Stromal Overgrowth in a Brenner Tumor Or Ovarian Fibroma with Minor Sex Cord Elements? Julia A
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Case Report Stromal Overgrowth in a Brenner Tumor or Ovarian Fibroma With Minor Sex Cord Elements? Julia A. Ross, MD, PhD, and Ozlen Saglam, MD Summary: Computed tomography obtained as part pausal woman was referred for computed tomogra- of a urinary tract assessment in a 68-year-old woman phy as part of a urinary tract assessment. The imaging incidentally detected a solid adnexal mass. Bilateral study incidentally revealed an adnexal mass with calci- salpingo-oophorectomy revealed a unilateral, 4-cm, fications. Ultrasonography was obtained and showed white to tan-yellow colored, focally calcified, left a 3.3 × 2.4 cm left adnexal mass with no blood flow, ovarian mass. Microscopically, the tumor was com- which was suspicious for a possible dermoid cyst. Sub- posed of bland fibroblasts, abundant collagen, and sequently, magnetic resonance imaging demonstrated areas of calcification with a minor component com- a 3 × 2.6 × 2.2 cm mass in the left ovary with a homo- posed of nests of epithelial cells with nuclear clefts geneous, low T2 signal and very minimal enhance- focally evident, some of which contained central lu- ment following the administration of gadolinium, mens with eosinophilic secretions. The major consid- a finding suspicious for ovarian fibroma (Fig 1A). erations were fibromatous overgrowth in a Brenner Her level of cancer antigen 125 was normal (3.1; nor- tumor or ovarian fibroma with minor sex cord ele- mal < 35 U/mL). Given the suspected benign nature of ments. Immunostains for cytokeratin 7 showed dif- the ovarian mass, surgery limited to bilateral salpin- fuse positivity in the epithelial nests, whereas cy- go-oophorectomy was performed. tokeratin 20 and inhibin were negative, further Grossly, the left ovary was firm with a smooth supporting the diagnosis of a Brenner tumor. and glistening external surface. The ovary was sec- tioned to reveal a 4-cm solid mass with a tan-yel- Background low to white-colored, focally calcified, cut surface Most ovarian neoplasms are surface epithelial tumors, (Fig 1B). The lesion replaced nearly the entire left 2% to 3% of which represent Brenner tumors.1 Inci- ovary measuring 4.5 × 2.8 × 2.2 cm. Microscopical- dental Brenner tumors are not uncommon in oopho- ly, the lesion had well-circumscribed borders. It was rectomy specimens, and the true incidence of these predominantly composed of fibrous stroma with lesions may be higher than estimated. The clinical bland spindle cells and collagen with large areas significance, if any, of incidental Brenner tumor is of calcification distributed in the abundant stromal unknown. Because of the common presence of mu- collagen (Fig 2A and B). Admixed with the fibrous cinous epithelium lining the central space in Brenner stroma and calcifications were multiple small epi- nests, a variety of mucinous tumors may arise with- thelial nests comprising 10% to 15% of the entire le- in a Brenner tumor. Brenner tumors also commonly sion, some of which had central lumens filled with occur in association with other ovarian tumors, in- eosinophilic secretions (Fig 2C). Although the epithe- cluding serous adenofibroma and mature cystic tera- lial nests made up a minor component of the lesion, tomas.2 Sex cord–stromal tumors represent approxi- they were scattered throughout multiple sections and mately 6% to 8% of ovarian neoplasms, with fibromas were found in close proximity of the calcifications accounting for the majority.3 A small portion of fibro- under high-power examination. The epithelial cells mas have minor sex cord elements. were relatively uniform in size with scant cytoplasm and nuclei with occasional longitudinal grooves. No Case Report related mucinous epithelium was identified. A 68-year-old white, gravida 4, para 4, postmeno- The epithelial nests showed strong and diffuse im- munoreactivity with cytokeratin (CK) 7 (Fig 2D) but From the Department of Pathology, Yale University School of Medi- were negative for CK20 and inhibin. The contralateral cine (JAR), New Haven, Connecticut, and H. Lee Moffitt Cancer ovary measuring 2.8 × 2.4 × 1.8 cm revealed cortical in- Center & Research Institute (OS), Tampa, Florida. clusion cysts. The fallopian tubes demonstrated para- Address correspondence to Ozlen Saglam, MD, Department of Pa- thology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL tubal cysts with no additional pathological findings. 33612. E-mail: [email protected]. No significant relationships exist between the authors and the Discussion companies/organizations whose products or services may be ref- erenced in this article. The pathological findings in this case supported the 366 Cancer Control July 2015, Vol. 22, No. 3 22.49 mm A B Fig 1A–B. — (A) Magnetic resonance imaging of the left ovarian mass that showed homogeneous, low T2 signal and minimal enhancement after the administration of gadolinium. (B) Gross pathology showing the cut surface of the 4-cm ovarian mass. clinical and radiological findings of a benign ovarian cystic lesions.5 The cytological features of borderline or neoplasm. The gross examination was characteristic of low-malignant potential Brenner tumors can be similar an ovarian fibroma with a solid, firm, cut surface. The to that of benign Brenner tumors; however, their archi- presence of focal microscopic epithelial nests within tectural features are more complex, forming papillae the fibrous stroma suggested the differential diagno- or polypoid structures.6 sis of ovarian fibroma with minor sex cord elements, Approximately 50% of Brenner tumors are associ- a rare entity described by Young and Scully in 1983.4 ated with calcifications and fibromas may show dense By definition, the sex cord elements represent less than calcifications as well.3,7,8 The distinction between a 10% of the lesion and are composed of granulosa cells, Brenner tumor with fibrous stroma and ovarian fibro- Sertoli cells, or indifferent cells of a sex cord–like type. ma may seem to be an academic exercise, particularly Our case was predominantly a fibrous tumor with a because both entities are benign; however, despite the small component of transitional-type epithelial islands benignity of both lesions, the characterization can be (10%–15%) distributed within fibrous stroma. By con- important because multiple reports of tumors metasta- trast to typical sex cord elements, the epithelial nests sizing to ovarian lesions such as Brenner tumor — and, in this case had cystic lumina with eosinophilic secre- to a lesser extent, fibroma — have been described.9-12 tions. In addition, the presence of nuclear grooves was These examples include renal cell carcinoma metas- an indication of a transitional-type epithelium. These tasizing to mixed Brenner tumor with mucinous cyst- entities can be further distinguished with immunohis- adenoma,9 squamous cell carcinoma of the cervix me- tochemistry, because sex cord–stromal elements stain tastasizing to Brenner tumor,10 breast cystosarcoma positively with inhibin and Brenner tumors stain with phyllodes to Brenner tumor,11 and breast adenocarci- CK7. In our case, the epithelial groups showed CK7 noma metastasizing to benign ovarian fibroma.12 positivity and inhibin negativity, supporting the find- ings on hematoxylin and eosin staining. Conclusions Given the patient’s presentation, which included Imaging, microscopic, and immunohistochemical fea- urinary tract complaints, the possibility of metastatic tures of a Brenner tumor with abundant fibrous stro- urothelial carcinoma was considered, but the nests of mal overgrowth were presented. The rare entity of transitional cells lacked significant proliferation, atyp- fibroma with minor sex cord elements was excluded ia, or mitotic activity. In general, metastatic tumors of by morphological and immunophenotypical features. the ovary present as multiple bilateral lesions, which Ovarian fibroma with an incidental Brenner tumor is in contrast to the unilateral presentation of this le- component may also be considered in the differential sion. Furthermore, urothelial carcinomas coexpress diagnosis. By contrast to the localized nature of the CK7 and CK20. The latter marker was negative in the epithelial component in a Brenner tumor with fibrous epithelial nests. stroma, the presence of relatively scattered epithelial The distinction can be more challenging in a case elements is an atypical finding in this case. Brenner of borderline or malignant Brenner tumor, or a transi- tumors can occur with other ovarian neoplasms; how- tional variant of high-grade serous carcinoma, as any ever, a description of Brenner tumor coexisting with and all of these may and, not infrequently, present as ovarian fibroma has, to our knowledge, never been de- July 2015, Vol. 22, No. 3 Cancer Control 367 A B C D Fig 2A–D. — (A) Ovarian mass with calcifications, abundant fibrous stroma, bland spindle cells, and collagen. Focal areas contain small epithelial nests with central lumens filled with eosinophilic secretions (H & E, × 40). (B) Higher power microscopy of fibromatous area (H & E, × 100). (C) Higher power view of epithelial nests with central lumens filled with eosinophilic secretions (H & E, × 100). (D) Cytokeratin 7 immunoreactivity of epithelial nests (× 100). H & E = hematoxylin and eosin. 4 Young RH, Scully RE. Ovarian stromal tumors with minor sex tailed. Although this may be the scenario in the case cord elements: a report of seven cases. Int J Gynecol Pathol. 1983;2(3): presented, the diagnosis of Brenner tumor is favored in 227-234. 5 Ulbright TM, Roth LM, Stehman FB. Secondary ovarian neoplasia. the presence of a single gross nodular lesion. Despite A clinicopathologic study of 35 cases. Cancer. 1984;53(5):1164-1174. the benign nature of both lesions, an awareness of the . 6 Roth LM, Gersell DJ, Ulbright TM. Ovarian Brenner tumors and transitional cell carcinoma: recent developments. Int J Gynecol Pathol. potential for tumors to metastasize to these lesions 1993;12(2):128-133. should be noted. 7 Green GE, Mortele KJ, Glickman JN, et al. Brenner tumors of the ovary: sonographic and computed tomographic imaging features. J Ultra- sound Med.