Ovarian Cancer

The Case of Olivia Carson You are a generalist in the community. You have a new patient. She is a 65 year old with a large pelvic mass arising from the right adnexum.

The Case of Olivia Carson What is the likelihood that she has ovarian cancer?

The Case of Olivia Carson What is the likelihood that she has ovarian cancer? Age Menopausal status Mass characteristics

Ovarian Neoplasms 90% benign 10% malignant

Incidence of Ovarian Cancer Age Group Incidence (per 100,000) 25-29 40-44 75-79

Incidence of Ovarian Cancer Age Group Incidence (per 100,000) 25-29 4 40-44 15 75-79 48

Predictive Value of Menopausal Status Malignant Premenopausal 7-13% Postmenopausal 8-45% Vasilev. Obstet Gynecol 1988

The Case of Olivia Carson The only other data you have is that she underwent an imaging study. Which study do you hope she has had?

Imaging of Ovarian Masses Sensitivity Specificity CT MRI US Scoutt. Clin Obstet Gynecol 1991

Imaging of Ovarian Masses Sensitivity Specificity CT Poor MRI 95% 88% US 75% 98% Scoutt. Clin Obstet Gynecol 1991

Transvaginal Ultrasound Cost effective High frequency Improved resolution

Ultrasound Evaluation of Adnexal Masses Simple cyst Complex cyst

Ultrasound Evaluation of Adnexal Masses Simple cyst Anechoic Smooth walls Complex cyst Cystic and solid Irregular outline Septa Papilla Heterogeneous

Ultrasound Findings Benign Malignant

Ultrasound Findings Benign Malignant Unilateral Bilateral Cystic Solid component Unilocular Multilocular Stable over time Growth No ascites Ascites

Ultrasound scoring system Simple cyst. Smooth borders. 1 Clear cyst. Either irregular border or low level echoes. 2 Clear cyst, postmenopausal. Both irregular border and low level echoes. 3 Solid component. Irregular border and echoes. 4-6 Mult septations, irregular border, nodularity. 7-9 As above plus ascites. 10 1-3 = benign 4-6 = equivocal 7-10 = malig

Transvaginal ultrasound: predictive value Pos predictive value Neg predictive value Premenopausal 82% 86% Postmenopausal 93% 71% Finkler. Obstet Gynecol 1988

The Case of Olivia Carson Her ultrasound shows a solid mass. If this were cancer, predict the histology.

Cancer Rule of Thumb Oncology recapitulates ontogeny

Embryology of the Ovary 3 cell types

Embryology of the Ovary Coelomic epithelium Mesenchyme Germ cells

Embryology of the Ovary Coelomic epithelium Mesenchyme Germ cells Epithelium Stromal cells Ova

Stromal Tumors: Histologic Subtypes Fibroblasts Granulosa cell tumors Thecal cells Sertoli-Leydig cells

Stromal tumors: Histologic subtypes Fibroblasts Fibromas Granulosa cells Granulosa cell tumor Thecal cells Thecoma Sertoli-Leydig cells Sertoli-Leydig cell tumor

The Case of Olivia Carson 65 year old with a large pelvic mass arising from the right adnexum. Solid mass on TV US. You do a careful history and determine that she has had new onset of vaginal bleeding.

Granulosa Cell Tumors Hormonally active Estrogen Inhibin MIS

The Case of Olivia Carson 65 year old with a HARD large pelvic mass arising from the right adnexum. Solid mass on TV US. Extensive ascites on TV US. Right pleural effusion.

Meig’s syndrome Fibroma Ascites (>200 ml) Hydrothorax

The Case of Olivia Carson 25 year old with acute pain and a HARD large pelvic mass arising from the right adnexum. Solid mass on TV US. Extensive ascites on TV US. Right pleural effusion. You note multiple skin lesions.

Gorlin’s Syndrome Ovarian fibromas Young women Multiple basal cell nevi and carcinomas Dental cysts Skeletal abnormalities Autosomal dominant

The Case of Olivia Carson 65 year old with a large pelvic mass arising from the right adnexum. Solid mass on TV US. What will you do to treat her?

Management of Stromal Tumors Washings USO Consider TAH BSO, nodes Granulosa cell tumors Sertoli-Leydig cell tumors Suspicious for malignancy

The Case of Olivia Carson You are a generalist in the community. You have a new patient. She is a 15 year old with a large pelvic mass arising from the right adnexum. What is the most likely tumor?

Histologic Subtypes: Germ Cell Tumors

Histologic subtypes: germ cell tumors Embryo Fetus Yolk sac Placenta

Histologic subtypes: germ cell tumors Dysgerminoma Embryo Embryonal ca Fetus Teratoma Yolk sac Placenta Endodermal sinus tumor Choriocarcinoma

The Case of Olivia Carson 15 year old with a large pelvic mass arising from the right adnexum. What pre-op labs do you want?

Tumor Markers: Germ Cell Tumors LDH AFP hCG

Histologic Subtypes: Germ Cell Tumors Dysgerminoma LDH Embryo Embryonal ca AFP/hCG Fetus Teratoma AFP Yolk sac Placenta Endodermal sinus tumor Choriocarcinoma hCG

The Case of Olivia Carson 15 year old with a large pelvic mass arising from the right adnexum. What will you do to treat her?

Germ Cell Tumors: Treatment USO plus staging Chemotherapy

The Case of Olivia Carson 15 year old with a large pelvic mass arising from the right adnexum. She underwent a USO at an outside hospital. A germ cell tumor was found on final path. What do you recommend?

The Case of Olivia Carson You are a generalist in the community. You have a new patient. She is a 65 year old with a TV US showing a 5 cm right ovarian cystic mass with one septation. Her CA-125 is 40. Do you refer her or keep her?

CA-125: Predictive Value 36% 82% 94% 80% Pos predictive value Neg predictive value Premenopausal 36% 82% Postmenopausal 94% 80% Finkler. Obstet Gynecol 1988

Combination US + CA-125: Positive Predictive Value US alone US + CA-125 Premenopausal 82% 71% Postmenopausal 93% 100% Finkler. Obstet Gynecol 1988

Combination US + CA-125: negative predictive value US alone US + CA-125 Premenopausal 85% 88% Postmenopausal 71% 100% Finkler. Obstet Gynecol 1988

The Case of Olivia Carson 65 year old with a TV US showing a 5 cm right ovarian cystic mass with one septation. Her CA-125 is 40. You explore her and find a smooth, benign-appearing cyst on the ovary. There is no extra-ovarian disease. What procedure do you do?

Ovarian Masses: Surgical Management Cyst aspiration Ultrasound guided Laparoscopic Laparoscopy Laparotomy

Ovarian Cyst Aspiration Benign appearing cyst

Ovarian Cyst Aspiration Status Recurrence rate Premenopausal 48% Postmenopausal 80% Bret. Radiol 1992

Cytology of Ovarian Aspirates Cannot distinguish between primary and malignant disease 10 - 66% false negative rate Ganjei. Acta Cytol 1984

Ovarian Cyst Aspiration Limited value High recurrence rate Unreliable cytology ? Upstaging a malignant tumor

Ovarian cancer staging

Effect of Intraoperative Rupture Stage Death Survival (mo) IA 3% 97 IC 12% 94 Surgical IC 20% 73 Sainz de la Cuesta. Obstet Gynecol 1994

The Case of Olivia Carson 65 year old with a TV US showing a 5 cm right ovarian cystic mass with one septation. Her CA-125 is 40. You do an RSO. Frozen section shows serous papillary carcinoma. There is no extra-ovarian disease. What do you do?

Apparent Stage I Disease 40% will have more advanced disease due to occult metastases. Peritoneal cytology 19% Aortic nodes 12% Peritoneum 10% Pelvic nodes 9% Diaphragm 8% Omentum 7%

Survival and Staging 5-year Survival Apparent Stage I 60% Surgical Stage I 90-100%

Surgical Staging Procedures Pelvic washings Systematic exploration of all intra-abdominal surfaces and viscera Peritoneal biopsies Diaphragmatic sampling Infracolic omentectomy Bilateral pelvic and para-aortic lymph node dissection

The Case of Olivia Carson 65 year old with a TV US showing a 5 cm right ovarian cystic mass with one septation. Her CA-125 is 40. You explore her and find a smooth, benign-appearing cyst on the ovary. There is no extra-ovarian disease. You do an RSO. Frozen section shows borderline tumor. What do you do?

Borderline Ovarian Cancer Earlier age at presentation Fertility sparing surgery (USO or cystectomy) is appropriate Avoid bivalving or wedge resection of grossly normal ovary Ideal to surgically stage, however does not change management Chemotherapy has no role

Cytoreductive Surgery Removal of the maximum amount of tumor possible.

Basis of Cytoreduction Residual disease Median survival (months) >1.5 cm 11 <1.5 cm 39 Griffiths. Natl Cancer Inst Monogr 1975

Surgical Procedures Bowel resection Ureteral/bladder resection Pelvic/aortic node dissection Peritoneal stripping Diaphragm stripping Liver/spleen/kidney/stomach resection

Survival and Aggressive Surgery Residual disease % patients Median survival (mo) 85 62 Any 14 20 N=163 Eisenkop. Gynecol Onc 1998

The Case of Olivia Carson What is the likelihood that she has ovarian cancer? Age Menopausal status Mass characteristics CA-125

Ovarian Cyst Aspiration Limited value High recurrence rate Unreliable cytology ? Upstaging a malignant tumor

Summary: Ovarian Cancer Epithelial Stromal Germ cell Incidence 65-70% 5-10% 15-20% Age 50-60 All <25 Natural hx Fast growth death Slow growth benign Fast growth live Tumor marker CA-125 hormones LDH, AFP, hCG Treatment Cytoreduction Chemo Surgery  Chemo

Summary: Stromal Tumors Fibroblasts Fibromas Granulosa cells Granulosa cell tumor Thecal cells Thecoma Sertoli-Leydig cells Sertoli-Leydig cell tumor

Summary: Germ Cell Tumors Dysgerminoma LDH Embryo Embryonal ca AFP/hCG Fetus Teratoma AFP Yolk sac Placenta Endodermal sinus tumor Choriocarcinoma hCG

Summary: Surgical Staging Procedures Pelvic washings Systematic exploration of all intra-abdominal surfaces and viscera Peritoneal biopsies Diaphragmatic sampling Infracolic omentectomy Bilateral pelvic and para-aortic lymph node dissection