Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

to hyperintense both on T1and T2-weighted images, presumably secondary to hemorrhage and possibly due to viscous proteinaceous material. Solid components are intermediate in signal intensity on T1and hyperintense on T2weighed images; postcontrast, solid components reveal an intense contrast enhancement. These tumors thus mimic a malignancy.

Polycystic Disease (Stein-Leventhal

Syndrome)

Polycystic ovarian disease (Stein-Leventhal syndrome) consists of oligomenorrhea, anovulation, hyperandrogenism, and obesity in a setting of enlarged, polycystic ovaries. Serum luteinizing hormone levels are increased and follicle-stimulating hormone levels are decreased. Infertility is common. The clinical presentation varies, however, some women have a normal menstrual cycle and some with imaging-confirmed polycystic ovarian disease have no clinical or endocrinologic findings. It is this latter finding that suggests that the presence of multiple peripheral ovarian cysts detected by imaging is not pathognomonic for polycystic ovarian disease.

Computed tomography detects enlarged ovaries containing numerous small cysts, generally uniform in size. In some women the cysts are sufficiently small, making their identification difficult. The cysts are close to water density. Hemorrhage is rare.

The diagnosis can be suggested by US. Ovaries tend to be more round rather than oval in configuration, and are markedly asymmetrical in about half of the women. In general, the ovaries are enlarged, although they overlap both in ovarian volume and number of follicles exists. Multiple peripheral cysts, at times with hyperechoic stroma, are detected with US in some but not all affected women.

Magnetic resonance reveals a hypointense signal from these cysts on T1and hyperintense signal on T2-weighted images.

Primary Epithelial Neoplasms

A majority of ovarian neoplasms are of epithelial origin, with adenocarcinoma being more common than adenoma. Especially when dis-

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cussing malignant ovarian neoplasms, some authors lump epithelial, germ cell, and stromal tumors together and treat them as a single entity. Some ovarian tumors, such as poorly differentiated carcinomas, defy subdivision.

The most common ovarian epithelial malignancy is a serous cystadenocarcinoma, followed by mucinous cystadenocarcinoma, then endometrioid carcinoma, clear cell carcinoma, and the least common being poorly differentiated carcinomas. Only rarely encountered are small cell carcinomas and squamous cell carcinomas.

Primary ovarian adenomas and adenocarcinomas are discussed together; the initial clinical approach is similar for both and many of the imaging findings overlap.

Serous and Mucinous Adenoma

and Adenocarcinoma

While ovarian cancer is less common than uterine or cervical cancer, it results in a higher mortality rate. The risk of developing an ovarian cancer is associated with older age, nulliparity, and a family history of ovarian cancer. Because of few initial symptoms, a late diagnosis (stage III or IV) for ovarian carcinoma is common and mortality has decreased little during the last several decades.

The prevalence of mucinous versus serous cystadenocarcinomas is age dependent; in women under the age of 40, most are mucinous while over the age of 40 most are serous. Younger women developing a malignant epithelial ovarian tumor are more likely to have a borderline and early-stage tumor than are older women; also, the 5-year survival rate is significantly better in younger patients.

Migratory thrombophlebitis is a known complication of a number of internal malignancies, including ovarian cancers (Fig. 12.18). Thrombocytosis and venous thrombosis is significantly more prevalent in patients with ovarian epithelial carcinoma than in those with benign cysts or controls.

Genetics: About 95% of ovarian cancer is sporadic. Yet epithelial ovarian cancers occur in certain families and an autosomal dominant transmission is evident. Cancers in these families occur at a younger age than the general population and daughters of mothers with ovarian

cancers develop their ovarian cancer at a significantly younger age than their mothers. Several distinct cancer syndromes have been described: hereditary site-specific ovarian cancer, hereditary breast–ovarian cancer syndrome, and as part of a nonpolyposis colorectal cancer syndrome (Lynch syndrome II). Mutations in the BRCA1 tumor suppressor gene, located on chromosome 17q21, are responsible for most cases of inherited predisposition to breast and ovarian cancer, followed by mutation of the BRCA2 tumor-suppressor gene.

Some sporadic ovarian cancers have mutations in the p53 tumor-suppressor gene. Invasive serous and undifferentiated ovarian carcinomas reveal p53 mutations and loss of genetic material in chromosome 17 and other chromosomal complexes, findings uncommon in mucinous and endometrioid carcinomas (44). KRAS mutations are found in up to half of mucinous ovarian carcinomas and mucinous borderline malignant tumors (44). Also, p53 protein accumulates similarly in both mucinous cystadenocarcinomas and borderline malignant

mucinous tumors, and in the latter tumors it can also be identified in morphologically benign tumor regions.

Associated Conditions: Women with a primary ovarian or uterine carcinoma are at increased risk of developing a second primary malignancy of the colon, breast, uterus, and other organs. This increased risk is explained, in part, by the therapy of the primary malignancy, although undoubtedly such factors as heredity and hormones also play a role. Most of these second primary tumors are detected by symptoms from the second tumor and not follow-up of the primary cancer.

The dominantly inherited Li-Fraumeni syndrome consists of a genetic predisposition to sarcomas, breast carcinomas, ovarian neoplasms, and other tumors. Members of LiFraumeni syndrome families also are at risk of developing multiple primary cancers, with the highest risk being in those who survive childhood cancer (45); about 50% of these families have germline mutations of tumor-suppressor gene p53.

A rare ovarian adenocarcinoma develops years after tamoxifen therapy.

Screening: Currently no consensus exists regarding screening for ovarian carcinoma, although several studies suggest that transabdominal US has a moderate sensitivity in detecting ovarian cancer. Endovaginal US identifies most normal-to-atrophic ovaries in postmenopausal women, and even in those with nonvisualized ovaries an assumption of no tumor can be made. Adding Doppler US improves the tumor detection rate. Both endovaginal US and Doppler US suffer from a high false-positive rate and thus a low specificity. Nevertheless, screening US is not universally recommended, but it probably is of value in those with a family history of ovarian cancer.

Neither CT nor MRI is indicated for screening ovarian cancer.

In some women, but probably only in a minority with stage I tumors, elevated serum CA-125 levels are detected prior to the cancer being clinically evident. Ovarian cancer syndrome families have been screened with serum CA 125 and endovaginal US, with mixed results. Serum CA 125 is a glycoprotein tumor marker; elevated levels are also found in a number of other malignancies, including breast, endometrium, colon, pancreas, and some nonmalignant conditions, such as endometriosis, PID, pregnancy, uterine leiomyomas, and some liver disorders. CA-125 levels fluctuate during the menstrual cycle. It is insensitive with mucinous cancers. Its current major use is in following response to therapy and evaluating recurrence.

Pathologic Study

Ovarian epithelial neoplasms range from adenomas to adenocarcinomas, either serous or mucinous. A cystic structure is quite common. Overall, the serous variety predominates, and serous cystadenomas are slightly more common than serous cystadenocarcinomas. Some carcinomas are associated with an underlying ovarian abnormality, such as a complex cyst. Especially with the mucinous variety, a tumor may show considerable histopathologic variability and contain both benign and malignant components.

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The best prognosis is with mucinous and endometrioid carcinomas, while a poorly differentiated carcinoma has the worst prognosis. With ovarian cystadenocarcinomas a better prognosis is associated with normotypic tumors, those having a mostly cystic content, a mononuclear infiltrate, limited histologic atypia, and no invasion.

Human papilloma virus RNA is detected in some ovarian carcinomas, although the biologic significance of this finding is not clear.

Most serous adenomas are unilocular and lined by a single cell layer, with a minority having solid papillary projections or a fibrous component. They vary in size considerably. About half of serous adenocarcinomas develop bilaterally. Serous adenomas, on the other hand, tend to occur unilaterally. Some consist mostly of an adenomatous component but contain foci of borderline or carcinomatous cells, thus suggesting a counterpart to the large bowel adenoma-carcinoma sequence—a controversial topic among pathologists. Serous ovarian carcinomas contain solid regions of tumor and varying amounts of necrosis and hemorrhage. Grade 1 tumors have a fine papillary structure, while grade 3 tumors consist of sheets of undifferentiated cells. In general, the less differentiated tumors are more prone to hemorrhage, necrosis, and increased solid components.

Primary ovarian serous carcinomas are histologically identical to the rare primary peritoneal papillary serous carcinoma. These serous tumors presumably have a multifocal origin. Confusion between these two entities abounds in a setting of a serous carcinoma discovered in the peritoneal cavity—is it a metastatic ovarian or a primary peritoneal tumor? The practical significance of such a differentiation is in the better prognosis with a primary peritoneal tumor.

A majority of mucinous ovarian tumors are benign. Both benign and malignant mucinous neoplasms are more common unilaterally. These tumors tend to be multilocular and an occasional one is huge. Similar to their serous counterpart, the cystic component of benign ones tends to be lined by a single cell layer, while the carcinomatous ones contain more solid components. More malignant ones often have less mucin and resemble other solid epithelial carcinomas.

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The term borderline malignant tumor of the ovary (also known as low malignant potential tumor) designates a slow-growing epithelial tumor having a low potential for invasion or metastasis. These tumors are considered by some to be a distinct histologic and clinical entity, although aside from a better prognosis than with a more typical ovarian carcinoma, nothing suggests that they represent a separate entity. They can be either serous or mucinous. The Federation Internationale de Gynecologie et Obstetrique (International Federation of Gynecology and Obstetrics) (FIGO) and World Health Organization (WHO) use stromal invasion, defined as destructive infiltrative growth, to differentiate between a serous borderline tumor and an invasive carcinoma. These borderline malignant tumors have a better prognosis than more malignant ones, most are FIGO stage 1 at initial diagnosis. Similar to benign tumors, if stage 1 borderline malignant tumors are completely resected, further imaging is of limited use; on the other hand, with a more advanced stage, baseline posttherapy CT or MRI are appropriate.

Evidence suggests that ovarian mucinous borderline tumors can be subdivided into two distinct subtypes: intestinal and müllerian. Histology of the intestinal subtype reveals intestinal differentiation, while müllerian ones contain no such differentiation. Intestinal subtype is more likely to be a higher stage than the müllerian subtype.

An intermediate category, or micropapillary serous carcinoma, does not manifest a destructive infiltrative growth pattern but behaves as a low-grade invasive carcinoma.

Detection

The role of imaging in women with a suspected or palpable abnormal pelvic tumor of indeterminate origin is to determine the site of origin for that mass and aid in establishing whether it is benign or malignant. No consensus exists about the initial imaging modality to be used. Transabdominal US is often the first imaging study performed, although endovaginal US is preferred by some.At times both are performed. Computed tomography also plays a role, with MRI gaining credence in some centers as the imaging modality of choice. Nevertheless, in many centers most ovarian carcinomas present

in an advanced stage and are detected on physical examination, with perhaps US being performed prior to exploratory laparotomy. At surgery the diagnosis is confirmed, the tumor is staged, and, as appropriate, it is either resected or debulked.

Calcifications in ovarian adenomas and adenocarcinomas have a fine, amorphous pattern and are scattered throughout the tumor. Some calcifications are sufficiently fine that they are identified as a diffuse increase in density throughout the tumor. In general, these calcifications suggest a serous tumor, in distinction to the coarser calcifications seen with mature teratomas.

These tumors range from solid to mostly cystic. Imaging shows most tumors as large, thinor thick-walled, unilocular or multilocular cysts containing nodules varying in size. Overall, mucinous tumors tend to be larger than their serous counterparts.

The most common appearance of a serous cystadenoma is that of a thin-walled unilocular cyst. Intracystic papillary projections are found in some, but their presence should raise suspicion for a carcinoma. The unilocular and thinwalled ones tend to mimic a functional cyst, and a diagnosis of ovarian carcinoma is not always straightforward.

Most mucinous cystadenomas and cystadenocarcinomas are multilocular. Thick septations, nodules, and intratumoral hemorrhage suggest a carcinoma. Nevertheless, considerable overlap exists in the imaging findings between benign and corresponding malignant neoplasms. The findings suggesting a malignancy include a prominent solid component, thickened tumor wall or septa, nodularity, and tumor necrosis. Tumor spread to peritoneum or other adjacent structures is more common with a malignant tumor than with benign disease, but overlap exists. Also, larger fluid collections are associated with malignancy.

The CT density of serous tumors is close to that of water, while mucinous ones approach soft tissue density. Septal thickness varies considerably.

Transabdominal US detects most larger ovarian carcinomas simply as abnormal cystic tumors, with cyst echogenicity varying depending on cyst content. Ultrasonography results are operator and equipment dependent.Attempts to differentiate benign from malignant neoplasms

using morphologic findings have not achieved wide acceptance, although the presence of a solid component suggests a malignant tumor. Adding complexity to the issue are borderline tumors that cannot be reliably differentiated from either benign or malignant tumors by their imaging characteristics or their RI and PI values.

Can endovaginal color Doppler US differentiate benign and malignant ovarian and tubal tumors? In general, a low tumor marker CA 125 and Doppler US evidence of a lack of tumor blood flow exclude ovarian malignancy. Centrally located blood vessels are more common with malignant tumors, but even if no flow is detected by color Doppler US an ovarian malignancy cannot be excluded. In general, while PI and RI tend to be lower for malignant ovarian tumors, the values overlap and it seems reasonable to conclude that neither index is sufficiently reliable to be used in differentiating benign from malignant ovarian tumors. A diastolic notch is found in many benign tumors but is uncommon in malignant tumors. No single Doppler US criterion can differentiate between benign and malignant tumors, although a combination of the above findings is useful. By combining the results of endovaginal US and Doppler US,a sensitivity of over 90% is achieved by some operators in suggesting malignancy. In general, the diagnostic accuracy of endovaginal US is significantly greater in premenopausal than in postmenopausal women.

Magnetic resonance signal intensity of mucinous cystadenomas and cystadenocarcinomas varies considerably depending on the amount of mucin and blood. Fluid in serous cystadenomas has characteristics of water on all MR sequences, except when modified by hemorrhage.

Larger papillary projections in epithelial ovarian neoplasms have a distinctive fibrous stalk terminating in papillae containing signal intensities similar to fluid on T2-weighted images; smaller papillae are isointense signal on T2-weighted images. Papillae enhance post–MR contrast.

Endometrioid Neoplasms

Endometrioid ovarian neoplasms often arise in a setting of endometriosis and most are malig-

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nant.Almost one third of these women also have an endometrial adenocarcinoma. An association between ovarian endometrioid carcinoma and long-term tamoxifen use has been suggested.

Histologically, an endometrioid adenocarcinoma is difficult to differentiate from a carcinoma arising adjacent to a region of endometriosis. Some endometrioid carcinomas contain a squamous carcinoma component or a clear cell carcinoma. An occasional endometrioid tumor contains a yolk sac tumor component; these are aggressive tumors having a poor prognosis.A rare well-differentiated endometrioid adenocarcinoma is associated with elevated serum a-fetoprotein levels.

The imaging appearance of most endometrioid carcinomas is similar to that of serous and mucinous ovarian adenocarcinomas. Occasionally an endometrioid carcinoma has a more solid component, probably related to necrosis. In distinction to serous and mucinous tumors, papillary projections are uncommon in endometrioid carcinomas.

Five-year survival of women with an ovarian endometrioid carcinoma is similar to those with a serous carcinoma.

Clear Cell Carcinoma

Clear cell carcinomas invade locally but have a better prognosis than their serous and mucinous counterparts (in distinction to uterine endometrial clear cell adenocarcinomas, which have a worse prognosis than non–clear cell endometrial carcinomas). A solid component, including nodules in a unilocular cyst is a common imaging appearance for these ovarian tumors. They tend to mimic serous cystadenocarcinomas in their imaging appearance.

Staging

Tumor stage is the major prognostic factor with ovarian epithelial cancers. The FIGO and TNM ovarian cancer staging systems are outlined in Table 12.5.

Ovarian malignancies tend to be initially diagnosed and staged during exploratory laparotomy. Evaluation under general anesthesia is relatively accurate for localized tumors,

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Table 12.5. FIGO and TNM staging of ovarian tumors

but is insensitive for more advanced lesions; extensive adnexal infiltration and lymphatic involvement are difficult to stage accurately. Complete staging includes hysterosalpingooophorectomy, para-aortic and retroperitoneal lymph node biopsy, omentectomy, peritoneal biopsy, and peritoneal washings.

Ovarian adenocarcinomas spread primarily to the peritoneal cavity, followed by adjacent structures and lymph nodes. The serous variety involves lymphatics more often than its muci-

nous counterpart. Hematogenous spread is a late occurrence. Peritoneal involvement, or pseudomyxoma peritonei, is more common with a mucinous carcinoma.

Chest radiography continues to be used to stage these tumors. Intravenous urography is rarely employed for staging. A barium enema is useful with the larger tumors to gauge colorectal invasion and with suspicion that an ovarian tumor may represent a colorectal metastasis rather than a primary tumor. In a number