Neoplastic Diseases of the

Ovary

Department of Obstetrics and

Gynecology
FEU-NRMF
 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

DiSaia et al, Clinical Gynecologic Oncology, 2007

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

Scully RE: Atlas of Tumor Pathology, 1979

 Serous Tumors
Composed of ciliated epithelial cells that
resemble those of the fallopian tube
Serous cystadenomas:
o Occur primarily during reproductive years
Boderline types:
o Occur in women 30-50 years
Serous cystadenocarcinoma:
o 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
 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 locule
containing clear, viscid fluid

• Miscroscopic:
– Lining epithelium is tall, pale staining secretory
 Mucinous cystadenoma
• Pseudomyxoma peritinei
– 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
 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
 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

Note: At least 2 of these features must be present to qualify as borderline

Janovski and Paramananthon: Ovarian tumors
Stuttgart, Georg Thieme Verlag, 1973
 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
Management:

• 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:
» Pelvic lymphadenectomy
» Tumor debulking
» Extensive biopsy of any peritoneal or omental implants
» The role of chemotherapy is still controversial
Invasive Ovarian Carcinomas
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

Scully RE: Atlas of Tumor Pathology, 1979

 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
 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.
Putative Associations of Increasing and Decreasing
Risks of Ovarian Epithelial Carcinoma

Increases Decreases
Age Breast-feeding
Diet Oral contraceptives
Family history Pregnancy
Industrialized country Tubal ligation and hysterectomy with
ovarian conservation
Infertility
Nulliparity
Ovulation
Ovulatory drugs
Talc (?)
Herbst et al: Am J Obstet Gynecol, 1994
 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
 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
 Ovarian Cancer
Diagnostic techniques:
• 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
Tumor Markers in Ovarian Cancer
• CA-125

• Carcino-embryonic antigen (CEA)

• Alpha-feto protein (AFP)

• Lactic dehydyhrogenase (LDH)

 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

 Ovarian Cancer
Additional diagnostic methods:
– CT scan

– MRI

– Barium enema or Colonoscopy

 Case 1
• A 55 y/o, postmenopausal woman consulted because of rapid
abdominal enlargement associated with weight loss of 8 lbs of
2 months duration. Pertinent PE findings are: palor,
abdominal girth of 89 cm with positive fluid wave and shifting
dullness, with a vague pelvoabdominal mass. Pelvic exam:
Normal external genitalia, cervix: firm, close and slightly
movable, the lower pole of a mass is palpable at the cul-de-
sac which seems solid and slightly movable. The uterus and
adnexa can not be fully assessed because of the massive
ascites.

• What is your diagnosis? Basis of your diagnosis?

• What diagnostic work-up/s will you request and why?
 Comparison between Surgical Findings of
Benign and Malignant Ovarian
Findings Benign Neoplasm
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
 Epithelial Ovarian Cancers
• Constitute 85-90% of ovarian cancers

• Histologic distribution in USA:

Serous cystadenocarcinomas =
42%
Mucinous cystadenocarcinoma = 12%
Endometrioid carcinoma = 15%
Undifferentiated carcinoma
Copeland LJ, Clin Gyneco Oncol, = 17%
th
7 Ed, 2007
 Ovarian Cancer
• Routes of spread:
• Ceolomic spread
» Spread through the peritoneal surfaces of both the
parietal and intestinal areas, as well as the under surface
of the diaphragm.

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

• Hematogenous 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
 FIGO Staging Classification of
FIGO Stage
I
Ovarian Cancer
Growth limited to the ovaries
Description

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
 FIGO Staging Classification 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
 FIGO Staging Classification 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 Classification of
Ovarian Cancer
FIGO Stage Description
IIV 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
 Carcinoma of the Ovary
Survival by FIGO Stage
(Patients treated 1990-1992)
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
 Case 2
• A 60 y/o nulligravid underwent exploratory laparotomy
because of an ovarian mass. Intraoperative finding were: the
ovary was enlarged to 12 x 9 cm with papillary excricences on
the surface; the uterus, both tubes and contralateral ovary
was grossly normal; omentum was studded with 1 cm nodular
lesions; the abdominal peritoneum, liver and diapragm are
free of tumor.

• What is the Stage of Ovarian Cancer?

 Case 3
• A 45 y/o G1P1 underwent exploratory laparotomy because of
an ovarian mass. Intraoperative finding were: the ovary was
enlarged to 20 x 11 cm with smooth external surface, which
on cut section showed multiple papillary growths; the uterus,
both tubes and contralateral ovary was grossly normal;
omentum was grossly normal but showed metastatic cells on
microscopic examination; the abdominal peritoneum, liver
and diapragm are free of tumor. PFC was positive for
malignant cells.

• What is the Stage of 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
 Ovarian Cancer
• 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
 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
Germ Cell Tumors of the Ovary
Classification of 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
Germ Cell Tumors of the Ovary
Treatment options:
 Surgery:
 Extent of primary surgery is dictated by the findings at surgery
and the reproductive desires
 USO = if preservation of fertility is desired
 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
 Case 4
• A 19 year old nulligravid consulted because of abdominal
enlargement of 1 month duration. Pertinent PE findings:
abdomen is globularly enlarged with a solid, movable non-
tender mass about 8 x 10 cm. Rectal exam showed an
unenlarged uterus with a right adnexal mass, predominantly
solid with cystic areas, movable and nontender.

• What is your impression?

• What work-up/s is/are necessary to arrived at a proper
diagnosis?
• What is the management?
 Sex Cord-Stromal Tumors of the
• Originate from theOvary
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
Management: Ovary
• 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