II. Epidemiology

  1. Most Ovarian Incidentalomas are benign (e.g. functional Ovarian Cysts, cystadenomas)
  2. Ovarian Cancer risk increases with age

III. History

  1. Ectopic Pregnancy risk (women of child-bearing age)
    1. Last Menstrual Period
    2. Contraception method
  2. Tubo-Ovarian Abscess risk
    1. Sexually Transmitted Infection (e.g. Gonorrhea or Chlamydia risk or potential exposures)
    2. Pelvic Inflammatory Disease history
  3. Adhesions risk
    1. Prior abdominal or pelvic surgeries
  4. Ovarian Cancer risks
    1. See Ovarian Cancer
    2. Age over 40 years old (most over 50)
    3. Delayed child bearing
    4. Unopposed Estrogen (e.g. Anovulatory Bleeding)
    5. Family History (esp. BRCA, Lynch Syndrome with Colon Cancer)
    6. Nulliparity
    7. Obesity
  5. Ovarian Cancer symptoms (esp. persistent, refractory >2 weeks)
    1. Abdominal Bloating, increased abdominal girth or early satiety
    2. Pelvic Pain or Abdominal Pain
    3. Unintentional Weight Loss
    4. Urinary tract symptoms (urine frequency, urgency or Urinary Incontinence)

IV. Exam

  1. Lymph Node exam (inguinal region and generally)
  2. Abdominal exam
    1. Abdominal masses
    2. Ascites
  3. Pelvic Exam
    1. Speculum exam
    2. Bimanual exam
      1. Performed in Adnexal Mass evaluation
      2. Useless in screening for Ovarian Cancer (esp. BMI>30 kg/m2)
        1. Buys (2011) JAMA 305(22):2295-303 [PubMed]
    3. Rectal Exam (consider)

V. Labs: General

  1. Pregnancy Test (urine HCG or serum HCG)
    1. Obtain in all women of child bearing age
    2. Exclude Ectopic Pregnancy
  2. Tuboovarian Abscess risk
    1. See Pelvic Inflammatory Disease
    2. Gonorrhea and Chlamydia DNA Probe
    3. Complete Blood Count with differential

VI. Labs: Biomarkers

  1. CA 125 indications
    1. Avoid as a screening tool
      1. High False Positive Rate (elevated in pregnancy, PID, Menstruation and Obesity)
      2. Test Sensitivity <50% in stage 1 disease)
    2. Follow algorithm (see below)
    3. Obtain as an adjunct to evaluation in those at Ovarian Cancer high risk
  2. Human Epididymis Protein 4 (HE4)
    1. Increased in 50% of Ovarian Cancer patients despite normal serum CA-125 Levels
    2. Less commonly due to benign ovarian tumors or Endometriosis
    3. Discriminatory values vary
    4. Only indicated in monitoring epithelial Ovarian Cancer or screening for its recurrence
  3. Biomarker panels
    1. As of 2023, panels with up to 5 biomarkers are FDA approved (e.g. Multivariant Index Assay)

VII. Differential Diagnosis: Adnexal Mass

  1. Ovary
    1. Functional cyst or Corpus Luteal Cyst
    2. Theca lutein cyst
    3. Benign ovarian tumor (Teratoma, cyst adenoma)
    4. Ovarian Torsion
    5. Ovarian Hyperstimulation Syndrome
    6. Ovarian Cancer
    7. Polycystic Ovary Syndrome
  2. Fallopian Tube
    1. Tuboovarian Abscess in Pelvic Inflammatory Disease
    2. Hydrosalpinx
    3. Ectopic Pregnancy
    4. Malignancy
  3. Uterus
    1. Leiomyomata or Uterine Fibroids (pedunculated)
    2. Endometriosis
  4. Gastrointestinal Tract
    1. Stool-filled bowel
    2. Diverticulitis
    3. Appendicitis or appendiceal abscess
    4. Inflammatory Bowel Disease
    5. Small Bowel leiomyoma
    6. Colon Cancer
    7. Krukenberg Tumor (metastasis to ovary)
  5. Urinary Tract
    1. Bladder Distention
    2. Urachal Cyst

VIII. Imaging: Ultrasound

  1. See Ovarian Cancer for other imaging techniques and their findings
  2. Technique
    1. Transvaginal Ultrasound
    2. Transabdominal Ultrasound (children and preteens)
  3. Characteristic findings suggestive of benign mass
    1. Premenopausal women with physiologic Ovarian Cysts <3 cm
    2. Postmentopausal women with simple cysts <1 cm
    3. Simple Ovarian Cyst with thin smooth walls
    4. Hemorrhagic Ovarian Cyst
    5. Endometrioma
    6. Benign Cystic Teratoma
    7. Fibroma
    8. Hydrosalpinx
  4. Intermediate lesions (based on ACR guidelines)
    1. Large, benign appearing cysts or BAC (round/oval, unilocular, smooth walled)
      1. Larger than 5 cm in early postmenopausal women
      2. Larger than 3 cm in late postmenopausal women
    2. Large, probably benign cysts or PBC (not round/oval, angulated margins, imaging inadequate)
      1. Larger than 5 cm in premenopausal women
      2. Larger than 3 cm in early postmenopausal women
      3. Larger than 1 cm in late postmenopausal women
  5. Characteristic findings suggestive of malignancy (Complex cyst or solid mass)
    1. Solid component within Ovarian Mass or cyst
    2. Thick septations >2-3 mm
    3. Large volume of free fluid or Ascites present
    4. Color Doppler Ultrasound shows high Blood Flow within mass
    5. Thick cyst wall >2-3 mm
      1. Also seen in benign conditions
        1. Hemmorhagic Ovarian Cyst
        2. Endometrioma
    6. Cyst size does not distinguish benign from malignant
      1. However size my risk stratify postmenopausal cysts (esp >10 cm)
      2. See Simple Ovarian Cyst

IX. Evaluation: Tools

  1. Various protocols combine labs and scoring systems to estimate Ovarian Cancer risk
  2. Lab Studies (see above)
    1. CA 125
    2. Human Epididymis Protein 4 (HE4)
  3. Scoring Systems
    1. Risk of Malignancy Index for Ovarian Cancer
    2. International Ovarian Tumour Analysis ADNEX
    3. Symptom Index for Ovarian Cancer
      1. General
        1. Four or more symptoms: Test Sensitivity 27%, Test Specificity 96%
        2. Symptoms present at least 12 times per month for <1 year
      2. Criteria
        1. Abdominal Bloating
        2. Abdominal Pain
        3. Difficulty eating
        4. Early satiety
        5. Increased abdominal size
        6. Pelvic Pain
      3. References
        1. Jain (2018) J Indian Acad Clin Med 19(1): 27-32 [PubMed]

X. Evaluation: Adult Protocol

  1. Based on initial tests
    1. Urine Pregnancy Test (bHCG) if not postmenopausal
    2. Pelvic Ultrasound
    3. Consider CA-125 in postmenopausal women with nondiagnostic pelvic Ultrasound
  2. Exclude pregnancy first (bHCG)
    1. Evaluate for Ectopic Pregnancy if bHCG positive
  3. Refer to gynecology if red flag findings on history or Ultrasound
    1. See referral indications below
    2. Family History of Ovarian Cancer or high risk (see BRCA)
    3. Ultrasound with concerning findings (see findings suggestive of malignancy above)
    4. Adnexal Mass >6 cm
    5. Postmenopausal AND CA-125 >35 U/ml
    6. Risk of Malignancy Index (RMI) >200
  4. Repeat Ultrasound in 4-12 weeks
    1. Refer to gynecology if persistent adexal mass present >12 weeks

XI. Management: Gynecology Referral Indications

  1. Prepubescent girls
    1. Refer all Adnexal Masses
    2. Causes
      1. Ovarian Malignancy in 25% of girls <18 years old (esp. germ cell tumors)
      2. Benign Dermoid Cysts (50% of Adnexal Masses)
    3. Labs
      1. Alpha Fetoprotein
      2. Beta-HCG
      3. L-Lactate Dehydrogenase
    4. Surgery Indications
      1. Suspected Ovarian Torsion
      2. Persistent mass or other concerns for malignancy
      3. Acute Abdominal Pain
  2. Pregnancy
    1. Acute presentation with positive Urine Pregnancy Test
      1. Evaluate for Ectopic Pregnancy (serial Quantitative hCG and pelvic Ultrasound)
    2. Adnexal Mass diagnosed during intrauterine pregnancy
      1. Simple Ovarian Cysts (<5 cm) are common during pregnancy
      2. Adnexal Masses are common in pregnancy (2.4%) and most (>70%) resolve after pregancy
      3. Adnexal Masses identified during pregnancy are malignant in 1 to 5% of cases
      4. Repeat imaging of benign or indeterminate masses at 18 to 20 weeks, and 32 to 36 weeks
      5. Refer large (>5 cm), complex, septated, irregular or bilateral Adnexal Masses
      6. MRI may be indicated in some cases
  3. Premenopausal women
    1. Ultrasound with complex cyst or solid mass (suspicious findings)
    2. Ultrasound with mass >10 cm
    3. Serial Ultrasounds (every 4-6 weeks) with mass that persists >12 weeks
    4. CA-125 is not recommended in evaluation of premenopausal or perimenopausal women
      1. However if obtained, a CA-125>200 U/ml should prompt referral in this group
  4. Postmenopausal women (highest risk for Ovarian Cancer)
    1. Ultrasound with complex cyst or solid mass
    2. Ultrasound with mass >10 cm
    3. Serial Ultrasounds (every 4-6 weeks) with mass that persists >12 weeks
    4. CA-125 >35 U/ml

XII. Management: General

  1. Monitor intermediate lesions (not clearly benign, but not clearly suspicious)
    1. Transvaginal Ultrasound repeated in 6-12 weeks
    2. Some lesions may be monitored less frequently, up to one year (e.g. endometrioma, Cystic Teratoma)

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