IMLE Preparatory Course

Lecture 60
Obstetrics and Gynecology

Premalignant & Malignant

Disorders of the Ovaries
Structure of the Ovary
 Frequency of Ovarian Neoplasm
(WHO Classification)

Class Frequency (%)

Epithelial stromal (Common epithelial) tumors 65
Germ cell tumors 20-25
Sex cord-stromal tumors 6
Lipid (lipoid) cell tumors <0.01
Gonadoblastoma <0.01

Soft-tissue tumors (not specific to the ovary)

Unclassified tumors
Secondary (metastatic) tumors
Tumor-like conditions (not true neoplasm)
 Differential Diagnosis of Adnexal Mass
Organ Cystic Solid

Ovary Functional cyst Neoplasm

Neoplastic cyst Benign
Benign Malignant
Malignant
Endometriosis

Fallopian tube Tubo-ovarian abscess Tubo-ovarian abscess

Hydrosalphinx Ectopic pregnancy
Parovarian cyst Neoplasm

Uterus Intrauterine pregnancy in bicornuate Pedunculated or intraligamentous

uterus myoma

Bowel Sigmoid or cecum distended with gas Diverticulitis

or feces Ileitis
Appendicitis
Colonic cancer

Miscellaneous Distended bladder Abdominal wall hematoma or abscess

Pelvic kidney Retroperitoneal neoplasm
Urachal cyst
 Classification

Epithelial: Sex chord Germ cell: Neoplasms

•Serous stromal: •Dysgerminoma metastatic to
•Endodermal sinus
•Mucinous •Granulosa cell tumor
the ovary:
•Endometroid •Bibroma •Teratoma •Breast
•Clear cell •Thecoma- •Embyonal •Stomach
•Transitional cell Sertoli-Leydig carcinoma •Endometrium
(Brenner) cell •Gonadoblastoma •Lymphoma
•Mixed germ cell
•Undifferentiated •Gynadoblastoma •Polyembyoma
Diagnostic Evaluation in the Presence
of an Adnexal Mass
 Complete physical examination

 Ultrasonography

 Colonoscopy or Barium enema, if symptomatic

 Intravenous pyelography, if indicated

 CT Scan or MRI

 Laparoscopy, Laparotomy
Epithelial Ovarian Neoplasms
 Arise from inclusion cysts lined with surface
(coelomic) epithelium within the adjacent
ovarian stroma

 Classified as:
 Benign (adenoma)
 Malignant (adenocarcinoma)
 Intermediate (Boderline malignant or Low
malignant potential)
Epithelial Ovarian Tumor Cell Types

Approximate Frequency (%)

Tumor Cell Type All Ovarian Ovarian
Neoplasms Cancers
Serous 20-50 35-40
Mucinous 15-25 6-10
Endometrioid 5 15-25
Clear cell (mesonephroid) <5 5
Brenner 2-3 Rare
 Serous Tumors
 Composed of ciliated epithelial cells that
resemble those of the fallopian tube
 Serous cystadenomas:
 Occur primarily during reproductive years
 Boderline types:
 Occur in women 30-50 years
 Serous cystadenocarcinoma:
 Occur in women older than 40 years
Benign Ovarian Tumors
 Symptoms:
 Initially are asymptomatic
 Lower abdominal discomfort
 Pelvic pain
 Dyspareunia
 Abdominal enlargement
 Frequent urination
 Constipation
Adnexal Tumors
 Indications for Surgery:
 Ovarian cystic structure >5 cm that has been
observed 6-8 weeks without regression
 Any solid ovarian lesions
 Any ovarian lesion with papillary vegetation on the
cyst wall
 Any adnexal mass >10 cm
 Palpable adnexal mass in premenarchal or
postmenopausal
 Torsion or rupture suspected
 Serous Cystadenoma

 Grossly :
 Papillary projections on the surface
 Inner cyst wall are mostly smooth

 Microscopic:
 Low columnar epithelium with occasional cilia
 Psammoma bodies- small granules, end product of degeneration
of papillary implants indicative of functional immunologic
response
 Mucinous Tumors
 Consist of epithelial cells filled with mucin,
resembling cells of the endocervix or intestinal cells
 Types:
 Mucinous cystadenoma
 Primarily during reproductive years
 Borderline types
 Mucinous cystadenocarcinoma
 Usually in 30- to 60-year age range
 Mucinous Cystadenoma
 May become huge (>300 lbs)
 Grossly:
 Round or ovoid, smooth capsule usually translucent or
bluish to whitish gray
 Interior divided by discreet septa into lobule containing
clear, viscid fluid

 Miscroscopic:
 Lining epithelium is tall, pale staining secretory type with
nuclei at basal pole, rich in mucin
Mucinous Cystadenoma
Mucinous Cystadenoma
 Pseudomyxoma peritonei
 Transformation of peritoneal mesothelium to a mucin
secreting epithelium
 Continuous secretion of mucus resulting in
accummulation in peritoneal cavity of
gelatinous material
 Evacuation at operation is followed by
reaccummulation
 Treatment: Repetitive surgical evacuation
 Long-term nutritional support
Brenner Tumor
 Grossly identical to a Fibroma of the ovary
 Arise from Walthard cell rests
 Microscopic:
 Marked hyperplastic fibromatous matrix interspersed
with nest of epithelioid cells
 Epithelioid cells show “coffee bean” pattern caused by
longitudinal grooving of nuclei
 Scattered reports of malignant Brenner; associated
endometrial hyperplasia
 Treament: Simple excision
Borderline Malignant Epithelial Ovarian
Tumors
 Synonyms: Borderline Tumors, Proliferative Cystadenomas
 Epithelial ovarian tumors with histologic and biologic features
intermediate between clearly benign and clearly
malignant ovarian neoplasms
 The malignant cells do not invade the stroma of the ovary
 Constitute approximately 15-20% of epithelial ovarian cancers
 Slower growth rate than invasive ovarian carcinomas
Borderline Malignant Epithelial Ovarian
Tumors
 Longer survival than invasive forms:
 5-year survival rate of all stages = 97%
 10-year survival rate of all stages = 89%
 Leake and colleagues, Gynecol Oncol, 1992

 Most common varieties:

 Serous
 Mucinous

 Commonly found in younger women

Borderline Malignant Epithelial Ovarian
Tumors
 Histologic criteria for diagnosis:
 Stratification of the epithelial lining of the papilla
 Formation of microscopic papillary projection or tufts
arising from the epithelial lining of the papillae
 Epithelial pleomorphism
 Atypicality
 Mitotic activity
 No stromal invasion present
Borderline Malignant Epithelial Ovarian
Tumors
Borderline Malignant Epithelial Ovarian
Tumors
 Management:
 Complete surgical extirpation of the tumor

 Unilateral involvement:
 Salpingo-oophorectomy is preferred over Cystectomy
 Thorough evaluation of the other ovary
 Peritoneal fluid cytology
 Partial omentectomy
 Bilateral involvement:
 Total abdominal hysterectomy with BSO
 Peritoneal fluid cytology
 Partial omentectomy
Borderline Malignant Epithelial Ovarian
Tumors
 Criteria for Conservative Therapy:
 Confirmed to be Stage IA
 Extensive histologic sampling of the tumor
confirms it to be borderline tumor
 Contralateral ovary appears normal
 Biopsy specimens of areas of omental or
peritoneal nodularity are negative
 Results of peritoneal cytologic tests are
negative for tumor cells
Borderline Malignant Epithelial Ovarian
Tumors
 Management:
 Complete surgical extirpation of the tumor

 Advanced stage:
 Same as bilateral involvement plus:
o Pelvic lymphadenectomy
o Tumor debulking
o Extensive biopsy of any peritoneal or omental implants
o The role of chemotherapy is still controversial
Invasive Ovarian Carcinomas
 Ovarian Cancer
 The 2nd most common gynecologic malignancy
 27% of gynecologic cancers

 The most frequent cause of death from

gynecologic cancers
 Due to advanced stage at the time of diagnosis
 53% of all deaths from gynecologic cancers

 Incidence increases with age, most marked

beyond 50 years, with increase continuing to age 70
years, and decrease after age 80 years
Probability of Females at Birth of
Ever Developing Cancer
All sites 1 in 3
Breast 1 in 7
Lung 1 in 18
Colon-rectum 1 in 18
Uterine corpus 1 in 38
Ovary 1 in 68
Cervix 1 in 130
 Primary Ovarian Neoplasms Related to
Age
Type <20 yr (%) 20-50 yr (%) >50 yr (%)

Coelomic epithelium 29 71 81

Germ cell 59 14 6

Specialized gonadal-stromal 8 5 4

Non-specific mesenchyme 4 10 9

In general, more than half of ovarian carcinomas occur in women older than 50.

The risk of malignancy in a primary ovarian tumor increases to approximately 33% in

women older than 45, whereas it is less than 1 in 15 for women 20-45 years of age.
 Risks of Ovarian Epithelial Carcinoma

Increases Decreases
Age Breast-feeding
Diet Oral contraceptives
Family history Pregnancy
Industrialized country Tubal ligation and
hysterectomy with ovarian
Infertility conservation
Nulliparity
Ovulation
Ovulatory drugs
Talc (?)
 Etiology of Ovarian Cancer
 Theory of “Incessant Ovulation”
 the risk of EOC is related directly to the number of
uninterrupted ovulatory cycles

 Gonadotropin Hypothesis
 exposure of ovarian epithelium to persistently high levels of
pituitary gonadotropins
 FSH promote the growth of epithelial ovarian cancer cells in
vitro
 Theory of “Incessant Ovulation”
 Surface epithelium is ruptured and undergoes rapid
proliferation and repair

 Invagination of the surface epithelium into the underlying

stroma forming inclusion cysts

 Epithelium lining these inclusion cysts undergoes neoplastic

transformation under the influence of oncogenic factors
Gonadotropin Hypothesis
 Increase gonadotropin levels

 Promotes estrogen biosynthesis in the ovarian

stroma

 Causes abnormal proliferation of the adjacent

epithelium
 Characteristics in Benign and Malignant
Ovarian Tumors

Clinical Finding Benign Malignant

Unilateral +++ +
Bilateral + +++
Cystic +++ +
Solid + +++
Mobile +++ ++
 Characteristics of Benign and Malignant
Ovarian Tumors

Clinical Finding Benign Malignant

Fixed + +++
Irregular + +++
Smooth +++ +
Ascites + +++
Cul-de-sac - +++
Nodulations
 Most Frequent Presenting Symptoms
of Ovarian Cancer
Symptom Relative frequency
Abdominal swelling XXXX
Abdominal pain XXX
Dyspepsia XX
Urinary frequency XX
Weight change X

Note: Symptoms are vague and not specific for ovarian cancer
A high index of suspicion is warranted in all women between the ages of
40 to 69 years who have persistent gastrointestinal symptoms that
cannot be diagnosed.
 Non-ovarian causes of Apparent
Adnexal Mass
 Diverticulitis

 Tubo-ovarian abscess

 Carcinoma of the colon or sigmoid

 Pelvic kidney

 Uterine or intraligamentous myoma

Ovarian Carcinoma
 Screening and Early Detection Tools:
 Periodic pelvic Examination
 Sonography
 Biomarkers (e.g. CA 125)

 Conclusion: There is NO evidence available yet

that the current screening modalities can be
used effectively for widespread screening for
ovarian cancer
Diagnostic Evaluation of Adnexal Mass
 Complete physical examination

 Appropriate imaging studies, tumor markers

 Chest X-ray Ca-125
 Ultrasonography CEA
 CT scan AFP, BhCG
 MRI LDH
 Colonoscopy or barium enema study, if
symptomatic
Ovarian Cancer
 Routine pelvic examination detect only 1 ovarian
cancer in 10,000 asymptomatic women
 Routine laboratory test are not of great value in
the diagnosis of ovarian tumors
 The major value of laboratory tests is in ruling
out other pelvic disorders
 Surgical exploration is the ultimate test as
to the nature of the disorder.
Tumor Markers in Ovarian Cancer
 CA-125

 Carcino-embryonic antigen (CEA)

 Alpha-feto protein (AFP)

 Lactic dehydyhrogenase (LDH)

 Human chorionic gonadotrophin (hCG)

 CA 125 and Ovarian Cancer
 Carcinoma Antigen (CA) 125 is expressed in
approximately 80% of ovarian epithelial cancers but
less frequently by mucinous types
 Also increased in tubal, endometrial, lung, breast and
pancreatic cancers
 Also increased in benign conditions
 The specificity appears better for increased values in
postmenopausal patients
Benign Conditions with Elevated CA 125

 Endometriosis
 Peritoneal inflammation, including PID
 Leiomyoma
 Pregnancy
 Hemorrhagic ovarian cysts
 Liver disease
Role of Ultrasound in Ovarian Cancer
 Ultrasound helped to define criteria to allow conservative
follow-up and the risk of malignancy of some adnexal masses
 Scoring systems have been proposed
 Parameters used:
 Unilocular or complex cysts
 Papillary projections
 Regular and smooth septa and/or cytstic walls
 Echogenicity
 Doppler color-enhanced flow
 Used to characterize ovarian mass as benign or
malignant, rather than for screening
Ultrasound Findings Suggestive of
Ovarian Malignancy
 Irregular borders
 Papulations
 Thick septations
 Ascites
 Matted bowel
Ultrasound and Ovarian Cancer
Ultrasound and Ovarian Cancer
Additional diagnostic methods

 CT scan

 MRI

 Barium enema or Colonoscopy

 Comparison between Surgical Findings
of Benign and Malignant Ovarian
Neoplasm

Findings Benign Malignant

Surface papilla Rare Very common
Intracystic papilla Uncommon Very common
Solid areas Rare Very common
Bilaterality Rare Common
Adhesions Uncommon Common
Ascites (100 ml or more) Rare Common
Necrosis Rare Common
Peritoneal implants Rare Common
Capsule intact Common Infrequent
Totally cystic Common Rare
Serous Cystadenocarcinoma
Serous Cystadenocarcinoma
Epithelial Ovarian Cancer
 Constitute 85-90% of ovarian cancers

Histologic distribution:
 Serous cystadenocarcinomas = 42%
 Mucinous cystadenocarcinoma = 12%
 Endometrioid carcinoma = 15%
 Undifferentiated carcinoma = 17%
 Clear cell carcinoma = 6%
 Ovarian Cancer
 Routes of spread:
 Ceolomic spread
o Spread through the peritoneal surfaces of
both the parietal and intestinal areas, as well as
the under surface of the diaphragm.

 Lymphatic route
o Para-aortic nodes are at risk through
lymphatics that run parallel to the ovarian
vessels

 Hematogenous spread
Pattern of spread
 Staging of Ovarian Cancer
 Staging is surgical and based on the operative findings at
the commencement of the procedure
 Staging Laparotomy:
 Midline longitudinal incision
 Peritoneal fluid cytology
 Systematic exploration of the abdominal cavity
 Total abdominal hysterectomy with bilateral salpingo-
oophorectomy
 Lymphadenectomy or lymph node evaluation
 Random biopsy of abdominal peritoneum and
suspicious areas
 FIGO Staging of Ovarian Cancer
FIGO Stage Description

I Growth limited to the ovaries

Ia Growth limited to one ovary; no ascites present containing

malignant cells; no tumor on the external surfaces; capsule
intact
Ib Growth limited to both ovaries; no ascites present
containing malignant cells; no tumor on the external
surfaces; capsule intact
Ic Tumor stage Ia or Stage Ib but with tumor on the external
surface of one or both ovaries; or with capsule
ruptured; or with ascites present containing malignant
cells or positive peritoneal washings
 Stage I: Growth limited to Ovaries

Tumors previously staged as IAii, IBii as stage IC

FIGO Staging of Ovarian Cancer
FIGO Stage Description

II Growth involving one or both ovaries with pelvic

extension
IIa Extension and/or metastases to uterus and/or tubes

IIb Extension to other pelvic tissues

IIc Tumor stage IIa or Stage IIb but with tumor on the surface
of one or both ovaries; or with capsule(s) ruptured; or
with ascites present containing malignant cells or
positive peritoneal washings
Stage II: Spread to Pelvic Tissues
 FIGO Staging of Ovarian Cancer
FIGO Stage Description
III Tumor involving one or both ovaries with peritoneal implants
outside the pelvis and/or positive retroperitoneal or inguinal
nodes; superficial liver metastasis equals stage III; tumor is
limited to the true pelvis but with histologically verified malignant
extension to small bowel or omentum
IIIa Tumor grossly limited to the true pelvis with negative nodes with
histologically confirmed microscopic seeding of abdominal
peritoneal surfaces
IIIb Tumor of one or both ovaries; histologically confirmed implants of the
abdominal surfaces, none exceeding 2 cm in diameter; nodes are
negative
IIIc Abdominal implants 2 cm in diameter and/or positive
retroperitoneal or inguinal nodes
 FIGO Staging of Ovarian Cancer

FIGO Stage Description

IV Growth involving one or both ovaries with

distant metastasis; if pleural effusion is present,
there must be positive cytologic test results to
allot a case to stage IV, parenchymal liver
metastasis equals stage IV
 Stage III: Spread to retroperitoneal nodes, peritoneum,
abdominal organs

 Stage IV: Distant metastases – pleural effusion, liver parenchyma

 Carcinoma of the Ovary
Survival by FIGO Stage

Stage Number 5-year Survival (%)

IA 342 86.9
IB 49 71.3
IC 352 79.2
IIA 64 66.6
IIB 92 55.1
IIC 136 57.0
IIIA 129 41.1
IIIB 137 24.9
IIIC 1,193 23.4
IV 360 11.1
Metastatic Ovarian Cancer
Ovarian Cancer- Prognostic Factors

 Tumor stage

 Tumor grade

 Cell type

 Amount of residual tumor after resection

Ovarian Cancer- Treatment options

 Surgery
 Removal of all resectable disease

 Post-operative or Adjuvant therapy

 Chemotherapy
 Radiation therapy
 immunotherapy
Surgery in Ovarian Cancer
 Standard surgical procedure:
 Total abdominal hysterectomy with bilateral
salpingo-oophorectomy
 Bilateral lymph node dissection
 Paraaortic lymph node dissection/
sampling/palpation
 Infracolic omentectomy
 Random biopsy of abdominal peritoneum in
early-stage disease
 Tumor debulking in advanced disease
 Surgery in Ovarian Cancer
 Conservative surgery: Unilateral Salpingo
Oophorectomy
 Criteria:
 Stage IA
 Well-differentiated tumor
 Peritoneal fluid cytology is negative for
malignant cells
 Omentum and peritoneal biopsies are
negative for metastasis
 Young woman desirous of pregnancy
Ovarian Cancer
 Adjuvant therapy:
 Chemotherapy
 The most common adjuvant used
 The chemotherapeutic agent used depends on the histologic
type
 Limiting factor: Toxicity
 Radiotherapy
 For early stage disease confine to the pelvis
 Immunotherapy
 Still in the experimental stage
Germ Cell Tumors of the Ovary
Germ Cell Neoplasms of the Ovary
 Dysgerminoma
 Endodermal sinus tumor
 Embryonal carcinoma
 Polyembryoma
 Choriocarcinomas
 Teratomas
 Immature (Solid, Cystic, or both)
 Mature
 Solid
 Cystic
 Mature cystic teratoma (Dermoid cyst)
 Mature cystic teratoma (dermoid cyst) with malignant transformation
 Monodermal or highly specialized
 Struma ovarii
 Carcinoid
 Struma ovarii and carcinoid
 Others
 Mixed forms (tumors composed of types in any combination)
 Germ Cell Tumors of the Ovary
 Ninety-seven percent (97%) are benign and
only 3% are malignant
 Most occur in young women
 Mostly in the 2nd and 3rd decades of life
 Staged surgically as with epithelial types
 Certain histologic types secretes a specific tumor
marker
 A single tumor may contain a mixture of
histologic types
 Germ Cell Tumors of the Ovary
 Treatment options:
 Surgery:
 Extent of primary surgery is dictated by the findings at surgery and the
reproductive desires
o USO = if preservation of fertility is desired
o THBSO = if childbearing has been completed
 Chemotherapy :
 Tremendous advances have been made that even in advanced
malignancies an excellent chance at long term control cure
 Radiotherapy:
 Rarely used today
Sex Cord Stromal Tumors
 Sex Cord-Stromal Tumors of the Ovary
 Originate from the ovarian matrix
 Consist of cell from the mebryonic sex cord and
mesenchyme
 Incidence increasing in the 5th, 6th and 7th
decades
 Approximately 90% of hormonally active ovarian
tumors
 Have propensity for indolent growth, tend to
recur late
 Sex Cord-Stromal Tumors of the Ovary
 Management:
 Surgery is adequate treatment in most cases
 USO = for those who are desirous of fertility
preservation and are Stage Ia
 THBSO = for advanced stage and older women
 Stage Ic or higher:
 Adjuvant therapy: Radiation or Chemotherapy