Ovarian Imaging and Ovarian Cancer

Patrick Yachimski—Harvard Medical School , Year- IIIGillian Lieberman, MD

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Objectives

1) Introduction to ovarian cancer

2) Indications for ovarian imaging

3) Basic ovarian ultrasonography

4) Imaging in advanced disease

5) Imaging in screening and prognosis

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Statistics

• 3rd leading gynecologic cancer

• >50% of GYN cancer deaths

• 1995: 26,000 new U.S. Cases14,500 U.S. Deaths

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Risk factors

• Age (peak incidence 6th decade)

• Nulliparity

• North American or Northern European descent

• Personal history breast, endometrial, colon CA

• Family history ovarian CA

• Familial ovarian CA syndromes

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Lifetime risk of ovarian CA

• 1.4% for all women

• 5% for women with 1st-degree relative with ovarian cancer

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Ovarian CA subtypesType % of ovarian

neoplasms% of malignant ovarian neoplasms

examples

Surface epithelial stromal cell tumors

65-70 90 Serous, mucinous, endometrioid, clear cell, Brenner

Germ cell tumors 15-20 3-5 Teratoma, dysgerminoma, choriocarcinoma

Sex cord stromal tumors

5-10 2-3 Fibroma, granulosa-theca cell

Metastases to ovaries

5 5

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Presenting Signs/Sx

• Pelvic pain• Pelvic mass• Weight loss• Abdominal distention• Early satiety• Urinary symptoms

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Presenting Signs/Sx (cont.)

• Ovarian torsion presenting as acute abdomen

• Pelvic mass on vaginal exam in asymptomatic woman

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Ovarian Ultrasound

Transabdominal3.5-5.0 MHZ transducerfull bladder as acoustic window

Transvaginal (TVS)5.0-7.5 MHz transducerempty bladder!

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Indications for TVS (v. transabdominal)

• Uncertain transabdominal findings

• Better characterization of lesion

• Strong FH ovarian CA

• Retroverted, retroflexed uterus

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Who gets ultrasound?

1)Women with symptoms described earlier

2)Women with acute lower quadrant or periumbilical pain

3) Asymptomatic women with pelvic mass on vaginal exam

4) Women with familial ovarian CA syndrome, annual TVS until age 35

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Ultrasound terminology

• Echogenic or hyperechoic– This means grey or white!– Solid organs

• Echolucent or hypoechoic– This means black!– Fluid or cysts

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Normal ovary

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Normal ovary• Ellipsoid• Central echogenic medulla• Homogeneous echotexture• Position variable• Anechoic follicles may be seen in

cortex

• Ovarian volume = (0.523 x length x width x height)• Normal volume:

– Premenopausal: 9.8 +/- 5.5 cc (upper limit nl as high as 22 cc)– Postmenopausal: 1.2-5.8 cc (>8.0 cc definitely abnormal)

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Normal ovary• Ellipsoid• Central echogenic medulla• Homogeneous echotexture• Position variable• Anechoic follicles may be seen in

cortex

• Ovarian volume = (0.523 x length x width x height)• Normal volume:

– Premenopausal: 9.8 +/- 5.5 cc (upper limit nl as high as 22 cc)– Postmenopausal: 1.2-5.8 cc (>8.0 cc definitely abnormal)

• TVS detects 20-90% of postmenopausal ovaries

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More normal ovaries

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Differential diagnosis of ovarian masses:

• Functional cyst• Follicular cyst• Corpus luteum cyst• Hemorrhagic cyst• Hematoma• Abscess

• Cystadenoma• Cystadenocarcinoma• Endometrioma• Ectopic pregnancy• Teratoma/Dermoid

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Let’s review some patients with adnexal pathology

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Patient A: right adnexa• History: 32 yo woman with 3 mo h/o right adnexal pain

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Patient A: right adnexa

FILM FINDINGS There is a right adnexalmass which is:

• Anechoic• Has well-defined, thin walls• Shows posterior acoustic

enhancement

Diagnosis:Classic functional ovarian cyst

*Functional cysts are the most common cause of ovarian enlargement in young women

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Patient A: left adnexa

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Patient A: left adnexa

FILM FINDINGS

• Heterogeneuous leftovarian mass withthrough transmission

• Characteristic cystic masswith echogenic mural nodule(“dermoid plug”)

Diagnosis:Left ovarian teratoma (a.k.a. ovarian dermoid)

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Patient B: right ovaryHistory: 34 yo woman with 1 wk h/o RLQ pain

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Patient B: right ovary

FILM FINDINGS

• Right ovarian mass; low level internal echoes with enhanced through transmission

Diagnosis:Endometrioma

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Patient C: left ovaryHistory: 19 yo woman with RLQ pain, dyspareunia

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Patient C: left ovary

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FILM FINDINGS

Left adnexal mass featuring:

•Hyperechoic (“lace- like” pattern)

•Smooth posterior wall

•Posterior acoustic enhancement

Diagnosis:

Hemorrhagic cyst

Hemorrhagic cyst may show septations and reticular pattern as clot hemolyzes, or may mimic a solid mass

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Patient D: left adnexaHistory: 86 yo woman with recent onset fatigue, weight loss, early satiety

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FILM FINDING: there is an irregular cystic lesion of the left ovary

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Ultrasound findings suggestive of malignancy in cystic lesions of the ovary:

• Irregular walls

• Thick, irregular septations

• Mural nodules

• Solid echogenic elements

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Patient D’s ultrasound is consistent with that of ovarian neoplasm:

Irregular walls

Mural nodules

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Complex cysts may be benign or malignant.

So, how do we tell the difference?

• Pre-test probability– It is uncommon for younger women to have some

forms of ovarian neoplasms—but not impossible! – So, we can not categorically r/o malignancy based on

Hx and Sx alone.

• Repeat TVS imaging?

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Recommendations:

• If unilocular cyst:– Repeat TVS in 4-6 wks

to demonstrate resolution

– Premenopausal woman with simple cystic adnexal mass <6-10 cm diameter, 70% will resolve spontaneously

• Simple, unilateral cyst, asymptomatic, nl gyn exam, nl Pap, nl CA-125:– <3 cm, follow with TVS– >3 cm, laparoscopy

• Laparotomy indicated:– Cyst >5 cm– Cyst with internal

septations and/or solid nodules

– Symptomatic– High CA-125

Premenopausal Postmenopausal

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A suspicious ovarian cyst should NEVER be percutaneously drained or aspirated!

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Call gyn onc!

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FIGO staging of ovarian CA:• Stage I—limited to ovaries

– Ia—one ovary, no ascites with + cytology, no tumor on external surface, capsule intact

– Ib—both ovaries, no ascites with + cytology, no tumor on external surface, capsule intact

– Ic—tumor stage Ib or Ic but with ascites, or + peritoneal washings, or capsule rupture

• Stage II—pelvic extension– IIa—uterus and/or fallopian tubes– IIb—other pelvic tissues– IIc—tumor stage IIa or IIb but with ascites, + peritoneal washings, or capsule

rupture

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FIGO staging (cont.):• Stage III—peritoneal mets/superficial liver mets/retroperitoneal nodes

– IIIa—limited to pelvis, negative nodes, microscopic seeding of peritoneum

– IIIb—peritoneal implants no larger than 2 cm diameter– IIIc—peritoneal implants >2 cm diameter, or + retroperitoneal or inguinal

nodes• Stage IV—pelvic extension

– Distant mets (including pleural effusion, intrahepatic mets)

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Staging:

• Ovarian CA is staged surgically

• 70% of women, when diagnosed, are advanced stage (stage III or IV)

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Early stage disease:

• Stage Ia and Ib generally do not require chemoRx

• However, rupture or “spillage” of early stage tumor can theoretically advance tumor stage

• Implantation mets at laparoscopy trochar puncture sites (micrometastases seeding scar tissue)

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5-year survival

• Stage I 73%

• Stage II 46%

• Stage III 17%

• Stage IV 5%

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Patient E: plain abdominal film

• History: 68 yo woman with several week h/o abdominal pain and constipation

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Patient E

FILM FINDINGS: (SUBTLE!)

1) Probable ascites (“ground glass” abdomen)

2) Suggestion of pelvic soft tissue density

3) No evidence bowel obstruction

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DDx pelvic soft tissue mass:

• Abscess• Distended bladder• Distended/filled bowel

loop• Feces in rectosigmoid• Hematoma • Ovarian cyst or neoplasm• Pregnancy• Fibroids, hydatid mole,

other uterine neoplasm

• Anterior sacral meningocele

• Bone tumor• Extraperitoneal neoplasm• Hydatid cyst• Pelvic kidney• Pelvic lipomatosis

Commo Uncommon

Source: Felson’s Gamut

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Abdominal CT of Patient E confirmed….

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Abdominal CT of Patient E confirmed….free fluid

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But what’s this?

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And this? (from a lower axial section)

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And this? (from a lower axial section)

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Answer:

Peritoneal implants from metastatic disease

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Pelvic CT of the same patient:

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Pelvic CT of the same patient:

FILM FINDINGS:

6x7 cm heterogeneous mass in right hemipelvis

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Pelvic section from Patient E:

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Pelvic section from patient E:

FILM FINDINGS:

Diffuse “omental caking”:

Soft tissue nodules (mets) embedded in omental fat

Diagnosis:Metastatic right ovarian cancer with omental cake, multiple peritoneal implants, and ascites

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Common sites of metastasis in Ovarian Cancer:

• Stomach• Large bowel• Small bowel• Pelvic ureter• Liver

• Pelvic nodes• Para-aortic nodes• Peritoneum

– Right subphrenic space– Greater omentum– Rectouterine pouch (of

Douglas)

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Different patients with metastatic disease:

Courtesy Jeong et al, , “Imaging Evaluation of Ovarian Masses”, Radiographics, 2000;20:1445-1470, at http://radiographics.rsnajnls.org

MR demonstrating peritoneal enhancement in patient with metastatic serous tumor

Ct showing calcified implants in Stage IIIa papillary ovarian CA

Patient F Patient G

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Staging laparotomy

• TAHBSO

• Omentectomy

• Peritoneal biopsy

• Lymph node biopsy

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Screening to detect early disease?

• Based on incidence, screening test with 99% specificity and 100% sensitivity would yield 1 in 21 women with disease (PPV 4.8%)

• 5-10% of women with suspicious adnexal mass will undergo surgery, and of these masses, only 13-21% will prove malignant

• Doppler sonography?– Malignant masses will have high diastolic flow

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TVS screening in asymptomatic women: a study from Japan (Sato et. al., 2000)

• Primary screening of asymptomatic women >30 yo, who also underwent annual screening for cervical CA

• 10 year study

• 183,034 women underwent primary screening– 4 TVS views– Secondary screening including full TVS, tumor markers

• 320 women underwent laparotomy– 22 women diagnosed with ovarian CA

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TVS screening in asymptomatic women: a study from Japan (Sato et. al., 2000)

• 17/22 had stage I disease (77%)

• 2/22 had stage II disease (9%)

• 2/22 had stage III disease (9%)

• 1/22 had stage IV disease (5%)

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TVS screening in asymptomatic women: a study from Japan (Sato et. al., 2000)

I 29.7% 58.8%

II 13.5% 9.4%

III 43.3% 22.4%

IV 13.5% 9.4%

Stage Pre-screening Post-screening

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TVS screening in asymptomatic women: a study from Japan (Sato et. al., 2000)

Summary:

• screening TVS in asymptomatic women led to earlier stage diagnosis when compared with controls

• Detection of early stage disease may lead to an improved 5-year survival

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CT in ovarian CA:

• Current uses of CT– Assess disease extent pre-op– Substitute for 2nd-look laparotomy

• High false negative rate for identifying residual disease post-chemo

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CT as prognostic test in women with known disease?

• Amount of residual disease post surgical reduction and prior to chemo is important prognostic indicator (Goldie-Coldman hypothesis)

• How often does optimal surgical reduction occur?

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Bristow et al., “A model for predicting surgical outcome in patients with advanced ovarian

carcinoma using computed tomography” (2000)

• Goal: predict outcome of primary cytoreductive surgery

• 41 patients (MGH and JHU)

• Optimal result: <=1 cm maximal diameter residual disease

• 25 radiographic features as potential indicators of surgical outcome

• Results:– 3 patients with stage IIIb disease– 29 patients with stage IIIc disease– 9 patients with Stage IV disease

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Bristow et al., “A model for predicting surgical outcome in patients with advanced ovarian

carcinoma using computed tomography” (2000)

• CT features most strongly associated with surgical outcome:– Peritoneal thickening– Peritoneal implants >=2 cm – Bowel mesentery involvement >=2 cm– Suprarenal paraaortic nodes >=1 cm– Omental extension– Pelvic sidewall involvement/hydroureter

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Bristow et al., “A model for predicting surgical outcome in patients with advanced ovarian

carcinoma using computed tomography” (2000)

• Features assigned point value to generate Predictive Index score

• 9 different gyn onc surgeons

• Unnecessary exploration (NPV)—women who undergo laparoscopy and are in retrospect found to be poor surgical candidates by virtue of their tumor burden

• Inappropriate unexploration (specificity)—women who do not undergo laparoscopy, and who in retrospect are found to be appropriate surgical candidates by virtue of their tumor burden

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Bristow et al., “A model for predicting surgical outcome in patients with advanced ovarian

carcinoma using computed tomography” (2000)

Predicitive Index Score Unnecessarily Explored (%)

Inappropriately Unexplored (%)

>=1 0 50.0>=2 0 45.0>=3 0 25.0>=4 0 15.0>=5 6.0 15.0>=6 10.6 15.0>=7 13.6 5.0>=8 26.9 5.0>=9 31.0 0>=10 37.5 0

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Bristow et al., “A model for predicting surgical outcome in patients with advanced ovarian

carcinoma using computed tomography” (2000)

Summary:

The ability of CT to quantify tumor burden may help to

1) identify women who will most benefit from laparoscopy

2) spare women with high tumor burden from unnecessary surgical morbidity

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Summary:We have covered:

• Introduction to ovarian cancer

• Indications for ovarian imaging

• Basic ovarian ultrasonography

• Imaging in advanced disease

• Imaging in screening and prognosis

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References:• Ascher et al, “Diagnostic Imaging Techniques in Gynecologic Oncology, in Hoskins et al, Principles

and Practice of Gynecologic Oncology (2nd ed.), Lippincott-Raven, 1997• Bristow et al, “A Model for Predicting Surgical Outcome in Patients with Advanced Ovarian

Carcinoma Using Computed Tomography”, Cancer October 1, 2000, Vol.89, No.7, pp.1532-1540• Cotran et al, Robbins Pathologic Basis of Disease, W.B. Saunders Company, 1999• Felson, Gamut• Jeong et al, “Imaging Evaluation of Ovarian Masses”, Radiographics. 2000;20:1445-1470 [cited

http://radiographics.rsnajnls.org/ 2001 January 17]• Kupesic et al, “Contrast-Enhanced, Three-Dimensional Power Doppler Sonography for

Differentiation of Adnexal Masses”, Obstetrics & Gynecology, Vol.96, No.3, September 2000, pp. 452-458

• Morrow and Curtin, Synopsis of Gynecologic Oncology (5th ed.), Churchill Livingstone, 1998• Ovarian Cancer: Screening, Treatment and Followup. NIH Consensus Statement Online 1994 April

5-7; [cited 2001 January 17] 12(3): 1-30• Salem, “The Uterus and Adnexa”, in Rumack et al, Diagnostic Ultrasound (2nd ed.), Mosby-Year

Book, 1998• Sato et al, “Usefulness of Mass Screening for Ovarian Carcinoma Using Transvaginal

Ultrasonography”, Cancer August 1, 2000, Vol.89, No.3, pp. 582-588

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• David Lin, M.D.• Beverlee Turner for her support and

PowerPoint expertise• Larry Barbaras and Ben Crandall our

WebMasters

Patrick YachimskiGillian Lieberman, MD