Home | | Obstetrics and Gynecology | Malignant Ovarian Neoplasms

Chapter: Obstetrics and Gynecology: Ovarian and Adnexal Disease

Malignant Ovarian Neoplasms

Ovarian cancer is the fifth most common of all cancers in women in the United States and the most common cause of gynecologic cancer.



Ovarian cancer is the fifth most common of all cancers in women in the United States and the most common cause of gynecologic cancer. The mortality rate of this disease is the highest of all the gynecologic malignancies, primarily because of the difficultyin detecting the disease before widespread dissemination. Of the estimated 25,000 new cases of ovarian cancer yearly, approximately 60% will die within 5 years. Sixty-five to seventy percent are diagnosed at an advanced state when the 5-year survival rate is 20–30%.

Risk Factors and Early Symptoms


Ovarian cancer presents most commonly in the fifth and sixth decades of life. The incidence of ovarian cancer in WesternEuropean countries and in the United States is higher, with a five- to sevenfold greater incidence than age-matched populations in East Asia. Whites are 50% more likely to develop ovarian cancer than blacks living in the United States.


Symptoms of ovarian cancer are often confused with benign conditions or interpreted as part of the aging process, with the final diagnosis often delayed.

The most common symptoms in order from highest percent-age to lowest are abdominal fullness or distension, abdomi-nal or back pain, decreased energy or lethargy, and urinary frequency.

Because no clinically applicable screening test is avail-able, approximately two-thirds of patients with ovarian cancer have advanced disease at the time of diagnosis.


The risk of a woman developing ovarian cancer during her lifetime is approximately 1 in 70. The risk increaseswith age until approximately age 70. In addition to age, the epidemiologic factors associated with development of ovarian cancer include nulliparity, primary infertility, and endometriosis. Approximately 8% to 13% of cases of ovarian cancer are caused by inherited mutations in the cancer-susceptibility genes BRCA-1 and BRCA-2. Addition-ally, women affected with hereditary nonpolyposis colo-rectal cancer (HNPCC; formerly called Lynch syndrome) have approximately a 13-fold greater risk of developing ovarian cancer than the general population.


Long-term suppression of ovulation may protect against the development of ovarian cancer, at least for epithelial celltumors. It has been suggested that so-called incessant ovu-lation may predispose to neoplastic transformation of the epithelial cell surfaces of the ovary. Oral contraceptives that prevent ovulation appear to provide significant protec-tion against the occurrence of ovarian cancer. Five years’ cumulative use of oral contraceptives decreases the lifetime risk by one-half. No evidence exists to implicate the use of postmenopausal hormone replacement therapy in the development of ovarian cancer.


Pathogenesis and Diagnosis


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. This processexplains widespread peritoneal dissemination at the time of diagnosis, even with relatively small primary ovarian lesions. Although epithelial cell ovarian cancers also spread by lymphatic and blood-borne routes, their direct extension into the virtually unlimited space of the peri-toneal cavity is the primary basis for their late clinical presentation.


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 (Box 46.3). These signs should not be ignored in postmenopausal women (median age, approximately 60 years).

 Box 46.3

Early Warning Signs of Ovarian Cancer

Increase in abdominal size

Abdominal bloating


Abdominal pain


Inability to eat normally

Urinary frequency


Back pain

Urinary incontinence of recent onset

Unexplained weight loss

The early diagnosis of ovarian cancer is made even more difficult by the lack of effective screening tests. CA-125 shouldnot be routinely used to screen for ovarian cancer, but, instead, should be used 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.


·            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.




The cell type of origin, similar to their benign counterparts, usu-ally categorizes malignant ovarian neoplasms: malignantepithelial cell tumors, which are the most common type;malignant germ cell tumors; and malignant stromal celltumors (see Box 46.1). Most malignant ovarian tumorshave histologically similar but benign counterparts. The relationship between a benign ovarian neoplasm and its malignant counterpart is clinically important. If the benign counterpart is found in a patient, removal of both ovaries is considered, because there is a possibility of future malig-nant transformation in the remaining ovary. The decision regarding removal of one or both ovaries, however, must be individualized based on age, type of tumor, desire for future fertility, genetic predisposition for malignancy, and the patient’s concern regarding future risks.



The staging of ovarian carcinoma is based on extent of spread of tumor and histologic evaluation of the tumor. The International Federation of Gynecology and Obste-trics (FIGO) classification of ovarian cancer is presented in Table 46.1.


Borderline Ovarian Tumors


Approximately 10% of seemingly benign epithelial cell tumors may contain histologic evidence of intraepithelial neoplasia, com-monly referred to as borderline malignancies, or “tumors of low malignant potential.” These tumors generally remain con-fined to the ovary, are more common in premenopausal women (30 to 50 years of age), and have good prognoses. About 20% of such tumors show spread beyond the ovary. They require carefully individualized therapy following the initial surgical resection of the primary tumor. If frozen section pathology demonstrates borderline histology, uni-lateral 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.


Epithelial Cell Ovarian Carcinoma


Approximately 90% of all ovarian malignancies are of the epithelial cell type, derived from mesothelial cells. The ovarycontains these cells as part of an ovarian capsule just over-lying the actual stroma of the ovary. When these meso-thelial cell elements are situated over developing follicles, they go through metaplastic transformation whenever ovulation occurs. Repeated ovulation is, therefore, associ-ated with the histologic change in these cells derived from coelomic epithelium.


Malignant epithelial serous tumors (serous cyst-adenocarcinoma) are the most common malignant epithe-lial 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 typi-cally 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.


Another epithelial cell variant that contains cells rem-iniscent of endocervical glandular mucous-secreting cells is the malignant mucinous epithelial tumor (mucinouscystadenocarcinoma). They make up approximatelyone-third of all epithelial tumors, the majority of which are benign or of low malignant potential; only 5% are can-cerous. These tumors have a lower rate of bilaterality and can be among the largest of ovarian tumors, often measur-ing more than 20 cm. They may be associated with wide-spread peritoneal extension with thick, mucinous ascites, termed pseudomyxomatous peritonei.


Although most epithelial carcinomas occur sporadi-cally, a small percentage (5% to 10%) occurs in familial or hereditary patterns involving first- or second-degree relatives with a history of epithelial ovarian cancer.


Having a first-degree relative (i.e., mother, sister, daughter) with an epithelial carcinoma gives a 5% lifetime risk for ovarian cancer, whereas having two first-degree relatives increases this risk to 20% to 30%. Such hereditary ovarian cancers generally occur earlier than nonhereditary tumors.


Women with breast/ovarian familial cancer syn-drome, a combination of epithelial ovarian and breast can-cers in first- and second-degree family members, are at two to three times the risk of these cancers as the general pop-ulation. 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 associ-ated with the BRCA-1 gene. Women with this gene muta-tion have a cumulative lifetime risk of 85% to 90% for breast cancer and 50% for ovarian cancer. Women of Ashkenazi Jewish ancestry have a 1% chance of carrying this gene, a 10-fold risk over the general population.


HNPCC 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 increased risk of cancer over the general population. Women in families with these syndromes should have more frequent screening tests and may benefit from risk-reducing salpingo-oophorectomy.



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.




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.


Germ Cell Tumors


Germ cell tumors are the most common ovarian cancers inwomen younger than 20 years of age. Germ cell tumors may befunctional, producing hCG or α-fetoprotein (AFP), both of which can be used as tumor markers. The most common germ cell malignancies are dysgerminoma and immatureteratoma. Other tumors are recognized as mixed germ cell tumors, endodermal sinus tumors, and embryonal tumors. Improved chemotherapeutic and radiation protocols have resulted in greatly improved 5-year survival rates.

Dysgerminomas are usually unilateral and are the mostcommon type of germ cell tumor seen in patients with gonadal dysgenesis (Fig. 46.5). These tumors often arise in benigncounterparts, called the gonadoblastoma. The tumors are particularly radiosensitive and chemosensitive.


Because of the young age of patients with dysgermino-mas, 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 evi-dence 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 dis-ease has spread outside the ovaries, conventional hysterec-tomy 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 over-all 5-year survival rate for patients with dysgerminoma is 90% to 95% when the disease is limited to one ovary.


Immature teratomas are the malignant counterpart ofbenign cystic teratomas (dermoids). These tumors are the sec-ond most common germ cell cancer and are most often found in women younger than 25 years of age. They are usually uni-lateral, 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 dis-ease is therefore diagnosed when it is limited to one ovary in two-thirds of patients. As with dysgerminoma, if an imma-ture teratoma is limited to one ovary, unilateral oophorec-tomy is sufficient. Treatment with chemotherapeutic agents provides a good prognosis.


Rare Germ Cell Tumors


Endodermal sinus tumors and embryonal cell carcino-mas are uncommon malignant ovarian tumors that havehad a remarkable improvement in cure rate. Until about 10 years ago, these tumors were almost uniformly fatal. New chemotherapeutic protocols have resulted in an over-all 5-year survival rate of more than 60%. These tumors typically occur in childhood and adolescence, with the pri-mary treatment being surgical resection of the involved ovary followed by combination chemotherapy. The endo-dermal sinus tumor produces AFP, whereas the embryonal cell carcinoma produces both AFP and β-hCG.


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. The hormonal output from these tumors is usually in the form of female or male sex steroids, or on occasion, adrenal steroid hormones.


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 celltumors may secrete large amounts of estrogen, which in some older women may cause endometrial hyperplasia or endometrial carci-noma. Thus, endometrial sampling is especially importantwhen 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, unilat-eral 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.


Sertoli–Leydig cell tumors (arrhenoblastoma) are the rare, testosterone-secreting counterparts to granulosa cell tumors. They usually occur in older patients and should be sus-pected in the differential diagnosis of perimenopausal or postmenopausal patients with hirsutism or virilization and an adnexal mass. Treatment of 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.


Other Ovarian Cancers


Rarely, the ovary may be the site of initial manifestation of lymphoma. These tumors are usually found in associ-ation with lymphoma elsewhere, although cases have been reported of primary ovarian lymphoma. Once diag-nosed, their management is similar to that for lymphoma of other origin.


Malignant mesodermal sarcomas (carcinosarcomas)are another rare type of ovarian tumor that usually show aggressive behavior and are diagnosed at late stages. The survival rate is poor, and clinical experience with these tumors is limited.

Cancer Metastatic to the Ovary


Classically, the term Krukenberg tumor describes an ovarian tumor that is metastatic from other sites such as the gastrointestinal tract and breast. Between 5% and 10% of women thought to have a primary ovarian malignancy ultimately will receive the diagnosis of a nongenital tract malignancy. Most of these tumors are characterized as infiltrative, mucinous carcinoma of predominantly signet-ring cell type and as bilateral and associated with wide-spread metastatic disease. On occasion, these tumors are associated with abnormal uterine bleeding or virilization, leading to the supposition that some may produce estro-gens or androgens. Breast cancer metastatic to the ovary is common, with autopsy data suggesting ovarian metastasis in one quarter of cases.


In approximately 10% of patients with cancer metasta-tic to the ovary, an extraovarian primary site cannot be demonstrated. In this regard, it is important to consider ovarian preservation versus prophylactic oophorectomy at the time of hysterectomy in patients who have a strong family history (first-degree relatives) of epithelial ovarian cancer, primary gastrointestinal tract cancer, or breast can-cer. In patients previously treated for breast or gastrointesti-nal 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 development of ovarian cancer. The prognosis for most patients with carci-noma metastatic to the ovary is generally poor.


Study Material, Lecturing Notes, Assignment, Reference, Wiki description explanation, brief detail
Obstetrics and Gynecology: Ovarian and Adnexal Disease : Malignant Ovarian Neoplasms |

Privacy Policy, Terms and Conditions, DMCA Policy and Compliant

Copyright © 2018-2023 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.