Benign Ovarian Tumor – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

The ovaries are a source of many tumor types (benign and malignant) because of the histologic variety of their constituent cells.Benign ovarian tumors create difficulties in differential diagnosis because of the need to identify malignancy and discriminate tumor from cysts, infectious lesions, ectopic pregnancy, and endometriomas.Tumors are often clinically silent until well developed; may be solid, cystic, or mixed; and they may be functional (producing sex steroids, as with arrhenoblastomas and gynandroblastomas) or nonfunctional.System(s) affected: Endocrine/Metabolic; Reproductive

Geriatric Considerations

Because incidence of malignancy increases with age, postmenopausal patients warrant comprehensive evaluation and follow-up.

Pediatric Considerations

Malignancy must be ruled out in premenarchal patients. Early neonatal cysts are rare.

Epidemiology

Incidence

30% of regularly cycling females50% of women without regular cyclesPredominant age: Premenarchal girls have a 5–35% risk of cancer in an ovarian tumor, and postmenopausal women have a 30% risk.

Risk Factors

As yet poorly characterized for benign tumors; cigarette smoking increases the relative risk for developing functional ovarian cysts 2-fold.Possible contributory factors are early menarche, obesity, infertility, and hypothyroidism.Risks for ovarian cancer include age >60 years; early menarche; late menopause; nulliparity; infertility; family history of ovarian, breast, or colon cancer; or a personal history of breast or colon cancer; or BRCA mutation.Risk for ovarian cancer is decreased in women who have used OCPs, been pregnant, or breastfed.

General Prevention

Although oral contraceptives do not appear to increase rates of cyst resorption, they do decrease risk for forming new ovarian cysts.A large British cohort of 5,479 women demonstrated that the resection of benign cysts has no impact on future risk for ovarian cancer.A case-control study of 299 women found no evidence that ovulation-induction treatment predisposes women to the development of borderline ovarian growths.

Etiology

Endometriosis with localized, repeated ovarian hemorrhagePhysiologic cystsTumorigenesis, with genetics as yet poorly defined

Diagnosis

A careful history is important.Usually asymptomaticPain related to torsion, endometriosis, or rupture

History

Early satietyDyspepsia/bloatingIncreased abdominal girthBowel pressure or bladder pressure sensationsMenstrual irregularitiesDyspareuniaHirsutism or sexual precocitySevere acneDeepening of the voiceVirilization

Physical Exam

Examine lymph nodes for enlargement.Chest auscultation can reveal a pleural effusion.Abdominal exam may identify ascites, masses, or increased abdominal girth.Pelvic exam is recommended.

Diagnostic Tests & Interpretation

Lab

Initial lab tests

Complete blood count for WBCs helpful if pelvic inflammatory disease (PID) suspectedPregnancy testUrinalysisSerum estrogens and androgens if signs of androgen excessSerum tumor markers may be considered but often confuse rather than help to resolve diagnosis; choose carefully: CA-125 should not be ordered in a premenopausal patient for screening purposes. If an ovarian tumor in a premenopausal patient is highly suspicious for cancer by US, a CA-125 level greater than 200 u is concerning. In a postmenopausal patient, cancer must be ruled out and a CA-125 >35 u is concerning.a-Fetoprotein and human chorionic gonadotropin (hCG) can be ordered for suspected germ call tumorDisorders that may alter lab results: CA-125: Endometriosis, peritonitis, PID, Meigs syndrome, uterine fibroids, hepatitis, pancreatitis, systemic lupus erythematosus, diverticulitisß-hCG: Pregnancy, hydatidiform molea-Fetoprotein: Hepatocellular carcinoma, hepatic cirrhosis, acute or chronic hepatitis

Imaging

Transvaginal US is the best means to determine the architecture of an ovarian cyst or mass.Transvaginal ultrasonography may differentiate tumors from other pelvic lesions and identify features that place the patient at greater risk for malignancy (e.g., solid component, papillations, multiple septations, ascites, bilaterality, fixed and irregular, rapidly enlarging, accompanied by cul-de-sac nodules).Transabdominal US can help identify ascites.Color-flow Doppler evaluation also may be helpful. Color flow to the solid component of the tumor is concerning for cancer. Gray scale may be an important method of differential diagnosis of ovarian growths.MRI with apparent diffusion coefficient mapping may be useful in the differential diagnosis of cystic masses. MRI can be helpful in better defining masses in women with low risk of ovarian cancer but who have an “indeterminant” mass on US.Cystoscopy if hematuria is present in the absence of infection or if IV pyelogram reveals intravesical surface irregularityAbdominopelvic CT scan with contrast material, if MRI unavailableBarium enema, colonoscopy, or IV pyelogram, as indicated

Diagnostic Procedures/Surgery

Exploratory laparoscopy or laparotomy

Pathological Findings

Follicular (fluid distension of atretic follicle) and corpus luteum cysts (corpus luteum hematoma). Follicular cysts are the most common ovarian cysts in the premenopausal nonpregnant female.EndometriomaPregnancy luteoma (composed of hyperplastic stromal theca–lutein cells)Serous and mucinous cystadenomas and mixed serous/mucinous cystadenomasGranulosa cell tumorsBenign connective tissue tumors (thecomas, fibromas, Brenner tumors)Cystic teratoma (dermoid cyst); teratomas are the most common benign neoplasms.Germinal inclusion cyst (regarded by some as the precursor for epithelial ovarian cancer)

Pregnancy Considerations

Most cysts discovered during pregnancy are corpus luteum or follicular cysts.The 2 most commonly encountered tumors during pregnancy are cystadenomas (serous or mucinous) and dermoid cysts.

Differential Diagnosis

Ovarian malignanciesEndometriomaUterine leiomyomaAppendicular cystsDiverticulitis or bowel abscessPID with tubo-ovarian abscessDistended urinary bladderEctopic pregnancyHydrosalpinxFunctional cysts (follicular and corpus luteum cysts)Polycystic ovariesOvarian lipoma

Treatment

Medication

Oral contraceptives decrease risk for forming new ovarian cysts. They do not aid in resorption of current ovarian cysts.

First Line

NSAIDs or narcotics may be helpful for discomfort.

Additional Treatment

General Measures

In premenopausal patients with cystic lesions <10 cm in diameter, simple observation for 4–6 weeks is acceptable. No evidence suggests that use of a contraceptive pill is more effective than time alone in facilitating ovarian cyst resorption.If a large cyst remains unchanged after 4–6 weeks of observation, then surgical exploration is indicated.Unilocular ovarian cysts <5 cm in premenopausal patients were not considered suspicious.

Surgery/Other Procedures

Cystectomy or wedge resection for cyst with benign featuresSurgical removal of tumor to establish diagnosis when: Premenopausal cysts >5 cm that persist >12 weeksMass is solid.Mass is >10 cm.Mass in a premenarchal or postmenopausal femaleSuspicion of torsion or rupturePostmenopausal cystsCysts with worrisome features on US (e.g., papillations)For masses that are worrisome for cancer, consider referral to a gyn-oncologist for initial surgery.

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

Most require only yearly exams.Varies by diagnosis

Patient Education

A variety of excellent patient education materials (e.g., “Ovarian Cyst”) can be downloaded from the American Association of Family Physicians and American College of Obstetricians and Gynecologists Internet sites: http://www.aafp.org/afp and http://www.acog.com.

Prognosis

Complete cure

Complications

Complications of untreated dermoid and mucinous cysts may include rupture and pseudomyxoma peritonei.

Additional Reading

1. Borgfeldt C, Andolf E. Cancer risk after hospital discharge diagnosis of benign ovarian cysts and endometriosis. Acta Obstet Gynecol Scand. 2004;83:395–400.

2. Clarke-Pearson D. Screening for Ovarian Cancer. NEJM. 2009;(361):170–7.

3. Crayford TJ, Campbell S, Bourne TH, et al. Benign ovarian cysts and ovarian cancer: a cohort study with implications for screening. Lancet. 2000;355:1060–3.

4. Cusidó M, Fábregas R, Pere BS, et al. Ovulation induction treatment and risk of borderline ovarian tumors. Gynecol Endocrinol. 2007;23:373–6.

5. Givens V, Mitchell G. Diagnosis and Management of Adnexal Masses. AAFP; 2009;80(8):815–822.

6. Holt VL, Cushing-Haugen KL, Daling JR. Oral contraceptives, tubal sterilization, and functional ovarian cyst risk. Obstet Gynecol. 2003;102:252–8.

7. Iyer VR, Lee SI, et al. MRI, CT, and PET/CT for ovarian cancer detection and adnexal lesion characterization. AJR Am J Roentgenol. 2010;194:311–21.

8. Kirilovas D, Schedvins K, Naessén T, et al. Conversion of circulating estrone sulfate to 17beta-estradiol by ovarian tumor tissue: a possible mechanism behind elevated circulating concentrations of 17beta-estradiol in postmenopausal women with ovarian tumors. Gynecol Endocrinol. 2007;23:25–8.

9. Labarge PY, et al. Short-term morbidity and long-term recurrence rate of ovarian dermoid cysts treated by laparoscopy vs. laparotomy. J Obstet Gynecol Can. 2006;28(9):789–93.

10. Marchesiini AC, et al. A critical analysis of Doppler velocimetry in the differential of malignant and benign ovarian masses. J Women Health. 2008;17(10):97–102.

11. Nakayama T, et al. Diffusion-weighted echo-planar MR imaging and ADC mapping in the differential diagnosis ovarian cystic masses: Usefulness of detecting keratinoid substances in mature cystic teratomas. J Magn Reson Imag. 2005;22(2):271–8.

12. Zwiesler D, Lewis SR, Choo YC, et al. A case report of an ovarian lipoma. South Med J. 2008;101:205–7.

Codes

ICD9

220 Benign neoplasm of ovary

Snomed

92260003 benign neoplasm of ovary (disorder)

Clinical Pearls

Cigarette smoking doubles the relative risk of developing a functional ovarian cyst.Transvaginal pelvic ultrasound is the imaging test of choice to initially determine the architecture of an ovarian cyst or mass.Malignancy must be ruled out in both premenarchal and postmenopausal patients.Do not order CA 125 on premenopausal patients with an ovarian mass unless it is highly suspicious for cancer.

Ovarian Hyperstimulation Syndrome – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Iatrogenic physiologic complication of controlled ovarian hyperstimulation (most often related to treatment for infertility)Results in ovarian enlargement, increased vascular permeability with resulting 3rd-space loss and intravascular fluid depletion, electrolyte imbalance, hemoconcentration, and ascitesClassification of OHSS is based on clinical symptoms and ultrasound findings. Mild: Abdominal distension and discomfortModerate: Abdominal distension, enlarged ovaries (8–10 cm3) and ascites on ultrasound (largest pocket <3 cm)Severe: Clinical evidence of ascites and/or hydrothorax, hemoconcentration >45%Critical: hemoconcentration >55%, creatinine clearance <50 mL/min, renal failure, thromboembolism, ARDSSymptoms of OHSS may occur early (within 10 days of hCG administration) or late (more than 10 days after hCG administration). Late OHSS is usually associated with a pregnancy and may often be more severe.

Epidemiology

Incidence

Predominant age: Women of reproductive ageWith controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF): Mild OHSS: 20–33% of cyclesModerate OHSS: 3–6% of cyclesSevere OHSS: 0.1–2% of cycles

Risk Factors

Previous history of OHSSYoung ageLow body weightPolycystic ovary syndrome (PCOS) or polycystic ovaries on ultrasoundLarge number of resting follicles (>10 follicles between 2 and 8 mm) per ovaryHigh doses of gonadotropinsLarge number of intermediate-sized folliclesNumber of oocytes retrievedRapidly rising estradiol levelsHigh estradiol levels >3000/4000 pg/mLUse of human chorionic gonadotropin (hCG) for luteal supportAchievement of a pregnancyMultiple pregnancy

General Prevention

Patients who have had OHSS are more at risk for OHSS in the future, and this should be taken into consideration in subsequent treatment cycles. Patients need to inform their health care providers of a history of OHSS when considering further assisted reproductive technology treatment.If a patient is noted to be at high risk of OHSS, the stimulation and monitoring protocol may be modified to reflect this risk. In some circumstances, consideration should be given to canceling the stimulation by withholding the preovulatory injection of hCG, proceeding with a lower dose of hCG, the use of a GnRH agonist to trigger ovulation in GnRH antagonist cycles, “coasting” or withholding stimulatory drugs for several days to allow for estradiol levels to plateau or decrease, avoiding the use of hCG for luteal supporting, or freezing all viable embryos without proceeding with an embryo transfer (1)[B].Recent evidence suggests that the off-label use of dopamine agonists (cabergoline 0.5 mg) after hCG administration may decrease the incidence of OHSS (2)[A].

Pathophysiology

Ovarian hyperstimulation leads to increased capillary permeability and intravascular fluid shifts.Fluid shifts can lead to ascites and pleural effusions.Intravascular volume depletion can lead to hemoconcentration, decreased renal perfusion, and thrombosis.The ovarian renin–angiotensin system, cytokines, and other inflammatory mediators such as vascular endothelial growth factor (VEGF) may play a role in the pathophysiology of OHSS.

Etiology

OHSS is an iatrogenic syndrome that occurs during controlled ovarian hyperstimulation (COH) for infertility treatment.Generally, OHSS is associated with the use of exogenous gonadotropins such as recombinant or purified follicle-stimulating hormone (FSH).OHSS rarely has been associated with types of ovarian stimulation such as clomiphene citrate.

Commonly Associated Conditions

InfertilityPCOSAssisted reproductive technologies

Diagnosis

OHSS is a clinical diagnosis based on history, physical exam, ultrasound findings, and laboratory results.

History

Details of stimulation cycle: Medications usedDate of oocyte retrieval and embryo transferSymptoms of dehydrationAbdominal pain and distensionNausea, vomiting, diarrheaShortness of breathLoss of appetiteWeight changesFluid intakeLethargyRisks factors such as PCOS or previous OHSS

Physical Exam

Vital signs, including O2 saturation if shortness of breathWeight (daily)Monitoring of ins and outs (daily or more often as needed)Chest and cardiovascular examAbdominal circumference measured at the umbilicus (daily)Gentle abdominal exam to detect ascites

Alert

Pelvic and bimanual examinations are contraindicated to avoid ovarian hemorrhage or rupture.

Diagnostic Tests & Interpretation

Lab

Initial lab tests

CBC Hemoconcentration (hematocrit >45% indicates severe disease, >55% indicates critical disease)WBC >15,000 indicates severe diseaseElectrolytes to look for hyponatremia and hyperkalemiaRenal function testsLiver enzymesCoagulation profileß-hCG

Follow-Up & Special Considerations

For patients with mild or moderate OHSS being monitored as an outpatient, CBC and electrolytes should be performed every 1–2 days, until improvement in symptoms.

Imaging

Initial approach

Abdominal/pelvic ultrasound to assess ovarian size, ovarian torsion or rupture, and abdominal ascitesCXR to evaluate pleural effusion in presence of shortness of breath

Follow-Up & Special Considerations

Repeat abdominal/pelvic ultrasound as needed to assess ascites and guide management for paracentesis.

Pathological Findings

Ovarian enlargementDecreased renal perfusionThromboembolismAbdominal ascitesPleural effusionsPericardial effusions

Differential Diagnosis

Hemorrhagic ovarian cystOvarian torsionEctopic pregnancyPelvic infection

Treatment

Medication

Heparin 5,000 units SC every 8–12 hours; all hospitalized patients should be on anticoagulation prophylaxis and graduated compression stockings to prevent thrombotic events (3)[C].Full anticoagulation therapy should be started if there is evidence of a thromboembolic event.

Additional Treatment

General Measures

Mild to moderate OHSS: Generally managed as outpatient Oral fluid intake of at least 1 L daily of a balanced electrolyte solution (sports drinks) (3)[C].Monitor daily weight, abdominal circumference, and urine output (3)[C].Avoid physical exertion or abdominal trauma.Monitor for development of further symptoms.Frequent follow-up is required.For moderate OHSS, frequent assessments every 1–2 days including a physical examination and blood work should occur.Consider hospitalization with worsening signs or symptoms: Severe abdominal painSevere oliguria or anuriaTense ascitesDyspnea or tachypneaHypotension, dizziness, or syncopeSevere electrolyte imbalance: Hyponatremia <135 mEq/L, hyperkalemia >5 mEq/L, hemocrit >45%Severe OHSS: Should be managed as an in-patient. Daily weight and abdominal circumferenceFrequent monitoring of vital signs every 2–8 hoursStrict monitoring of input and output to maintain urine output of 20–30 cc/hourBed rest or reduced activity; the enlarged ovaries are at risk of torsion and ovarian hemorrhage either spontaneously or from injury or trauma.With severe illness, oral fluids should be limited and rehydration provided with IV fluids until evidence of symptom resolution such as spontaneous diuresis.IV fluids should be administered to maintain urine output to 20–30 mL/hour. Normal saline with 5% dextrose is preferred to Ringer’s lactate (3)[C].Once 3rd-space edema reenters the intravascular space, hemoconcentration reverses, and the patient begins to diurese spontaneously.Monitor leukocyte count, hematocrit and hemoglobin, electrolytes, creatinine, and liver enzymes.Thrombosis prophylaxis (3)[C]Intensive monitoring may be required for pulmonary support in cases of acute respiratory distress syndrome, thromboembolic events, or for renal failure.

Issues for Referral

Consultation with a reproductive endocrinology specialist or a gynecologist with experience in the management of OHSS and its complications.

Surgery/Other Procedures

Paracentesis/thoracentesis may be required for symptomatic control and for pulmonary and/or renal compromise. An ultrasound-guided approach for paracentesis is recommended to avoid the enlarged ovaries. Indications for paracentesis include severe discomfort or pain, respiratory compromise, evidence of hydrothorax, or persistent oliguria/anuria despite adequate fluid replacement.Surgery should be avoided whenever possible in these patients.When ovarian hemorrhage is suspected, surgery may be necessary. The goal should be hemostasis, and the ovaries should be conserved when possible.In a situation of ovarian torsion, surgery may be performed to attempt to revascularize the ovary by unwinding the adnexa.

In-Patient Considerations

Inpatients should have a CBC and electrolytes daily. Renal function, liver enzymes, and coagulation profile should be repeated as needed.

Initial Stabilization

Vital signs and O2 saturation

Admission Criteria

Abdominal pain suspicious of torsion or hemorrhageIntolerance of food or liquidsHypotensionSignificant ascites or plural effusionsHemoconcentration: Hematocrit >50%; white blood cell (WBC) count >25,000Hyponatremia (Na <135 mEq/L)Hyperkalemia (K >5.0 mEq/L)

IV Fluids

With severe illness, IV fluid rehydration should be used. After an initial bolus of 500–1,000 mL, fluid administration should continue to maintain a urine output of at least 20–30 mL/hour. D5NS is preferred over Ringer’s lactate because of the risk of hyponatremia.Albumin 25% (50–100 g) should be reserved for situations in which IV fluids are inadequate to maintain hemodynamic stability or urine output.Diuretics should be used cautiously and only after intravascular volume has been restored. Diuretics may aggravate hypovolemia and hemoconcentration.

Discharge Criteria

Tolerating oral liquids and dietResolution of hemoconcentration and electrolyte imbalancesAdequate urine output

Ongoing Care

Follow-Up Recommendations

Patients discharged from the hospital should be followed with frequent health care provider contact until symptom resolution.

Patient Monitoring

Patients who have conceived should have an early ultrasound to confirm pregnancy and rule out multiple gestations and then routine antenatal care as indicated by their pregnancy.

Diet

Consume 1.0–1.5 L daily of a balanced salt solution, such as a sports drink, until resolution of symptoms.

Patient Education

Monitor oral intake and urinary output.Reduce activity to avoid abdominal trauma or impact.www.acog.org

Prognosis

OHSS is a self-limiting disease that will run its course over 10–14 days in the absence of an ensuing pregnancy and may persist for weeks in a pregnant patient. Supportive treatment is initiated to prevent further deterioration of the patient’s condition.

Complications

Ovarian hemorrhageOvarian torsionArterial and venous thrombosisAcute respiratory distress syndromeLiver failureRenal failure

Pregnancy Considerations

Patients who conceive a multiple gestation are at higher risk of OHSS.Studies have shown an increased risk of prematurity, low birth weight, pregnancy-induced hypertension, and gestational diabetes in women who had severe OHSS (4)[B].

References

1. Vloeberghs V, Peeraer K, Pexsters A, et al. Ovarian hyperstimulation syndrome and complications of ART. Best Pract Res Clin Obstet Gynaecol. 2009;23:691–709.

2. Youssef MA, van Wely M, Hassan MA, et al. Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis.Human reproduction update. 2010

3. Practice Committee of American Society for Reproductive Medicine. Ovarian hyperstimulation syndrome. Fertil Steril. 2008;90:S188–93.

4. Raziel A, Schachter M, Friedler S, et al. Outcome of IVF pregnancies following severe OHSS. Reprod Biomed Online. 2009;19:61–5.

Codes

ICD9

256.1 Other ovarian hyperfunction

Snomed

213201002 hyperstimulation of ovaries (disorder)129635004 ovarian hyperstimulation syndrome (disorder)

Clinical Pearls

Patients who have had OHSS are more at risk for OHSS in the future, and this should be taken into consideration in subsequent treatment cycles.Abdominal and pelvic exams are contraindicated in patients with OHSS to avoid ovarian hemorrhage or rupture.OHSS is a self-limiting disease that will run its course over 10–14 days in the absence of an ensuing pregnancy and may persist for weeks in a pregnant patient. Management is mainly supportive to prevent and identify complications until resolution of symptoms.

Ruptured Ovarian Cyst – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Ovarian cysts are very common in reproductive-age women.Occasionally, once a cyst reaches a certain size or following an episode of strenuous activity or sexual intercourse, a cyst may rupture.A ruptured ovarian cyst may be asymptomatic or may cause extreme pain due to the presence of irritating fluid or blood in the abdominal cavity.A ruptured ovarian cyst may require surgical intervention.

Description

Types of ovarian cysts that may rupture fall into two groups: physiologic and pathologic (1)[C].

Physiologic or functional cysts form as a result of normal hormonal stimulation of the ovary. Most are asymptomatic and spontaneously resolve in 60–90 days. Follicular cysts form when a growing follicle fails to rupture and release an egg. Most common type of functional cystUnilateral and filled with serous fluidCorpus luteum cysts occur when an egg is released and pregnancy does not occur. The residual structure does not regress and may hemorrhage internally (hemorrhagic cysts).Theca-lutein cysts result from excessive stimulation of beta-human chorionic gonadotropin such as in infertility patients, molar pregnancies, or choriocarcinoma.Pathologic cysts are caused by a process other than normal hormonal stimulation. When followed, these cysts remain stable in size or may grow. Endometriomas are cysts or collections of blood clot that form as a result of cycling endometrial tissue on the ovary. Also called “chocolate cysts” due to their appearance.Mature cystic teratoma (dermoid) develop from totipotent germ cells. Most commonly, they contain mucinous material and hair.Up to 14% are bilateral and can grow very large.Less than 1% rupture spontaneously but may lead to shock, hemorrage, and acute peritonitis.Cystadenomas may have solid or mucinous areas and are usually benign but may have borderline malignant areas. They rarely rupture.Other cystic-appearing adnexal structures include paratubal cysts, tubo-ovarian abscess, hydrosalpinx, ectopic pregnancy.

Diagnosis

A ruptured ovarian cyst may be asymptomatic or present as abdominal pain, varying from dull to acute.The broad range of presentations can prove to be a diagnostic dilemma for many physicians.

History

A general past medical and surgical history should be reviewed.Risk factors for gynecologic pain should be elicited: Possibility of pregnancyMenstrual history with attention to symptoms suggestive of endometriosis or history of cystsSexually transmitted disease historyLevonorgestrel-containing intrauterine device (up to 12% of users experience ovarian cysts) (2)[B]Infertility treatmentOther causes of acute abdominal pain should also be considered, including gastrointestinal and urologic etiologies.

Alert

Patients with bleeding diathesis or undergoing anticoagulation therapy may experience significant bleeding from hemorrhagic cysts.

Physical Exam

An uncomplicated ruptured ovarian cyst usually produces dull pain on palpation during the abdominal and pelvic exams. Enlargement of one of the adnexa may be present.A complicated ovarian cyst rupture may have more of an “acute abdomen” presentation due to the presence of blood or fluid in the abdominal cavity.

Diagnostic Tests & Interpretation

Lab

Serum quantitative beta-human chorionic gonadotropin (b-hcg) to rule out pregnancyComplete blood count (CBC) to evaluate for infection and monitor hemodynamic statusCervical cultures if pelvic inflammatory disease is suspectedUrinalysis to evaluate possibility of infection or stonesBlood type and cross matching if the patient is hemodynamically unstable and surgery is planned

Imaging

Transvaginal ultrasound: Most widely used and the gold standard of gynecologic imaging modality due to its cost-effectiveness and availability, and it is well-tolerated (1)[C],(3)[B] The presence of intraperitoneal fluid or blood in the absence of other gynecologic pathology is suggestive of a ruptured cyst.The ovaries may contain cysts, be slightly edematous, contain areas of hemorrhage, or appear normal.An ovarian cyst may be the causative factor in an episode of ovarian torsion. A torsed ovary is diagnosed by no blood flow to the ovary on ultrasound exam.

Alert

A torsed ovary requires immediate surgical intervention.

Follow-Up & Special Considerations

CT scan may be used if the ultrasound is unclear or the diagnosis is uncertain.

Diagnostic Procedures/Surgery

Traditionally, culdocentesis, or aspirating a small amount of peritoneal fluid transvaginally, has been used to diagnose the presence of fluid or hemoperitoneum from a ruptured cyst.Culdocentesis can also be used therapeutically as the removal of irritative blood or fluid from the abdominal cavity may relieve pain.

Differential Diagnosis

Should include all causes of acute abdominal pain, both gynecologic and nongynecologic, such as:

Ectopic pregnancyOvarian torsionPelvic inflammatory diseaseOvarian hyperstimulation syndrome (OHSS)AppendicitisDiverticulitisNephrolitiasisBowel perforation

Treatment

Medication

Pain due to an uncomplicated cyst rupture is usually self-limiting and can be managed on an outpatient basis with pain medication and rest (4)[B].

First Line

NSAID medications are the most effective at relieving pain due to peritoneal irritation.

Second Line

Narcotic pain medications may also be necessary acutely.

Additional Treatment

For patiets with painful, recurrent ovarian cysts, oral contraceptive pills can be prescribed to suppress ovulation. This may help prevent the formation of new cysts but will not impact cysts that have already formed (5)[A].

Issues for Referral

Referral to a gynecologic oncologist should be made in any postmenopausal female with an adnexal mass that has concerning ultrasound findings, an elevated CA-125, ascites, a nodular, fixed pelvic mass and a family history of breast or ovarian cancer. (1)[C],(3)[B]

Surgery/Other Procedures

If pain from a ruptured cyst is severe and persistent, the patient is unstable, or the diagnosis is uncertain, surgical evaluation is recommended (4)[B].

Laparoscopy is the better choice over laparotomy because it is less-invasive, better tolerated by patients, and can usually be done on an outpatient basis. (1)[C],(3)[B]Surgery includes suction-evacuation of any fluid or blood found in the pelvis as well as achieving hemostasis, if needed, at the site of the cyst. If a cyst wall is present, it should be removed.In the vast majority of cases, oophorectomy is not necessary.Laprascopic excision of the cyst and capsule of endometriomas substantially decreases risk of recurrence (6)[A].

Ongoing Care

Follow-Up Recommendations

Most functional cysts resolve spontaneously without treatment and “watchful waiting” with serial transvaginal ultrasounds for 2–3 cycles is appropriate.If cysts fail to resolve or develop concerning ultrasound findings (increasing size or complexity, nodules, septations, excrescences), they may be pathologic and surgical evaluation is recommended (5)[A].Concern for malignancy: The vast majority of ruptured ovarian cysts are a result of functional cysts in reproductive-age women and the risk of malignancy is very low. See “Issues for Referral” section.

Pregnancy Considerations

Ovarian cysts in pregnancy: With the widespread use of ultrasonography during pregnancy, up to 4% of pregnant women are found to have adnexal masses, most of which are follicular cysts which spontaneously resolve by 16 weeks’ gestation.Less than 2% will spontaneously rupture or torse during pregnancy; however, this can lead to preterm labor and delivery, which may cause poor obstetric outcomes.If they are painful, are large (>8 cm), or have ultrasound characteristics that are concerning for malignancy, elective surgical evaluation can be done during the 2nd trimester. (1)[C],(3)[B]

Patient Education

www.acog.org

References

1. Stany MP, Hamilton CA et al. Benign disorders of the ovary. Obstet. Gynecol. Clin. North Am. 2008;35:271–84, ix

2. Mirena [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2009.

3. Management of Adnexal Masses ACOG Practice Bulletin No. 83. American College of Obstetricians and Gynecologists. Obstet Gynecol 2007;110:201–14.

4. Bottomley C, Bourne T et al. Diagnosis and management of ovarian cyst accidents. Best Pract Res Clin Obstet Gynaecol. 2009;23:711–24.

5. Grimes DA, Jones LB, et al. Oral contraceptives for functional ovarian cysts. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD006134. DOI: 10.1002/14651858.CD006134.pub3

6. Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery versus ablative surgery for ovarian endometriomata. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD004992. DOI: 10.1002/14651858.CD004992.pub3

Additional Reading

Raziel A, Ron-El R, et al. Current management of ruptured corpus luteum. Eur J Obstet Gynecol Reprod Biol 1993 Jun; 50:77–81.

Møller LM et al. [Complications of gynaecological operations. A one-year analysis of a hospital database] Ugeskr. Laeg. 2005;167:4654–9.

Saunders BA, Podzielinski I, Ware RA, Goodrich S, DeSimone CP, Ueland FR, Seamon L, Ubellacker J, Pavlik EJ, Kryscio RJ, van Nagell JR et al. Risk of malignancy in sonographically confirmed septated cystic ovarian tumors. Gynecol. Oncol. 2010;118:278–82.

Huchon C, Staraci S, Fauconnier A et al. Adnexal torsion: a predictive score for pre-operative diagnosis. Hum. Reprod. 2010;25:2276–80.

Hoo WL, Yazbek J, Holland T, Mavrelos D, Tong EN, Jurkovic D et al. Expectant management of ultrasonically diagnosed ovarian dermoid cysts: is it possible to predict outcome?Ultrasound Obstet Gynecol. 2010;36:235–40.

Falcone T. Risk of complications from gynecological surgery is lower with laparoscopy than with laparotomy. Evidence Based Obstetrics and Gynecology 2004;4:185–6.

Codes

ICD9

620.2 Other and unspecified ovarian cyst

Snomed

95598005 ruptured cyst of ovary (disorder)

Clinical Pearls

Functional ovarian cysts are very common in reproductive-age women and usually resolve spontaneously in 60–90 days.If a cyst does rupture, the pain is usually self-limited and can be treated with oral pain medications on an outpatient basis.Surgery may be necessary if pain is extreme or if the patient is unstable. This usually involves laprascopically evacuating irritating fluid and blood from the abdominal cavity, achieving hemostasis, and removing the cyst wall if possible.

Ovarian Cancer – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

There are over 21,000 new cases of ovarian cancer annually, and 14,000 women will die of their disease, making this the most lethal of gynecologic cancers.

Description

Malignancy that arises from the epithelium (85–90%), stroma, or germ cells of the ovary; also, tumors metastatic to the ovary; histologic types include:

Epithelial: Serous (tubal epithelium)Mucinous (cervical and GI mucinous epithelium)Endometrioid (endometrial epithelium)Clear cell (mesonephroid)Brenner (transitional cell epithelium)CarcinosarcomaStromal: Granulosa cell tumorTheca cell tumorSertoli–Leydig cell tumorsGynandroblastomaLipid cell tumorGerm cell: Teratoma (immature)DysgerminomaEmbryonal carcinomaGonadoblastomaEndodermal sinus tumorEmbryonal carcinomaChoriocarcinomaMetastatic disease from: BreastEndometriumLymphomaGI tract (Krukenberg tumor)Primary peritonealSystem(s) affected: GI; Reproductive; Endocrine; Metabolic

Epidemiology

Incidence

21,550 new cases/year in the US; 14,600 deaths/yearLeading cause of gynecologic cancer death in women; mortality from ovarian cancer has decreased only slightly during the last 4 decades.62% diagnosed at advanced stagePredominant age: Epithelial: Mid-50sGerm cell malignancies: Usually observed in patients <20 years of age

Prevalence

Lifetime risk for general population: 1 in 70 women develops ovarian cancer.

Risk Factors

90% of ovarian cancer is sporadic and not inherited, but family history is the most significant risk factor. 1 1st-degree relative increases risk to 5%; 2 relatives, to 7%; individuals in families with familial cancer syndromes have 20–60% risk of developing ovarian cancer.Nulligravity (or infertility), early menarche, late menopause, endometriosisEnvironmental (talc, smoking, obesity)

Genetics

Breast/ovarian cancer syndrome: Early-onset breast or ovarian cancer, autosomal dominant transmission, usually associated with BRCA-1 or BRCA-2 mutationLynch II syndrome: Autosomal dominant inheritance; increased risk for colorectal, endometrial, stomach, small bowel, breast, pancreas, and ovarian cancers; defect in mismatch repair genes

General Prevention

For epithelial cancer, frequency of ovulation appears to be important. The following factors are protective:

Use of oral contraceptives: 5 years of use decreases risk by 20%; 15 years, by 50%.MultiparityBreastfeedingTubal ligation or hysterectomy: The progestin component of oral contraceptive preparations (OCPs) may protect against ovarian cancer by regulating apoptosis of the ovarian epithelium.Recent studies have shown that no clear association exists between ovarian cancer and use of ovulation-induction agents such as clomiphene, but more long-term studies are necessary (1)[B].Nonsteroidal anti-inflammatory drug (NSAID) and acetaminophen use have been shown to reduce risk of ovarian cancer (2)[B].Women with family histories of ovarian cancer or premenopausal breast cancer should be referred for genetic counseling (3)[B].Prophylactic oophorectomy is advised for mutation carriers after child-bearing is completed or by age 35 (3)[B]. Risk of primary peritoneal carcinoma is 1% after prophylactic oophorectomy.Screening: No effective screening exists for ovarian cancer: Routine use of CA-125 and transvaginal ultrasound for screening in women of average risk is discouraged. Annual pelvic examinations are recommended, particularly in postmenopausal women. An adnexal mass in a premenarchal female or a palpable adnexa in a postmenopausal female warrants further evaluation.Women with a family history of a hereditary ovarian cancer syndrome should undergo pelvic examinations, CA-125 determination, and transvaginal ultrasonography every 6–12 months beginning at ages 25–35.

Pathophysiology

Malignant transformation of the ovarian epithelium from repeated minor trauma during ovulation may lead to this change.Most ovarian cancer (62%) presents as advanced disease. Metastatic disease may develop at the same time as the primary tumor.

Commonly Associated Conditions

AscitesPleural effusionDecrease of serum albuminBreast carcinomaBowel obstructionCarcinomatosis

Diagnosis

History

BloatingEarly satiety, anorexia, dyspepsiaSense of abdominal fullness, increased abdominal sizeAbdominopelvic pain or crampingUrinary frequency or urgency in absence of infectionFatigueDyspareuniaWeight lossSevere pain secondary to ovarian rupture or torsion most frequent in germ cell tumorsPrecocious puberty (choriocarcinoma, embryonal carcinoma)

Physical Exam

AscitesCul de sac and/or pelvic nodularityPelvic massPleural effusionOmental massCachexiaAdenopathyHirsutism in androgen-secreting germ cell tumors

Diagnostic Tests & Interpretation

Lab

Initial lab tests

CA-125 (not specific for ovarian cancer)Liver function tests (LFTs) to rule out hepatic diseaseComplete blood count (CBC)UrinalysisSerum albuminCarcinoembryonic antigen (CEA) if GI primary suspectedIf nonepithelial tumor suspected: Chorionic gonadotropin (ß-hCG [dysgerminoma, choriocarcinoma, embryonal carcinoma]), a-fetoprotein (endodermal sinus tumor, embryonal carcinoma), lactate dehydrogenase (LDH [dysgerminoma]), or inhibin (granulosa cell tumor)

Follow-Up & Special Considerations

Disorders that may alter lab results: CA-125 may be elevated from gynecologic causes (e.g., menses, pregnancy, endometriosis, peritonitis, myomas, pelvic inflammatory disease) and with ascites, pleural effusion, congestive heart failure (CHF), pancreatitis, systemic lupus erythematosus (SLE), or liver disease.

Imaging

Initial approach

Pelvic ultrasoundCXRAbdominopelvic CT scan with contrast material

Follow-Up & Special Considerations

Patients with ovarian cancer need current mammography.Barium enema or colonoscopy if a colon primary is suspected

Diagnostic Procedures/Surgery

Surgery is necessary for definitive diagnosis.Endometrial biopsy if abnormal bleeding presentParacentesis if patient not an operative candidate

Pathological Findings

Epithelial ovarian cancer commonly involves the peritoneal surfaces of the abdomen and pelvis, especially the cul de sac, paracolic gutters, and diaphragmatic surfaces.

Differential Diagnosis

GI, fallopian, or endometrial malignanciesIrritable bowel syndromeColitisHepatic failure with ascitesDiverticulitisPelvic kidneyTubo-ovarian abscess or hydrosalpinxUterine fibroidsEndometriomasPhysiologic cystsBenign or borderline neoplasms

Treatment

Medication

First Line

After surgery, most patients will require chemotherapy. Stage 1a, grade 1 and most stage 1b, grade 1 tumors do not require adjuvant therapy. Patients with clear cell carcinomas, grade 3 tumors, or tumors staged 1c or worse require adjuvant therapy. Patients should be encouraged to participate in clinical trials whenever possible.Paclitaxel (Taxol) is recommended in combination with platinum-based therapy as the 1st-line treatment of epithelial ovarian cancer (4)[A].Intraperitoneal (IP) chemotherapy in combination with IV chemotherapy improves survival in advanced ovarian cancer (5)[A]. IP chemotherapy is associated with more toxicity.Contraindications: Poor functional status, excessive toxicity, hypersensitivityPrecautions: All regimens cause bone marrow suppression. Cisplatin is associated with ototoxicity, renal toxicity, and peripheral neuropathy. Taxol can cause neutropenia and neuropathy.Antiemetic: Ondansetron (Zofran), dronabinol (Marinol), metoclopramide (Reglan), prochlorperazine (Compazine), promethazine (Phenergan)

Second Line

Liposomal doxorubicinCarboplatin/gemcitabineTopotecanTaxotereEtoposideBevacizumabCyclophosphamideTamoxifen may be used in recurrent disease when chemotherapy is not appropriate (6)[B].

Surgery/Other Procedures

Surgical exploration with staging and debulking is critical. Maximal cytoreduction of tumor burden enhances effectiveness of adjuvant therapy and is associated with longer survival.For epithelial malignancies, careful staging, tumor excision/debulking includes: Cytologic evaluation of peritoneal fluid (or washings from peritoneal lavage)Bilateral salpingo-oophorectomy with hysterectomy and tumor reductive surgeryExcision of omentumInspection and palpation of peritoneal surfacesCytologic smear of right hemidiaphragmatic surfaceBiopsy of adhesions or any suspicious areasBiopsy of paracolic recesses, pelvic sidewalls, posterior cul de sac, and bladder peritoneumPelvic and para-aortic lymph node biopsiesGerm cell cancers (less likely to be bilateral): Salpingo-oophorectomy (unilateral if only 1 ovary involved) in young patient

Ongoing Care

Prognosis

5-year survival rates for ovarian cancer based on FIGO data:

Complications

Pleural effusionPseudomyxoma peritoneiAscitesToxicity of chemotherapyBowel obstructionMalnutritionElectrolyte disturbancesFistula formation

References

1. Mahdavi A, Pejovic T, Nezhat F. Induction of ovulation and ovarian cancer: a critical review of the literature. Fertil Steril. 2006;85:819–26.

2. Collaborative Group on epidemiological Studies of Ovarian cancer: Beral V; Doll R; Hermon C, et al. Ovarian cancer and oral contraceptives: Collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008;371:303–14.

3. Eisen A, Rebbeck TR, Wood WC, et al. Prophylactic surgery in women with a hereditary predisposition to breast and ovarian cancer. J Clin Oncol. 2000;18:1980–95.

4. McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996;334:1–6.

5. Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34–43.

6. Orlando M, Costanzo, MV, Chacon RD. Randomized trial of combination chemotherapy versus monotherapy in relapsed ovarian carcinoma: a meta-analysis of published data. J Clin Oncol. 2007;25:280s.

Codes

ICD9

183.0 Malignant neoplasm of ovary

Snomed

93934004 primary malignant neoplasm of ovary (disorder)

Clinical Pearls

Family history of ovarian cancer or early-onset breast cancer is the most significant risk factor for the development of ovarian cancer, yet the vast majority of cases remain sporadic and not inherited.The diagnosis of ovarian cancer should be suspected in women with persistent bloating, upper abdominal discomfort, or gastrointestinal symptoms of unknown etiology.