Well-demarcated nests of urothelial cells are embedded in a fibrous stroma. These cell nests often have cystic lumens filled with eosinophilic material shown here or mucin if the lumen is lined by metaplastic mucinous cells (not shown here). Condensed encircling stroma is often seen, but is very subtle in this example.
A nest of urothelial cells with several microcysts is the characteristic feature of Brenner tumor. The surrounding fibrous stroma resembles that of ovarian stroma and shows condensation around the epithelial nests.
These microcysts can be lined by metaplastic mucinous epithelium (resembling endocervical cells), squamous epithelium, or ciliated cells. In this image, the lining is somewhat attenuated and difficult to place in any of the above categories. Eosinophilic material or mucin are frequently found inside the cystic lumens.
The neoplastic cells have oval and round nuclei with characteristic longitudinal grooves, often described as coffee bean nuclei. Nucleoli are small and conspicuous. Note that there is no cytologic atypia in benign Brenner tumor. If cytologic atypia and mitotic figures were present, one would consider a diagnosis of borderline Brenner tumor.
Brenner tumor with stromal calcifications.
Brenner tumors are surface epithelial tumors comprised of transitional (urothelial) epithelium. They constitute ~ 2% of ovarian epithelial tumors, and the vast majority (99%) of them are benign and incidental findings. Less than 1% are borderline or malignant. ~20-25% are found in conjunction with mucinous or serous cystadenomas and benign teratomas.1
Transitional cell tumors of the ovary are classified as follows (1993 WHO Classification): Brenner tumor, Brenner tumor of borderline malignancy, Malignant Brenner tumor and Transitional cell carcinoma, non-Brenner type.3
Borderline Brenner tumors:
Resembles low-grade papillary transitional cell carcinomas in the bladder, with stratified transitional epithelium in broad papillary fronds. Mild nuclear atypia with increased N/C ratio is seen in low-grade borderline Brenner, and more prominent nuclear atypia is seen in high-grade borderline Brenner.2 Mitotic figures may be found occasionally, which should be largely absent in benign Brenner tumors.
Malignant Brenner tumor versus "pure" transitional cell carcinoma:
Malignant Brenner tumors MUST have adjacent foci of benign or borderline Brenner tumor. With this continuity of benign/borderline to malignant epithelium, one can reasonably assume malignant Brenner tumors arise from pre-existing Brenner tumors. But if these Brenner elements are not present, they are called "pure transitional cell carcinomas" or "transitional cell carcinoma, non-Brenner type". Distinguishing malignant Brenner tumor from transitional cell carcinoma is very important as the latter presents at a later stage and is a more aggressive neoplasm.
Both malignant Brenner Tumor and transitional cell carcinoma resembles high-grade transitional cell carcinoma of the bladder. Stromal invasion, areas of necrosis, increased hyperchromasia and pleomorphism of nuclei, and numerous mitotic figures are key features. There are two main architectural patterns: (1) malignant stratified transitional cells lining papillary fronds (2) "Brenner-type" nests. In both patterns, nests and cords of malignant cells invade into desmoplastic stroma.2
"Pure" transitional cell carcinomas (non-Brenner type) have a worse outcome than malignant Brenner tumors. ~80% of malignant Brenner tumors present at stage I, while two-thirds of pure transitional cell carcinomas have visceral spread at time of diagnosis. It appears that transitional cell carcinoma are quite different tumors from the Brenner tumors, as they do not demonstrate urothelial differentiation immunohistochemically and have a markedly different clinical course and response to therapy.1,2
Age range is 40-80 (mean age of diagnosis = 50). Typically these are asymptomatic incidental findings on imaging or surgery for indications unrelated to the ovary. Like all adnexal masses they may be involved in torsion. The majority are unilateral. Malignant forms are very rare.
Benign and borderline brenner tumors can be treated by oophorectomy. Malignant and transitional cell carcinoma are treated by surgical staging for ovarian cancer with tumor debulking and adjuvant chemotherapy. Given the rarity of malignant forms, various chemotherapy regimens have been used with little reported success. It appears that transitional cell carcinoma, though presenting at a later stage than malignant Brenner tumor, is more responsive to chemotherapy.
Malignant Brenner and transitional cell carcinoma (non-Brenner type) are very rare but associated with a poor prognosis. 80% of malignant Brenner tumor present at stage I, however, two-thirds of transitional cell carcinoma present at a high stage, with involvement adjacent pelvic structures.1
1 Nucci MR, Oliva E. Gynecologic Pathology: Foundations in Diagnostic Pathology. Philadelphia, PA: Elsevier; 2009: 436-441.
2 Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd Ed. Philadelphia, PA: Elsevier; 2007: 585-587.
3 Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. 7th Ed. Philadelphia, PA: Elsevier; 2005: 1093