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The case of a metastasizing malignant Brenner tumor of the ovary in a 67-year-old patient is presented. Following a subtotal operation (hysterectomy with both adnexa and omentectomy), a complete remission of 7 month duration was obtained by means of a combined chemotherapy. By changing the therapy over to cisplatinum, one succeeded up to now in controlling the local recurrence, quickly developing after that. The therapeutic proceedings in cases of such rare tumors are discussed.

The results of the treatments of the ovarian tumors are very different according to the numerous statistics. These discrepancies are linked with the difficulties in interpreting the histologic and cytologic criteria. Clinicians and pathologists are sensibilized by the severity of the ovarian cancer and carry out heavy therapies out of proportion with the potential evolution of the tumor. The aim of this work, which was presented at a meeting during the Assises d'anatomic pathologique (Brussels, 26-28 March 1981), is to specify the histologic and cytologic characters permitting to isolate the ovarian border-lesions which have a much better prognosis than the ovarian carcinomas grade I.

Argyrophil cells were identified by the single-impregnation Grimelius technique in 11 of 28 (39%) Brenner tumors, accounting for less than 1% of the tumor cell population in all the cases. All tumors with argyrophil cells were stained to demonstrate calcitonin, somatostatin, gastrin, adrenocorticotropic hormone, neurotensin, insulin, glucagon, and serotonin; and four of them (three benign and one borderline) were also stained for chromogranins with the monoclonal antibody LK2H10. Serotonin was present in nine of the 11 cases with argyrophil cells. Neurotensin and somatostatin were found in one borderline tumor, which also contained serotonin. Chromogranin reactivity was demonstrated in all four cases in which it was examined. Ultrastructural examination of one tumor revealed that the argyrophil cells contained secretory granules, 80 nm in diameter, and had elongated cytoplasmic processes that extended between the more numerous nonargyrophil tumor cells. The argyrophil cells of Brenner tumors are similar to those of urothelium in the frequency with which they are immunoreactive for serotonin and the rarity with which they are reactive for peptide hormones. These cells differ from those of mucinous ovarian tumors, which often contain both serotonin and peptide hormones. The findings of this study lend additional support to the close similarity of the epithelial components of Brenner tumors and urothelium.

A case is reported of an unusually large benign cystic Brenner tumor. Larger solid tumors have been reported, and, additionally, proliferating Brenner tumors are most often large and cystic. However, the tumor described in this presentation appears to be the largest entirely cystic Brenner tumor reported to date.

A 64-year-old woman with a 45,X karyotype and Turner's syndrome and recent onset of right lower quadrant pain was found to have a mucinous cystadenoma with focal areas of borderline malignancy and a typical Brenner tumor in the right adnexa. Ovarian tumors in patients with a 45,X karyotype and Turner's syndrome are extremely rare. The present paper is the first report of concurrence of these 2 tumors in an affected individual. The simultaneous occurrence and intimate admixture of these tumors in a patient believed to be devoid of germ cells would seem to favor a common histogenesis from the germinal epithelium.

A study of 213 ovarian tumors was undertaken with respect to the published assumption that there may be a relationship between presence of crystals of silicate in the ovarian tissue and neoplastic transformation. The histological review gave the opportunity to classify these tumors according to the recommendations of the World Health Organization. The frequency of histological types, age distribution and the site of involvement were determined. These data were compared to those in the literature. Our findings confirm the high incidence of serous tumors and bilaterality reported by others as well as the high risk of ovarian cancer in women in their fifties. A comparative study of the age distribution of cytadenomas was made. It suggests that cystadenomas might be considered as a precursor to the cystadenocarcinomas because of their appearance at younger age. A deliberate search for silicate crystals in periovarian adhesions and in tumor tissue showed a minimal incidence of crystalline material. This does not support a direct relationship between silicate crystals and ovarian tumors. However, it is suggested that neoplastic changes may occur in the ovarian surface as a result of adhesions engendered by deposition of silicate crystals.

Ovarian tumors of low malignant potential (LMP) must be distinguished from benign, "proliferating" ovarian tumors and from frank ovarian carcinoma. Serous and mucinous tumors of LMP demonstrate epithelial stratification, the formation of epithelial tufts, cytologic atypia, and mitotic activity, but they do not demonstrate stromal invasion by epithelial cells, which is a feature of frank carcinoma. Mucinous carcinoma may also be recognized by epithelial stratification exceeding three cell layers and the formation of true cribriform glandular patterns. Although controversial, we do not at present recognize a LMP tumor of endometrioid type but prefer to classify those endometrioid neoplasms with a prominent fibrous stroma and glandular complexity similar to adenomatous endometrial hyperplasia as proliferating endometrioid adenofibromatous and cystadenofibromatous tumors. There is only mild cytologic atypia in such tumors. Because of the moderate to marked cytologic atypia that occurs in some clear cell neoplasms with a prominent fibrous stroma, we believe those tumors do merit a designation of LMP tumors. In both the proliferating endometrioid and LMP clear cell adenofibromatous and cystadenofibromatous tumors, carcinoma must be excluded by an absence of stromal invasion, which is frequently recognized by a confluent glandular pattern. The histologic features of proliferating Brenner tumors are similar to those of low grade, papillary, noninvasive, urothelial carcinoma, whereas we propose that Brenner tumors of LMP show high grade cytologic atypia but remain noninvasive in the ovary.

Fifty-six Brenner tumors of 51 patients were analyzed. The incidence of bilaterality was 9.8%. Most tumors were smaller than 2 cm, and constituted incidental finding. Most of the patients were 30-49 years old (mean 49.7, main 44). A high incidence of associated malignant neoplasms was noticed among the patients with Brenner tumor but was considered coincidental. No evidence of hormone secretion by the tumor was found. Out of 31 tumors, 27 occupied the cortex. Urothelial metaplasia of the ovarian surface epithelium was demonstrated in one case, and continuation of the Brenner column with the surface of ovary in another. There were 12 cases of mixed Brenner tumor in this series (21.1%). The most frequent associated constituents of the mixed Brenner tumors are mucinous cystadenomas. These tumors represent a single mixed neoplasm originating in a multipotential celomic cell which proliferates and differentiates into several mullerian forms. The histogenesis of medullary and hilar Brenner tumors can be explained on the basis of celomic metaplasia. Uncertainty persists in explaining the histogenesis of Brenner tumors mixed with mature cystic teratoma.

Although the first Brenner tumor was reported in 1898 by MacNaughton-Jones, it was not until 1907 that Fritz Brenner described the tumor that bears his name. Since then more than 500 cases have been reported with bilaterality ranging from 3.7 to 8.0 per cent. However, this percentage is probably high. The tumor was originally thought to arise from follicular epithelium. Several other etiologies of the Brenner tumor have been suggested, including celomic surface epithelium, Walthard rests, teratoma, urothelium, and rete ovarii. The majority of Brenner tumors are inert, but there have been reports suggesting endocrine activity. The question of malignant transformation of the Brenner tumor has gained attention since Von Numers described the first malignant Brenner tumor in 1945. The determination of malignancy of these tumors has been hampered by vague histologic criteria for malignancy. The confusion surrounding the histogenesis, hormonal capabilities, and malignant potential of the Brenner tumor has persisted. A case report of bilateral Brenner tumors of the ovaries is presented as well as a review of the literature with emphasis on the bilaterality of Brenner tumors.

Brenner tumor is an uncommon ovarian tumor whose etiology and hormonal activity have aroused controversies. The salient features of three cases of this tumor seen at the University of Port Harcourt Teaching Hospital, Nigeria, between March 1981 and March 1987 are discussed. In one case, the tumor was bilateral and was associated with secondary polycythemia. Another case was associated with a full term pregnancy and here the tumor contained luteinized stromal cells. Although such cells are usually associated with estrogenic activity, the full term pregnancy in this case will suggest at best a low level of hormonal activity. The last case was an incidental microscopic lesion in a postmenopausal woman.

A case of bilateral malignant Brenner tumor of the ovary in a 43-year-old woman was studied by light- and electron microscopy. The morphologic criteria of this rare lesion are discussed and the pertinent literature reviewed.

The histology of 36 benign and four proliferative Brenner tumors is reviewed, and the ultrastructural features of benign Brenner tumors are described. Evidence is presented for the origin of these tumors from celomic inclusion cysts through transitional metaplasia of the cyst lining and progressive growth of branching cords of transitional epithelium. Ovarian lesions associated with the Brenner tumor are described, particularly those containing mucinous epithelia, and their significance is discussed.

The histologic, histochemical, immunohistochemical, and ultrastructural features of Brenner tumor (BT) were studied. BT was compared with transitional bladder cells, and close similarities between the two tissues were identified. Abundant glycogen in all cellular layers, an alcianophilic/sialomucinic surface mucous coat, and argyrophilic cells characterized both BT and bladder epithelium. Immunohistochemically, chromogranin and neuron-specific enolase reactivity was observed in all cases examined. An additional relevant finding was the presence of serotonin-storing cells in both BT and urothelium. Moreover, carcinoembryonic antigen, epithelial membrane antigen, and keratin reaction were found in BT and urothelium, indicating an additional antigenic similarity. Additionally, malignant Brenner tumor was ultrastructurally found to share many common features with the bladder tissue. The distinct histochemical, ultrastructural, and antigenic pattern of BT, primarily of the transitional type, is emphasized.

This paper reports 5 cases of Brenner tumor of the ovary treated in our hospital from 1967 to 1985. The patients' mean age was 54.6 years. Three lesions were solid, 1 cystic and the other occurred on the wall of a borderline malignant mucinous cystadenoma. All the 5 cases were benign by pathology. The clinical symptoms were abdominal pain in 3 cases, 2 of which had a torsion of the tumor pedicle, abdominal mass in 1 and abdominal swelling in the other. All the cases possessed the same feature that the tumor was composed of both hyperplastic epithelial nest and fibrous stroma. In histology, there were 3 transitional epithelial cell types and 2 basal cell-like types. Histogenesis of the Brenner tumor, according to the authors' observation, was shown by: 1. The epithelial cell nests of Brenner tumor were similar to the transitional epithelium of the urinary tract in 60% of these cases; basal-like cell in the early stage of differentiation comprised 40%, 2. In 80% of patients, there was observed, in the cell nuclei, a longitudinal groove, which resembled the cells of Walthard cell nests; 3. The transitional epithelial cells were found in the cyst wall of 1 polycystic tumor; another case was complicated with mucinous cystadenoma and there was no sharp demarcation between the two tumors under microscope. It suggests that the histogenesis imply that the Brenner tumor may arise from the coelomic epithelium of para-mesonephros. The authors also believe that certain Brenner tumors have endocrine activity, but the relation between which and the tumor stroma luteinization should be further studied.

Brenner's tumor is a rare fibroepithelial ovarian neoplasia, histologically characterized by an epithelial component similar to the transitional epithelium of the urinary tract. The histogenesis of neoplasm, which only rarely secretes estrogens, is still controversial. The Authors describe the clinical and anatomopathological features of six cases come to their observation. Only one of these was malignant; the woman died 18 months after diagnosis. There is no strict correlation between histological picture and biological behaviour. Only this one can give assurance on the benign or malignant nature of Brenner's tumor.

The clinicopathologic features of a case of malignant Brenner tumor with bilateral ovarian involvement are described. The tumor was apparently confined within the ovaries at initial laparotomy. However, multiple skeletal metastases developed 4 months later and the patient died of the disease 6 months after diagnosis.

Three new and eleven previously reported testicular or paratesticular tumors that resembled ovarian tumors of common epithelial type are discussed. The 14 tumors occurred in patients ages 11-68 (average 47) years of age. The exact location for 12 of the tumors is known; 5 involved primarily the testicular parenchyma, 3, the tunica vaginalis, and 4, paratesticular tissue. Five tumors were serous, four of which were in the borderline category. Four tumors were Brenner tumors, admixed in one case with an adenomatoid tumor. Single examples of mucinous cystadenoma, mucinous cystadenocarcinoma, endometrioid adenoacanthoma, clear cell adenocarcinoma, and a benign tumor of mixed cell types complete the list. Follow-up of from 3 months to 14 years is available in eight cases; only one tumor, the clear cell adenocarcinoma, is known to have been clinically malignant. A fourth lesion in this article was a paratesticular mass composed of endometrial glands and stroma and bundles of smooth muscle. It arose in an 82-year-old man who had been treated with estrogens for prostatic adenocarcinoma.

The clinical and pathologic features of 16 malignant Brenner tumors (MBT) having an associated benign Brenner component were compared with 29 primary ovarian transitional cell carcinomas (TCC), neoplasms differing from MBT only in that a benign Brenner component was absent. Transitional cell carcinoma represented a more aggressive neoplasm. Twenty of twenty-nine (69%) presented in advanced stages (II-IV) compared with only three of sixteen (19%) MBT. Among stage IA tumors, only three of seven (43%) patients with TCC were well at last contact, compared with nine of eleven (88%) patients with Stage IA MBT. In addition to not having a benign Brenner component, TCC lacked the prominent stromal calcification common in most benign and malignant Brenner tumors. Transitional cell carcinoma is sufficiently different from MBT in that it is reasonable to suppose that ovarian TCC arises directly from pluripotential surface epithelium of the ovary and from cells with urothelial potential, rather than from a benign or proliferative Brenner tumor precursor.

A human ovarian Brenner tumor presenting a wide spectrum of benign and malignant histologic features was studied for its patterns of intermediate filament expression. All epithelial elements of the tumor, regardless of their morphologic type, contained cytokeratins as their only intermediate filament component. Differences were detected, however, between tumor nests that displayed transitional epithelium and those with squamoid features. These differences were manifested by the presence of cytokeratin 18, in the former type only, and by the abundance of cytokeratins 10/11 in the latter. We also detected mixed epithelial nests in which both features were present, suggesting that the transitional epithelium transforms in polar fashion into squamous epithelium. Examination of cytokeratin patterns found in urothelium and in the surface epithelium of the ovary pointed to certain differences from the Brenner tumor epithelia. The significance of these latter findings with regard to cellular transformation and histogenesis of the Brenner tumor are discussed.

We present the fourth case report of an extraovarian Brenner tumor, which was an incidental finding in a total hysterectomy 53-year-old woman. The morphology and pathogenesis of Brenner tumors are discussed.

A patient with malignant Brenner tumor of the ovary is presented. The tumor responded to combined therapy with radiation plus doxorubicin + cyclophosphamide despite earlier failure on a single alkylating agent (levophenylalanine mustard). The patient next exhibited a brief response to chemotherapy with hexamethylmelamine + cyclophosphamide + amethopterin + 5-fluorouracil. The histologic findings and ultrastructure of the tumor are discussed in detail. The morphologic features are consistent with the proposed origin of Brenner tumors from coelomic epithelium through a process of secondary urothelial metaplasia.

It will be reported about 33 cases of Brenner-tumors, observed between 1932 to 1974. Symptomatic, therapy, progress, morphology of these tumors as well as their coincidence with other pathological changes on genitals will be demonstrated. A short casuistic description of 3 cases with proliferating and 1 case of malignant Brenner-tumor will be given. In the discussion, it will be informed about the frequency, age, diagnostic and prognostic problems of proliferating and malignant tumors. The problem of hormonal activity of some of Brenner-tumors and finally the modern views over histogenesis will be considered and discussed.

A 79-year-old woman with primary liposarcoma of the heart, an extremely rare malignancy, coexistent with Brenner tumor was reported. The histological features of the sarcoma on the routine histological slides were so varied that it was necessary to differentiate the histology from that of malignant fibrous histiocytoma or pleomorphic rhabdomyosarcoma. Most of the tumor cells including fibroblastic and bizarre giant cells, however, were stained intensely with histochemical methods for lipids and consequently diagnosed as pleomorphic liposarcoma originated from the epicardium. Electron microscopically, lipid droplets were demonstrated in the cytoplasm of the tumor cells, supporting the histological diagnosis. No distant or nodal metastases were noted.

The Brenner tumor of the ovary has been the topic of voluminous clinical and pathologic literature since its original description by Macnaughton-Jones in 1898. One of the major problems confronting most investigators of this uncommon neoplasm has been the question of histogenesis. There is general agreement that the tumor is derived from surface (coelomic) epithelium, as are the serous and mucinous cystadenomas. Most Brenner tumors are asymptomatic except for some which have features suggestive of estrogen production. The major pathologic variants are the proliferating and the malignant Brenner tumors; a poor prognosis is associated with the latter neoplasm. Approximately 30% of all benign Brenner tumors have a second histologic type of tumor in the ipsilateral or contralateral ovary, a serous or mucinous cystadenoma in most cases. Brenner tumors have also been reported in the broad ligament and in the testis on rare occasions.

An exceedingly rare ovarian neoplasm composed of mixed thyroid and Brenner tumor is reported. Review of the literature yielded only one well-documented case previously described. Although the possibility of a "collision" of two different tumors cannot be completely discarded, a possibility of an endodermal teratoma (thyroid-urothelium) is also proposed.

A case of a malignant Brenner tumor of a postmenopausal woman presenting with vaginal bleedings is described. Clinical and laboratory findings demonstrated estrogenic secretory function and action. The presence of aromatase activity based on in vitro tumor microsomal metabolism of androgen to estrogen is described. Tumor cytosol contained progestin and androgen binding components in the absence of estrogen binding activity. Estrogen binding activity was undetectable both by biochemical as well as histochemical assays.