MALIGNANT BRENNER TUMOR WITH PERITONEAL METASTASIS

A case of malignant Brenner tumor with peritoneal metastasis in a 67-year-old woman was reported. The multilocular cystic tumor of right ovary was 420 g in weight, and their cystic walls were covered with multilayered tumor cells showing papillary pattern very frequently. The tumor was histologically transitional cell carcinoma with occasional glandular structures but no squamous differentiation corresponding to grade 2 or 3 urinary bladder carcinoma. The pattern of benign Brenner tumor was not Identified, but there was some area of proliferating Brenner tumor. Immunohistochemically, carcinoembryonic antigen was detected in several tumor cells, especially in the intercellular spaces among them, and cytokeratin was detected only in some tumor cells. Ultrastructurallly, the malignant Brenner tumor shared many common features with the benign one and also bladder tumor. Intercellular spaces with microvilli were frequently found and thought to be important for diagnosis. The morphologic criteria of this rare tumor are discussed.     

Bilateral malignant brenner tumor: Report of a case with ultrastructural study

An unusual case of bilateral malignant Brenner tumor with liver and omental metastases is reported. The tumor was histologically a transitional cell carcinoma comparable to a grade III bladder carcinoma. A benign component was not identified, but there were a few nests of malignant epithelial cells distributed in a dense stroma, a pattern identical to that seen in a benign Brenner tumor. Whether this represents malignant change in a previously benign focus or a well differentiated part of a de novo carcinoma is unclear. Nevertheless it is suggested that the current histologic criteria for malignant Brenner tumor be modified to exclude the requirement of an intimately associated benign Brenner tumor.Ultrastructurally the malignant Brenner tumor has many features of the benign Brenner tumor. Some features, notably the basal lamina, micropinocytotic vesicles, and intracytoplasmic microfibrils, are herein described for the first time in a malignant Brenner tumor.     

Epithelial mucosubstances and argyrophil cells in Brenner tumours

Brenner tumours of various degree of malignancy were investigated by histochemical methods. The cells lining the cystic cavities in the benign Brenner tumours contained various amounts of PAS-positive, diastase resistant secretory material mixed with small amounts of sulpho- and carboxymucin. The borderline and malignant tumours contained more acidic mucins than the benign tumours. All tumours contained glycogen. Argyrophil and argentaffin cells have not earlier been detected in the Brenner tumours but in this study they were detected in twelve of the 18 Brenner tumours. These cells were not proliferating and therefore Brenner tumour should not be included in the group of APUDomas.     

Benign and malignant Brenner tumor of the ovary: a clinicopathological and immunohistochemical study]

The clinicopathological and immunohistochemical features of 7 cases of benign and malignant Brenner tumor of the ovary, including 5 benign and 2 malignant tumors are described. Microscopically, all of the benign cases were composed of both epithelial nest and fibrous stroma. Two cases of the malignant Brenner tumor showed that the histologic features resembled the structure of non-keratinized squamous carcinoma or transitional cell carcinoma. Immunohistochemistry showed that tumor cells of the epithelial nest were keratin and EMA positive in 7 cases; CEA-positive in 5 cases; and negative in 2 cases of benign Brenner tumor. The results indicated that Brenner tumor is an epithelial neoplasm in nature. The diagnostic criteria and histogenetic origin are discussed.     

Unusual presentation of benign cystic brenner tumor with exuberant psammomatous calcifications

Transitional cell tumors of the ovary comprise about 1% to 2% of all ovarian neoplasms. Most of these tumors are benign Brenner tumors and account for about 5% of benign surface epithelial-stromal tumors. Spicules of calcifications are found in the stroma of about 50% of benign Brenner tumors. Although diagnostic challenges might occur more frequently with either of the borderline or malignant Brenner tumors, this problem is not that common when diagnosing a benign Brenner tumor. This study reports a case of benign Brenner tumor with exuberant dystrophic calcifications that obscured most of the epithelium and posed a diagnostic challenge in differentiating it from the more common malignant counterparts such as serous carcinoma and specifically psammocarcinoma.     

MALIGNANT BRENNER TUMOR -A CASE REPORT

A 55-year-old female had a partly cystic, partially solid tumor of the left ovary. Histologically, the tumor revealed typical benign features of Brenner tumor mixed with malignant areas showing large epithelial nests composed of marked pleomorphic cells. Only 4 cases of malignant Brenner tumor have been reported including ours to our knowledge in Japan.     

Case report of a malignant Brenner tumor with hyperestrogenism

A rare malignant Brenner tumor of the ovary presenting with hyperestrogenism in a 79 year old woman was examined immunohistochemically and by light and electron microscopy. High pre-operative serum and urinary estrogen concentrations, low serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and histologically confirmed atypical endometrial hyperplasia suggested the presence of hyperestrogenism. The reduction in serum and urinary estrogen and the increase in serum LH and FSH concentrations after tumor removal confirmed that the tumor was synthesizing estrogen. Histologically, the malignant element was predominantly a squamous cell carcinoma. Transitional cell carcinoma was partially found on the cyst wall. There was a spectrum of morphologic changes between benign and malignant elements with an intermediate area with a proliferating Brenner tumor. Immunohistochemically, only the carcinoembryonic antigen was positive exclusively on the malignant element as well as in the microcyst in the benign epithelial cord, whereas all of the markers for germ cell tumors were negative. The ultrastructural features of the stromal cells were of two types: fibroblasts and steroidproducing cells. The latter type of cells might correspond morphologically to estrogen-producing cells. The present case is the fourth report showing a malignant Brenner tumor combined with apparent hyperestrogenism.     

Brenner tumors but not transitional cell carcinomas of the ovary show urothelial differentiation: immunohistochemical staining of urothelial markers, including cytokeratins and uroplakins

To determine whether Brenner tumors and transitional cell carcinomas (TCCs) of the ovary are urothelial in type, the immunoprofiles of 14 Brenner tumors, including three malignant examples, and eight ovarian TCCs were compared with those of Walthard nests, urothelium, 12 urinary bladder TCCs and 17 ovarian adenocarcinomas (serous, endometrioid, mucinous, and undifferentiated type). The immunohistochemical stains used included those for cytokeratins CKs 5/6, CK7, CK8, CK13, and CK20, vimentin, CA125, and the specific urothelial differentiation marker uroplakin III. CK7 and CK8 were broadly expressed in most tumors of ovary and bladder examined, while vimentin was focally present in some ovarian TCCs and adenocarcinomas. As in normal and neoplastic bladder urothelium, urothelial markers, including uroplakin III, CK13, and CK20, were detected in the epithelial nests of Brenner tumors. Brenner tumor cells also expressed uroplakins Ia and II. CA125 was observed focally in some Brenner tumors. In contrast, TCCs of the ovary and Walthard nests lacked uroplakins and were essentially negative for CK20 and CK13 but quite strongly expressed CA125. This immunophenotype closely resembled that found in ovarian adenocarcinomas. Thus, it appears that the only true urothelial-type ovarian neoplasm is the Brenner tumor, whereas ovarian TCC most likely represents a poorly differentiated adenocarcinoma with a morphologic transitional cell pattern. These results may explain the controversies as expressed in the recent literature concerning TCC of the ovary and establish its place among the ovarian adenocarcinomas of müllerian type.     

Cytologic diagnosis of adenoid cystic carcinoma of salivary glands.

The cytomorphologic features in fine-needle aspiration (FNA) biopsies from 31 primary and 33 recurrent adenoid cystic carcinomas (ACC) were investigated. The correct FNA diagnosis was established in 24 of 31 primary ACC (77%). The diagnostic clue in aspirates from ACC are large globules of extracellular matrix, partially surrounded by basaloid tumor cells. In FNAs with predominance of basaloid tumor cells, but lacking characteristic globules, all other benign and malignant salivary gland tumors of epithelial-myoepithelial differentiation should be considered in the cytologic diagnosis. Pleomorphic adenoma is most frequently confused with ACC, and therefore, the cytologic findings in FNAs from 50 pleomorphic adenomas were compared with those diagnosed as ACC. Furthermore, rare neoplasms of salivary glands with epithelial-myoepithelial cell differentiation, including basal-cell adenoma and carcinoma, epithelial-myoepithelial carcinoma, and polymorphous low-grade adenocarcinoma, as well as some nonsalivary gland neoplasms presenting an adenoid cystic pattern, must be considered. The cytologic features of these entities are discussed in detail with respect to the cytologic diagnostic criteria of ACC.     

Cytological features of cystadenocarcinoma in cyst fluid of the parotid gland: Diagnostic pitfalls and literature review

Cystadenocarcinoma is a rare malignant tumor, with an estimated incidence of 2% of malignant salivary gland tumors. Cytological diagnosis of cystadenocarcinoma is important for differential diagnosis between benign lesions and malignant tumors with cystic growth. We report a case of cystadenocarcinoma causing difficulty in cytological diagnosis. A 23‐year‐old man presented with an asymptomatic mass in the left parotid gland that had been present for 2 years. The mass was elastic hard, measuring 30 × 35 mm in diameter. Preoperative fine‐needle aspiration cytology (FNAC) showed a small number of tumor cell clusters in the cystic fluid. The cluster was arranged in a ball‐like structure and was cohesive with overlapping. Tumor cells had a small vacuolated, soap‐bubble appearance in the cytoplasm. The papillary‐cystic variant of acinic cell carcinoma (ACC‐PCV) was suggested from these findings on FNAC. Histologically, the tumor was not encapsulated, but formed large cystic spaces against a background of fibrous connective tissue. The tumor cells in the cystic dilated duct showed papillary structures, which were continuous with the lining cuboidal cells. There was neither a definite double‐layered arrangement in cystic ducts and solid islands nor histological findings characteristic of the papillary‐cystic or follicular pattern of ACC‐PCV. As tumor cells with a small vacuolated, soap‐bubble appearance of the cytoplasm are common findings of both cystadenocarcinoma and ACC‐PCV, they are of little use for differentiation; however, they are so characteristic that the majority of benign salivary gland lesions with cystic structures can be excluded, if enough attention is paid. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Fine-needle aspiration cytology of cystic ovarian lesions

A 4-year study (January 1986 through December 1990) was performed to evaluate the cytomorphologic features of cystic ovarian lesions. Fluid from 103 cases was obtained either during surgical removal of the ovary (48 cases; mean age 50 years) or by fine needle aspiration (55 cases; mean age 32 years). Of the 48 cystic lesions with histologic correlation, 30 (62.5%) were neoplastic and 18 (37.5%) were non-neoplastic. Ten (18%) of the 55 aspirates were unsatisfactory. The remaining 45 cases (82%) were benign, predominantly non-neoplastic entities which included follicle, corpora luteal, and endometriotic cysts. Neoplastic cystic lesions included serous, mucinous, and Brenner tumors, germ cell neoplasms, a sex cord-stromal tumor, and an undifferentiated carcinoma. Follicle and corpora luteal cysts were composed of loose cell clusters of granulosa cells and/or luteinized granulosa cells. Endometriotic cysts contained hemosiderin-laden macro-phages and endometrial cells. Serous and mucinous cystadenomas were composed of cohesive sheets and/or papillary clusters of epithelial cells. A cystic Brenner tumor showed sheets of cells with grooved nuclei, and a benign cystic teratoma contained mature squamous cells admixed with vacuolated cells of presumed sebaceous origin. Although the distinction between benign and malignant entities posed few diagnostic difficulties, borderline tumors could not be distinguished from well-differentiated cystadenocarcinomas. The results of this study indicate that the majority of cystic ovarian lesions can be diagnosed accurately on cytology. Cytologic evaluation of non-neoplastic ovarian cysts is important for women who want to retain their fertility and in the clinical management of women with neoplastic lesions. Diagn Cytopathol 1994; 11:9–14. © 1994 Wiley-Liss, Inc.     

Primary squamous carcinoma of the ovary likely arising from a monodermal cystic mucinous teratoma

We present a 58-year-old woman with primary squamous carcinoma of the ovary likely arising from a monodermal cystic mucinous teratoma. Noninvolved ovary showed no Brenner tumor, endometriosis, transitional carcinoma, endometrioid adenocarcinoma, or typical multigerm layer classic mature teratoma. Moreover, no other primary site was possible because there were no prior or concomitant squamous carcinomas, or history of cervical intraepithelial neoplasia. The tumor showed strong positivity for p63 and CK5/6, reactivity that also extended from the squamous carcinoma into the basal-cell lining of the mucinous cyst of a likely monodermal teratoma. This basal-cell pattern was absent in a series of conventional benign and borderline cystic mucinous cystadenomas of the ovary, but clearly present in the mucinous cysts part of mature teratomas. We present this as a unique case of squamous carcinoma likely arising from a monodermal cystic mucinous teratoma. Moreover, we submit that the p63 and CK5/6 staining pattern may help to differentiate monodermal cystic mucinous teratoma from conventional cystic mucinous tumors.     

Hepatobiliary cystadenocarcinoma with cystadenoma elements of the gall bladder in an old man

Hepatobiliary cystadenoma and cystadenocarcinoma of the gall bladder have rarely been reported. An 88-year-old Japanese man was admitted to our clinic because of hypochondralgia and jaundice. Imaging techniques revealed hemobilia and a multilocular cystic tumor in the fundus of the gall bladder, and cholecystectomy was performed. Grossly, the tumor (3.5 x 3 x 3 cm) was multicystic, containing seromucous fluid. The tumor was located in the fibromuscular layer and subserosa of the gall bladder fundus, and protruded into the serosal surface, not into gall bladder lumen. The mucosa appeared free of tumor involvement, and no gall stones were recognized. Microscopically, the tumor was located in the fibromuscular layer, subserosa and tiny focus of the mucosal surface. The tumor consisted of mucin-rich benign columnar cells, dysplastic mucous cells, malignant papillotubular cells and invasive carcinoma cells. Malignant and atypical tumor cells were located in the center of the tumor and in the tiny area of the mucosal surface, while benign tumor cells were located in the peripheral portions of the tumor and in the serosal side. Neither ovarian stroma-like mesenchymal stroma nor an oncocytic change in tumor cells was recognized. Non-tumorous gall bladder showed chronic cholecystitis. Immunohistochemically, benign and carcinoma cells were positive for cytokeratins, epithelial membrane antigen, CA19-9, MUC1, MUC5AC and MUC6, and carcinoma cells were also positive for carcinoembryonic antigen and p53 protein. The present case indicates that hepatobiliary cystadenocarcinoma without mesenchymal stroma may occur in the gall bladder of old men, and suggests that hepatobiliary cystadenoma without mesenchymal stroma may transform into hepatobiliary cystadenocarcinoma in the gall bladder.     

Ultrastructure of the benign and borderline Brenner tumours

One benign Brenner tumour and one Brenner tumour of borderline malignancy were investigated by electron microscopy. The cells of the benign Brenner tumour nests and the cells in the borderline tumour were similar in ultrastructure. The intercellular spaces were large and reinforced by a moderate number of desmosomes. The nuclei were round or oval. The nuclear membrane was irregular in shape with deep infoldings corresponding to the characteristic nuclear groovings seen by light microscopy. Only few secreting cells could be found in the benign of Brenner tumour. The cystic cavities of the borderline Brenner tumour were lined by nonciliated secreting and ciliated nonsecreting cells. The secretory granules were PAS-positive and diastaseresistant. The granules stained homogeneously and strongly with the PASM-method at the electron microscopical level indicating the presence of 1.2-hydroxyl groups. The Brenner tumours have many similarities to the transitional epithelium and to the Muellerian-derived tubular structures. The findings support the theory that Brenner tumours are of coelomic origin and develop by direct metaplasia from the ovarian surface epithelium.     

Common epithelial tumors of the ovary: proliferating and of low malignant potential

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.     

Nucleolar organizer regions in malignant salivary gland tumors.

Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: mucoepidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoepidermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior.     

Brenner tumor of the ovary: a correlative histologic, histochemical, immunohistochemical, and ultrastructural investigation

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.     

Nucleolar Organizer Regions in Malignant Salivary Gland Tumors

Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: muco-epidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoep-idermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior. Acta Pathol Jpn 42: 727–733, 1992.     

A case of intracystic apocrine papillary tumor: Diagnostic pitfalls for malignancy

Intraductal/intracystic papillary carcinoma (IPC) of the breast is defined as a malignant non-invasive papillary tumor arising from the ductal–lobular system. Based on the presence of myoepithelial cells in the cystic wall, IPC is distinguished from encapsulated papillary carcinoma (EPC). Here, we report a case of an intracystic apocrine papillary tumor in the breast of a 49-year-old woman. Histopathologic examination revealed that the entire papillary structures and cyst wall were comprised of apocrine cells, some of which showed nuclear atypia with macronucleoli. Immunohistochemical examination revealed a lack of myoepithelial cells in the papillary fronds and cyst wall. Although the dense proliferation of apocrine cells mimicked a cribriform pattern, detailed examination identified a delicately intermingled interstitium in the cribriform-like growth area in the present case. We judged the current case to be benign apocrine papilloma. Only a few apocrine variants of IPC or EPC have been reported to be malignant or potentially malignant. Since even benign apocrine lesions are known to lack myoepithelial cells, histopathologic evaluation regarding malignant potential requires caution in apocrine variants. The detection of clearly benign areas and knowledge of the “pseudo-cribriform” pattern should provide clues to distinguish between benign and malignant apocrine papillary tumors.     

p63 expression in ovarian tumours: a marker for Brenner tumours but not transitional cell carcinomas

AIMS: To investigate p63 expression in ovarian neoplasms. METHODS AND RESULTS: Immunohistochemistry using an antibody that detects all p63 isoforms was performed on 103 primary ovarian neoplasms of different histological types. Diffuse nuclear immunoreactivity of p63 was demonstrated in the 17 benign and five borderline Brenner tumours. Only one of the six malignant Brenner tumours displayed p63 expression. p63 immunoreactivity was absent in all the ovarian transitional cell carcinomas (TCC), but was demonstrated extensively in TCCs of the urinary bladder. Besides focal p63 expression in epidermal basal cells of immature and mature teratomas, all other ovarian lesions were devoid of p63 expression. p63 expression was also demonstrated in cervical transitional cell metaplasia and Walthard cell nests of fallopian tubes. CONCLUSIONS: Expression of p63 protein is apparently cell lineage specific and in ovarian neoplasms is confined to benign and borderline Brenner tumours. The loss of expression in malignant Benner tumours suggests a role for p63 in Brenner carcinogenesis. The distinct patterns of p63 expression in TCCs in the ovary and urinary bladder may help in their differential diagnosis.