MALIGNANT OVARIAN NEOPLASMS

‫فاطمه عالی محمدی‬ ‫فائزه صادقی‬

 Epidemiology:
the fifth most common cause of cancer death in women (following, in order, lung, breast, colorectal, and pancreatic)
most commonly in the fifth and sixth decades of life

The risk of a woman developing ovarian cancer during her lifetime is approximately 1 in 70

Risk Factors:

age(The risk increases with age until approximately 70 years)

nulliparity
primary infertility
endometriosis
inherited mutations in the cancer susceptibility genes BRCA1 and BRCA2
Lynch syndrome

Long-term suppression of ovulation may protect against the development of ovarian cancer, at least for epithelial cell
tumors. Five years of cumulative suppression of ovulation through the use of oral contraceptives appears to decrease
the lifetime risk of ovarian cancer by one-half.
No evidence exists to implicate the use of postmenopausal hormone therapy in the development of ovarian cancer.
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 symptoms
The most common symptoms are abdominal bloating or distension, abdominal or pelvic pain, decreased energy or
lethargy, early satiety, and urinary urgency.
Because no clinically applicable screening test is available, approximately two-thirds of patients with ovarian cancer have
advanced disease at the time of diagnosis.

Pathogenesis
Malignant ovarian epithelial cell tumors spread primarily by direct extension within the peritoneal cavity as a result of direct
cell sloughing from the ovarian surface.
Although epithelial cell ovarian cancers also spread by lymphatic and bloodborne routes, their direct extension into the
virtually unlimited space of the peritoneal cavity is the primary basis for their late clinical presentation.

Diagnosis
Currently, it appears that the best way to detect early ovarian cancer is for both the patient and her clinician to be aware of
early warning signs. These signs should not be ignored in postmenopausal women(median age at diagnosis is 63 years).

Early Warning Signs of Ovarian Cancer

• Increase in abdominal size • Abdominal bloating • Fatigue
• Abdominal pain • Indigestion • Inability to eat normally
• Urinary frequency • Constipation • Back pain
• Urinary incontinence of recent onset • Unexplained weight loss
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 screening tests
Neither pelvic ultrasound nor CA-125 should be routinely used to screen for ovarian cancer.

CA-125 should be used primarily to follow response to therapy and evaluate for recurrent disease. CA-125 can
also be used to evaluate the presence of ovarian cancer in selected cases:
In premenopausal women with symptoms, a CA-125 measurement has not been shown to be useful in most
circumstances, because elevated levels of CA-125 are associated with a variety of common benign conditions ,
including uterine leiomyomata, pelvic inflammatory disease, endometriosis, adenomyosis, pregnancy, and even
menstruation. Non gynecologic conditions associated with elevated CA-125 include cirrhosis, pleural effusion, and
peritoneal effusion. In postmenopausal women with a pelvic mass, a CA-125 measurement may be helpful in
predicting a higher likelihood of a malignant tumor than a benign tumor. However, a normal CA-125 measurement
alone does not rule out ovarian cancer, because up to 50% of early-stage cancers and 20% to 25% of advanced
cancers are associated with normal values.

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 Histologic Classification

1) malignant epithelial cell tumors, which are the most common type

2) malignant germ cell tumors

3) malignant stromal cell tumors

Most malignant ovarian tumors have a histologically similar but benign counterpart. The relationship between a
benign ovarian neoplasm and its malignant counterpart is clinically important: If a benign ovarian neoplasm is
found in a patient, removal of both ovaries is considered, because there is a possibility of future malignant
transformation in the remaining ovary.

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 Borderline Ovarian Tumors

Approximately 10% of seemingly benign epithelial cell tumors may contain histologic evidence of
intraepithelial neoplasia, commonly referred to as borderline malignancies, or “tumors of low
malignant potential”.
These tumors generally remain confined to the ovary, are more common in premenopausal
women (ages 30–50 years), and have good prognoses.
About 20% of such tumors show spread beyond the ovary.
If frozen section pathology demonstrates borderline histology, unilateral oophorectomy with a
staging procedure and follow-up is appropriate, assuming the woman wishes to retain ovarian
function and/or fertility and understands the risks of such conservative management.

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 Epithelial Cell Ovarian Carcinoma

Approximately 90% of all ovarian malignancies are of the epithelial cell type, derived from mesothelial cells.
Repeated ovulation is, therefore, associated with the histologic change in these cells derived from coelomic
epithelium.

1) Malignant epithelial serous tumors (serous cystadenocarcinoma) are the most common malignant epithelial
cell tumors. Approximately 50% of these cancers are thought to be derived from their benign precursors (serous
cystadenoma), and as many as 30% of these tumors are bilateral at the time of clinical presentation. They are
typically multiloculated and often have external excrescences on an otherwise smooth capsular surface.
Calcified, laminated structures, psammoma bodies, are found in more than one-half of serous carcinomas.

2) malignant mucinous epithelial tumor: Another epithelial cell variant that contains cells reminiscent of
endocervical glandular mucous-secreting cells is the malignant mucinous epithelial tumor (mucinous
cystadenocarcinoma). They make up approximately one-third of all epithelial tumors, the majority of which are
benign or of low malignant potential; only 5% are cancerous. These tumors have a lower rate of bilaterality
and can be among the largest of ovarian tumors, often measuring more than 20 cm. They may be associated
with widespread peritoneal extension with thick, mucinous ascites, termed pseudo-myxomatous peritonei.
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 3) Hereditary Epithelial Ovarian Cancer
breast/ovarian familial cancer syndrome, a combination of epithelial ovarian and breast cancers in first- and second-degree
family members, are at two to three times the risk of these cancers as the general population. Women with this syndrome
have an increased risk of bilaterality of breast cancer and developing ovarian tumors at a younger age. This syndrome has
been associated with the BRCA1 or BRCA2 gene mutations, which are inherited in an autosomal-dominant fashion. Women
with these gene mutations have a cumulative lifetime risk of 50% to 85% for breast cancer and 15% to 45% for ovarian
cancer. Women of Ashkenazi Jewish ancestry have a 1 in 40 chance of carrying this gene, a 10-fold risk over the general
population.
Lynch syndrome occurs in families with first- and second-degree members with combinations of colon, ovarian,
endometrial, and breast cancers. Women in families with this syndrome may have a threefold or more increased risk of
ovarian cancer over the general population, with those cancers occurring at a younger age. Women in families with these
syndromes should have more frequent screening tests and may benefit from risk-reducing salpingo-oophorectomy.

4) Endometrioid Tumors
Most endometrioid tumors are malignant. These tumors contain histologic features similar to those of endometrial carcinoma
and are commonly found in association with endometriosis or are coincident with endometrial cancer of the uterus.

5) Other Epithelial Cell Ovarian Carcinomas

Of the remaining epithelial cell carcinomas of the ovary, clear cell carcinomas are thought to arise from mesonephric
elements, and Brenner tumors are thought to arise rarely from their benign counterpart. Brenner tumors may occur in the
same ovary that contains mucinous cystadenoma; the reason for this is unclear.
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 Germ Cell Tumors
Germ cell tumors are the most common ovarian cancers in women younger than 20 years.
Germ cell tumors may be functional, producing β-hCG or α-fetoprotein (AFP), both of which can be used as tumor markers.

Dysgerminoma

Dysgerminomas are usually unilateral and are the most common type of germ cell tumor seen in patients with gonadal
dysgenesis. These tumors often arise in benign counterparts, called the gonadoblastoma. The tumors are particularly
radiosensitive and chemosensitive . Because of the young age of patients with dysgerminomas, removing only the involved
ovary while preserving the uterus and contralateral tube and ovary may be considered if the tumor is less than approximately
10 cm and if no evidence of extraovarian spread is found. Unlike the epithelial cell tumors, these malignancies are more
likely to spread by lymphatic channels, and, therefore, the pelvic and periaortic lymph nodes must be sampled at the time of
surgery. If disease has spread outside the ovaries, conventional hysterectomy and bilateral salpingo-oophorectomy are
necessary, usually followed by cisplatin-based chemotherapy that is used in combination with bleomycin and etoposide. The
prognosis of these tumors is generally excellent. The overall 5-year survival rate for patients with dysgerminoma is 90% to
95% when the disease is limited to one ovary.
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 Immature teratoma

Immature teratomas are the malignant counterpart of benign cysticteratomas (dermoids). These tumors are the second
most common germ cell cancer and are most often found in women younger than age 25 years. They are usually
unilateral, although, on occasion, a benign counterpart may be found in the contralateral ovary. Because these tumors are
rapidly growing, they may produce painful symptomatology relatively early, due to hemorrhage and necrosis. The disease
is, therefore, diagnosed when it is limited to one ovary in two-thirds of patients. As with dysgerminoma, if an immature
teratoma is limited to one ovary, unilateral oophorectomy is sufficient. Treatment with chemotherapeutic agents provides a
good prognosis.

Rare Germ Cell Tumors

Endodermal sinus tumors and embryonal cell carcinomas are uncommon malignant ovarian tumors that have had a
remarkable improvement in cure rate. Previously, these tumors were almost uniformly fatal. New chemotherapeutic
protocols have resulted in an overall 5-year survival rate of more than 70%. These tumors typically occur in childhood and
adolescence, with the primary treatment being surgical resection of the involved ovary followed by combination
chemotherapy. The endodermal sinus tumor produces AFP, whereas the embryonal cell carcinoma produces both AFP
and β-hCG.
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 Gonadal Stromal Cell Tumors
The gonadal stromal cell tumors make up an unusual group of tumors characterized by hormone production; hence,
these tumors are called functioning tumors. They can be both benign and malignant though malignant forms are more
rare. The hormonal output from these tumors is usually in the form of female or male sex steroids or, on occasion,
adrenal steroid hormones.

granulosa cell tumor

The granulosa cell tumor is the most common in this group. These tumors occur in all ages, although, in older patients,
they are more likely to be benign. Granulosa cell tumors may secrete large amounts of estrogen, which, in some older
women, may cause endometrial hyperplasia or endometrial carcinoma. Thus, endometrial sampling is especially
important when ovarian tumors such as the granulosa tumor are estrogen producing. Surgical treatment should include
removal of the uterus and both ovaries in postmenopausal women as well as in women of reproductive age who no
longer wish to remain fertile. In a young woman with the lesion limited to one ovary with an intact capsule, unilateral
oophorectomy with careful surgical staging may be adequate. This tumor may demonstrate recurrences up to 10 years
later. This is especially true with large tumors, which have a 20% to 30% chance of late recurrence.

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 Sertoli-Leydig cell tumors

Sertoli-Leydig cell tumors (arrhenoblastoma) are the rare, testosterone secreting counterparts to granulosa cell tumors. They
usually occur in older patients and should be suspected in the differential diagnosis of perimenopausal or postmenopausal
patients with hirsutism or virilization and an adnexal mass. Treatment for these tumors is similar to that for other ovarian
malignancies in this age group and is based on extirpation of uterus and ovaries. Other stromal cell tumors include fibromas and
thecomas, which rarely demonstrate malignant potential, and their malignant counterparts, the fibrosarcoma and malignant
thecoma.

Cancer Metastatic to the Ovary

Classically, the term Krukenberg tumor describes an ovarian tumor that is metastatic from other sites such as the GI tract and
breast.Most of these tumors are characterized as infiltrative, mucinous carcinoma of predominantly signet-ring cell type.
They are often bilateral and associated with widespread metastatic disease. On occasion, these tumors are associated with
abnormal uterine bleeding or virilization, leading to the supposition that some may produce estrogens or androgens. In
patients previously treated for breast or GI cancer, consideration should be given to the incidental removal of the ovaries at the
time of hysterectomy, because these patients have a high predilection for the development of ovarian cancer. The prognosis for
most patients with carcinoma metastatic to the ovary is generally poor.
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 MANAGEMENT OF OVARIAN CANCERS

Primary surgical therapy

Each procedure includes the following:
1. Peritoneal cytology
2. Inspection and palpation of the entire peritoneal cavity
3. Partial omentectomy
4. Sampling of the pelvic and periaortic lymph nodes
chemotherapy
First-line chemotherapy is with paclitaxel (Taxol) combined with carboplatin or cisplatin.
Radiation therapy
has only a limited role in the management of ovarian cancer.

Follow-up

clinical history and examination

various imaging studies (ultrasound and/or CT)
serum tumor markers such as CA 125 in epithelial cell tumors

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