Article

Brenner Tumors of the Ovary

Sonographic and Computed Tomographic Imaging Features

Gretchen E. Green, MD, Koenraad J. Mortele, MD, Jonathan N. Glickman, MD, PhD, Carol B. Benson, MD

Objective. The purpose of this study was to describe the sonographic appearance of ovarian Brenner tumors with computed tomographic (CT) correlation. Methods. Twenty-two female patients (age range, 3278 years; mean, 58 years) with 25 ovarian Brenner tumors were identified from pathologic records from 1990 to 2005. Corresponding pathologic reports and images (17 sonographic and 14 CT) were reviewed independently. Results. Tumors ranged in size from 0.3 to 12 cm (mean, 2.5 cm); all were benign. Sixteen (64%) of 25 were found incidentally. Eight (36%) of 22 patients had a total of 12 associated benign ovarian neoplasms (1 was contralateral); 3 patients had bilateral Brenner tumors. Eight (47%) of 17 tumors were not seen on sonography, and 5 (36%) of 14 were not seen on CT. Of the tumors seen on imaging, most were solid (67% on sonography and 78% on CT). Four tumors appeared at least partially cystic, of which 3 had coexistent cystic ovarian lesions. Conclusions. Brenner tumors are most often solid neoplasms found incidentally and frequently seen in association with other benign ovarian epithelial neoplasms. Key words: genitourinary system; neoplasm; ovary; sonography.

Abbreviations CT, computed tomographic

Received April 18, 2006, from the Departments of Radiology (G.E.G., K.J.M., C.B.B.) and Pathology (J.N.G.), Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts USA. Revision requested May 5, 2006. Revised manuscript accepted for publication May 17, 2006. Address correspondence to Gretchen E. Green, MD, Department of Radiology, Brigham and Womens Hospital, 75 Francis St, Boston, MA 02115 USA. E-mail: gegreen@partners.org

renner tumors are uncommon ovarian neoplasms most often found incidentally in women between their fifth and seventh decades of life. Although they are predominantly solid on imaging and pathologic examination, association with serous and mucinous cystadenomas in up to 30% may account for a cystic appearance when the Brenner tumor itself is visually inseparable from the coexistent cystic neoplasm or very small.1 The purpose of this study was to describe the sonographic appearance of pathologically documented ovarian Brenner tumors with computed tomographic (CT) correlation.

Materials and Methods

Subjects Electronic surgical pathologic records from 1990 until 2005 at Brigham and Womens Hospital were searched for the term Brenner tumor, and matching records were identified and reviewed retrospectively. Only patients

2006 by the American Institute of Ultrasound in Medicine J Ultrasound Med 2006; 25:12451251 0278-4297/06/$3.50

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who underwent preoperative sonographic or CT imaging at our institution were included in the study. The electronic record search yielded 56 patients with ovarian Brenner tumors from 1990 to 2005. Of these, 22 patients underwent sonography, CT, or both preoperatively at our institution. Among the 22 patients, there were 25 Brenner tumors. Patients ranged in age from 32 to 78 years (mean age, 58 years). Patient medical histories and indications for examination are listed in Table 1. Histories were not available for 3 patients. Image Analysis Our study was conducted with Institutional Review Board approval. The need for informed consent was waived for this retrospective study. For cases in which sonographic or CT examinations had been performed, the images were reviewed: sonography by 1 author (C.B.B.), CT by 1 author (K.J.M.), and both modalities by 1 author (G.E.G.). The following features were recorded: size, laterality, solid or cystic appearance, presence or absence of calcifications or a coexisting neoplasm, and endometrial stripe thickness (when available). Pathologic Examination Hematoxylin-eosinstained paraffin sections were reviewed by 1 author (J.N.G.), and the diagnoses were confirmed. The following histologic parameters were recorded on the basis of histologic analysis and review of the original pathologic reports: gross configuration (solid or cystic), tumor size (in centimeters), gross tumor color, microscopic calcifications, and the presence of coexisting ovarian neoplasms or tumorlike lesions.

Results
Sonography was performed for 17 (68%) of the 25 tumors (Table 2). Eight (47%) of these 17 tumors were not seen on sonography (Table 3) and were identified on pathologic examination only. Two ovaries with Brenner tumors (measuring 0.6 and 1 cm, respectively) were not visualized on sonography; the remaining 6 ovaries containing Brenner tumors (size range, 0.31 cm) were visualized but thought to be normal. Of the 9 tumors seen on sonography, 6 (67%) appeared solid; 3 were at least partially cystic; and 5 (56%) had calcifications (Figure 1). Fourteen (56%) of 25 tumors were evaluated with CT scans (Table 2). Five (36%) of these were not seen on CT (Table 3) and were identified on pathologic examination only (size range, microscopic to 2.3 cm). Of the 9 tumors seen on CT, 7 (78%) appeared solid; 2 were partially cystic; and 5 had calcifications (Figure 2). On CT, the calcifications were linear in 3 and punctate in 2, one of which was peripheral and the other central in location (Figure 3). Six tumors had both CT and sonography before surgery. Four (67%) of these were not seen on sonography (Figure 4) or CT (Figure 5) (size range, 0.32.3 cm). Fifteen (60%) of 25 tumors were found on the left side; 9 (36%) were found on the right; and laterality could not be determined for 1 tumor removed as a component of a large midline mass (4%). Three (14%) of 22 patients had bilateral Brenner tumors. Twelve coexisting ovarian neoplasms were present in 8 (36%) of 22 patients (Table 4). Eight coexisting tumors were in the same ovary as the Brenner tumor (Figures 68), and 2 were contralateral. Two coexisting tumors were present in 1 patient, but laterality could not be determined because it was not known from which ovary the Brenner tumor arose. At pathologic examination, the Brenner tumors ranged in size from 0.3 to 12 cm (mean, 2.5 cm). One was described as microscopic, and size was not available for 2 tumors. All Brenner tumors were benign. Nineteen (76%) of 25 were solid. Most were tan-yellow and hard-firm to palpation on gross pathologic examination. Two (8%) of 25 were at least partially cystic. Gross pathologic findings were not available for 4 (16%) of 25 tumors; 3 of these were between 0.3 and 0.5 cm (size was not available for 1). Two of the solid tumors contained calcifications; neither of the 2
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Table 1. Patient Histories and Clinical Indications for Examinations

History/Indication n (%)

Incidental finding, asymptomatic Mass* Palpable mass Pain Vaginal bleeding Unknown Total

7 5 2 2 3 3 22

(32) (23) (9) (9) (14) (14) (100)

*It could not be determined from clinical history whether the mass in question was diagnosed on outside imaging, via physical examination, or both.

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Table 2. Sonographic and CT Features of Brenner Tumors

Tumor Side Size, cm CT Features Sonographic Features Calcifications

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Left Right Right Left Left Right Left Left Right Right Left Left Left Right Left Left Left NA Left Right Right Left Right Left Left

NA 2.3 2 4.5 1 4.9 0.3 4 0.6 4 0.7 3 6 1 1.5 1 0.3 NA 6.5 1.0 5.5 4.5 Microscopic 12 0.5

Solid Not seen NA Solid NA NA NA NA Not seen NA NA Solid Cystic/solid Not seen Solid NA Not seen Solid NA NA Solid Solid Not seen Cystic/solid NA

Cystic/solid* Not seen Cystic NA Not seen Solid Not seen Solid Not seen Solid Not seen NA Cystic/solid Not seen NA Not seen Not seen NA Solid Solid NA NA NA NA Solid

No No No Yes No Yes No No No Yes No No Yes (CT) No (sonography) No Yes No No No No Yes Yes Yes No No No

NA indicates not applicable (study not performed or information not available). *Sonography did not show an ipsilateral serous cystadenofibroma as separate from the solid Brenner tumor. Pathologic examination showed cortical inclusion cysts that accounted for the cystic appearance. The tumor was solid/cystic on pathologic examination as well.

partly cystic tumors was thought to contain calcifications on pathologic examination. One patient had endometrial thickening seen preoperatively on sonography; this patient had vaginal bleeding but was also taking tamoxifen for breast cancer. The endometrium was reported as either normal or atrophic on either pathologic or radiologic examination in the remainder of patients who had not previously undergone hysterectomy.

Discussion
The largest study of clinicopathologic features of Brenner tumors was conducted in 402 patients in 1960.2 Brenner tumors were originally known as transitional cell tumors because of their histologic similarity to the urothelium. They account for up to 3.2% of ovarian epithelial neoplasms.3 The true incidence may be higher but is not definitely known; many are found incidentally on pathologic examination for oophorectomy per-

Table 3. Size of Tumors Not Seen

Ovary Not Visualized on Sonography (n = 2) Tumor Size, cm Ovary Containing Tumor Thought to be Normal on Sonography (n = 6) Tumor Not Seen on CT (n = 5)

0.6 1.0

0.3 0.3 0.7 1.0 1.0 2.3

Microscopic 0.3 0.6 1.0 2.3

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Figure 1. A, Transverse sonogram of the right ovary shows a Brenner tumor appearing as a shadowing hypoechoic mass (calipers) with punctate echogenic foci. B, Transverse sonogram of the left ovary in a different patient shows a Brenner tumor also appearing as a shadowing hypoechoic mass (calipers).

formed for other reasons. To the best of our knowledge, ours is the largest single-institution group of patients with Brenner tumors for which imaging was available described in the English language. The average age of the patients in our series was 58 years. Investigators have reported average patient ages of 46.53 to 634 years. Age also correlates with disease: most benign Brenner tumors are found in women between the ages of 30 and 59 years,5 whereas borderline and malignant tumors have a higher age range (4560 years).6 Patients in our series were asymptomatic (7 [32%] of 22) or had symptoms unrelated to the Brenner tumor. Similarly, most Brenner tumors reported in the literature are found incidentally or as the result of symptoms from a coexistent neoplasm, typically due to mass effect. Among
Figure 2. Axial contrast-enhanced CT shows a solid left adnexal mass (arrow) with peripheral and central calcifications; this was a 4.7-cm solid Brenner tumor at pathologic examination.

symptomatic patients, common symptoms include vaginal bleeding, a palpable pelvic mass, and pelvic pain.3 Although tumoral estrogenic activity manifesting as vaginal bleeding has been reported,7 it is uncommon in the literature, as was also true for our patient population (vaginal bleeding occurred in 3 [14%] of 22 patients, 1 of whom was taking tamoxifen). Our incidence of 36% of patients with ovarian neoplasms associated with Brenner tumors was slightly higher than the rate of 30% reported in the literature, as was our incidence of bilaterality (14%), which has been reported as 5% to 7%.6 It is unclear whether a common pathogenetic mechanism exists for Brenner tumors and other epithelial tumors to explain their common association or whether a specific factor predisposes to bilaterality.
Figure 3. Axial contrast-enhanced CT of the pelvis shows a Brenner tumor appearing as a soft tissue density mass in the left adnexa (arrow) with a punctate central calcification.

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Table 4. Ovarian Neoplasms Associated With Brenner Tumors

Type of Neoplasm n

Mucinous cystadenoma Fibroma-thecoma Serous cystadenofibroma Serous papillary adenofibroma Adenofibroma

4 2 2 (1 contralateral) 3 (1 contralateral) 1

Figure 4. Coronal sonogram of the left ovary shows a simple cyst. A Brenner tumor measuring 0.3 cm was not seen on sonography.

At pathologic examination, Brenner tumors are composed of epithelial nests surrounded by proliferating dense stromal tissue (Figures 911). The fibrous component is less prominent in borderline or malignant tumors than in benign lesions. Benign tumors are generally solid at pathologic examination, as was the case with 76% of the tumors in our series. Complex cystic tumors contain varying amounts of stroma and are more commonly found with borderline or
Figure 5. Transverse contrast-enhanced CT in another patient also shows a simple left ovarian cyst (white arrow); a 0.3-cm Brenner tumor was not seen. A uterine lipoleiomyoma is incidentally shown (black arrow).

malignant histologic findings, often in the form of papillary solid projections within a cystic mass.8 Size also correlates with histologic grade: most benign tumors are smaller than 5 cm, and those with borderline or malignant histologic findings are larger than 5 cm at diagnosis. All Brenner tumors in our series were benign, in keeping with the preponderance of benign tumors reported in the literature.1 Sonography and CT may both show Brenner tumors, but both techniques are limited in specificity because of the tumors nonspecific appearance, and sensitivity may be limited by the tumors small size, the presence of a coexistent epithelial lesion, or both. The diagnosis may be suggested in a patient with an incidental small solid ovarian mass. Imaging characteristics of benign Brenner tumors are generally similar to those of other solid ovarian masses. Sonography, although helpful in
Figure 6. Axial unenhanced CT shows a cystic/solid left adnexal mass (white arrow), which was found to represent a Brenner tumor with coexistent left-sided serous cystadenofibroma. The study had been performed because of clinical concern for a retroperitoneal hematoma (black arrow) due to a decreased hematocrit level after cardiac catheterization.

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Figure 7. A, Contrast-enhanced axial CT shows a multiloculated cystic mass in the left adnexa (arrows); at pathologic examination, this was a 12-cm Brenner tumor with coexistent mucinous cystadenoma. B, A more cephalad axial image from the same patient also shows a right-sided multiloculated cystic adnexal mass (arrow), found to be a microscopic Brenner tumor with coexistent multiloculated cystic papillary serous adenoma.

differentiating solid from cystic masses, is of more limited utility in detecting small tumors. Athey and Siegel3 identified 3 of 4 tumors prospectively on sonography; 8 (47%) of 17 tumors in our series were not seen on sonography retrospectively.3 Moon et al4 reported that 5 (63%) of 8 patients had either a predominantly solid or at least a partly solid appearance on CT, lower than our result of 78%. Calcifications have been reported in 50% of Brenner tumors on sonography3 and 83% on CT4; both of these modalities showed 56% prevalence of calcifications in our series. Magnetic resonance imaging may also show Brenner tumors, given their not infrequent incidental appearance on pelvic imaging studies. Magnetic resonance imaging may show a T1Figure 8. Coronal sonogram of the right adnexa shows a solid mass of mixed echogenicity (arrows). At pathologic examination, a 4.9-cm Brenner tumor was found with a coexisting 12-cm fibroma-thecoma.

and T2-weighted hypointense solid component containing fibrous tissue, mimicking a fibroma.9 In a tumor with a cystic component, signal intensity may be similar to that of fluid (T1, hypointense; T2, hyperintense) or may have characteristics suggesting hemorrhage (T1, hyperintensity).8 Enhancement of the solid component, septa, or both may be present. Despite the large size of some benign Brenner tumors (>10 cm), lack of local invasion, lymphadenopathy, ascites, or metastasis (ie, peritoneal metastases and omental caking) helps distinguish it from malignant ovarian neoplasms. It is not surprising that the smallest Brenner tumors in our series were not visible on sonography or CT and were only found incidentally on pathologic examination, given that their small size
Figure 9. Low-power (original magnification 40) image of nests of epithelium (arrows) within a fibrous stroma.

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Figure 10. Higher-power (original magnification 200) image of a benign epithelial nest (arrow).

may not cause contour deformity, and, as solid masses, they would most often appear similar to ovarian tissue. When visible as a solid mass, the imaging differential diagnosis includes fibroma, fibrothecoma, pedunculated leiomyoma, and metastasis.10,11 The differential diagnosis for cystic neoplasms includes serous and mucinous cystadenoma/cystadenocarcinoma, teratoma, clear cell carcinoma, endometrioid carcinoma, and possibly necrotic primary malignancy or metastasis. If estrogenic activity is present (manifested by a thickened endometrium), differential considerations include granulosa cell tumors and SertoliLeydig cell tumors. In patients with solid ovarian masses smaller than 5 cm, no sign of local invasion or metastasis, and no known primary malignancy, surgical excision may not be warranted in all cases.
Figure 11. Low-power (original magnification 40) image of a Brenner tumor with coexistent mucinous cystadenoma.

Because sonographic and other imaging findings of Brenner tumors with a cystic component are indistinguishable in most cases from those of malignancy, surgical excision is generally warranted and is curative for benign Brenner tumors. Few data are available for patients with borderline or malignant Brenner tumors, but the prognosis (as based on the stage at presentation) is likely similar to that of other malignant epithelial ovarian neoplasms. In conclusion, Brenner tumors are most often solid neoplasms commonly found incidentally and frequently seen in association with other epithelial neoplasms. They should be included in the differential diagnosis of solid ovarian neoplasms. A cystic component suggests the presence of a coexistent cystic epithelial neoplasm, such as a serous or mucinous cystadenoma.

References
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