Two Women with Ovarian Cancer: Mystery Metastasis vs. Primary

Jennifer Erdrich, HMS III

Gillian Lierberman, MD

Two Women with Ovarian Cancer:Two Women with Ovarian Cancer:Mystery Metastasis vs. Primary TumorMystery Metastasis vs. Primary Tumor

Jennifer Jennifer ErdrichErdrich, HMS III, HMS IIIGillian Lieberman, MDGillian Lieberman, MD

July 2006



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Ovarian CancerOvarian Cancer

55thth most common cause of female cancer death most common cause of female cancer death

5 year survival rate < 35%5 year survival rate < 35%

Mortality has only decreased slightly in 30 yrsMortality has only decreased slightly in 30 yrs

Most diagnosis made at advanced diseaseMost diagnosis made at advanced disease



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Ovarian TumorsOvarian Tumors

Majority derive from epithelial cellsMajority derive from epithelial cells

Benign ovarian tumors more common in Benign ovarian tumors more common in women ages 20women ages 20--4545

Malignant ovarian tumors more common in Malignant ovarian tumors more common in women ages 40women ages 40--6565



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Ovarian TumorsOvarian TumorsRisk FactorsRisk Factors

NulliparityNulliparity

Family HistoryFamily History

Heritable Mutations Heritable Mutations (BRCA1, BRCA2)(BRCA1, BRCA2)

Protective FactorsProtective Factors

Oral ContraceptivesOral Contraceptives

Tubal LigationTubal Ligation

Presenting SymptomsPresenting Symptoms

Lower abdominal painLower abdominal pain

Abdominal enlargementAbdominal enlargement

GI complaintsGI complaints

DysuriaDysuria

Back painBack pain

FatigueFatigue

CrampingCramping

Vaginal BleedingVaginal Bleeding



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Ovarian Neoplasm ClassificationOvarian Neoplasm Classification

OVARIANTUMORS

EPITHELIALSerous

MucinousEndometroid

GERM CELLTeratoma

Yolk Sac TumorDysgerminoma

Mixed

SEX CORDGranulosa Cell

5% of ovarian tumors arise from metastases



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Our Patient: Ms. XOur Patient: Ms. X

36 year old woman36 year old woman Increasing pelvic mass for last 2 months Increasing pelvic mass for last 2 months Abdominal distensionAbdominal distension Early satietyEarly satiety



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Ms. X: Ultrasound FindingsMs. X: Ultrasound Findings

Uterus:Uterus:Normal size Normal size No masses No masses Endometrial thickness 0.88 cm Endometrial thickness 0.88 cm

(within (within nlnl))

Ovary:Ovary:Ovarian enlargementOvarian enlargementRelationship to uterus unclearRelationship to uterus unclear

UterusUterus

PACS, BIDMC



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Ms. X: Ultrasound FindingsMs. X: Ultrasound Findings

Ovarian enlargement: 12.79cmOvarian enlargement: 12.79cm

Another view shows bilateral Another view shows bilateral enlargement with left ovary enlargement with left ovary measuring 7.89 cmmeasuring 7.89 cm

=> Patient diagnosed with => Patient diagnosed with ovarian cystsovarian cysts

PACS, BIDMC



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Ms. X: CT FindingsMs. X: CT Findings

The patientThe patient’’s symptoms s symptoms worsen over the course worsen over the course of 2 months. of 2 months.

CT shows massive CT shows massive ascites.ascites.

PACS, BIDMC



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CT: Normal compared to Ms. XCT: Normal compared to Ms. X

Normal Female Pelvis Ms. X

PACS, BIDMC



1111

Ms. X: CT FindingsMs. X: CT Findings Bilateral ovarian masses Bilateral ovarian masses –– variable attenuation, solid and cystic componentsvariable attenuation, solid and cystic components

PACS, BIDMC



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Ms. X up to this point:Ms. X up to this point:

Bilateral ovarian massesBilateral ovarian masses

Worsening symptomsWorsening symptoms

Her age makes these more likely to be benign:Her age makes these more likely to be benign:benign: 20benign: 20--45 yrs45 yrsmalignant: 40malignant: 40--65 yrs65 yrs

However, the massive ascites on CT looks ominousHowever, the massive ascites on CT looks ominous

DdxDdx is extensive at this point as these images cannot is extensive at this point as these images cannot even determine benign vs. malignant status with any even determine benign vs. malignant status with any certainty certainty

Does the WHO Classification System help to further Does the WHO Classification System help to further characterize Ms. Xcharacterize Ms. X’’s condition?s condition?



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Ovarian Ovarian NeoplasmsNeoplasmsEpithelialEpithelial Germ CellGerm Cell Sex CordSex Cord MetsMets

FrequencyFrequency 6565--70%70% 1515--20%20% 55--10%10% 5%5%

Percent of Percent of TumorsTumors

90%90% 33--5%5% 22--3%3% 5%5%

Age group Age group affectedaffected

20+20+ 00--2525 All agesAll ages VariableVariable

TypesTypes SerousSerousMucinousMucinousEndometroidEndometroid

TeratomaTeratomaDysgerminomaDysgerminomaChoriocarcinomaChoriocarcinoma

GranulosaGranulosa CellCellSertoliSertoli--LeydigLeydigFibromaFibroma

KRUKENBERG TUMOR



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Another look at the CT for Ms. XAnother look at the CT for Ms. X

This coronal CT shows This coronal CT shows gastric thickeninggastric thickening

It becomes apparent on It becomes apparent on a second look at the a second look at the axial images alsoaxial images also……

PACS, BIDMC



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Another look at the CT for Ms. XAnother look at the CT for Ms. X

PACS, BIDMC

The original axial CT image that demonstrated ascites also shows gastric thickening on a second look.



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Could this be a Could this be a KrukenbergKrukenberg Tumor?Tumor?

Profile of patients with Profile of patients with KrukenbergKrukenberg::–– Young, premenopausal womenYoung, premenopausal women–– Abdominal pain that is vague early in the disease, Abdominal pain that is vague early in the disease,

but more severe as the disease progressesbut more severe as the disease progresses–– Abdominal swellingAbdominal swelling–– Menstrual regularity still maintainedMenstrual regularity still maintained–– Ovarian tumors are large, bilateral and associated Ovarian tumors are large, bilateral and associated

with asciteswith ascites



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The next step for Ms. XThe next step for Ms. X

Endoscopy!Endoscopy!A single biopsy has 70% sensitivity for A single biopsy has 70% sensitivity for

diagnosing gastric cancerdiagnosing gastric cancer Seven biopsies increase the sensitivity to 98%Seven biopsies increase the sensitivity to 98%Ms. X undergoes endoscopy, which shows an Ms. X undergoes endoscopy, which shows an

ulcerated, ulcerated, fungatingfungating, infiltrative mass with , infiltrative mass with recent bleeding in the body and recent bleeding in the body and cardiacardia; ; duodenum determined to be normalduodenum determined to be normal



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Ms. X: EndoscopyMs. X: Endoscopy

DxDx: gastric : gastric adenocarcinomaadenocarcinoma, predominantly signet ring cell, predominantly signet ring cellPACS, BIDMC

Ulceration best seen here

Duodenum looks normal – smooth pink mucosa

ulceration

Normal rugal folds

ulceration



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Ms. XMs. X

Imaging modalities used: Imaging modalities used: US, CT, endoscopyUS, CT, endoscopy

DxDx: gastric adenocarcinoma : gastric adenocarcinoma with mets to ovaries with mets to ovaries ((KrukenbergKrukenberg tumor)tumor)

Other findings: elevated Other findings: elevated CEA and CACEA and CA--125; anemia; 125; anemia; met in culmet in cul--dede--sacsac

Surgery: ovarian resection, Surgery: ovarian resection, gastric resectiongastric resection

Currently: chemotherapyCurrently: chemotherapy

Signet Ring Cells: mucin filled cells with nuclear displacement.

Characteristic of Krukenberg Tumor. Ruhul Quddus, MD: www.brown.edu/.../female/krunkenberg2.html

http://www.brown.edu/.../female/krunkenberg2.html



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Primary vs. Metastatic Ovarian TumorPrimary vs. Metastatic Ovarian Tumor

The Case of Ms. DThe Case of Ms. D–– 56 year old woman w 4 months abdominal pain, 56 year old woman w 4 months abdominal pain,

chronic constipationchronic constipation–– PMH: GERD, HTNPMH: GERD, HTN–– Physical Exam: pelvic masses felt bilaterally, Physical Exam: pelvic masses felt bilaterally,

cervix described as wrinkled but not cervix described as wrinkled but not erythematouserythematous–– normal colonoscopy 2 years agonormal colonoscopy 2 years ago

Her presentation is similar to Ms.XHer presentation is similar to Ms.XWhat does CT reveal?What does CT reveal?



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Ms. D: CT FindingsMs. D: CT Findings

CT shows bilaterally enlarged ovaries with cystic and solid components

PACS, BIDMC



2222


CT shows omental caking, peritoneal studding, and free pelvic fluid

PACS, BIDMC

omental caking diffuse peritoneal studdingLight gray, soft tissue densities throughout



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CT shows complications from the ovarian tumors: obstructive renal failure and large bowel dilatation

PACS, BIDMC

Nonuniform enhancing renal parenchyma; absence of contrast in collecting system

Dilatation of large bowel



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Ms. DMs. D

Exploratory surgery found studding of the Exploratory surgery found studding of the small and large bowel, small and large bowel, omentumomentum, and , and peritoneum. peritoneum.

It was determined that Ms. D had a primary It was determined that Ms. D had a primary mucinmucin producing tumor that had spread producing tumor that had spread throughout her abdomen. throughout her abdomen.



2525

Ms. X and Ms. DMs. X and Ms. D

These women illustrate two examples of ovarian These women illustrate two examples of ovarian tumorstumors–– Ms. X: stomachMs. X: stomachovary (Met)ovary (Met)–– Ms. D: ovary Ms. D: ovary abdomen (Primary)abdomen (Primary)

Their presenting symptoms and radiographic findings Their presenting symptoms and radiographic findings are similar. are similar.

The findings alone cannot establish whether the The findings alone cannot establish whether the malignancies are primary or metastatic.malignancies are primary or metastatic.



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Ms. X and Ms. DMs. X and Ms. D

Surgery and histology are critical in diagnosis, Surgery and histology are critical in diagnosis, staging and developing a treatment plan.staging and developing a treatment plan.

Both were advanced in their disease at diagnosis. Both were advanced in their disease at diagnosis. Could their tumors be detected earlier?Could their tumors be detected earlier?



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Could screening have Could screening have helped these women?helped these women?

Possible screening testsPossible screening tests–– Pelvic ExamPelvic Exam–– Serum markers: CEA, CASerum markers: CEA, CA--125125–– UltrasoundUltrasound–– CTCT



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Possible screening testsPossible screening tests–– Pelvic ExamPelvic Exam

Early stage tumors rarely found due to deep anatomic Early stage tumors rarely found due to deep anatomic location of the ovarylocation of the ovary

–– Serum markers: CEA, CASerum markers: CEA, CA--125125Nonspecific Nonspecific –– these markers can be elevated in a these markers can be elevated in a

number of conditionsnumber of conditions

–– UltrasoundUltrasound–– CTCT



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Radiographic characteristics that help differentiate Radiographic characteristics that help differentiate benign and malignant benign and malignant adnexaladnexal massesmasses

BenignBenign MalignantMalignant

Simple cyst, < 10 cm Simple cyst, < 10 cm Solid, or solid and cysticSolid, or solid and cystic

SeptationsSeptations < 3mm< 3mm Multiple Multiple septationsseptations > 3mm> 3mm

UnilateralUnilateral BilateralBilateral

CalcifcationCalcifcation (especially teeth)(especially teeth) AscitesAscites

Gravity dependent layering of Gravity dependent layering of cyst contentscyst contents



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Ultrasound as a Screening ToolUltrasound as a Screening Tool

US Findings US Findings Suggesting MalignancySuggesting Malignancy–– Solid component, often Solid component, often

nodular/papillarynodular/papillary–– SeptationsSeptations (>2(>2--3 mm)3 mm)–– Doppler demonstrates Doppler demonstrates

flow in solid componentflow in solid component–– Presence of ascitesPresence of ascites–– Enlarged peritoneal Enlarged peritoneal

nodesnodes

US Screening StudiesUS Screening Studies–– Sensitivity has ranged Sensitivity has ranged

from 80from 80--100%100%–– Specificity has ranged Specificity has ranged

from 94from 94--99%99%–– US has performed poorly US has performed poorly

in detecting early stage in detecting early stage ovarian cancer in high ovarian cancer in high risk womenrisk women



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Possible screening testsPossible screening tests–– Pelvic ExamPelvic Exam–– Serum markers: CEA, CASerum markers: CEA, CA--125125–– UltrasoundUltrasound

–– CTCTMost useful for evaluating Most useful for evaluating metastaticmetastatic disease (M Stage)disease (M Stage)Cannot rely on it for T or N StagingCannot rely on it for T or N StagingCT is used to monitor recurrenceCT is used to monitor recurrence

Screening RisksScreening Risks–– Unnecessary surgery as followUnnecessary surgery as follow--up to positive testsup to positive tests



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SummarySummary

Case examples of metastatic and primary ovarian tumorsCase examples of metastatic and primary ovarian tumors

Pelvic and abdominal anatomyPelvic and abdominal anatomy

Radiographic imaging is essential in diagnosis.Radiographic imaging is essential in diagnosis.–– Menu of Tests for these patients: US, CT, endoscopy. Menu of Tests for these patients: US, CT, endoscopy.

Ultrasound CT Endoscopy

PACS, BIDMC



3333

SummarySummary

Ovarian tumor classificationOvarian tumor classification–– System organized by cell of origin: System organized by cell of origin:

epithelial, germ cell, epithelial, germ cell, sex cord, metastasissex cord, metastasis

Radiographic features can help differentiate Radiographic features can help differentiate benign vs. malignant:benign vs. malignant:–– evaluation of cystic/solid componentsevaluation of cystic/solid components–– unilateral/bilateralunilateral/bilateral–– septationsseptations, number and thickness, number and thickness

OVARIANTUMORS

EPITHELIALSerous

MucinousEndometroid

GERM CELLTeratoma

Yolk Sac TumorDysgerminoma

Mixed

SEX CORDGranulosa Cell



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SummarySummary

Ovarian cancerOvarian cancer–– 55thth most common cause of female cancer deathmost common cause of female cancer death–– Low survival rateLow survival rate

ScreeningScreening–– Screening ModalitiesScreening Modalities

Imaging: Ultrasound, CTImaging: Ultrasound, CT

Other: Physical exam, biomarkersOther: Physical exam, biomarkers–– Screening StudiesScreening Studies

Current screening ineffective at detecting malignancies earlyCurrent screening ineffective at detecting malignancies early

Screening could pose risk of unnecessary proceduresScreening could pose risk of unnecessary procedures



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ReferencesReferences

Carlson, Karen J. Screening for ovarian cancer. UpCarlson, Karen J. Screening for ovarian cancer. Up--toto--Date, March 2006.Date, March 2006.

Chen, LeeChen, Lee--may, Jonathan S. may, Jonathan S. BerekBerek. Epithelial ovarian cancer: clinical manifestations, . Epithelial ovarian cancer: clinical manifestations, diagnositcdiagnositc evaluation, staging, and evaluation, staging, and histopathology. Uphistopathology. Up--toto--Date, May 2006. Date, May 2006.

Chen, LeeChen, Lee--may, Jonathan S. may, Jonathan S. BerekBerek. Epithelial ovarian cancer: pathogenesis, epidemiology, and ris. Epithelial ovarian cancer: pathogenesis, epidemiology, and risk factors. Upk factors. Up--toto--Date, May Date, May 2006. 2006.

FerrazziFerrazzi, E, , E, ZanettaZanetta, G, , G, DordoniDordoni, D, et al. , D, et al. TransvaginalTransvaginal ultrasonographicultrasonographic characterization of ovarian masses: comparison of characterization of ovarian masses: comparison of five scoring systems in a multicenter study. Ultrasound five scoring systems in a multicenter study. Ultrasound ObstetObstet GynecolGynecol 1997; 10:192.1997; 10:192.

HainsworthHainsworth, John D, F Anthony Greco. Adenocarcinoma of unknown primary sit, John D, F Anthony Greco. Adenocarcinoma of unknown primary site. Upe. Up--toto--date, December 2005. date, December 2005.

KinkelKinkel, K, , K, HricakHricak, H, Lu, Y, et al. US characterization of ovarian masses: A meta, H, Lu, Y, et al. US characterization of ovarian masses: A meta--analysis. Radiology 2000; 217:803.analysis. Radiology 2000; 217:803.

Kumar, Kumar, VinayVinay, , AbulAbul AbbasAbbas, Nelson , Nelson FaustoFausto. Pathologic Basis of Disease. The Female Genital Tract: 1092. Pathologic Basis of Disease. The Female Genital Tract: 1092--1117, The 1117, The Gastrointestinal Tract, 826. 2005Gastrointestinal Tract, 826. 2005

McGraw Hill Company. Gynecologic Oncology: Evaluation of the patMcGraw Hill Company. Gynecologic Oncology: Evaluation of the patient with a suspected ovarian neoplasm, Radiographic ient with a suspected ovarian neoplasm, Radiographic Evaluation, 2006. Evaluation, 2006.

Schneider, Arthur S, Philip A Schneider, Arthur S, Philip A SzantoSzanto. Pathology. Ovaries, 295. Pathology. Ovaries, 295--297,2006. 297,2006.

SchroySchroy, Paul C. Clinical features and diagnosis of gastric cancer. Up, Paul C. Clinical features and diagnosis of gastric cancer. Up--toto--Date, April 2006.Date, April 2006.



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AcknowledgementsAcknowledgements

Melissa Melissa GerlachGerlach, MD, MDAlice Fisher, MDAlice Fisher, MDGillian Lieberman, MDGillian Lieberman, MD Pamela LepkowskiPamela Lepkowski Larry Larry BarbarasBarbaras

Documents

Two Women with Ovarian Cancer: Mystery Metastasis vs. Primary