Ovarian Cancer

1
Ovarian Cancer
Annette Chen, MD Division Gynecologic
Oncology UMass Memorial Medical Center
2
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.

3
The Case of Olivia Carson

• What is the likelihood that she has ovarian
  cancer?

4
The Case of Olivia Carson

• What is the likelihood that she has ovarian
  cancer?
• Age
• Menopausal status
• Mass characteristics

5
Ovarian Neoplasms

• 90 benign
• 10 malignant

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Incidence of Ovarian Cancer
Age Group Incidence (per 100,000)
25-29
40-44
75-79
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Incidence of Ovarian Cancer
Age Group Incidence (per 100,000)
25-29 4
40-44 15
75-79 48
8
Predictive Value of Menopausal Status
Status Malignant
Premenopausal 7-13
Postmenopausal 8-45
Vasilev. Obstet Gynecol 1988
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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?

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

• Cost effective
• High frequency
• Improved resolution

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Ultrasound Evaluation of Adnexal Masses

• Simple cyst

• Complex cyst

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Ultrasound Evaluation of Adnexal Masses

• Simple cyst
• Anechoic
• Smooth walls

• Complex cyst
• Cystic and solid
• Irregular outline
• Septa
• Papilla
• Heterogeneous

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Ultrasound Findings
Benign Malignant





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Ultrasound Findings
Benign Malignant
Unilateral Bilateral
Cystic Solid component
Unilocular Multilocular
Stable over time Growth
No ascites Ascites
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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
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Transvaginal ultrasound predictive value
Pos predictive value Neg predictive value
Premenopausal 82 86
Postmenopausal 93 71
Finkler. Obstet Gynecol 1988
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The Case of Olivia Carson

• Her ultrasound shows a solid mass.
• If this were cancer, predict the histology.

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Cancer Rule of Thumb

• Oncology recapitulates ontogeny

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Embryology of the Ovary

• 3 cell types

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Embryology of the Ovary

• Coelomic
• epithelium
• Mesenchyme
• Germ cells

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Embryology of the Ovary

• Coelomic
• epithelium
• Mesenchyme
• Germ cells

Epithelium
Stromal cells
Ova
24
Stromal Tumors Histologic Subtypes

• Fibroblasts
• Granulosa cell tumors
• Thecal cells
• Sertoli-Leydig cells

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Stromal tumors Histologic subtypes

• Fibroblasts Fibromas
• Granulosa cells Granulosa cell tumor
• Thecal cells Thecoma
• Sertoli-Leydig cells Sertoli-Leydig cell tumor

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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.

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Granulosa Cell Tumors

• Hormonally active
• Estrogen
• Inhibin
• MIS

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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.

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Meigs syndrome

• Fibroma
• Ascites (gt200 ml)
• Hydrothorax

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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.

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Gorlins Syndrome

• Ovarian fibromas
• Young women
• Multiple basal cell nevi and carcinomas
• Dental cysts
• Skeletal abnormalities
• Autosomal dominant

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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?

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Management of Stromal Tumors

• Washings
• USO
• Consider TAH BSO, nodes
• Granulosa cell tumors
• Sertoli-Leydig cell tumors
• Suspicious for malignancy

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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?

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Histologic Subtypes Germ Cell Tumors
Germ cell


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

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Tumor Markers Germ Cell Tumors

• LDH
• AFP
• hCG

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Histologic Subtypes Germ Cell Tumors
Germ cell

• Dysgerminoma
• LDH

Embryo

• Embryonal ca
• AFP/hCG

Fetus

• Teratoma
• AFP

Yolk sac Placenta

• Endodermal sinus tumor
• Choriocarcinoma
• hCG

41
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?

42
Germ Cell Tumors Treatment

• USO plus staging
• Chemotherapy

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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?

44
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?

45
CA-125 Predictive Value
Pos predictive value Neg predictive value
Premenopausal 36 82
Postmenopausal 94 80
Finkler. Obstet Gynecol 1988
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Combination US CA-125 Positive Predictive Value
US alone US CA-125
Premenopausal 82 71
Postmenopausal 93 100
Finkler. Obstet Gynecol 1988
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Combination US CA-125 negative predictive value
US alone US CA-125
Premenopausal 85 88
Postmenopausal 71 100
Finkler. Obstet Gynecol 1988
48
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?

49
Ovarian Masses Surgical Management

• Cyst aspiration
• Ultrasound guided
• Laparoscopic
• Laparoscopy
• Laparotomy

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Ovarian Cyst Aspiration

• Benign appearing cyst

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Ovarian Cyst Aspiration
Status Recurrence rate
Premenopausal 48
Postmenopausal 80
Bret. Radiol 1992
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Cytology of Ovarian Aspirates

• Cannot distinguish between primary and malignant
  disease
• 10 - 66 false negative rate

Ganjei. Acta Cytol 1984
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Ovarian Cyst Aspiration

• Limited value
• High recurrence rate
• Unreliable cytology
• ? Upstaging a malignant tumor

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Ovarian cancer staging
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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
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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?

57
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

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

60
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?

61
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

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Cytoreductive Surgery

• Removal of the maximum amount of tumor possible.

63
Basis of Cytoreduction
Residual disease Median survival (months)
gt1.5 cm 11
lt1.5 cm 39
Griffiths. Natl Cancer Inst Monogr 1975
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Surgical Procedures

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

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Survival and Aggressive Surgery
Residual disease patients Median survival (mo)
0 85 62
Any 14 20
N163
Eisenkop. Gynecol Onc 1998
66
The Case of Olivia Carson

• What is the likelihood that she has ovarian
  cancer?
• Age
• Menopausal status
• Mass characteristics
• CA-125

67
Ovarian Cyst Aspiration

• Limited value
• High recurrence rate
• Unreliable cytology
• ? Upstaging a malignant tumor

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Summary Ovarian Cancer
Epithelial Stromal Germ cell
Incidence 65-70 5-10 15-20
Age 50-60 All lt25
Natural hx Fast growth ?death Slow growth ?benign Fast growth ?live
Tumor marker CA-125 ?hormones LDH, AFP, hCG
Treatment Cytoreduction Chemo Surgery Surgery ? Chemo
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Summary Stromal Tumors

• Fibroblasts Fibromas
• Granulosa cells Granulosa cell tumor
• Thecal cells Thecoma
• Sertoli-Leydig cells Sertoli-Leydig cell tumor

70
Summary Germ Cell Tumors
Germ cell

• Dysgerminoma
• LDH

Embryo

• Embryonal ca
• AFP/hCG

Fetus

• Teratoma
• AFP

Yolk sac Placenta

• Endodermal sinus tumor
• Choriocarcinoma
• hCG

71
SummarySurgical 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