“ “Clinical management of adnexal masses”

PROF. SANTIAGO DEXEUSPROF. SANTIAGO DEXEUS

Dr. Gustavo MissónDr. Gustavo Missón

Introduction

Adnexal masses are the fourth most

common gynecological cause for

hospitalization and 90% have benign

characteristics.

Adnexal Mases USAAdnexal Mases USA

ANNUAL HOSPITALIZATION: 289000 PATIENTSANNUAL HOSPITALIZATION: 289000 PATIENTS

RISK OF RISK OF MALIGNANCYMALIGNANCY

13% in pre menopause13% in pre menopause45% in post menopause45% in post menopause

L Van Lie (2000)L Van Lie (2000)48 Meeting of the ACOG48 Meeting of the ACOG

N= 4.359October 1991 – October 1999average: 37.22 years (14-85)

Rate of malignancy: 2.1%IUDEXEUS-1999

ADNEXAL MASSESADNEXAL MASSES

ADNEXAL MASSESADNEXAL MASSESColor DopplerColor Doppler

Absence of pathological flowAbsence of pathological flow

3.0% Malignant tumor

4.2% Malignant tumor

Kurjak et al,1993

MªA Pascual y col.,1996

PRIORITYPRIORITY

Differential diagnosisDifferential diagnosis Diagnostic studies and interpretationDiagnostic studies and interpretation ManagementManagement

AnatomyAnatomy

““Adnexa”Adnexa”› Area next to the Area next to the

uterus containing uterus containing ligaments, vessels, ligaments, vessels, tubes, ovariestubes, ovaries

BackgroundBackground

Prevalence of adnexal masses is Prevalence of adnexal masses is 2 to 8%2 to 8%

› Random TVUS of 335 asymptomatic Random TVUS of 335 asymptomatic premenopausal women, 7.8% with premenopausal women, 7.8% with adnexal masses 2.5 cm or larger adnexal masses 2.5 cm or larger (6.6% were ovarian cysts.(6.6% were ovarian cysts.

› Transvaginal sonographic ovarian findings in a random sample of women 25-40 years old. Transvaginal sonographic ovarian findings in a random sample of women 25-40 years old. Ultrasound Obstet Gynecol 1999 May;13(5):345-50. Ultrasound Obstet Gynecol 1999 May;13(5):345-50.

BackgroundBackground

Prevalence of adnexal masses is 2 Prevalence of adnexal masses is 2 to 8%to 8%

› TVUS in 8794 asymptomatic TVUS in 8794 asymptomatic postmenopausal women, 2.5% were postmenopausal women, 2.5% were found to have adnexal cystsfound to have adnexal cysts

› Alcazar JL; Jurado M. Natural history of sonographically detected simple unilocular adnexal Alcazar JL; Jurado M. Natural history of sonographically detected simple unilocular adnexal cysts in asymptomatic postmenopausal women. Gynecol Oncol 2004 Mar;92(3):965-9.cysts in asymptomatic postmenopausal women. Gynecol Oncol 2004 Mar;92(3):965-9.

Differential DiagnosisDifferential Diagnosis

Physiologic cystsPhysiologic cysts› Follicle develops but never ruptures, continues to Follicle develops but never ruptures, continues to

growgrow› Simple, smooth-walled Simple, smooth-walled

Functional cystsFunctional cysts› Corpus luteum does not involute or continues to Corpus luteum does not involute or continues to

growgrow Most are small (<2.5 cm), but can be largerMost are small (<2.5 cm), but can be larger Usually no symptoms, unless rupture or torsionUsually no symptoms, unless rupture or torsion

Differential Diagnosis Differential Diagnosis

Ectopic pregnancy Ectopic pregnancy PID PID HydrosalpinxHydrosalpinx Benign neoplasmsBenign neoplasms

› Serous or mucinous cystadenomaSerous or mucinous cystadenoma› EndometriomaEndometrioma› Cy.DermoidCy.Dermoid› Fibroids (exophytic, broad ligament)Fibroids (exophytic, broad ligament)

MalignancyMalignancy› Primary vs. mtsPrimary vs. mts

Non-Gyn EtiologyNon-Gyn Etiology

AbdominalAbdominal› AppendicitisAppendicitis› DiverticulitisDiverticulitis› Inflammatory bowel Inflammatory bowel

diseasedisease Inclusion cystsInclusion cysts

› Peritoneal or omentalPeritoneal or omental Retroperitoneal Retroperitoneal

massesmasses› Pelvic kidneyPelvic kidney

Diagnosis: HistoryDiagnosis: History HistoryHistory

› PainPain MidcycleMidcycle physiologic or functional cyst physiologic or functional cyst Dysmenorrhea/dyspareuniaDysmenorrhea/dyspareunia endometriosis endometriosis Sudden onset, severeSudden onset, severetorsion, rupture, hemorrhagetorsion, rupture, hemorrhage Chronic aching, bloatingChronic aching, bloatingneoplasmneoplasm

› Nonspecific GI symptomsNonspecific GI symptoms May suggest ovarian cancer in postmenopausal female May suggest ovarian cancer in postmenopausal female May suggest appendicitis or GI etiology in younger May suggest appendicitis or GI etiology in younger

womenwomen

› FHFH Breast, colon, or ovarian cancerBreast, colon, or ovarian cancer

Diagnosis: Physical ExamDiagnosis: Physical Exam Physical exam—should include Physical exam—should include

bimanual and rectovaginal exambimanual and rectovaginal exam

› FeverFever PID, appy, diverticulitis PID, appy, diverticulitis› Shouldn’t be able to palpate a Shouldn’t be able to palpate a

postmenopausal ovarypostmenopausal ovary› Cul de sac nodularity, tender ligamentsCul de sac nodularity, tender ligaments

endometriosisendometriosis› Cervical motion tendernessCervical motion tendernessPIDPID› Fixed, irregular, solid may suggest Fixed, irregular, solid may suggest

neoplasianeoplasia

Diagnosis: Physical ExamDiagnosis: Physical Exam

Will probably need more than an H&P Will probably need more than an H&P to make a diagnosisto make a diagnosis

› 84 women underwent pelvic examination 84 women underwent pelvic examination prior to surgery, blinded to surgical prior to surgery, blinded to surgical indicationindication

› Attending, resident, student examined Attending, resident, student examined patientpatient

› Padilla L, Radosevich D, Milad M. Limitations of the pelvic examination for evaluation of the Padilla L, Radosevich D, Milad M. Limitations of the pelvic examination for evaluation of the female pelvic organs . Int J of Gyn 2005; 88 (1): 84 – 88.female pelvic organs . Int J of Gyn 2005; 88 (1): 84 – 88.

Diagnosis: Physical ExamDiagnosis: Physical Exam

› Exam is a “limited screening tool” for Exam is a “limited screening tool” for detection of adnexal massesdetection of adnexal masses

› Sensitivity at detecting adnexal masses: p Sensitivity at detecting adnexal masses: p >0.04>0.04

Diagnosis: LabsDiagnosis: Labs

LabsLabs› ββ-HCG to exclude ectopic-HCG to exclude ectopic› RPC if infection suspectedRPC if infection suspected› Tumor makersTumor makers

CA-125 (more to come)CA-125 (more to come) Others useful in adolescents/premenopaual Others useful in adolescents/premenopaual

women with adnexal masses and high women with adnexal masses and high suspicionsuspicion LDHLDHDysgerminomaDysgerminoma HCGHCGchoriocarcinomachoriocarcinoma AFPAFPEndodermal sinus tumorEndodermal sinus tumor

MalignancyMalignancy

PostmenopausalPostmenopausal› Roughly 50 per 100,000 women, relative risk of Roughly 50 per 100,000 women, relative risk of

~3.5~3.5› 80% of ovarian cancers occur in women over 5080% of ovarian cancers occur in women over 50

Family historyFamily history SymptomsSymptoms

› Vague, chronic aching, bloating, +/- GI symptomsVague, chronic aching, bloating, +/- GI symptoms Physical examinationPhysical examination

› Remember. . . Not really usefulRemember. . . Not really useful Ultrasound findingsUltrasound findings CA-125CA-125

Family HistoryFamily History Lifetime risk of ovarian cancer in Lifetime risk of ovarian cancer in

general population 1.5%general population 1.5%› In BRCA 1 carrier 45-55%In BRCA 1 carrier 45-55%› In BRCA 2 carrier 15-25%In BRCA 2 carrier 15-25%

Not all mutations have been identifiedNot all mutations have been identified› Two to three relatives with ovarian cancer Two to three relatives with ovarian cancer

increases lifetime risk to 5% (15% if first increases lifetime risk to 5% (15% if first degree relatives) degree relatives)

› Carlson KJ; Skates SJ; Singer DE. Screening for ovarian cancer. Ann Intern Med 1994 Jul 15;121(2):124-32. Carlson KJ; Skates SJ; Singer DE. Screening for ovarian cancer. Ann Intern Med 1994 Jul 15;121(2):124-32.

CA-125CA-125

Not specific to ovarian cancer, also elevated Not specific to ovarian cancer, also elevated in:in:

Other cancers (endometrial, fallopian tube, germ cell, Other cancers (endometrial, fallopian tube, germ cell, cervical, pancreatic, breast, colon)cervical, pancreatic, breast, colon)

Benign conditions (endometriosis, fibroids, PID, Benign conditions (endometriosis, fibroids, PID, adenomyosis, functional ovarian cysts, pregnancy)adenomyosis, functional ovarian cysts, pregnancy)

Other diseases (renal, heart, liver, and many others)Other diseases (renal, heart, liver, and many others) Also abnormal in 1% of Also abnormal in 1% of normalnormal females females

Bast R; Klug T; St John E; Jenison E; Niloff J; Lazarus H; Berkowitz R; Leavitt T; Griffiths C; Bast R; Klug T; St John E; Jenison E; Niloff J; Lazarus H; Berkowitz R; Leavitt T; Griffiths C; Parker L; Zurawski V; Knapp R. A radioimmunoassay using a monoclonal antibody to Parker L; Zurawski V; Knapp R. A radioimmunoassay using a monoclonal antibody to monitor thmonitor th

course of epithelial ovarian cancer. N Engl J Med 1983 Oct 13;309(15):883course of epithelial ovarian cancer. N Engl J Med 1983 Oct 13;309(15):883

CA-125CA-125

Normal value <35Normal value <35› Rarely >100-200 in benign conditionsRarely >100-200 in benign conditions

CA-125CA-125 Utility as screening tool for ovarian cancerUtility as screening tool for ovarian cancer

› CA-125 increased in roughly 80% of ovarian CA-125 increased in roughly 80% of ovarian cancerscancers

› About 50% sensitivity for Stage I, 90% for Stage IIAbout 50% sensitivity for Stage I, 90% for Stage II

Study of 5550 healthy Swedish womenStudy of 5550 healthy Swedish women› Followed women with elevated and normal CA-Followed women with elevated and normal CA-

125 levels125 levels› Serial pelvic exams, U/S, serial CA-125 levelsSerial pelvic exams, U/S, serial CA-125 levels› Of 175 women with elevated CA-125, 6 with Of 175 women with elevated CA-125, 6 with

ovarian cancer ovarian cancer › Of the remaining women with normal CA-125 Of the remaining women with normal CA-125

levels, 3 had ovarian cancerlevels, 3 had ovarian cancer› Einhorn N; Sjovall K; Knapp RC; Hall P; Scully RE; Bast RC Jr; Zurawski VR Jr. Prospective evaluation of serum CA Einhorn N; Sjovall K; Knapp RC; Hall P; Scully RE; Bast RC Jr; Zurawski VR Jr. Prospective evaluation of serum CA

125 levels for early detection of ovarian cancer. Obstet Gynecol 1992 Jul;80(1):14-8. 125 levels for early detection of ovarian cancer. Obstet Gynecol 1992 Jul;80(1):14-8.

CA-125 (follow)CA-125 (follow)

BIOMARKERSBIOMARKERS

› Ca 125› Ca 19.9› Ca 15.3› BCGH› Alpfa-phetoprotein

› HE-4

UltrasoundUltrasound

Simple cystSimple cyst› Less than 2.5 cmLess than 2.5 cm› Unlikely malignantUnlikely malignant› Probably a follicleProbably a follicle

Homogeneous Homogeneous appearance may appearance may suggest suggest endometriomaendometrioma

www.uptodate.com

UltrasoundUltrasound

Features suggestive Features suggestive of malignancy:of malignancy:› Solid componentSolid component› Doppler flowDoppler flow› Thick septationsThick septations› SizeSize› Presence of ascites Presence of ascites

or other peritoneal or other peritoneal massesmasses

Ultrasound: The DePriest ScoreUltrasound: The DePriest ScoreDe Priest PD, Shenson D, Fried A, Hunter JE, Andrew SJ, Gallion HH, et al A morphology index based on sonographic De Priest PD, Shenson D, Fried A, Hunter JE, Andrew SJ, Gallion HH, et al A morphology index based on sonographic findings in ovarian cancer. Gynecol Oncol. 1993 Oct;51(1):7-11findings in ovarian cancer. Gynecol Oncol. 1993 Oct;51(1):7-11

Morphology indexMorphology index U/S on 121 patients who U/S on 121 patients who

underwent exlapunderwent exlap Morphology score <5 Morphology score <5

(80)(80)all benign, 100% NPVall benign, 100% NPV Morphology score >10 (5)Morphology score >10 (5)

all malignant, 100% PPVall malignant, 100% PPV Morphology score Morphology score ≥ 5, 45% ≥ 5, 45%

PPV for malignancy (but, PPV for malignancy (but, PPV only 14% for PPV only 14% for premenopausalpremenopausal women) women)

There are other There are other morphology indices—this is morphology indices—this is not the only onenot the only one

So now what?So now what?ManagementManagement

Premenopausal femalesPremenopausal females› If size <10 cm, mobile, cystic, If size <10 cm, mobile, cystic,

unilateralunilateralfollow, place patient on follow, place patient on monophasic OC, repeat U/S in 2-3 monthsmonophasic OC, repeat U/S in 2-3 months 70% of these will resolve70% of these will resolve88

› If size >10 cm, fixed, solid, or other If size >10 cm, fixed, solid, or other concerning featuresconcerning featurestake it outtake it out

› If mass persists or enlarges at repeat If mass persists or enlarges at repeat scanscantake it outtake it out

What about the Postmenopausal What about the Postmenopausal Female?Female?

Modesitt studyModesitt study99

› 15,106 asymptomatic women over 50 who underwent TVUS15,106 asymptomatic women over 50 who underwent TVUS› If no abnormalitiesIf no abnormalitiesannual screeningannual screening› If abnormalIf abnormalrepeat U/S in 4-6 weeks with Doppler and CA-125repeat U/S in 4-6 weeks with Doppler and CA-125› 18% with unilocular ovarian cysts <10 cm in diameter18% with unilocular ovarian cysts <10 cm in diameter

69.4% resolved69.4% resolved 5.8% developed solid component5.8% developed solid component 16.5% developed septum16.5% developed septum 6.8% persisted as unilocular6.8% persisted as unilocular

› 10 patients with unilocular lesion who developed ovarian cancer, 10 patients with unilocular lesion who developed ovarian cancer, all of whom either:all of whom either: developed a septum or solid component on U/S,developed a septum or solid component on U/S, underwent complete resolution of the cyst,underwent complete resolution of the cyst, or developed cancer in the contralateral ovaryor developed cancer in the contralateral ovary

› Thus. . . The risk of developing ovarian cancer in a woman with a Thus. . . The risk of developing ovarian cancer in a woman with a unilocular, small cyst is VERY low (0.1%)unilocular, small cyst is VERY low (0.1%)

ManagementManagement

PostmenopausalPostmenopausal› If asymptomatic, normal exam, simple cyst on U/S, If asymptomatic, normal exam, simple cyst on U/S,

normal CA-125,unilateral, normal CA-125,unilateral, ≤ 5 cm≤ 5 cm follow with serial U/S and CA-125 q 3-6 months until 12 follow with serial U/S and CA-125 q 3-6 months until 12

months, then annually thereaftermonths, then annually thereafter› If above except complex appearance and ≤ 5 cmIf above except complex appearance and ≤ 5 cm

Repeat U/S and CA-125 in 4 weeksRepeat U/S and CA-125 in 4 weeks ResolutionResolution Persistence or decreasing complexityPersistence or decreasing complexityfollow q 3-6 months with follow q 3-6 months with

U/S and CA-125 U/S and CA-125 Increasing CA-125 or increasing complexityIncreasing CA-125 or increasing complexitysurgerysurgery

› If complex, ≤ 5 cm, and elevated CA-125If complex, ≤ 5 cm, and elevated CA-125 Take it out Take it out

› If symptomatic, ≥ 5 cm, clinically apparent, non-simple If symptomatic, ≥ 5 cm, clinically apparent, non-simple in appearance, or elevated CA-125in appearance, or elevated CA-125take it out. take it out.

Management Algorithm (there are many of these)

Van Nagell, JR, et al. Am J of Obstet & Gynecol 2005:193,30-35Van Nagell, JR, et al. Am J of Obstet & Gynecol 2005:193,30-35

Biopsy of peritoneal implants

Biopsy of growths ovarian / tubal

Cystectomy / oophorectomy

ADNEXAL MASSES

Anatomical Pathology in surgery

Concordance with definitive biopsy > 95%

When should I refer to an When should I refer to an oncologist?oncologist?

ACOG Guidelines:ACOG Guidelines:

Premenopausal (< 50 Years Old)Premenopausal (< 50 Years Old)› CA-125 > 200 U/mLCA-125 > 200 U/mL› AscitesAscites› Evidence of abdominal or distant metastasis (by exam or imaging Evidence of abdominal or distant metastasis (by exam or imaging

study)study)› Family history of breast or ovarian cancer (in a first-degree relative)Family history of breast or ovarian cancer (in a first-degree relative)

Postmenopausal (>= 50 Years Old)Postmenopausal (>= 50 Years Old)› CA-125 > 35 U/mLCA-125 > 35 U/mL› AscitesAscites› Nodular or fixed pelvic massNodular or fixed pelvic mass› Evidence of abdominal or distant metastasis (by exam or imaging Evidence of abdominal or distant metastasis (by exam or imaging

study)study)› Family history of breast or ovarian cancer (in a first-degree relative)Family history of breast or ovarian cancer (in a first-degree relative)

ACOG Committee Opinion: number 280, December 2002. The role of the generalist ACOG Committee Opinion: number 280, December 2002. The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer. Obstet Gynecol 2002;100:1413–6obstetrician-gynecologist in the early detection of ovarian cancer. Obstet Gynecol 2002;100:1413–6

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