Gynecology:

Neoplastic Diseases of the Ovary

Lecturer: Rommel Dueñas, MD

Transcriber: Patrick Angelo R. Bautista February 2020

References and Legends

• {💻} Powerpoint and {📕} Gynecology Manual {📋} Arya Stark Trans
• {📖} Chapter 33, Comprehensive Gynecology 7th Ed.

Table of Contents
I. Adnexal Mass / Ovarian Tumor 1
II. Ovarian Carcinoma 1
III. Epithelial Ovarian Neoplasm 7
IV. Borderline Ovarian Tumor 8
V. Germ Cell Tumors of the Ovary 8
VI. Sex Cord-Stromal Tumors of the Ovary 9
VII. Primary Peritoneal and Fallopian Tube Cancer 10

I. ADNEXAL MASS / OVARIAN TUMOR

• Usually presents as a hypogastric mass.
• It is common in 50’s and 60’s year-old women
o but can also occur in younger women.
• If you have a young patient with enlarging abdomen:
o One of the differential diagnoses is pregnancy.
o Uterus may be the cause of the enlargement
§ specifically, due to myomas.
o Another differential diagnosis is ovarian new growth.

Differential Diagnoses 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
Hydrosalpinx Ectopic pregnancy
Parovarian cyst Neoplasm
Uterus Intrauterine pregnancy Pedunculated or II. OVARIAN CARCINOMA
in bicornuate uterus intraligamentous
Epidemiology {📕}
myoma
• The incidence starts to rise steeply at 40 years old and continues
Bowel Sigmoid or cecum Diverticulitis
distended with gas or Ileitis
with age. In 2012, one (0.6) out of 100 women would have a
feces Appendicitis likelihood of getting ovarian cancer before age 75. The estimated
Colonic cancer national standardized mortality rate was 3.9 per 100,000.
Miscellaneous Distended bladder Abdominal wall • In 2015, cancer of the ovary will be the 10th leading site for both
Pelvic kidney hematoma/abscess sexes combined (2%), and the 5th among women (4%) in the
Urachal cyst Retroperitoneal Philippines. There will be 2,657 new cases. In 2015, there will be
neoplasm 1,610 deaths.
• In a patient who presents with a hypogastric or adnexal mass, the
etiology may arise from the gastro-intestinal tract (GIT) or Type <20 yr 20-50 yr >50 yr
genito-urinary tract (GUT). (%) (%) (%)
o Even retention of the urine may present as a mass (urinoma). Coelomic epithelium 29 71 81
Germ cell 59 14 6
Diagnostic Evaluation in the Presence of an Adnexal Mass {💻} Specialized gonadal-stromal 8 5 4
• Complete physical examination Non-specific mesenchyme 4 10 9
• Ultrasonography In general, more than half of ovarian Ca occur in women >50.
• Colonoscopy or Barium enema, if symptomatic The risk of malignancy in a primary ovarian tumor increases to ∼33% in
• Intravenous pyelography, if indicated women >45, whereas it is <1 in 15 for women 20-45 years of age.
• CT Scan or MRI
• Laparoscopy, Laparotomy

Ovarian Tumor: Symptoms {💻}

• Initially are asymptomatic • Abdominal enlargement
• Lower abdominal discomfort • Frequent urination
• Pelvic pain • Constipation
• Dyspareunia

Ovarian Tumor: 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

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Ovarian Ca: Risk Factor
Genetic {💻+📕}
• A strong family history of either breast or ovarian Ca is the most
important risk factor for the development of epithelial ovarian Ca.
• The germline mutations of the BRCA tumor suppressor gene on
chromosome 17q are responsible for a large proportion of
hereditary cancers.
• Approximately 10 to 15% of all epithelial cancers have a
hereditary predisposition.
• Breast-ovarian cancer family syndrome
o The lifetime risk of ovarian cancer:
§ one 1st degree = 1.5-5%
§ 2 or more = 7-12%
§ In women with BRCA1 germline mutation = 40%.
§ In women with BRCA2 germline mutation = 10-20%
• Site-specific ovarian cancer
o linked to BRCA 1 mutation
o there is excess of ovarian CA but not breast CA
• Hereditary Non-Polyposis Colon Cancer / Lynch Syndrome II
o This accounts for only approx. 1% of all ovarian cancers.
o The cumulative incidence is 12%.
Reproductive Factors
• Parity and Pregnancy
o Increasing parity ≥5 reduces the risk.
• Age at menarche and menopause
o Ages at menarche and menopause are weak predictors on
risk of epithelial ovarian cancer.
• Lactation
o confers protection against ovarian cancer risk most significant
with duration of 18 months or more.
Exogenous Hormones
• Use of fertility drugs
o its use does not increase the risk for ovarian cancer.
§ An increased risk was seen only in association with
borderline serous tumors.
• Use of OCP
o Use of oral contraceptives confers long-term protection
against ovarian cancer.
• Use of HRT
o Long-term use of unopposed estrogen and of estrogen plus
progestin (sequential) are associated with increased ovarian
cancer risk.
Gynecologic Related Conditions and Surgery
• Endometriosis
o linked to an increased risk of epithelial ovarian cancer
particularly the endometrioid and clear cell types.
• Pelvic Inflammatory Disease
o PID is positively associated with epithelial ovarian cancer
• Polycystic Ovarian Disease
o The relationship between PCOS and epithelial ovarian cancer
is less extensively evaluated but points to an increased risk.
• Tubal Ligation and Hysterectomy
o Tubal ligation confers a reduction in the risk for ovarian Ca.
o Hysterectomy confers risk reduction to a less degree.
Environmental and Lifestyle Risk Factors
• Obesity
o Adult obesity and obesity in early adulthood confer an
increased risk of ovarian cancer.
• Cigarette smoking
o Current cigarette smoking increases the risk for the
development of mucinous epithelial ovarian cancer but not the
other histologic types.
o Stopping smoking returns the risk to normal in the long term.
• Alcohol consumption
o There is no association between moderate alcohol intake
and ovarian cancer risk.
• Dietary factors
o Diet characterized by high meat and fat intake may increase
the risk of epithelial ovarian cancer
• Physical Activity
o Recreational physical activity confers at best a weak to
modest protection against epithelial ovarian cancer.
• Caffeine and Tea intake
o The association between caffeine intake and ovarian cancer
risk is not very well-established.
o The consumption of tea may reduce the risk of epithelial
ovarian cancer.
• Talc and Others
o There is no causal relationship between perineal talc use
and ovarian cancer.
Ovarian Ca: Etiology and Theories {💻+📕}
Theory of Incessant Ovulation
• Repeated damage and trauma to the ovarian epithelium during
each ovulatory cycle increases the potential for genetic mutation
and ovarian neoplasm during the repair process. The risk of EOC
is related directly to the number of uninterrupted ovulatory cycles.
o Nulligravid – always ovulating, increased risk
o Pregnancy – no ovulation for 9 months, decreased risk
o Use of OCPs – inhibits ovulation, decreased risk
o Fertility drugs (Clomiphene) – increased risk
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
• Early menarche, late menopause
• Tubal ligation, hysterectomy
Pituitary-Gonadotropin Hypothesis
• High levels of gonadotropins increase the stimulation of estrogen
which can cause ovarian epithelial cells to become entrapped in
inclusion cysts and undergo malignant change.
• exposure of ovarian epithelium to persistently high levels of
pituitary gonadotropins
• FSH promote the growth of epithelial ovarian cancer cells in vitro
Increase gonadotropin levels
⬇
Promotes estrogen biosynthesis in the ovarian stroma
⬇
Causes abnormal proliferation of the adjacent
epithelium
• Breastfeeding, pregnancy, OCPs
• Fertility pills
Androgen / Progesterone Hypothesis
• Androgens may stimulate ovarian cancer formation
• Progestins are protective against ovarian cancer
Inflammation Hypothesis
• Factors that predispose to inflammation may stimulate ovarian
cancer formation
o PID, Endometriosis – increases risk
o Use of NSAIDs – protective
Ovarian Stromal Hypothesis
• There may be a failure of apoptosis of granulosa and theca cells
after ovulation. These cells continue to produce steroid hormones,
thereby stimulating the formation of cancer.
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Ovarian Ca: Presentation {💻} Manual Notes on Diagnosis and Diagnostics: {📕}
Among patients presented with hypogastric mass, associated
Characteristics in Benign and Malignant Ovarian Tumors symptoms like pain should be evaluated.
Clinical Finding Benign Malignant • it includes location, quality, time of onset.
Unilateral +++ + • This pain is secondary to distension of the ovarian capsule or
Bilateral + +++ compression of other adjacent structures.
Cystic +++ + • If it is related to nausea and vomiting, it may imply torsion.
Solid Other symptoms include menstrual disturbance.
+ +++
• Presence of severe dysmenorrhea or menorrhagia,
Mobile +++ ++ hyperandrogenism and findings of polycyclic ovaries is
Fixed + +++ suggestive of PCOS.
Irregular + +++ • In the presence of solid ovarian mass in premenarcheal or
Smooth +++ + postmenopausal patient ↑ the likelihood of granulosa cell tumor.
Ascites + +++ Other symptoms include dyspepsia, early satiety, abdominal
Cul-de-sac nodulations - +++ bloatedness or fullness, changes in bowel or caliber of stool
The presence of effusion, ascites, or lymphadenopathy (cervical,
supraclavicular, groin) should be noted.
Most Frequent Presenting Symptoms of Ovarian Cancer Among these patients with ovarian mass, pelvic and rectovaginal
Symptom Relative Frequency examination is mandatory.
Abdominal swelling xxxx
Abdominal pain xxx Preoperative Assessment: Clinical Findings {📋}
Dyspepsia xx • Describe the appearance and onset of the hypogastric mass
Urinary frequency xx o if the mass is present for a year, without any growth – think of
Weight change x a benign course (slow growth pattern)
Note: Symptoms are vague and not specific for ovarian cancer o If the mass is fast growing, with associated constitutional
A high index of suspicion is warranted in all women between the ages symptoms (weight loss, easy fatigability 2° to anemia, think of
of 40-69 years who have persistent gastrointestinal symptoms that a malignant course (rapid growth pattern)
cannot be diagnosed. o Pressure symptoms related to GIT and GUT – may present
with urinary frequency and dribbling, and/or constipation
Non-ovarian Causes of Apparent Adnexal Mass
• Diverticulitis Tumor Markers in Ovarian Cancer
• Tubo-ovarian abscess • Carcinoma Antigen 125 (CA-125)
• Carcinoma of the colon or sigmoid • Human Epididymis protein 4 (HE4)
• Pelvic kidney • Carcino-embryonic antigen (CEA)
• Uterine or intraligamentous myoma • Alpha-feto protein (AFP)
• Lactic dehydrogenase (LDH)
Ovarian Ca: Screening {💻+📕} • Human chorionic gonadotrophin (hCG)
• Screening and Early Detection Tools
o Periodic pelvic Examination Manual Notes on Screening: {📕}
o Sonography Tumor markers such as LDH, AFP, and serum βhCG are
o Biomarkers (e.g. CA-125)
recommended among patients <40 years old
Conclusion: There is NO evidence available yet that the current Non-mucinous CA-125, HE4
screening modalities can be used effectively for widespread
Mucinous CA 19-9, CEA, CA-125
screening for ovarian cancer.
Immature Teratoma AFP, LDH, CA-125
Manual Notes on Screening: {📕} Epithelial Stromal Tumor AFP
NO sufficient evidence to recommend Multimodality Screening Embryonal Carcinoma hCG, AFP
(MMS) using CA-125 and transvaginal ultrasound as part of ovarian Dysgerminoma hCG, LDH
Ca screening for the average risk woman age 50-74 and Choriocarcinoma hCG
postmenopausal. Granulosa Cell Tumor Inhibin, AMH
In general population, Salpingectomy for sterilization and as part
of hysterectomy should be done. CA-125 and Ovarian Cancer
In high-risk women (BRCA carriers), risk reducing Salpingo- • expressed in approximately 80% of ovarian epithelial cancers but
oophorectomy (RRSO) should be done. less frequently by mucinous types
• The recommended age for RRSO is 35-40 years for BRCA1 • increased in tubal, endometrial, lung, breast and pancreatic Ca
carriers and 40-45 for BRCA2 carriers. • increased in benign conditions
Genetic Counselling: All women with EOC, FT, PPC, should • specificity appears better for ↑ values in postmenopausal patients
undergo genetic counselling. Genetic Testing (BRCA1, BRCA2)
should be offered even in the absence of family history.

Ovarian Ca: Diagnosis and Diagnostics {💻+📕}

Diagnostic Evaluation of Adnexal Mass
• Complete physical examination
• Appropriate imaging studies, tumor markers
o Chest X-ray o CA-125, HE4
o Ultrasonography o CEA
o CT Scan o AFP, βhCG
o MRI o LDH
• Colonoscopy or barium enema study, if symptomatic

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Diagnostic Techniques {💻} Risk of Malignancy (RMI) {📕+📋}

• Routine pelvic examination detects only 1 ovarian cancer in • result of ≥200 increases the likelihood of ovarian malignancy
10,000 asymptomatic women. • Includes: (multiply these 3 to get the RMI score)
• Routine laboratory tests are not of great value in the diagnosis of a. menopausal status
ovarian tumors. b. serum CA-125
• Major value of laboratory tests – rule out other pelvic disorders c. ultrasound findings
• Surgical exploration is the ultimate test as to the nature of the • Ultrasound Findings (U):
disorder. o multilocularity
o solid areas
Ultrasound (Transvaginal / Transrectal) {💻} o bilateral lesions
• Ultrasound helped to define criteria to allow conservative follow- o ascites
up and the risk of malignancy of some adnexal masses o extraovarian tumor
• Scoring systems have been proposed Score Parameter
• Parameters used: 0 If none are present
o Unilocular or complex cysts 1 If one is present
o Papillary projections 3 If two or more are present
o Regular and smooth septa and/or cystic walls • Menopausal status (M):
o Echogenicity o >1 year of amenorrhea
o Doppler color-enhanced flow o >50 who has undergone total hysterectomy
• Used to characterize ovarian mass as benign or malignant, rather Score Parameter
than for screening. 1 If none are present
• Ultrasound Findings Suggestive of Malignancy: 3 If one or both are present
o Irregular borders
• Serum CA-125: use the absolute value
o Papillations
o Thick septations
SAMPLE PROBLEM: a 55-year-old female consults at the OPD due to a
o Ascites
hypogastric mass. Her TVS result reveals solid hyperechoic areas on
o Matted bowel both ovaries. Serum CA-125 is 43 units/mL. What is the RMI? Interpret.
RMI = U x M x CA-125
U (3) x M (3) x 43 = 387 (>200)
Patient’s mass is most likely malignant

Risk of Malignancy Algorithm (ROMA) {📕+📋}

• predicts the risk of ovarian malignancy using:
a. menopausal status
b. serum CA-125
c. serum HE4

Manual Notes on Ultrasound: {📕} Risk Low High

Ultrasound Prediction Model in Epithelial Ovarian Ca (EOC) Premenopausal <7.4% >7.4%
• B Rule (Benign tumor) Postmenopausal <25.3% >25.3%
o presence of solid components, where the largest solid
component is <7 mm in largest diameter OVA1 {📋}
o Presence of acoustic shadowing • first blood test to evaluate the likelihood that a woman’s ovarian
o Smooth multilocular tumor mass is benign or malignant
o No blood flow • improved sensitivity of ovarian cancer from 72 to 92%
• M Rule (Malignant tumor) • not for surveillance or diagnosis but this may complement clinical
o Irregular solid tumor decision making.
o Presence of ascites
o At least 4 papillary structures
CASE 1: A 55 y/o, postmenopausal woman consulted because of
o Irregular multilocular solid tumor
rapid abdominal enlargement associated with weight loss of 8 lbs of 2
o Largest diameter of at least 100 mm months duration. Pertinent PE findings are: pallor, abdominal girth of
o Very strong blood flow 89 cm with positive fluid wave and shifting dullness, with a vague
pelvoabdominal mass.
Additional Diagnostic Methods: {💻} Pelvic exam:
• CT Scan • Normal external genitalia
• MRI • Cervix: firm, close and slightly movable, the lower pole of a mass is
• Barium enema or Colonoscopy palpable at the cul-de-sac which seems solid and slightly
movable.
• The uterus and adnexa cannot be fully assessed because of the
Manual Notes on ADNEX: {📕} massive ascites.
Assessment of Different Neoplasia in Adnexa (ADNEX)
• includes 3 clinical predictors and 6 ultrasound predictors What is the diagnosis? Ovarian New Growth, probably malignant
• Clinical Predictors: Basis of diagnosis?
o Age • Rapid enlargement of the mass
o Serum CA-125 • Weight loss
o Type of oncology centre • Massive ascites
• Ultrasound Predictors: • Solid mass with limited mobility
Diagnostic work-up?
o Diameter of lesion
• Ultrasonography: Transvaginal and Transabdominal
o Proportion of solid tissues
o Differentiate solid from cystic, detect omental and liver mets
o >10 cyst locules o Differentiate between ascites and intracystic fluid
o Number of papillary projections • Hematologic exams: CBC and Platelet count, Blood chemistries
o Acoustic shadows • MRI / CT Scan: Detect other organ / LN involvement
o Ascites

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Ovarian Ca: Staging {💻+📕} • Conservative Surgery: Unilateral Salpingooophorectomy

• Staging is surgical and based on operative findings at the o Criteria:
commencement of the procedure. § Stage IA
§ Well-differentiated tumor
General Guidelines {📋} § Peritoneal fluid cytology is negative for malignant cells
• There should be histologic confirmation of the disease. § Omentum and peritoneal biopsies are negative for
metastasis
o Primary site: should be indicated; if it cannot be delineated,
§ Young woman desirous of pregnancy
the case should be listed as “undesignated”
o Histologic type and grade: should also be indicated
• Other major recommendations:
• Pleural effusion should be aspirated for cytology.
o Histologic type and grading should be designated at staging
o Primary site (ovary, Fallopian tube or peritoneum) should be
Guidelines for Complete Surgical Staging {📋+💻}
designated where possible
TAHBSO, PFC, BLND, PALS, IO, RPB
o Tumors that may otherwise qualify for stage I but involved
• Systemic abdominal exploration via midline incision
with dense adhesions justify upgrading to stage II if tumor
o Midline longitudinal incision
cells are histologically proven to be present in the adhesions
• Sampling of washings of 4 areas of peritoneal cavity
o Peritoneal Fluid Cytology (PFC)
Review: Ovarian Tumor: Indications for Surgery {💻}
• Inspection and palpation of all peritoneal surfaces
• Ovarian cystic structure >5 cm that has been observed 6-8 weeks
o Systematic exploration of the abdominal cavity
without regression
• Biopsy and resection of suspicious lesions, masses, adhesions
• Any solid ovarian lesions
• Removal of primary ovarian/fallopian tube tumor with intact
• Any ovarian lesion with papillary vegetation on the cyst wall
capsule (intracystic drainage/ rupture) • Any adnexal mass >10 cm
o decompression of cyst of an apparent clinical stage IA/IB
• Palpable adnexal mass in premenarchal or postmenopausal
disease will upstage the cancer to stage IC1 (surgical spillage)
• Torsion or rupture suspected
• Total Abdominal Hysterectomy + Bilateral Salpingooophorectomy
• Unilateral Salpingooophorectomy with frozen section and Ovarian Carcinogenesis {📋}
complete surgical staging
Type I Benign Type II Malignant
o for young patients with Stage IA-IC, good histologic type,
Genetic Instability Lack of p53 mutation With p53 mutation
grade 1 or 2 disease, wanting to retain their fertility Genetically stable ↑ proliferation index
• Infracolic Omentectomy (IO) (MIB)
o for gross omental involvement → infragastric omentectomy Possible Borderline tumors Serous Tubal
• Random biopsy of abdominal peritoneum & suspicious areas / precursors Endometriosis Intraepithelial
Random Peritoneal Biopsy (RPB) Cancer (STIC)
o 2 samples from each of the following: under-surface of the left Epithelial tumors Low-grade, Serous, High grade,
hemi-diaphragm, bladder reflection, cul-de-sac, right and left Mucinous, Clear cell, Serous,
paracolic recesses, pelvic side walls Endometrioid, Brenner Endometrioid
• Systematic lymphadenectomy / LN evaluation (Pelvic, Paraaortic) Prognosis Slow growing, Present at late
o Bilateral Lymph Node Dissection (BLND) indolent course, good stage, Aggressive
o Paraaortic Lymph Node Sampling (PALS) STIC – the premalignant lesion of ovarian cancer, just like in cervical
cancer → CIN; uterine cancer → hyperplasia.
• For mucinous tumors, or other types of tumors with the
For type II, STIC is the reason why malignancies may arise from the
appendix grossly involved with tumor, do appendectomy. fallopian tube. This is a new theory, which implicates the fallopian tube,
• There are still no good quality evidence to support the use of especially the fimbrial end, as the source, or possible precursor of a high
laparoscopy for the surgical management of early stage ovarian Ca. grade serous tumor.
• Tumor Debulking
o There should be zero residual for debulking.

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Ovarian Ca: Route / Pattern of Spread {💻+📖} CASE 2: A 60 y/o nulligravid underwent exploratory laparotomy
• Coelomic spread because of an ovarian mass.
o Spread through the peritoneal surfaces of both the parietal Intraoperative findings were:
and intestinal areas, and the under surface of the diaphragm. • ovary was enlarged to 12 x 9 cm with papillary excrescences on
o Ovarian carcinomas infiltrate the peritoneal surfaces of the the surface.
parietal and intestinal areas, as well as the undersurface of the • uterus, both tubes and contralateral ovary was grossly normal.
diaphragm, particularly on the right side. • omentum was studded with 1 cm nodular lesions.
o This is important because tumors that appear at operation to be
• abdominal peritoneum, liver and diaphragm are free of tumor.
confined to the ovary may have small areas of diaphragmatic What is the Stage? Stage IIIB
involvement as the sole site of extraovarian spread.
o Most ovarian carcinomas, particularly the serous type, appear to CASE 3: A 45 y/o G1P1 underwent exploratory laparotomy because
of an ovarian mass.
arise from microscopic ovarian sites and do not become clinically
Intraoperative findings were:
evident until there is widespread metastatic disease.
• ovary was enlarged to 20 x 11 cm with smooth external surface,
• Lymphatic route which on cut section showed multiple papillary growths.
o Para-aortic nodes are at risk through lymphatics that run • uterus, both tubes and contralateral ovary was grossly normal.
parallel to the ovarian vessels. • omentum was grossly normal but showed metastatic cells on
• Hematogenous spread microscopic examination.
• abdominal peritoneum, liver and diaphragm are free of tumor.
• PFC was positive for malignant cells.
What is the Stage? Stage IIIA

Ovarian Ca: Prognosis {💻+📕}

• Prognostic Factors:
o Tumor stage
o Tumor grade
o Cell type
o Amount of residual tumor after resection

Ovarian Ca: Treatment {💻+📕}

Treatment Options:
• Surgery
o Removal of all resectable disease
o Interval debulking surgery
• Post-operative or Adjuvant Therapy
o Chemotherapy
§ Depends on the stage, tumor grade and histologic type
§ Epithelial: Carboplatin and Paclitaxel (or Docetaxel)
2
• Paclitaxel 175 mg/m , Carboplatin AUC 5-6
2
• Docetaxel 75 mg/m , Carboplatin AUC 5-6 / AUC7
2 2
• Cisplatin 75 mg/m , Cyclophosphamide 750 mg/m
§ GCT and SCT:
• Bleomycin, Etoposide, Cisplatin (BEP) regimen
• Vincristine, Actinomycin D, Cisplatin (VAC) regimen
• PVB regimen
• CAP regimen
o Radiation therapy
o Immunotherapy

Adjuvant Therapy is not indicated in:

• All cases of low malignant potential
• EOC of Stage IA- IB, grade 1-2
• GCT of Stage I, grade 1 (pure dysgerminoma or immature
• teratoma)
• SCST of Stage IA

Ovarian Ca: Follow-up {💻+📕}

After completion of treatment:
• Every 3 months (4 visits) → Every 4 months (3 visits) → every 6
months (2 visits) → annually thereafter
• Appropriate tumor marker every visit
• Transvaginal ultrasound with or without Doppler every 4-6 months
• Chest X-ray if indicated
• CT Scan, MRI, PET annual (first 3 years)

Ovarian Ca: Complications {💻+📕}

• Malignant Effusion
• Malignant Bowel Obstruction

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III. EPITHELIAL OVARIAN NEOPLASM {💻+📖} • Most endometrioid carcinomas arise directly from the surface
epithelium of the ovary, as do the other epithelial tumors.
• Arise from inclusion cysts lined with surface (coelomic) epithelium • Grossly:
within the adjacent ovarian stroma o Smooth outer surface
• Classified as: o On cut section, they are solid and cystic, with the cysts
o Benign (adenoma) containing friable smooth masses and bloody fluid
o Malignant (adenocarcinoma) • Microscopic:
o Intermediate (Borderline malignant / Low malignant potential) o Well-differentiated endometrioid adenocarcinoma accounts
• common among postmenopausal women, but can also occur in for the majority of cases.
women of the reproductive age group. o Characterized by a confluent or cribriform proliferation of
glands lined by tall stratified columnar epithelium with sharp
1. Serous Tumors luminal margins.
• Low-grade (formerly well-differentiated) serous tumors consist of o Mitotic figures are commonly seen
ciliated epithelial cells that resemble those of the fallopian tube. o Squamous differentiation is present in up to 50% of cases
• Serous tumors are the most frequent ovarian epithelial tumors.
• The malignant forms account for ≥40%of ovarian cancers. 4. Clear Cell Carcinomas (Mesonephromas)
• Composed of ciliated epithelial cells that resemble those of the
• Most clear cell neoplasms of the ovaries are carcinomas
fallopian tube
• Contain cells with abundant glycogen and so-called hobnail cells
o Serous cystadenomas: Occur during reproductive years
in which the nuclei of the cells protrude into the glandular lumen.
o Borderline types: Occur in women 30-50 years
• Tumors with identical histologic features are found in the
o Serous cystadenocarcinoma: Occur in women >40 years endometrium, cervix, and vagina, the latter two often associated with
intrauterine diethylstilbestrol (DES) exposure.
Serous Cystadenoma • Molecular evaluation of these tumors suggests a homology to similar
• Grossly: pathology occurring in the kidney, which may have therapeutic
o Papillary projections on the surface implications.
o Inner cyst walls are mostly smooth • Clear cell ovarian tumors are not related to DES exposure and
• Microscopic: comprise approximately 5% of ovarian cancers.
o Low columnar epithelium with occasional cilia • Occur primarily in women 40-70 years of age and highly aggressive.
o Psammoma bodies: Characteristic • Most common epithelial ovarian neoplasm to be associated with
§ small granules, end product of degeneration of papillary paraneoplastic hypercalcemia.
implants • Relationship with endometriosis is strongest among all types of
§ indicative of functional immunologic response ovarian carcinoma.
• Endometriotic implants are commonly present in close proximity
2. Mucinous Tumors to the tumor or elsewhere in the pelvis or abdomen.
• Grossly:
• Consist of epithelial cells filled with mucin, resembling cells of the
o Tumors range up to 30 cm diameter with a mean of 15 cm.
endocervix or may mimic intestinal cells.
o Cut surfaces reveal a thick-walled unilocular cyst with multiple
o Mucinous cystadenomas: Occur during reproductive years
yellow-beige fleshy nodules protruding into the lumen.
o Borderline types
o Multiloculated cystic mass with cysts containing watery or
o Mucinous cystadenocarcinoma: Usually in 30-60 years mucinous fluid.
• Accounts for ∼25% of ovarian tumors and ∼10% of ovarian cancers
• Microscopic:
o Solid pattern is characterized by sheets of polyhedral cells
Serous Cystadenoma with abundant clear cytoplasm separated by delicate
• may become huge (>300 lbs) fibrovascular septae or dense hyalinized fibrotic stroma.
• Grossly: o In tubulopapillary pattern, cells are often columnar with a
o Round or ovoid, smooth capsule usually translucent or bluish hobnail appearance, with the nucleus protruding from the
to whitish gray papillae, gland, or cyst into the lumen.
o Interior divided by discreet septa into locule containing clear,
viscid fluid 5. Brenner Tumors
• Microscopic:
o Lining epithelium is tall, pale staining secretory type with • Arise from Walthard cell nests
nuclei at basal pole, rich in mucin • consists of cells that resemble the transitional epithelium of the
• Pseudomyxoma peritonei bladder and Walthard nests of the ovary.
o Transformation of peritoneal mesothelium to a mucin • Grossly:
secreting epithelium o Grossly identical to a Fibroma of the ovary
o Continuous secretion of mucus resulting in accumulation in • Microscopic:
peritoneal cavity of gelatinous material o Marked hyperplastic fibromatous matrix interspersed with
o Evacuation at operation is followed by reaccumulation nest of epithelioid cells
• Treatment o Epithelioid cells show “coffee bean” pattern caused by
o Repetitive surgical evacuation longitudinal grooving of nuclei
o Long-term nutritional support • Nearly all are benign but there are scattered reports of malignant
Brenner; associated endometrial hyperplasia
3. Endometrioid Adenocarcinoma • Treatment: simple excision

• Most endometrioid ovarian neoplasms are carcinomas.

• Consists of cells resembling those of the endometrium.
• Most arise from the surface epithelium of the ovary.
• less frequent (∼5%) than serous or mucinous, but the malignant
variety accounts for ∼20% of ovarian carcinomas
• Endometrioid Carcinomas usually occur in women in their 40s or 50s
• They may be seen in conjunction with endometriosis and ovarian
endometriomas.

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IV. BORDERLINE OVARIAN TUMOR {💻}
• aka Atypical Proliferative Tumor of the Ovary (APT) or
Ovarian Tumor of Low Malignant Potential (LMP)
• 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
• Most common varieties:
o Serous
o Mucinous
• Commonly found in younger women
• Longer survival than invasive forms:
o 5-year survival rate of all stages = 97%
o 10-year survival rate of all stages = 89%
Leake and colleagues, Gynecologic Oncology, 1992
BOT: 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 BOT
BOT: Management
• Complete surgical extirpation of the tumor
• Unilateral involvement:
o Salpingo-oophorectomy is preferred over Cystectomy
o Thorough evaluation of the other ovary
o Peritoneal fluid cytology
o Partial omentectomy
• Bilateral involvement:
o Total abdominal hysterectomy with BSO
o Peritoneal fluid cytology
o Partial omentectomy
• Criteria for Conservative Therapy:
o Confirmed to be Stage IA
o Extensive histologic sampling of the tumor confirms it to be
borderline tumor
o Contralateral ovary appears normal
o Biopsy specimens of areas of omental or peritoneal nodularity
are negative
o Results of peritoneal cytologic tests are (-) for tumor cells
• Advanced Stage:
o Complete surgical extirpation of the tumor
o Same as bilateral involvement plus:
§ Pelvic lymphadenectomy
§ Tumor debulking
§ Extensive biopsy of any peritoneal or omental implants
§ The role of chemotherapy is still controversial
V. GERM CELL TUMORS OF THE OVARY
• These tumors are derived from the germ cells of the ovary.
• As a group, they are the 2nd most frequent type of ovarian neoplasms
and account for ∼20%-25% of all ovarian tumors.
Old trans Notes: {📋}
• Common in the reproductive age group
• Histologically, they may be composed of extraembryonic elements
or may have features that resemble any or all of the three
embryonic layers (ectoderm, mesoderm, or endoderm).
• Germ cell tumors are the main cause of ovarian malignancy in
young women, particularly those in their teens and early 20s.
• 97% are benign and only 3% are malignant
PPT Notes: {💻}
• Most occur in young women
• Mostly in the 2nd and 3rd decades of life
• Staged surgically as with epithelial types
• Certain histologic types secrete a specific tumor marker
• A single tumor may contain a mixture of histologic types
• Benign: Mature Cystic Teratoma (Dermoid Cyst)
• Malignant:
o Dysgerminoma
o Endodermal Sinus Tumor (Yolk Sac Tumor)
o Immature Teratoma
o Embryonal Carcinoma
o Choriocarcinoma
• Treatment Options:
o 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
o Chemotherapy: Tremendous advances have been made that
even in advanced malignancies an excellent chance at long
term control cure
o 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 non-tender.
What is your impression? Ovarian New growth probably malignant,
probably Germ Cell Tumor
What work-up/s is/are necessary to arrive at a proper diagnosis?
• Ultrasonogram
• Tumor markers: AFP, hCG, LDH
• Blood exams
What is the management?
• Exploratory laparotomy, USO with Frozen section of the ovary
• If malignant: lymphadenectomy, PFC, Infracolic omentectomy,
random biopsy of peritoneum, adhesions and suspicious areas for
metastasis
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1. Benign {📋+📖}
1.1 Benign Cystic Teratoma (Dermoids)
• BCTs are the most common germ cell tumors and account for
25% of all ovarian neoplasms.
• They primarily occur during the reproductive years but may occur
in postmenopausal women and in children.
• Ability to produce adult tissue:
o skin, bone, teeth, hair, dermal tissue.
• commonly floats, and causes torsion of the ovary.
• Dermoids are usually unilateral, but 10% to 15% are bilateral.
o The outside wall of the tumor tends to be smooth, with a
yellowish appearance caused by the sebaceous fatty material
that fills the tumor.
o Hair is also a prominent feature once the cyst is opened
1.2 Struma Ovarii
• dermoids with thyroid tissue exclusively or with thyroid tissue as
a major component.
• Thyroid tissue can be functional → clinical hyperthyroidism
1.3 Carcinoid Tumor
• ovarian teratomas that histologically resemble similar tumors in
the gastrointestinal tract.
• Commonly seen in patients with Turner Syndrome, or gonadal
dysgenesis.
2. Malignant {📋+📖}
2.1 Dysgerminoma
• Most common malignant germ cell tumor
• Analogous to the male seminoma
• Appearance of the mass is bosselated / lobulated
• This secretes serum β-hCG
• They consist of primitive germ cells with stroma infiltrated by
lymphocytes.
• They are analogous to seminoma in the male testis and comprise
approximately 1% of ovarian malignancies.
• Occur primarily in women younger than 30 years.
• Some arise in dysgenetic gonads.
• Approximately 15% of dysgerminomas produce hCG related to
areas of syncytiotrophoblast tissue.
2.2 Endodermal Sinus Tumor / Yolk Sac Tumor / Tedum Tumor
• 2nd most common germ cell tumor
• Characteristic: Schiller-Duval Bodies
• The endodermal sinus tumor, or yolk sac tumor, which comprises
10% of malignant germ cell tumors, in part resembles the yolk sac
of the rodent placenta, thus recapitulating extraembryonic tissues.
• The tumor secretes a-fetoprotein, which is a specific marker
useful for identifying and following these tumors clinically.
• These rapidly growing tumors occur in females between 13
months and 45 years of age. A median age of 19 years at
diagnosis was noted by Kurman and Norris.
• The yolk sac tumor is the prototype for a-fetoprotein production.
2.3 Immature Teratoma
• 3rd most common germ cell tumor
• Characteristic: Neuroepithelium
• Immature teratomas are malignant and account for as many
• as 20% of the malignant ovarian tumors found in women younger
than 20 years, but less than 1% of all ovarian cancers.
• They rarely occur in women after menopause.
• They consist of immature embryonic structures that can be
admixed with mature elements.
• ∼1/3 of immature teratomas express serum a- fetoprotein.
2.4 Embryonal Carcinoma
• Commonly observed in sexual precocity
• This secretes serum β-hCG and α-feto protein
• An embryonal carcinoma is a rare malignant germ cell tumor
• composed of primitive embryonal cells.
• It occurs in young females between the age of 4-28 years.
• Trophoblastic elements may be present; both hCG and AFP have
also been reported to be present.
2.5 Choriocarcinoma
• Gives a false-positive pregnancy test
• This secretes serum β-hCG
• Non-gestational choriocarcinoma is a highly malignant rare
germ cell tumor resembling extraembryonic tissues.
o Like gestational choriocarcinoma, it consists of malignant
cytotrophoblasts and syncytiotrophoblast;
• hCG is a useful tumor marker.
• This tumor mostly develops in women younger than 20 years,
primarily in the ovary.
• usually fatal and did not appear to respond to single-agent
chemotherapy (Methotrexate, Actinomycin D) with the same
frequency as gestational trophoblastic disease.
VI. SEX CORD-STROMAL TUMORS OF THE OVARY
• Originate from the ovarian matrix
• Consist of cell from the embryonic 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 are derived from the sex cords of the
ovary and the specialized stroma of the developing gonad.
• The elements can have a male or female differentiation and some
of these tumors are hormonally active.
• This group accounts for approximately 6% of ovarian neoplasms and
most hormonally functioning ovarian tumors.
o For the female derivatives: the sex cord component is the
granulosa cell and the stromal component is the theca cell or
fibroblast.
o For the male counterpart: the similar components are the
Sertoli cell and Leydig cell.
• Management:
o 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
o Stage Ic or higher:
§ Adjuvant therapy: Radiation or Chemotherapy
1. Benign {📋+📖}
1.1Fibroma
• Common benign solid ovarian mass
• Meigs’ Syndrome Triad: pleural effusion, ascites, fibroma
• The most common benign solid ovarian tumor and accounts for
4% of all ovarian tumors.
• Can occur at any age but more common in older women.
• It does not secrete hormones.
• These tumors contain spindle cells and the tumors can grow
• to a large size.
• They are benign, and excision is adequate treatment.
• They are associated with ascites in approximately 40% of cases if
the tumor is >10 cm.
• They can also be responsible for hydrothorax with a benign
ascites Meigs’ syndrome); regresses following tumor removal.
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1.2 Thecoma Clinical Findings

• benign tumor that consists entirely of stroma (theca) cells.
• Predominantly occurs in women in their perimenopausal and
menopausal years.
• These tumors can be associated with estrogen production but not
as frequently as granulosa cell tumors.
• Management:
o Reproductive years: removal of tumor alone
o Older women: TAHBSO
• Rarely, thecomas have been reported to be malignant, and these
are most likely fibrosarcomas.
2. Malignant {📋+📖}
2.1 Granulosa-Theca Cell Tumor
• Characteristic: Cal-Exner Bodies
o Rosette formation of the Granulosa cells.
• This secretes inhibin and anti-Mullerian hormone
• GTC consist primarily of granulosa cells and a varying proportion
of theca cells, fibroblasts, or both.
• Functional GTC are primarily estrogenic.
• In postmenopausal women:
o these tumors can produce increased levels of blood
estrogens, uterine bleeding, occasionally endometrial Ca.
• In menstruating women:
o the functional GTC can produce abnormal menstrual patterns,
menorrhagia, amenorrhea.
• Tumor markers may be helpful for monitoring the clinical course of
granulosa cell tumors.
2.2 Sertoli-Leydig Cell Tumor (Androblastomas)
• Sertoli-Leydig cell tumors are very rare.
• Sertoli (sex cord) and Leydig (Stromal) cells are present in varying
amounts, and the tumor may consist almost entirely of Sertoli or
Leydig cells.
• These tumors tend to occur in young women of reproductive age
and frequently are the cause of masculinization and hirsutism.
• The symptoms of virilization usually regress after tumor removal,
but temporal hair recession and a deeper voice tend to remain.
• Rarely, they have also been reported to have estrogenic activity,
leading to the same symptoms and signs as those of granulosa
cell tumors.
• Tumor marker: Testosterone
• The mean age at diagnosis of fallopian tube carcinoma is 58
years, with a range of 26-85 years.
• However, in women with BRCA-associated fallopian tube
carcinoma, the age at diagnosis is considerably younger
• Many women are asymptomatic; however, the most commonly
reported signs and symptoms include:
o Abdominal vaginal bleeding or serosanguinous vaginal
discharge (35-60%)
o Palpable adnexal mass (10-60%)
o Crampy lower abdominal pain caused by distention and forced
peristalsis (20-50%)
• Hydrops tubae profluens
o Term used to describe intermittent expulsion of clear or
serosanguinous fluid from the vagina caused by contraction of
a distended, distally occluded fallopian tube
Pathologic Criteria for Diagnosis of Primary Peritoneal Cancer
• Both ovaries must be physiologically normal in size or enlarged by
a benign process
• Involvement in the extraovarian sites must be greater than
involvement on the surface of either ovary
• Microscopically, the ovarian component must be 1 of the following
o Non-existent
o Confined to the ovarian surface epithelium with no evidence of
cortical invasion
o Involving ovarian surface epithelium and underlying cortical
stroma but with any given tumor size smaller than 5 x 5 mm
o Tumor smaller than 5x5 mm within the ovarian substance with
or without surface disease
• The histologic and cytologic characteristics of the tumor must be
predominantly of the serous type that is similar or identical to
ovarian serous papillary adenocarcinoma of any grade
Criteria for Diagnosis of Primary Fallopian Tube Cancer
• The main tumor is in the tube and arises from the endosalpinx
• Histologically, the pattern reproduces the epithelium of the tubal
mucosa and often shows a papillary pattern;
• If the wall is involved, the transition between benign and malignant
epithelium should be demonstrable;
• The ovaries and endometrium are either normal or contain less
tumor than the tube.

VII. PRIMARY PERITONEAL & FALLOPIAN TUBE CA

not discussed
Risk Factors:
• Primary risk factor for fallopian tube cancer is an inherited mutation
in the BRCA1 and BRCA2 tumor suppressor genes associated
with hereditary breast and ovarian cancer syndromes
• Women with BRCA1 and BRCA2 mutations have a 40% to 60%
and 20% to 30% lifetime risk, respectively, for developing ovarian,
fallopian tube, or peritoneal cancer
• Peritoneal Cancer has also been associated with older age at
diagnosis and increased rates of obesity when compared with
ovarian cancer

Pathogenesis:
• The pathogenesis of peritoneal carcinoma is not well-
characterized
• The germinal epithelium of the ovary and mesothelium of the
peritoneum arise from the same embryonic origin, and it was
previously suggested that primary peritoneal cancer may develop
from a malignant transformation of these cells (Lauchlan, 1972)
• Another proposed theory was a field effect, with the coelomic
epithelium lining the abdominal cavity (peritoneum) and ovaries
(germinal epithelium) manifesting a common response to an
oncogenic stimulus (Parmley, 1974; Truon, 1990)
• Molecular studies have been inconclusive

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