Ovarian Imaging and Ovarian Cancer

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January Ovarian Imaging and Ovarian Cancer Patrick Yachimski Harvard Medical School, Year- III MD

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 2

Statistics 3 rd leading gynecologic cancer >50% of GYN cancer deaths 1995: 26,000 new U.S. Cases 14,500 U.S. Deaths 3

Risk factors Age (peak incidence 6 th decade) Nulliparity North American or Northern European descent Personal history breast, endometrial, colon CA Family history ovarian CA Familial ovarian CA syndromes 4

Lifetime risk of ovarian CA 1.4% for all women 5% for women with 1 st -degree relative with ovarian cancer 5

Ovarian CA subtypes Type % 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 Metastases to ovaries 5-10 2-3 Fibroma, granulosa-theca cell 5 5 6

Presenting Signs/Sx Pelvic pain Pelvic mass Weight loss Abdominal distention Early satiety Urinary symptoms 7

Presenting Signs/Sx (cont.) Ovarian torsion presenting as acute abdomen Pelvic mass on vaginal exam in asymptomatic woman 8

Ovarian Ultrasound Transabdominal 3.5-5.0 MHZ transducer full bladder as acoustic window Transvaginal (TVS) 5.0-7.5 MHz transducer empty bladder! 9

Indications for TVS (v. transabdominal) Uncertain transabdominal findings Better characterization of lesion Strong FH ovarian CA Retroverted, retroflexed uterus 10

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 11

Ultrasound terminology Echogenic or hyperechoic This means grey or white! Solid organs Echolucent or hypoechoic This means black! Fluid or cysts 12

Normal ovary BIDMC files 13

Normal ovary Ellipsoid Central echogenic medulla Homogeneous echotexture Position variable Anechoic follicles may be seen in cortex BIDMC files 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) 14

Normal ovary Ellipsoid Central echogenic medulla Homogeneous echotexture Position variable Anechoic follicles may be seen in cortex BIDMC files 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 15

More normal ovaries 16

Differential diagnosis of ovarian masses: Functional cyst Follicular cyst Corpus luteum cyst Hemorrhagic cyst Hematoma Abscess Cystadenoma Cystadenocarcinoma Endometrioma Ectopic pregnancy Teratoma/Dermoid 17

Let s review some patients with adnexal pathology 18

Patient A: right adnexa History: 32 yo woman with 3 mo h/o right adnexal pain 19 BIDMC files

Patient A: right adnexa FILM FINDINGS There is a right adnexal mass which is: Anechoic Has well-defined, thin walls Shows posterior acoustic enhancement Diagnosis: Classic functional ovarian cyst BIDMC files *Functional cysts are the most common cause of ovarian enlargement in young women 20

Patient A: left adnexa BIDMC files 21

Patient A: left adnexa FILM FINDINGS Heterogeneuous left ovarian mass with through transmission Characteristic cystic mass with echogenic mural nodule ( dermoid plug ) Diagnosis: Left ovarian teratoma (a.k.a. ovarian dermoid) 22

Patient B: right ovary History: 34 yo woman with 1 wk h/o RLQ pain 23 BIDMC files

Patient B: right ovary FILM FINDINGS Right ovarian mass; low level internal echoes with enhanced through transmission Diagnosis: Endometrioma 24

Patient C: left ovary History: 19 yo woman with RLQ pain, dyspareunia 25 BIDMC files

Patient C: left ovary FILM FINDINGS Left adnexal mass featuring: Hyperechoic like pattern) ( lace- Smooth posterior wall Posterior acoustic enhancement Diagnosis: Hemorrhagic cyst BIDMC files Hemorrhagic cyst may show septations and reticular pattern as clot hemolyzes, or may mimic a solid mass 26

Patient D: left adnexa History: 86 yo woman with recent onset fatigue, weight loss, early satiety BIDMC files FILM FINDING: there is an irregular cystic lesion of the left ovary 27

Ultrasound findings suggestive of malignancy in cystic lesions of the ovary: Irregular walls Thick, irregular septations Mural nodules Solid echogenic elements 28

Patient D s ultrasound is consistent with that of ovarian neoplasm: Irregular walls Mural nodules 29

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? 30

Recommendations: Premenopausal 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 Postmenopausal 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 31

A suspicious ovarian cyst should NEVER be percutaneously drained or aspirated! 32

Call gyn onc! 33

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 34

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) 35

Staging: Ovarian CA is staged surgically 70% of women, when diagnosed, are advanced stage (stage III or IV) 36

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) 37

5-year survival Stage I 73% Stage II 46% Stage III 17% Stage IV 5% 38

Patient E: plain abdominal film History: 68 yo woman with several week h/o abdominal pain and constipation 39 BIDMC files

Patient E FILM FINDINGS: (SUBTLE!) 1) Probable ascites ( ground glass abdomen) 2) Suggestion of pelvic soft tissue density 3) No evidence bowel obstruction 40 BIDMC files

DDx pelvic soft tissue mass: Commo Uncommon 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 Source: Felson s Gamut 41

Abdominal CT of Patient E confirmed. 42 BIDMC files

Abdominal CT of Patient E confirmed.free fluid 43 BIDMC files

But what s this? 44 BIDMC files

And this? (from a lower axial section) 45 BIDMC files

And this? (from a lower axial section) Patrick Yachimski Answer: Peritoneal implants from metastatic disease 46 BIDMC files

Pelvic CT of the same patient: Patrick Yachimski 47 BIDMC files

Pelvic CT of the same patient: Patrick Yachimski FILM FINDINGS: 6x7 cm heterogeneous mass in right hemipelvis 48 BIDMC files

Pelvic section from Patient E: Patrick Yachimski 49 BIDMC files

Pelvic section from patient E: Patrick Yachimski 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 50 BIDMC files

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) 51

Different patients with metastatic disease: Patient F Patient G Courtesy Jeong et al,, Imaging Evaluation of Ovarian Masses, Radiographics, 2000;20:1445-1470, at http://radiographics.rsnajnls.org Ct showing calcified implants in Stage IIIa papillary ovarian CA MR demonstrating peritoneal enhancement in patient with metastatic serous tumor 52

Staging laparotomy TAHBSO Omentectomy Peritoneal biopsy Lymph node biopsy 53

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 54

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 55

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%) 56

TVS screening in asymptomatic women: a study from Japan (Sato et. al., 2000) Stage Pre-screening Post-screening I 29.7% 58.8% II 13.5% 9.4% III 43.3% 22.4% IV 13.5% 9.4% 57

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 58

MD CT in ovarian CA: Current uses of CT Assess disease extent pre-op Substitute for 2 nd -look laparotomy High false negative rate for identifying residual disease post-chemo 59

MD 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? 60

MD 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 61

MD 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 62

MD 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 63

MD Bristow et al., A model for predicting surgical outcome in patients with advanced ovarian carcinoma using computed tomography (2000) Predicitive Index Score Unnecessarily Explored (%) >=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 Inappropriately Unexplored (%) 64

MD 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 65

MD Summary: We have covered: Introduction to ovarian cancer Indications for ovarian imaging Basic ovarian ultrasonography Imaging in advanced disease Imaging in screening and prognosis 66

MD References: Ascher et al, Diagnostic Imaging Techniques in Gynecologic Oncology, in Hoskins et al, Principles and Practice of Gynecologic Oncology (2 nd 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 (5 th 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 (2 nd 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 67

MD David Lin, M.D. Beverlee Turner for her support and PowerPoint expertise Larry Barbaras and Ben Crandall our WebMasters 68