Adnexal MassesAdnexal Masses

Todd D. Tillmanns MDTodd D. Tillmanns MD

Associate ProfessorAssociate Professor

Division of Gynecologic OncologyDivision of Gynecologic Oncology

University of TennesseeUniversity of Tennessee

And West ClinicAnd West Clinic

EvaluationEvaluation

History and PhysicalHistory and Physical Family HistoryFamily History U/SU/S

Thickened wall, solid and cystic Thickened wall, solid and cystic components, excrescences, ascitescomponents, excrescences, ascites

CTCT Omental cake, ascites, mesenteric Omental cake, ascites, mesenteric disease, liver disease, disease, liver disease,

CA-125CA-125 Premenopausal –vs- postmenopausalPremenopausal –vs- postmenopausal

Epithelial Ovarian CarcinomaEpithelial Ovarian Carcinoma

SerousSerous MucinousMucinous EndometrioidEndometrioid Clear CellClear Cell BrennerBrenner Mixed epithelialMixed epithelial UndifferentiatedUndifferentiated

Ovarian Serous Ovarian Serous CystadenocarcinomaCystadenocarcinoma

15% of all ovarian 15% of all ovarian malignanciesmalignancies

Psamoma bodies Psamoma bodies in 30%in 30%

Bilateral in 1/3 of Bilateral in 1/3 of Stage I casesStage I cases

Ovarian Papillary Serous Ovarian Papillary Serous CystadenocarcinomaCystadenocarcinoma

Ovarian CancerOvarian Cancer Low Malignant Low Malignant Potential TumorPotential Tumor

Ovarian Mucinous Ovarian Mucinous CystadenocarcinomaCystadenocarcinoma

12% of ovarian 12% of ovarian malignanciesmalignancies

Bilateral in stage I Bilateral in stage I 5-10%5-10%

Must consider Must consider metastatic metastatic disease from disease from intestinal primaryintestinal primary

Endometrioid Endometrioid AdenocarcinomaAdenocarcinoma

15% of ovarian 15% of ovarian malignanciesmalignancies

Concommitant Concommitant endometrial cancer in endometrial cancer in 15-30% of cases15-30% of cases

Associated with Associated with endometriosis in 10%, endometriosis in 10%, and in one study 40% of and in one study 40% of stage I (Sainz de la Cruz stage I (Sainz de la Cruz 1996)1996)

15% bilateral in stage I15% bilateral in stage I

Sex Cord Stromal TumorsSex Cord Stromal Tumors

Granulosa stromal cellGranulosa stromal cell Granulosa cellGranulosa cell Thecoma FibromaThecoma Fibroma

Lipid Cell Lipid Cell GynandroblastomaGynandroblastoma UnclassifiedUnclassified

Granulosa Cell TumorGranulosa Cell Tumor

This is a granulosa cell tumor of This is a granulosa cell tumor of ovary with a variegated cut ovary with a variegated cut surface. surface.

These tumors are derived from These tumors are derived from the ovarian stroma and often the ovarian stroma and often have a component of thecoma. have a component of thecoma.

They are often hormonally They are often hormonally active and can produce large active and can produce large amounts of estrogenamounts of estrogen

Germ Cell TumorsGerm Cell TumorshCGhCG AFPAFP LDHLDH

DysgerminomaDysgerminoma ++ -- ++

Endodermal Sinus TumorEndodermal Sinus Tumor -- ++ ++

Embryonal CarcinomaEmbryonal Carcinoma ++ ++ ++

PolyembryomaPolyembryoma ++ ++ --

ChoriocarcinomaChoriocarcinoma ++ -- --

DysgerminomaDysgerminoma

Sertoli Leydig TumorSertoli Leydig Tumor Differentiate Differentiate

towards testicular towards testicular structuresstructures

<1% of all ovarian <1% of all ovarian cancerscancers

Many are Many are masculinizing, masculinizing, although estrogen although estrogen production may production may predominatepredominate

Benign Adnexal MassesBenign Adnexal Masses

Benign ovarian / tubal cystsBenign ovarian / tubal cysts EndometriosisEndometriosis LeiomyomasLeiomyomas Infectious processesInfectious processes

Simple follicular cystSimple follicular cyst Follicle cysts. Here is a benign Follicle cysts. Here is a benign

cyst in an ovary. This is probably a cyst in an ovary. This is probably a follicular cyst. Occasionally such follicular cyst. Occasionally such cysts may reach several cysts may reach several centimeters in size and, if they centimeters in size and, if they rupture, can cause abdominal rupture, can cause abdominal pain. pain.

Corpus Luteum CystCorpus Luteum Cyst

The corpus luteum The corpus luteum secretes progesterone secretes progesterone which induces a secretory which induces a secretory endometrium.endometrium.

It normally regresses in 14 It normally regresses in 14 days unless it is rescued days unless it is rescued by increasing by increasing concentrations of human concentrations of human chorionic gonadotropin chorionic gonadotropin from a pregnancy from a pregnancy

Paratubal CystParatubal Cyst Here is another common Here is another common

incidental finding: a incidental finding: a benign paratubal cyst. benign paratubal cyst.

Sometimes such simple Sometimes such simple cysts are found adjacent cysts are found adjacent to ovary and are called to ovary and are called parovarian cysts. parovarian cysts.

They are filled with clear They are filled with clear serous fluid and lined by serous fluid and lined by flattened cuboidal flattened cuboidal epithelium.epithelium.

Mature Cystic TeratomasMature Cystic Teratomas Here are bilateral mature Here are bilateral mature

cystic teratomas of the ovaries. cystic teratomas of the ovaries. These are a form of ovarian These are a form of ovarian

germ cell tumor. germ cell tumor. Histologically, a variety of Histologically, a variety of

mature tissue elements may mature tissue elements may be found. be found.

These tumors are often called These tumors are often called "dermoid cysts" because they "dermoid cysts" because they are mostly cystic.are mostly cystic.

Ovarian FibromaOvarian Fibroma

This is the cut surface of a fibroma. This is the cut surface of a fibroma. Such neoplasms slowly enlarge Such neoplasms slowly enlarge

over the yearsover the years

EndometriomaEndometrioma At laparoscopy the appearance At laparoscopy the appearance

of endometriosis is quite of endometriosis is quite variable. It can take one of the variable. It can take one of the following appearances:following appearances:

blue or black powder-burn blue or black powder-burn lesions lesions

red, blue, white or non-red, blue, white or non-pigmented lesions pigmented lesions

scarring and peritoneal defects scarring and peritoneal defects ovarian cysts ovarian cysts

LeiomyomataLeiomyomata

Leiomyomas may occur in Leiomyomas may occur in tissues outside of the uterus. tissues outside of the uterus. 

Ligaments and connective Ligaments and connective tissues in the pelvis also tissues in the pelvis also contain muscle fibers that may contain muscle fibers that may give rise to leiomyomas.   give rise to leiomyomas.      

Tuboovarian AbscessTuboovarian Abscess This is an example of a This is an example of a

tubo-ovarian abscess tubo-ovarian abscess from Neisseria from Neisseria gonorrheae. gonorrheae.

Here, there is no clear Here, there is no clear boundary between tube boundary between tube and ovary and the and ovary and the dilated tube is filled dilated tube is filled with purulent material.with purulent material.

AppendicitisAppendicitis

Screening GuidelinesScreening Guidelines ““Routine screening for ovarian cancer by Routine screening for ovarian cancer by

ultrasound, the measurement of serum ultrasound, the measurement of serum tumor markers, or pelvic examination is tumor markers, or pelvic examination is not recommended. There is insufficient not recommended. There is insufficient evidence to recommend for or against the evidence to recommend for or against the screening of asymptomatic women at screening of asymptomatic women at increased risk of developing ovarian increased risk of developing ovarian cancer.” cancer.”

•U.S.Preventive Services Taskforce, Guidelines from Guide to Clinical Preventive Services, 2nd edition, 1996

Screening GuidelinesScreening Guidelines NIH Consensus Conference (1994)NIH Consensus Conference (1994)

women with presumed hereditary cancer syndrome women with presumed hereditary cancer syndrome should undergo annual pelvic exams, CA-125 should undergo annual pelvic exams, CA-125 measurements, and TVUS until childbearing is measurements, and TVUS until childbearing is complete or at age 35, at which time prophylactic complete or at age 35, at which time prophylactic bilateral oopherectomy is recommended.bilateral oopherectomy is recommended.

ACP ACP counsel high risk women about potential harms and counsel high risk women about potential harms and

benefits of screeningbenefits of screening

Screening GuidelinesScreening Guidelines American Cancer Society, AAFP and American Cancer Society, AAFP and

ACOG do not recommend screening for ACOG do not recommend screening for ovarian cancer in the general populationovarian cancer in the general population

Canadian Task Force on Periodic Health Canadian Task Force on Periodic Health Examination Examination ““insufficient evidence to recommend for or insufficient evidence to recommend for or

against screening in high-risk women”against screening in high-risk women”

Ovarian Cancer Ovarian Cancer Screening TrialsScreening Trials

1.1. The United Kingdom Collaborative Trial of The United Kingdom Collaborative Trial of Ovarian Cancer Screening: will compare Ovarian Cancer Screening: will compare TVUS and multimodal screeningTVUS and multimodal screening

2.2. The European Study: RCT to screen The European Study: RCT to screen women with TVUS at 18-month or 3-year women with TVUS at 18-month or 3-year intervalsintervals

3.3. The NIH Prostate, Lung, Colorectal, and The NIH Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: 10-year Ovarian Cancer Screening Trial: 10-year study using multimodal strategystudy using multimodal strategy

GOG-199GOG-199Non-randomized trialNon-randomized trial RRSO (1000)RRSO (1000) - CA-125 – quarterly- CA-125 – quarterly - QOL – every 6 months- QOL – every 6 months

Screening (2400)Screening (2400) - CA-125 – quarterly- CA-125 – quarterly - QOL – every 6 months- QOL – every 6 months - TVUS - yearly- TVUS - yearly

Screening RecomendationsScreening Recomendations

ACOG: ACOG: Annual gynecologic exam-Annual gynecologic exam-ination with an annual pelvic ination with an annual pelvic examination is recommended examination is recommended for preventative health care.for preventative health care.

Who Should be Referred Who Should be Referred According to ACOGAccording to ACOG

Premenopausal womenPremenopausal women who have a pelvic who have a pelvic mass that is suspicious for a malignant ovarian mass that is suspicious for a malignant ovarian neoplasm as suggested by one of the following:neoplasm as suggested by one of the following: High CA-125 (>200 U/ml)High CA-125 (>200 U/ml) Ascites Ascites Evidence of abdominal or distant metastasesEvidence of abdominal or distant metastases Family history of one or more first degree relatives Family history of one or more first degree relatives

with ovarian or breast cancerwith ovarian or breast cancer

OVA1OVA1 The U.S. Food and Drug Administration today cleared a test The U.S. Food and Drug Administration today cleared a test

that can help detect ovarian cancer in a pelvic mass that is that can help detect ovarian cancer in a pelvic mass that is already known to require surgery. The test, called OVA1, already known to require surgery. The test, called OVA1, helps patients and health care professionals decide what helps patients and health care professionals decide what type of surgery should be done and by whom.OVA1 identifies type of surgery should be done and by whom.OVA1 identifies some women who will benefit from referral to a gynecological some women who will benefit from referral to a gynecological oncologist for their surgery, despite negative results from oncologist for their surgery, despite negative results from other clinical and radiographic tests for ovarian cancer. other clinical and radiographic tests for ovarian cancer. The test combines the five separate results into a single The test combines the five separate results into a single numerical score between 0 and 10 to indicate the likelihood numerical score between 0 and 10 to indicate the likelihood that the pelvic mass is benign or malignant.OVA1 is intended that the pelvic mass is benign or malignant.OVA1 is intended only for women, 18 years and older, who are already selected only for women, 18 years and older, who are already selected for surgery because of their pelvic mass. It is not intended for surgery because of their pelvic mass. It is not intended for ovarian cancer screening or for a definitive diagnosis for ovarian cancer screening or for a definitive diagnosis of ovarian cancer. Interpreting the test result requires of ovarian cancer. Interpreting the test result requires knowledge of whether the woman is pre- or post-menopausal.knowledge of whether the woman is pre- or post-menopausal.

OVA1 is developed by Vermillion Inc., headquartered in OVA1 is developed by Vermillion Inc., headquartered in Fremont, Calif., in conjunction with researchers at The Fremont, Calif., in conjunction with researchers at The Johns Hopkins University in Baltimore.Johns Hopkins University in Baltimore.

Hereditary RiskHereditary Risk Hereditary OV-Hereditary OV-Ca is estimated to represent only Ca is estimated to represent only 5-5-

10%10% of all ovarian cancer of all ovarian cancer A woman with a germline mutation of A woman with a germline mutation of BRCA-1 or BRCA-1 or

BRCA-2BRCA-2 has a lifetime risk of has a lifetime risk of 15-45%15-45% of developing of developing ovarian cancerovarian cancer

BRCA-1 or BRCA-2: Should be offered genetic BRCA-1 or BRCA-2: Should be offered genetic counseling.counseling.

Having Having one first degree relativeone first degree relative with ovarian cancer with ovarian cancer (mother, sister, daughter) gives a (mother, sister, daughter) gives a 5% lifetime risk5% lifetime risk for for ovarian canceovarian cance

Two first degree relativesTwo first degree relatives increases lifetime risk to increases lifetime risk to 20-30%20-30%

Conditions found in association Conditions found in association with increased CA-125with increased CA-125

GynecologicGynecologic Endometriosis, fibroids, hemorrhagic ovarian cysts, Endometriosis, fibroids, hemorrhagic ovarian cysts,

menstruation, PID, pregnancy (1menstruation, PID, pregnancy (1stst trimester) trimester) GI and HepaticGI and Hepatic

Pancreatitis, colitis, chronic active hepatitis, cirrhosis, Pancreatitis, colitis, chronic active hepatitis, cirrhosis, diverticulitisdiverticulitis

MalignanciesMalignancies Bladder, breast, uterine, lung, liver, non-hodgkins Bladder, breast, uterine, lung, liver, non-hodgkins

lymphoma, ovary, pancreas, colon (metastatic)lymphoma, ovary, pancreas, colon (metastatic) MiscellaneousMiscellaneous

Pericarditis, polyarteritis nodosa, renal disease, Pericarditis, polyarteritis nodosa, renal disease, Sjogrens syndrome, systemic lupus erythematosusSjogrens syndrome, systemic lupus erythematosus

Morphology Index for TumorsMorphology Index for Tumors Ov-Volume (cmOv-Volume (cm33)= W x Ht x thickness x 0.523)= W x Ht x thickness x 0.523

00 11 22 33 44

VolumeVolume <10 cm3<10 cm3 10-50 cm10-50 cm33 >50-200 cm>50-200 cm33 >200-500 >200-500 cmcm33

>500 cm>500 cm33

Cyst Wall Cyst Wall StructureStructure

SmoothSmooth

<3 mm <3 mm thicknessthickness

SmoothSmooth

>3 mm>3 mm

thicknessthickness

PapillaryPapillary

ProjectionsProjections

< 3 mm< 3 mm

PapillaryPapillary

ProjectionProjection

> > 3 mm 3 mm

Predom Predom solidsolid

Septa Septa StructureStructure

No SeptaNo Septa Thin Thin septasepta

< 3mm< 3mm

Thick SeptaThick Septa

3 mm-10 3 mm-10 mmmm

Solid areaSolid area

>> 10 mm 10 mm

PredomPredom

SolidSolid

De Priest et al. Gynecol Oncol 1993;51:7-11

Morphology Index in Morphology Index in Premenopausal PatientsPremenopausal Patients

62 patients 62 patients 4 patients with malignancy, all had scores 4 patients with malignancy, all had scores >> 5, 3 5, 3

were stage I and 1 was stage IIIwere stage I and 1 was stage III All tumors < 5 were benignAll tumors < 5 were benign No ovarian cancer had a volume No ovarian cancer had a volume << 10 cm 10 cm33

M/C benign tumors in the pre-menopausal group M/C benign tumors in the pre-menopausal group were endometriosis and corpus luteum cystswere endometriosis and corpus luteum cysts

All Ov-Ca had a papillary projection or solid All Ov-Ca had a papillary projection or solid component protruding from a wallcomponent protruding from a wall

De Priest et al. Gynecol Oncol 1993;51:7-11

U/S Scoring System to Differentiate U/S Scoring System to Differentiate Benign from MalignantBenign from Malignant

Series of operations after U/S evaluationSeries of operations after U/S evaluation 705 adnexal masses (565 benign and 141 705 adnexal masses (565 benign and 141

malignant) malignant) Mean age 44.5 years (14-81y/o) Mean age 44.5 years (14-81y/o) 1995-2001 tertiary care hospital Spain1995-2001 tertiary care hospital Spain 441(66%) premenopausal441(66%) premenopausal Scoring system performance unchanged by Scoring system performance unchanged by

menopausal statusmenopausal status

Alcazar JL et al. Am J Obstet Gynecol 2003;188:685-692

Multivariate Significant Multivariate Significant Parameters on U/SParameters on U/S

ParameterParameter Odds ratioOdds ratio p-valuep-valueThick papillary projectionThick papillary projection 1.9(1.1-4.0)1.9(1.1-4.0) 0.040.04

High velocity/ low resistHigh velocity/ low resist 5.3(2.5-11.1)5.3(2.5-11.1) <.0001<.0001

Solid areaSolid area 8.6(4.2-17.8)8.6(4.2-17.8) <.0001<.0001

Central flowCentral flow 15.5(7.3-32.8)15.5(7.3-32.8) <.0001<.0001

Alcazar JL et al. Am J Obstet Gynecol 2003;188:685-692

Prospective U/S Studies with Prospective U/S Studies with Scoring Systems in useScoring Systems in use

StudyStudy SensSens SpecSpec PPVPPV NPVNPV AccuracyAccuracy

(%)(%) (%)(%) (%)(%) (%)(%) (%)(%)SassoneSassone6565 8888 7474 8383 8080

De PriestDe Priest 100100 8181 7474 100100 8888

FerrazziFerrazzi 8484 8383 7272 9191 8383

AlcazarAlcazar 100100 9595 9191 100100 9797

Sassone AM et al. Obstet Gynecol 1991;78:70-6 // De Priest et al. Gynecol Oncol 1993;51:7-11 // Ferazzi E et al. Ultrasound Obstet Gynecol 1997;10:192-7 // Alcazar JL et al. Am J Obstet Gynecol 2003;188:685-692

Ultrasound / CTUltrasound / CTUltrasound / CTUltrasound / CT Which is best at predicting an ovarian Which is best at predicting an ovarian

malignancy should cost be a factormalignancy should cost be a factor Adnexal masses which is best defining Adnexal masses which is best defining

malignancy –vs-benignmalignancy –vs-benign

Ultrasound

CT –vs- U/S to diagnose CT –vs- U/S to diagnose Premenopausal Adnexal MassesPremenopausal Adnexal Masses

161 premenopausal patients with associated 161 premenopausal patients with associated CA-125 levelsCA-125 levels

83 persistent masses after 3 month review83 persistent masses after 3 month review U/S better at diagnosing U/S better at diagnosing

Serous cysts, serous cystadenoma, endometrioma Serous cysts, serous cystadenoma, endometrioma and Ov-Caand Ov-Ca

CT better at diagnosingCT better at diagnosing Mature teratomasMature teratomas

Mallarini GS.etal. Ultra Obstet Gynecol 1997;9:339

U/S Adnexal Mass U/S Adnexal Mass >> 3 cm 3 cm

1987-1993 referral center in Germany1987-1993 referral center in Germany 1072 ovarian tumors1072 ovarian tumors Average follicular diameter 15-25 mmAverage follicular diameter 15-25 mm Unilocular cysts treated with 50 micro Unilocular cysts treated with 50 micro

grams ethinyl estradiol for at least 2 cyclesgrams ethinyl estradiol for at least 2 cycles All women examined at 4-6 weeks if All women examined at 4-6 weeks if

unchanged or increasedunchanged or increased surgery surgery

Osmers RGW et al. Obstet Gynecol 1996;175:428-434

1072 Consecutive Ovarian tumors in 1072 Consecutive Ovarian tumors in Premenopausal WomenPremenopausal Women

Adnexal MassAdnexal Mass NumberNumber %%

Functional Ovarian TumorsFunctional Ovarian Tumors 570570 53 53

Endometriosis or Non-epi cystsEndometriosis or Non-epi cysts 264 25264 25

Benign NeoplasmsBenign Neoplasms 192 18192 18

Low Malignant Potential TumorsLow Malignant Potential Tumors 9 19 1

Ovarian MalignancyOvarian Malignancy 3737 3 3

Functional TumorsFunctional Tumors Functional TumorsFunctional Tumors 90% regressed 90% regressed Frequency of functional cysts with ageFrequency of functional cysts with age

AgeAge # # (%) of functional cysts(%) of functional cysts <20 <20 59 59 (70%)(70%) 21-30 21-30 181 181 (66%)(66%) 31-40 31-40 182 182 (50%)(50%) 41-5041-50 125 125 (43%)(43%) >51>51 20 20 (36%)(36%)

Osmers RGW et al. Obstet Gynecol 1996;175:428-434

Ovarian Cancer and Ovarian Cancer and PregnancyPregnancy

California Cancer RegistryCalifornia Cancer Registry Years 1991-1999Years 1991-1999 4,846,505 deliveries 4,846,505 deliveries Prenatal diagnosisPrenatal diagnosis 115 (0.024 per 1000) 115 (0.024 per 1000) Delivery diagnosisDelivery diagnosis 56 (0.012 per 1000) 56 (0.012 per 1000) Post Partum diagnPost Partum diagn 82 (0.017 per 1000) 82 (0.017 per 1000) TotalTotal 253 (0.052 per 1000)253 (0.052 per 1000)

Smith LH et al. Obstet Gynecol 2003;189:1128-1135

Adnexal Masses in PregnancyAdnexal Masses in Pregnancy

Regional Center East CarolinaRegional Center East Carolina 12 year experience12 year experience 60 adnexal masses of 37,929 deliveries60 adnexal masses of 37,929 deliveries Incidence of 1/632 or 0.15%Incidence of 1/632 or 0.15% Mean gestattional age at diagnosis 12 weeks Mean gestattional age at diagnosis 12 weeks

with mean age at surgery of 20 weekswith mean age at surgery of 20 weeks 54 operations by laparotomy, 2 laparoscopic 54 operations by laparotomy, 2 laparoscopic 55/56 elective, 1 non-elective for torsion55/56 elective, 1 non-elective for torsion Term delivery in 69%Term delivery in 69%

Sherard GB et al. Obstet Gynecol 2003;189:358-362

Adnexal Masses in PregnancyAdnexal Masses in Pregnancy

Histologic DiagnosisHistologic Diagnosis nn %%

Mature teratomaMature teratoma 3030 5050

CystadenomaCystadenoma 1212 2020

Functional cystFunctional cyst 88 1313

FibromaFibroma 11 22

Paratubal cystParatubal cyst 11 22

Low Malig Potential Tumor Low Malig Potential Tumor 55 88

Cancer (2 imm tera, 1 dysgerm)Cancer (2 imm tera, 1 dysgerm) 33 55

Sherard GB et al. Obstet Gynecol 2003;189:358-362

Ovarian Conservation -vs- Ovarian Conservation -vs- OophorectomyOophorectomy

Nurses Health StudyNurses Health Study Prospective Observational StudyProspective Observational Study Increased mortality in women prophylactic Increased mortality in women prophylactic

oophorectomy if not given ERToophorectomy if not given ERT Primarily as a result of CHD and Lung CancerPrimarily as a result of CHD and Lung Cancer Did not improve survival at any age (<45, 45-Did not improve survival at any age (<45, 45-

54, >55 y/o)54, >55 y/o) Less frequent for all cases of cancerLess frequent for all cases of cancer

Parker, WH et al. Ovarian Conservation at the time of hysterectomy and long term Health Outcomes in the Nurses’ Health Study. Obstet Gynecol 2009;113:1027-1037

Specific Guide LineSpecific Guide Line

Work UpHistory & Physical

CXR, abd/pelvic CT scan or U/SObtain family cancer history

CA 125, CBC, Chem Profile, BE/colonoscopy if symptomatic

Adnexal Mass

Surgical Candidate?

Counsel Patient on Risks of

Pregnancy Loss, Preterm Delivery, Fetal Morbidity, Torsion, Possibility of benign disease –vs- LMPT –vs- Malignancy

Questions / CommentsQuestions / Comments

Even my family has Even my family has stopped listening stopped listening to me!to me!

Love is Love is unconditional with unconditional with NoraNora