Neoplastic Diseases of the Ovary

8/12/2019 Neoplastic Diseases of the Ovary

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Neoplastic Diseases of theOvary

Department of Obstetrics andGynecology

FEU-NRMF


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Frequency of Ovarian Neoplasm(WHO Classification)

Class Frequency (%)

Epithelial stromal (Common epithelial) tumorsGerm cell tumors

Sex cord-stromal tumors

Lipid (lipoid) cell tumors

Gonadoblastoma

Soft-tissue tumors (not specific to the ovary)

Unclassified tumors

Secondary (metastatic) tumors

Tumor-like conditions (not true neoplasm)

6520-25

6


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Differential Diagnosis of Adnexal MassOrgan Cystic Solid

Ovary Functional cystNeoplastic cyst

Benign

Malignant

Endometriosis

Neoplasm

Benign

Malignant

Fallopian tube Tubo-ovarian abscessHydrosalphinx

Parovarian cyst

Tubo-ovarian abscess

Ectopic pregnancy

Neoplasm

Uterus Intrauterine pregnancy in bicornuateuterus

Pedunculated or intraligamentous

myoma

Bowel Sigmoid or cecum distended with gas

or feces

Diverticulitis

IleitisAppendicitis

Colonic cancer

Miscellaneous Distended bladderPelvic kidney

Urachal cyst

Abdominal wall hematoma or abscess

Retroperitoneal neoplasm

DiSaia et al, Clinical Gynecologic Oncology, 2007


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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


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Epithelial Ovarian NeoplasmsArise 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)


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Epithelial Ovarian Tumor Cell Types

Tumor Cell Type

Approximate Frequency (%)

All Ovarian

Neoplasms

Ovarian

CancersSerous

Mucinous

Endometrioid

Clear cell (mesonephroid)Brenner

20-50

15-25

5


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Serous TumorsComposed of ciliated epithelial cells that

resemble those of the fallopian tubeSerous cystadenomas:

oOccur primarily during reproductive years

Boderline types:oOccur in women 30-50 years

Serous cystadenocarcinoma:

o

Occur in women older than 40 years


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Benign Ovarian TumorsSymptoms:

Initially are asymptomatic

Lower abdominal discomfort

Pelvic pain

Dyspareunia

Abdominal enlargement

Frequent urination

Constipation


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Adnexal TumorsIndications 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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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


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Mucinous Tumors Consist of epithelial cells filled with mucin,resembling cells of the endocervix or intestinal

cells

Types:

Mucinous cystadenomaPrimarily during reproductive years

Borderline types

Mucinous cystadenocarcinomaUsually in 30- to 60-year age range


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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


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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


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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 patterncaused by longitudinal grooving of nuclei

Scattered reports of malignant Brenner;

associated endometrial hyperplasia


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Borderline Malignant Epithelial

Ovarian Tumors Synonyms: Borderline Tumors, Proliferative

Cystadenomas

Epithelial ovarian tumors with histologic andbiologic 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


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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:

SerousMucinous

Commonly found in younger women


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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 borderlineJanovski and Paramananthon: Ovarian tumors

Stuttgart, Georg Thieme Verlag, 1973


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Ovarian TumorsManagement:

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


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Ovarian TumorsManagement:

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


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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


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Invasive Ovarian Carcinomas


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Epithelial Ovarian Tumor Cell Types

Tumor Cell Type

Approximate Frequency (%)

All Ovarian

Neoplasms

Ovarian

CancersSerous

Mucinous

Endometrioid

Clear cell (mesonephroid)Brenner

20-50

15-25

5


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Ovarian Cancer The 2ndmost common gynecologic malignancy27% 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 markedbeyond 50 years, with increase continuing to

age 70 years, and decrease after age 80 years


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Primary Ovarian Neoplasms

Related to AgeType 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.


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Putative Associations of Increasing and Decreasing

Risks of Ovarian Epithelial Carcinoma

Increases Decreases

Age

Diet

Family history

Industrialized country

Infertility

NulliparityOvulation

Ovulatory drugs

Talc (?)

Breast-feeding

Oral contraceptives

Pregnancy

Tubal ligation and hysterectomy with

ovarian conservation

Herbst et al: Am J Obstet Gynecol, 1994


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Characteristics in Benign and MalignantOvarian Tumors

Clinical Finding Benign MalignantUnilateral +++ +

Bilateral + +++

Cystic +++ +

Solid + +++

Mobile +++ ++


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Characteristics of Benign and Malignant

Ovarian Tumors

Clinical Finding Benign Malignant

Fixed + +++

Irregular + +++

Smooth +++ +Ascites + +++

Cul-de-sac

Nodulations

- +++


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Most Frequent Presenting

Symptoms of Ovarian CancerSymptom 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.


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Non-ovarian causes of Apparent

Adnexal Mass Diverticulitis

Tubo-ovarian abscess

Carcinoma of the colon or sigmoid

Pelvic kidney


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Ovarian CarcinomaScreening and Early Detection Tools:

Periodic pelvic Examination

Sonography Biomarkers (e.g. CA 125)

Conclusion:There is NO evidence available yetthat the current screening modalities can be

used effectively for widespread screening for

ovarian cancer


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Ovarian Cancer

Diagnostic techniques:

Routine pelvic examination detect only 1ovarian 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


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Tumor Markers in Ovarian Cancer

CA-125

Carcino-embryonic antigen (CEA)

Alpha-feto protein (AFP)

Lactic dehydyhrogenase (LDH)


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CA 125 and Ovarian Cancer Carcinoma Antigen (CA) 125 is expressed inapproximately 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


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Benign Conditions with Elevated

CA 125

Endometriosis

Peritoneal inflammation, including PID

Leiomyoma

Pregnancy

Hemorrhagic ovarian cysts

Liver disease


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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


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Ovarian CancerAdditional diagnostic methods:

CT scan

MRI

Barium enema or Colonoscopy


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Case 1

A 55 y/o, postmenopausal woman consulted because of rapidabdominal 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?


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Comparison between Surgical Findings of

Benign and Malignant Ovarian NeoplasmFindings Benign MalignantSurface 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 CommonCapsule intact Common Infrequent

Totally cystic Common Rare


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Epithelial Ovarian Cancers Constitute 85-90% of ovarian cancers

Histologic distribution in USA:

Serous cystadenocarcinomas =

42%

Mucinous cystadenocarcinoma = 12%

Endometrioid carcinoma = 15%

Undifferentiated carcinoma = 17%Copeland LJ, Clin Gyneco Oncol, 7th

Ed, 2007


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Ovarian Cancer

Routes of spread:

Ceolomic spread

Spread through the peritoneal surfaces of both theparietal 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


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Staging of Ovarian Cancer

Staging is surgical and based on the operative

findings at the commencement of the

procedure Staging Laparotomy:

Midline longitudinal incision


Systematic exploration of the abdominal cavity

Total abdominal hysterectomy with bilateral salpingo-

oophorectomy

Lymphadenectomy or lymph node evaluation


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FIGO Staging Classification of

Ovarian CancerFIGO Stage DescriptionI 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


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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


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Ovarian CancerFIGO 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 thetrue 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


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Ovarian Cancer

FIGO Stage Description

IIV Growth involving one or both ovaries with distant metastasis; ifpleural effusion is present, there must be positive cytologic test

results to allot a case to stage IV; parenchymal liver metastasis equals

stage IV


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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


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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 nodularlesions; the abdominal peritoneum, liver and diapragm are

free of tumor.

What is the Stage of Ovarian Cancer?


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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?


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Ovarian CancerPrognostic Factors

Tumor stage

Tumor grade

Cell type

Amount of residual tumor after resection


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Ovarian CancerTreatment options: Surgery

Removal of all resectable disease

Post-operative or Adjuvant therapy Chemotherapy

Radiation therapy

immunotherapy


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Ovarian Cancer Staging Laparotomy: Midline longitudinal incision


Systematic exploration of the abdominal cavity

Total abdominal hysterectomy with bilateral salpingo-

oophorectomy

Lymphadenectomy or lymph node evaluation

Random biopsy of abdominal peritoneum andsuspicious areas


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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


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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


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Germ Cell Tumors of the Ovary


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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)


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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 2ndand 3rddecades of life

Staged surgically as with epithelial types

Certain histologic types secretes a specific

tumor marker

A single tumor may contain a mixture of


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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 advancedmalignancies an excellent chance at long term control cure

Radiotherapy: Rarely used today


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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?


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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, 6thand 7th

decades

Approximately 90% of hormonally active

ovarian tumors

Have propensity for indolent growth, tend to

recur late


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Sex Cord-Stromal Tumors of the

OvaryManagement: 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

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Neoplastic Diseases of the Ovary