than BRCA1.
• DNA mismatch repair mutation / Lynch syndrome.
• Family history of ovarian, breast, endometrial or colon cancer.

• Obesity.
• Endometriosis → Especially associated with endometrioid and clear cell ovarian carcinoma.

Protective Factors

• Multiple pregnancies.
• Breastfeeding.
• Combined oral contraceptive pills → Suppress ovulation; protection increases with duration of use.
• Tubal ligation, salpingectomy, hysterectomy.
• Risk-reducing bilateral salpingo-oophorectomy in BRCA/Lynch carriers after completion of childbearing.

Pathogenesis Note

• High-grade serous carcinoma often arises from fimbrial fallopian tube epithelium / STIC, not only from ovarian surface epithelium.

III. Clinical Features

Early Stage

• Often asymptomatic.
• May be found incidentally as an adnexal mass.
• Vague nonspecific symptoms → delayed diagnosis is common.

Advanced Stage

• Abdominal distention → Mass and/or ascites.
• Bloating, fullness, early satiety, decreased appetite.
• GI/urinary pressure symptoms: Constipation, change in bowel habit, urinary urgency/frequency.
• Pelvic/abdominal pain; acute severe pain may indicate torsion, rupture or hemorrhage.
• Pleural effusion, dyspnea.
• Weight loss, anemia/cachexia.

Hormone-Producing Tumors

• Granulosa-theca tumor → Estrogen effects: AUB, postmenopausal bleeding, precocious puberty.
• Sertoli-Leydig tumor → Androgen effects: Hirsutism, amenorrhea, virilization, deep voice.
• Struma ovarii → Thyroid tissue; may cause hyperthyroidism.

Physical Examination

• Bimanual examination: Adnexal mass, often solid, irregular or fixed if malignant.
• Advanced disease: Ascites, pleural effusion, abdominal mass, cachexia, lymphadenopathy.
• Benign signs: Smooth, mobile, unilateral; malignant signs: Solid, fixed, irregular, bilateral, ascites.

IV. Spread

Patterns of Spread

• Transcoelomic/peritoneal spread → most characteristic ovarian cancer spread.

• Implants on peritoneum, omentum, bowel serosa, pouch of Douglas, liver capsule and diaphragm.
• Omental metastasis → "omental cake".

• Lymphatic spread → Pelvic and para-aortic lymph nodes.
• Hematogenous spread → Less common.

V. Screening

General Population

• No recommended screening for average-risk asymptomatic women.
• CA-125, transvaginal US and pelvic examination do not reduce ovarian-cancer mortality in average-risk women.
• Problem: Low sensitivity/specificity for early disease → false positives and unnecessary surgery.

High-Risk Patients

• High-risk groups: BRCA1/2 mutation, Lynch syndrome, strong family history.
• Genetic counseling and testing are central.
• CA-125 + transvaginal US may be used for surveillance in selected high-risk patients, but this is not proven to reduce mortality.
• Main proven risk-reduction strategy: Risk-reducing bilateral salpingo-oophorectomy after childbearing.

VI. Diagnosis

Initial Evaluation

• History: Symptoms, duration, family history, BRCA/Lynch risk, previous breast/endometrial/colon cancer, infertility/endometriosis.
• Physical examination: Abdominal + pelvic/bimanual examination; assess ascites, pleural effusion and cachexia.
• Pregnancy test in reproductive-age patients.

Ultrasound

• Transvaginal US ± transabdominal US → First-line imaging.
• Detects mass, size, laterality and structure.
• Suspicious US findings:

• Solid areas, papillary projections, thick septations, multilocular-solid mass.
• Irregular wall, bilateral masses, ascites/peritoneal nodules.
• Doppler vascularity in solid components.

Tumor Markers

• CA-125 → Mainly epithelial ovarian cancer; nonspecific.

• False elevation: Endometriosis, PID, fibroids, menstruation, pregnancy, liver disease.
• More useful in postmenopausal than premenopausal women.

• HE4 → Epithelial ovarian cancer marker; used with CA-125 in ROMA score.
• LDH → Dysgerminoma.
• AFP → Yolk sac tumor / endodermal sinus tumor.
• β-hCG → Choriocarcinoma, embryonal carcinoma, some dysgerminomas.
• Inhibin B/AMH/estradiol → Granulosa cell tumor.
• Testosterone/androgens → Sertoli-Leydig cell tumor.

Genetics and Staging Imaging

• Genetic testing/counseling: BRCA1/2 and Lynch syndrome when family/personal history or tumor type suggests inherited risk.
• CT abdomen/pelvis/chest → Main staging and preoperative assessment for suspected malignancy.
• MRI → Characterization of indeterminate adnexal mass.
• PET-CT → Selected cases or unclear metastatic disease.

Definitive Diagnosis

• Definitive diagnosis: Histopathology.
• If malignancy is suspected, avoid simple percutaneous biopsy of a resectable ovarian mass because rupture/spillage may upstage disease.
• Diagnosis is usually obtained during laparoscopy/laparotomy by removal of the mass/ovary, commonly unilateral salpingo-oophorectomy with frozen section if available.
• If malignancy is confirmed → Surgical staging/debulking by gynecologic oncology.