Ovarian Cancer Classification and Pathology

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Primary ovarian cancers are classified according to the structures of the ovary from which they are derived. Most develop from the epithelial cells that cover the ovarian surface or that line inclusion cysts. These cells are ultimately derived from the coelomic epithelium of mesodermal origin and share cytologic markers with mesothelium. Germ cell malignancies constitute the next most common group and the least common tumors are derived from ovarian stromal cells.

Epithelial malignancies account for 85% to 90% of ovarian cancers. The majority of epithelial lesions are seen in patients who are 40 years or older. Under the age of 40 years, epithelial malignancies are uncommon, and most malignancies seen in women under the age of 30 years are of germ cell origin. The histologic types of the epithelial tumors are listed in Table 118-3. The majority of lesions, about 75%, are of the serous type, followed by the mucinous, endometrioid, clear cell, mixed, Brenner, and undifferentiated histologies. The cellular patterns of different histotypes resemble different derivatives of the Mullerian duct in different portions of the female reproductive tract. For example, serous epithelial cells resemble cells that line the Fallopian tube, endometrioid epithelial cells resemble the endometrium, and mucinous epithelial cells resemble the uterine endocervix.

Invasive Histologies
Serous carcinomas may have a complex admixture of cystic and solid areas with extensive papillations, or they may contain a predominantly solid mass with areas of necrosis and hemorrhage (Figure 118-1). The poorly differentiated tumors may have some areas with a papillary pattern, but other portions may be indistinguishable from the other histologic patterns described below (Figure 118-2). Stage I or II lesions are most frequently unilateral, with about 10% to 20% involving both ovaries. Conversely, about 50% to 70% of stage III serous carcinomas are bilateral.

Mucinous tumors tend to be large, with many masses over 20 cm in diameter (Figure 118-3). The histologic pattern resembles uterine endocervical glands. The lesions frequently contain areas of hemorrhage, necrosis, and various quantities of mucin. These tumors are bilateral in 10% to 20% of cases. Occasionally, mucin is secreted into the peritoneal cavity and produces a condition known as pseudomyxoma or myxoma peritonei. A mucocoele of the appendix may also be seen in conjunction with this tumor.

Endometrioid carcinomas of the ovary resemble typical carcinomas of the endometrium. These tumors may be seen with synchronous endometrial carcinoma, and when they are, both lesions may be of low stage. Rarely, endometrioid carcinomas arise in conjunction with pelvic endometriosis, resulting from malignant transformation of a benign process (Figure 118-4). Bilaterality is seen in 10% - 15% of stage I and II disease, and in about 30% of stage III.

Clear cell carcinomas were formerly called mesonephromas, a term that has been abandoned because clear cell tumors are derived from tissues that are embryologically distinct from mesonephros. About one fourth of clear cell tumors are associated with endometriosis. Clear cell tumors are only rarely bilateral.

Brenner tumors are uncommon, representing less than 1% of all epithelial malignancies. Mixed epithelial tumors may contain small areas of Brenner tumor histology, which have a histologic pattern similar to that of transitional cell. Malignant Brenner tumors are unilateral.

Borderline Tumors
Borderline tumors, or those of low malignant potential, are important to differentiate from those that are frankly invasive. The treatment and prognosis for borderline lesions are considerably different from those for invasive malignancies. Borderline tumors tend to remain confined to a single ovary at the time of diagnosis, and also tend to occur in younger, premenopausal women (Figure 118-5). They may be confused with a well-differentiated invasive ovarian cancer, and the treatment for the two may be different. Thus, in a young patient who has a lesion confined to the ovary that is suspected of having an epithelial ovarian cystadenocarcinoma, a borderline tumor must be excluded, because bilateral oophorectomy, hysterectomy, and chemotherapy are unnecessary in these patients. In women under the age of 40 years, about 60% to 70% of non-benign ovarian neoplasms are borderline, whereas in women over 40 years, only 10% are borderline.

Histologic criteria for borderline tumors include (1) the presence of epithelial cell proliferation with a “piling up” of cells, so-called pseudostratification; (2) cytologic atypia, but with rare mitoses; and (3) no evidence of stromal invasion. Borderline tumors tend to remain confined to the ovary, but may be associated with peritoneal disease, which represents either dissemination or the multifocal evolution of the disease. In those rare patients with peritoneal involvement, death can occur by progressive intestinal obstruction.

Primary Peritoneal Carcinomas
Malignancy that arises primarily from the peritoneal cells is referred to as peritoneal carcinoma or primary peritoneal (papillary) adenocarcinoma. There is some debate as to whether these should all be classified as peritoneal mesotheliomas, or whether this latter group is a specialized variety of a poorly differentiated peritoneal tumor. Some of the lesions appear identical to those tumors that arise from the surface epithelium of the ovaries, and the cells of the peritoneum have the ability to recapitulate any of the histologic patterns seen in ovarian cancer. Thus, the most common pattern of a peritoneal carcinoma is a papillary serous carcinoma.

Knowledge of primary peritoneal carcinomas is important. This lesion explains many instances of unknown primary when no clear explanation for peritoneal carcinomatosis can be documented. Also, the existence of this phenomenon explains the occurrence of ovarian cancer after oophorectomy. In these patients, the presence of carcinomatosis that involves the surface of the ovaries but without ovarian enlargement, probably represents peritoneal carcinoma with secondary or concomitant involvement of the ovarian surfaces. In this manner, the ovaries are the “innocent bystanders” of the process. Therapeutically, primary peritoneal malignancy should be treated as one would manage an epithelial ovarian cancer.

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Chemotherapy for Advanced Stage Epithelial Ovarian Cancer   Follow-up Examinations in Ovarian Cancer   Ovarian Cancer - Patterns of Spread   Ovarian Cancer Prevention   Ovarian Cancer Etiology and Epidemiology   Biology and Prognosis of Ovarian Neoplasms   Ovarian Cancer Screening   Management of Advanced Invasive Ovarian Cancer   Assessment of Response in Patients who are Clinically free of Disease   Staging of Ovarian Cancer   Ovarian Cancer Embryology   Genetic Risk for Epithelial Ovarian Cancer   Epithelial Ovarian Cancer   Immunotherapy in Ovarian Cancer   Consolidation Bhemotherapy and Immuno-therapy in Ovarian Cancer   Palliative Radiotherapy in Ovarian Cancer   Intraperitoneal Chemotherapy for Epithelial Ovarian Cancer   Treatment of Early stage Ovarian Cancer   Treatment of Advanced Stage Epithelial Ovarian Cancer   Ovarian Cancer Clinical Features   Survival of Patients with Advanced Ovarian Cancer   Ovarian Cancer Diagnosis

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