07 - Radiol Clin N Am 2007 - Ovarian Cancer.pdf - książki - Bio Med 21 - bibiariel

149

RADIOLOGIC

CLINICS

OF NORTH AMERICA

Radiol Clin N Am 45 (2007) 149–166

Ovarian Cancer

Svetlana Mironov, MD *, Oguz Akin, MD , Neeta Pandit-Taskar, MD ,

Lucy E. Hann, MD

- Epidemiology

- Relevant histopathology

- Ovarian cancer screening

- Lesion characterization

- Staging

- Posttreatment follow-up

- Recurrent ovarian tumor resectability

- Summary

- References

Epidemiology

Ovarian cancer is a leading cause of death from gy-

necologic malignancy and the ﬁfth most common

cause of cancer death in women. It is estimated

that in 2006, 20,180 new cases of ovarian cancer

will be diagnosed, and 15,310 women will die of

this disease in the United States [1] . Detection of

stage I disease can have a signiﬁcant impact on

5-year survival, which approaches 80% to 90% in

patients with stage I disease, but ranges from 5% to

50% in women with stage III–IV disease. Currently,

almost 60% to 65% of patients present with stage

III at the time of diagnosis, making ovarian cancer

one of the most lethal malignancies.

are separated into two major categories: invasive

(80%) and noninvasive (borderline) tumors

(20%), which are associated with different prognos-

tic characteristics. Epithelial invasive tumors are

subdivided further into ﬁve histopathologic groups:

serous tumor (50%), mucinous neoplasm (20%),

endometrioid carcinoma (20%), clear cell carci-

noma (10%), and undifferentiated tumor (<5%).

Another subtype of epithelial tumor is Brenner

tumor, which is almost invariably benign.

The primary goal of radiologic assessment is dif-

ferentiation of malignant tumors from benign

tumors, rather than determination of histologic

subtype. Sometimes it is possible, however, to sug-

gest the histologic subtype of an epithelial neo-

plasm based on particular imaging features [2] .

For the most common epithelial neoplasms, se-

rous cystadenocarcinomas are bilateral in more

than 50% of cases, with peak age of presentation

70 to 75 years old. The typical imaging ﬁnding is

a large-volume ascites out of proportion to the

size of bilateral complex adnexal masses of irregular

shape with polypoid excrescences on the surface.

Widespread peritoneal carcinomatosis with omen-

tal inﬁltration by the tumor (so-called omental cak-

ing) is invariably present in cases of serous papillary

carcinoma.

Relevant histopathology

Primary ovarian neoplasms are differentiated by the

cell origin, such as surface epithelium, germ cell,

and stromal cells. Approximately 90% of primary

ovarian cancers are epithelial tumors, arising from

the surface epithelium. Based on the degree of dif-

ferentiation, epithelial tumors are divided into

three major categories: well differentiated (10%),

moderately differentiated (25%), and poorly differ-

entiated (65%). Less differentiated tumors are asso-

ciated with worse prognosis. Epithelial neoplasms

Department of Radiology, Cornell University Weill Medical College, Memorial Sloan-Kettering Cancer Center,

1275 York Avenue, C278, New York, NY 10021, USA

* Corresponding author.

E-mail address: mironovs@mskcc.org (S. Mironov).

doi:10.1016/j.rcl.2006.10.012

radiologic.theclinics.com

150

Mironov et al

Mucinous neoplasms are seen in older patients

with a later peak age of 75 to 80 years. These tumors

manifest as large, unilateral, multiseptated masses

with a variable ratio of solid to cystic components.

The presence of an enhancing solid component

within a multicystic mass is a strong indicator of

malignant etiology. A benign counterpart of mucin-

ous cystadenocarcinoma, mucinous cystadenoma,

typically has the appearance of a multiloculated

cystic mass with thin septations ( Fig. 1 ). Different

compartments or locules within the mass have dif-

ferent densities of mucin on CT and different signal

intensities on MR imaging.

Endometrioid cancers are usually bilateral mixed

solid and cystic masses, which can be associated

with endometrial hyperplasia and even concomi-

tant endometrial carcinoma. Clear cell tumor

manifests at the younger age of 55 to 59 years and

has the typical appearance of a solitary complex cys-

tic mass with a vascular solid mural nodule. It is as-

sociated with endometriosis and occasionally may

arise within endometriomas [3] . Finally, undiffer-

entiated tumors are solid, usually bilateral masses

with varying degrees of necrosis. They are generally

associated with poor prognosis.

Approximately 20% of all epithelial neoplasms

are borderline tumors, also referred to as ‘‘tumors

of low malignant potential.’’ These neoplasms are

associated with better prognosis. The patients

(>90% of whom present with stage I disease) are

10 to 15 years younger than women with invasive

epithelial carcinoma. Borderline tumors can be se-

rous or mucinous. The risk of contralateral involve-

ment in serous borderline tumor is 25% to 60%.

Patients with serous borderline tumors, which ex-

press micropapillary features, have increased risk

of relapse compared with patients without micro-

papillary features. The tumor can recur as a low-

grade serous carcinoma years after initial treatment.

Mucinous borderline tumors often manifest as large

unilateral cystic masses with thin septations. The

risk of bilateral involvement is low, and peritoneal

involvement and ascites are rare. A woman with

a borderline mucinous neoplasm should undergo

appendectomy along with thorough gastrointesti-

nal investigation to rule out a primary gastrointesti-

nal neoplasm. Imaging features of borderline

tumors are similar to those of malignant masses,

and there are no speciﬁc features that allow conﬁ-

dent differentiation of borderline neoplasms from

stage I disease [4,5] . Borderline tumors are treated

with surgical excision and staging. Patients with

borderline tumors treated with conservative unilat-

eral oophorectomy or cystectomy to preserve fertil-

ity require close monitoring and prolonged

imaging follow-up because they have an increased

recurrence rate compared with women treated

with complete total abdominal hysterectomy and

bilateral salpingo-oophorectomy.

Nonepithelial ovarian neoplasms include malig-

nant germ cell tumors and malignant sex cord tu-

mors. Malignant germ cell and sex cord tumors

account for approximately 10% of primary ovarian

cancers.

Malignant germ cell tumors are more frequent in

young patients. The most common subtypes are

dysgerminoma, immature teratoma, and endoder-

mal sinus tumor. Dysgerminoma is an equivalent

of seminoma in male patients. Patients present

with a unilateral, predominantly solid mass with

varying degrees of necrosis and hemorrhage. Nodal

metastases are more frequent than peritoneal dis-

ease. The patients are treated with unilateral salpin-

go-oophorectomy and chemotherapy. Immature

Fig. 1. Two different patients with mucinous ovarian

neoplasms. (A) Mucinous borderline tumor of the

ovary. Contrast-enhanced axial section through the

pelvis shows a large multiloculated cystic mass (ar-

row) with thin internal septations, suggesting a rela-

tively benign process. No ancillary ﬁndings, such as

ascites or peritoneal carcinomatosis, are evident.

(B) Malignant counterpart of mucinous ovarian

tumor—mucinous cystadenocarcinoma (arrow). The

mass is more complex than cystadenoma and contains

a considerable enhancing heterogeneous solid com-

ponent (asterisk), characteristic of malignant

neoplasms.

Ovarian Cancer 151

ovarian teratoma is usually a unilateral solid mass

with coarse calciﬁcations and occasionally a small

amount of fat within the mass. Mature elements

may coexist within the same ovary and within the

contralateral ovary in 10% of cases. Immature tera-

toma metastasizes via peritoneal surfaces.

Sex cord tumors derive from ovarian stroma and

account for only 1% to 2% of all ovarian malignan-

cies. Of the different subtypes of sex cord tumors,

only granulosa cell tumors are seen with consider-

able frequency. These tumors are predominantly

solid and are hormonally active, contributing to

early detection. Granulosa cell tumors are divided

into juvenile and adult types. Adult granulosa cell

tumors present in perimenopausal women with

uterine bleeding secondary to estrogen-induced en-

dometrial hyperplasia. Untreated endometrial hy-

perplasia can progress to endometrial carcinoma

in 5% to 25% of patients. Granulosa cell tumors

can be androgenic and present with virilization.

The typical imaging ﬁndings are solid, usually uni-

lateral masses. They can have a typical spongelike

appearance on MR imaging owing to multiple cystic

components. Granulosa cell tumors have a predis-

position to hemorrhage; 15% patients can present

with hemoperitoneum resulting from occasional

tumor rupture. These tumors are treated with surgi-

cal resection and generally have a good prognosis.

They can recur as peritoneal implants many years

after surgery, however, and prolonged follow-up is

required. Care should be exercised in evaluation

of patients treated for granulosa cell cancer. Recur-

rent peritoneal implants may appear as well-

circumscribed, round and oval homogeneous

intraperitoneal masses, which are difﬁcult to differ-

entiate from unopaciﬁed bowel loops on CT [6,7] .

Secondary neoplasms of the ovary (metastases)

are relatively rare, accounting for only 5% of cases.

The most frequent offenders are gastric carcinoma

(particularly adenocarcinoma with signet features,

so-called Krukenberg’s tumors), colon cancer, pan-

creatic cancer, breast cancer, and melanoma. Metas-

tases are frequently bilateral and at imaging range

from solid enhancing lesions with different degrees

of necrosis to complex cystic masses of various

sizes. Although multilocularity at ultrasound or

MR imaging favors the diagnosis of primary rather

than secondary neoplasm, accurate distinction

between primary and secondary ovarian tumor is

difﬁcult [8] .

Lymphoma of the ovaries is extremely rare and

usually is a manifestation of non-Hodgkin disease.

Lymphoma should be suspected in the presence of

bilateral solid homogeneous ovarian masses with

little contrast enhancement [9] .

Primary peritoneal carcinoma may arise years af-

ter oophorectomy and may resemble the pattern of

spread of ovarian carcinoma with ascites and peri-

toneal tumor implants. Relevant clinical and surgi-

cal history is essential for differential diagnosis.

Ovarian cancer screening

The goal of ovarian cancer screening is to reduce

mortality by detection of potentially curable stage

I invasive epithelial ovarian cancers. Serum CA-

125 measurements and ultrasound are used either

singly or in combination [10–18] . Criteria for an

abnormal ultrasound screening are ovary enlarged

for age, persistent ovarian mass, or cyst with nodu-

larity and septations. Because physiologic changes

such as hemorrhagic cysts may give false-positive re-

sults, it is important that only persistent abnormal-

ities be considered abnormal. The glycoprotein

serum CA-125 marker is elevated in 80% of ovarian

cancers, most of which are advanced at presenta-

tion, but CA-125 is elevated in only 50% of stage

I ovarian tumors. CA-125 also is insensitive for mu-

cinous and germ cell tumors, but these tumors with

good prognosis are less signiﬁcant for screening.

Radiologists should be aware of the current liter-

ature regarding ovarian cancer screening to respond

appropriately to patients’ concerns about disease

prevention and screening strategies. Results of large

screening trials vary according to the screening

methods and study design [10–18] . Studies that

use CA-125 alone report a higher percentage of ad-

vanced tumors with fewer stage I tumors; however,

more recent studies that use serial CA-125 measure-

ments have shown improved results [19] . When ul-

trasound is used primarily, more stage I tumors are

detected, but because ultrasound lacks speciﬁcity,

many women with abnormal screening results

may undergo unnecessary surgery for benign

disease.

Another issue is that screening, particularly the

initial prevalent screen, may identify borderline,

germ cell tumors or granulosa cell tumors that are

biologically less aggressive. Alternatively, high-

grade serous tumors may develop and reach an ad-

vanced stage in the interval between screens ( Fig. 2 )

[20] , and primary peritoneal cancers may develop

without any evident ovarian mass.

Results for any screening test are improved if the

prevalence of disease is high in the screened popu-

lation. Lifetime risk of ovarian cancer is only 1.3%

in the general population, but it is increased to 12%

in women with genetic predisposition. Women

with Lynch II hereditary nonpolyposis colon cancer

syndrome have an approximately 10% lifetime risk

of developing ovarian cancer [21,22] . Lifetime risk

of invasive epithelial cancer is even higher (15–

65%) for women with BRCA mutations. BRCA mu-

tations often are associated with high-grade serous

152

Mironov et al

Fig. 2. A 53-year-old woman with family history of ovarian and breast cancer developed bilateral stage III high-

grade papillary serous ovarian cancer within a 6-month interval between screening ultrasounds. (A and B)

Ultrasound revealed bilateral simple follicles, normal-sized ovaries with volume of 6 mL bilaterally; CA-125

was normal at 16 U/mL. (C–G) Ultrasound 6 months later; right ovarian volume increased to 19 mL, and left ovar-

ian volume was 16 mL. The ovaries contained solid hypervascular masses and had lobulated contours. CA-125

was elevated to 67 U/mL. (H and I) CT scan revealed bilateral ovarian enlargement (black arrow) and leiomyom-

atous uterus. Left para-aortic adenopathy (white arrows) and small pelvic ascites also were present.

Ovarian Cancer 153

ovarian cancers or peritoneal cancers that are less

frequently detected at an early stage by screening

[20,23–26] . A report of 1100 women at moderate

or high risk found 13 ovarian cancers; 10 were

found at screening, but only 2 of these were stage

I tumors [16] . Three ovarian tumors, all of an ad-

vanced stage, were undetected by screening. In addi-

tion, 29 women with benign disease underwent

diagnostic surgery [16] . These results illustrate the

difﬁculties of ovarian cancer screening even in

women at high risk.

To date, there is no evidence that screening re-

duces mortality from ovarian cancer. Current guide-

lines state that screening is not recommended in

premenopausal or postmenopausal women with

or without a family history of ovarian cancer [16] .

For women at high risk because of BRCA mutations

or other hereditary factors suggesting genetic pre-

disposition, screening may be performed until pro-

phylactic oophorectomy after childbearing years

[20,27,28] .

studied 211 adnexal masses including 28 malignan-

cies to determine the best discrimination between

benignity and malignancy by gray-scale and Dopp-

ler. A nonhyperechoic solid component within

a mass, central blood ﬂow on color Doppler imag-

ing, free intraperitoneal ﬂuid, and septations within

a mass had 93% sensitivity and 93% speciﬁcity for

diagnosis of malignancy.

On spectral Doppler, ovarian cancers generally

have low-resistance waveforms because tumor neo-

vasculature lacks smooth muscle, and arteriovenous

shunting may occur [35] . Although initial reports

suggested high sensitivity and speciﬁcity for resis-

tance index cutoff value of 0.4 and pulsatility index

of 1, subsequent studies found speciﬁc values less

reliable because many benign lesions, including

corpora lutea, may have similar waveforms

[35,40,44–48] . These benign lesions are more com-

mon in premenopausal women; when low-resis-

tance ovarian ﬂow is seen in a postmenopausal

woman, the ﬁnding should be considered highly

suspicious for malignant ovarian neoplasm.

Current evidence is that the combination of ovar-

ian morphology and Doppler perform best for

characterization of adnexal masses. Buy and co-

workers [49] used gray-scale ultrasound and duplex

and color Doppler to evaluate 132 adnexal masses,

including 98 benign, 3 borderline, and 31 malig-

nant masses. Adding color Doppler to gray-scale

morphologic information increased speciﬁcity

from 82% to 97% and increased positive predictive

value from 63% to 97%, but there was no added in-

formation from duplex Doppler indices. A large

meta-analysis comparing morphologic assessment,

Doppler ultrasound, color Doppler ﬂow imaging,

and combined techniques for characterization of

adnexal masses using summary receiver operator

curves found the best diagnostic performance for

combined techniques (0.92), followed in decreas-

ing order by morphologic assessment alone

(0.85), Doppler indices (0.82), and color Doppler

ﬂow (0.73) [30] .

It is impossible to differentiate histologic sub-

types of primary ovarian tumors by ultrasound ap-

pearance, but there are some features that should be

considered. Epithelial ovarian tumors are typically

cystic, but endometrioid tumors may be solid. Mu-

cinous cystadenocarcinomas are more septated

than serous cystadenocarcinomas and may have

ﬂuid with low-level echoes. Malignant germ cell tu-

mors are predominately solid, as are stromal tu-

mors. Primary ovarian carcinomas are frequently

bilateral, varying with subtype; approximately

50% of serous cystadenocarcinomas and 30% of

endometrioid cancers are bilateral, whereas clear

cell and mucinous tumors are bilateral in 20% of

cases [8,35,50] .

Lesion characterization

In patients with a known or suspected adnexal

mass, ultrasound is highly accurate in the assess-

ment of tumor location (eg, differentiation of uter-

ine from adnexal masses) and in distinguishing

between a benign and malignant adnexal lesion.

The optimal use of ultrasound requires the analysis

of morphologic features and Doppler ﬁndings

[29–32] .

Ovarian masses with septations greater than 3

mm, mural nodularity, and papillary projections

suggest the diagnosis of malignant ovarian neo-

plasm [33–35] . The most signiﬁcant feature is the

presence of solid components within an ovarian

mass [36] . Some benign lesions, most commonly

endometriomas and hemorrhagic cysts, may have

similar appearance to malignant ovarian tumors.

For premenopausal women, it is important that

ovarian lesions have follow-up to exclude transient

physiologic changes that may mimic ovarian carci-

noma. Morphologic scoring systems are used to

standardize diagnosis of ovarian cancer by assign-

ing numerical scores for various ultrasound

features, such as size, wall thickness, solid compo-

nents, and number and thickness of septations

[37–40] , but similar excellent interobserver vari-

ability is reported when subjective criteria are

used [41] .

Color and pulsed Doppler techniques may aid di-

agnosis of ovarian cancer. Central color Doppler

ﬂow within solid components of an ovarian mass

has been shown to be an accurate predictor of ma-

lignancy [36,42,43] . Brown and colleagues [36]

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