Mucinous tumors of the ovary: a review.

Mucinous ovarian tumors are among the most difficult ovarian neoplasms for surgical pathologists to interpret. Approximately 20% of primary ovarian mucinous tumors are borderline tumors, noninvasive (intraglandular; intraepithelial) carcinomas, or invasive carcinomas; the remainder are cystadenomas. The borderline tumors may be of intestinal type or mullerian (endocervical-like) type. The intestinal-type tumors are by far the most common. Their frequently heterogeneous composition with coexisting elements of cystadenoma, stromal microinvasion, noninvasive carcinoma, and invasive carcinoma requires careful gross examination and extensive sampling of the tumors. The inherent glandular complexity of proliferating mucinous tumors complicates recognition of stromal invasion. Some mucinous carcinomas with expansile (confluent) invasion may be very difficult to discriminate from extensive noninvasive carcinoma. Interobserver reproducibility probably requires use of an arbitrary minimum size criterion for the diagnosis of expansile invasion. Primary invasive carcinomas with an infiltrative growth pattern are less common. Rarely, distinct mural nodules of reactive or neoplastic type are found in the cystic wall of a mucinous tumor. Pseudomyxoma peritonei almost never results from a ruptured primary ovarian mucinous neoplasm, but often produces secondary borderline-like ovarian tumors with prominent pseudomyxoma ovarii. Prognosis of mucinous tumors is highly dependent on stage and histologic composition. Borderline tumors, noninvasive carcinomas, microinvasive tumors, and invasive carcinomas with an expansile growth pattern are generally stage I and have an excellent prognosis with only occasional examples of metastatic spread. Invasive carcinomas with an infiltrative growth pattern are more aggressive, accounting for almost all high-stage mucinous tumors, and are responsible for most deaths caused by tumor. A high index of suspicion that a mucinous tumor is actually a metastasis from another organ is required by pathologists and gynecologists to prevent misdiagnosis of a metastatic neoplasm as a primary ovarian tumor. Secondary mucinous tumors are significantly more often bilateral, <10 cm in maximal dimension, and of high stage. Numerous immunohistochemical stains proposed to aid in the differential diagnosis of primary vs. secondary mucinous tumors also are reviewed.     

Ovarian metastases from carcinoma of the gallbladder and extrahepatic bile ducts simulating primary tumors of the ovary. A report of six cases

Six cases in which ovarian metastases from carcinoma of the gallbladder or bile ducts were discovered during the life of the patient are described. The patients ranged from 33 to 72 (average, 57) years of age. In one case, the ovarian tumor was discovered 5 weeks before a gallbladder carcinoma was detected: in three cases, gallbladder tumors and ovarian metastases were discovered simultaneously; and in two cases, ovarian metastases were recognized 1 and 2 years after the biliary tumors. The ovarian tumors were bilateral in five cases. One of them was a 13-cm multiloculated, cystic neoplasm that simulated a primary mucinous tumor of the ovary. The remaining neoplasms were uniformly or predominantly solid and ranged up to 6.5 cm in diameter. They typically had lobulated external surfaces and were often multinodular on sectioning. Three ovarian tumors posed significant problems in differential diagnosis on microscopic examination. One of them closely simulated an endometrioid carcinoma, another simulated a mucinous cystadeno-carcinoma, and a third suggested the possible diagnosis of a Sertoli-Leydig cell tumor. Features helpful in establishing the metastatic nature of the ovarian tumors in these and the other cases included bilaterality, surface implants, multinodularity, and extraovarian spread. The gallbladder and bile ducts are rare sources of metastatic tumors, which may simulate primary ovarian neoplasms.     

Mucinous ovarian tumors associated with mucinous adenocarcinomas of the cervix. A clinicopathological analysis of 16 cases

Sixteen cases of mucinous adenocarcinoma of the cervix that were associated with a mucinous tumor of one or both ovaries are reported. The patients ranged from 25 to 70 (average, 44) years of age; two of them had the Peutz-Jeghers syndrome. Eight patients complained of abdominal swelling; most of the remainder had symptoms of uterine origin. Twelve patients had bilateral and four had unilateral ovarian tumors, which were typically large and cystic. Microscopic examination of most of the ovarian tumors revealed various combinations of benign-appearing, borderline, and carcinomatous mucinous epithelium within the same specimen. Most of the cervical tumors were deeply invasive; 10 of them were of the adenoma malignum type. Although there were varying degrees of uncertainty in individual cases, consideration of several features including the extent and distribution of disease in the abdomen, the comparative histology of the tumors, and the pattern of ovarian involvement suggested that 10 of the ovarian tumors were independent primary tumors, three were metastatic from the cervix, and in three cases the ovaries contained both primary and metastatic tumors.     

Expression of mesothelin, fascin, and prostate stem cell antigen in primary ovarian mucinous tumors and their utility in differentiating primary ovarian mucinous tumors from metastatic pancreatic mucinous carcinomas in the ovary.

Metastatic pancreatic mucinous adenocarcinomas in the ovaries can be difficult to distinguish from primary ovarian mucinous neoplasms because the former can simulate the latter grossly and histologically and both tumor types share the same cytokeratin 7/cytokeratin 20 immunoprofile. We previously reported the utility of loss of Dpc4 expression in distinguishing metastatic pancreatic carcinomas from primary ovarian mucinous tumors. Recently several new pancreatic carcinoma markers have been identified, including mesothelin, fascin, and prostate stem cell antigen (PSCA). In this study we investigate the expression patterns of these markers in 35 primary ovarian mucinous tumors (28 atypical proliferative [borderline] tumors and 7 invasive carcinomas) and 11 metastatic pancreatic mucinous carcinomas in the ovary. Primary ovarian mucinous tumors expressed mesothelin (17%), fascin (26%), and PSCA (43%) less frequently than metastatic pancreatic adenocarcinomas (73%, 73%, and 82%, respectively). Expression of all three markers was seen only in metastatic pancreatic adenocarcinomas (45%), and coexpression of at least two markers was observed significantly more frequently in metastatic (82%) than primary ovarian mucinous tumors (17%). Our results indicate that an immunohistochemical panel including Dpc4, mesothelin, fascin, and PSCA is useful for evaluating difficult mucinous tumors in the ovary when the differential diagnosis includes metastatic pancreatic adenocarcinoma.     

Well-differentiated serous ovarian carcinoma presenting as a breast mass: a case report and flow cytometric DNA study

Ovarian carcinoma metastatic to the breast is uncommon. We report a rare occurrence of ovarian carcinoma that initially presented as a breast mass. Complete examination revealed bilateral ovarian tumors with widespread peritoneal and abdominal disease. One of the ovarian tumors was a papillary serous tumor of low malignant potential, and the other was a well-differentiated papillary serous carcinoma. Although the neoplasm within the breast resembled serous ovarian carcinoma with psammoma bodies, the initial presentation and the presence of an apparent intraductal component created a potential for its misdiagnosis as a primary breast carcinoma. Using DNA flow cytometry, we demonstrated the relationship between the breast, lymph node, and peritoneal metastases and the serous carcinoma, thereby supporting the histologic diagnoses.     

Primary and metastatic mucinous adenocarcinomas of the ovary: Evaluation of the diagnostic approach using tumor size and laterality

OBJECTIVE: To evaluate the usefulness of the recently proposed algorithm (Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol 2003; 27: 985-93 [5]) that classifies mucinous adenocarcinomas of the ovary as primary when they were unilateral > or =10 cm and as metastatic when they were unilateral <10 cm or bilateral. METHODS: Malignant ovarian neoplasms, which were resected in Chiang Mai University Hospital between 1992 and 2003, were histologically reviewed. Mucinous adenocarcinomas involving the ovary were identified. The medical records and radiologic materials were reviewed in correlation with the pathologic features to identify the primary site. RESULTS: There were 74 cases of mucinous adenocarcinomas; 16 were primary ovarian; 52, metastatic; and 6 of indeterminate primary site (primary versus metastatic). Primary mucinous adenocarcinomas had a mean size of 16.4 cm and bilateral involvement in 13%. Metastatic mucinous adenocarcinomas had a mean size of 11.7 cm and bilateral involvement in 77%. Excluding the 6 tumors of indeterminate primary site, the proposed algorithm correctly classified primary and metastatic tumors in 84% of 68 cases. Of 21 unilateral mucinous adenocarcinomas > or =10 cm, 62% were primary ovarian. Of 5 unilateral tumors <10 cm, 80% were metastatic. Of 42 bilateral mucinous adenocarcinomas, 95% were metastatic. CONCLUSION: The algorithm provided high accuracy in the overall prediction of primary and metastatic mucinous adenocarcinomas of the ovary, with major strength in the identification of metastatic tumors by bilaterality or size <10 cm. However, the prediction of primary mucinous adenocarcinomas by unilaterality and size > or =10 cm was less reliable than previously reported. Due to the overlapping features between primary and metastatic tumors and the higher frequency of the latter, the possibility of metastases should always be borne in mind in the evaluation of mucinous adenocarcinomas of the ovary.     

Urachal adenocarcinoma metastatic to the ovaries: case report and literature review.

We report a urachal adenocarcinoma metastatic to both ovaries in a 50-year-old Japanese woman. Pelvic examination and imaging studies revealed a large cystic tumor occupying the pelvis and another cystic tumor between the umbilicus and the urinary bladder. A laparotomy was performed. Histopathological examination revealed a urachal tumor that was a well-differentiated invasive mucinous adenocarcinoma; the overlying urothelium was intact. The right and left ovarian tumors were well-differentiated mucinous adenocarcinomas. The urachal and ovarian tumors were immunoreactive for cytokeratin 20 and carcinoembryonic antigen, but negative for cytokeratin 7. The patient is alive with lymph node and bone metastases 6 months postoperatively. This is the eighth reported case of an adenocarcinoma of the bladder with ovarian metastasis.     

Accuracy of frozen section in distinguishing primary ovarian neoplasia from tumors metastatic to the ovary.

Frozen section is widely used in the intra-operative assessment of patients with ovarian tumors. The diagnosis of malignancy is usually straightforward but in some cases it may be difficult to distinguish whether tumors are of ovarian origin or represent matastases from other sites. Recently, Seidman and colleagues presented a simple algorithm based on tumor size and unilateral versus bilateral involvement to aid in intra-operative assessment of ovarian mucinous neoplasms. In this study we have reviewed the accuracy of frozen section in distinguishing primary ovarian malignancies from tumors metastatic to the ovaries encountered in two hospitals over a 5-year period. The algorithm was also applied to our cases retrospectively irrespective of histological type. Nine hundred fourteen ovarian frozen sections were performed in the study period including 266 cases with a final diagnosis of malignancy. Thirty-seven malignancies (13.9%) were of metastatic origin (exclusing one lymphoma), 21 of which (58.8%) were correctly identified on frozen section. In 5 additional cases metastatic origin was included in the differential diagnosis while a primary ovarian tumor was favored un 11 cases (29.7%). Application of the algorithm to the metastatic tumors led to correct classification in 26/33 (78.8%) assessable cases. Conversely, 195/228 primary ovarian malignancies were correctly identified intra-operatively but the possibility of extra-ovarian malignancy was considered or not excluded in 33 cases (14.5%). Application of the algorithm to the latter problematic primary ovarian tumors overall was not helpful in distinguishing primary or metastatic origin. However if only low-grade primary adenocarcinomas were considered then 10/12 assessable cases were correctly assigned. In conclusion frozen section is only moderately successful in distinguishing primary ovarian malignancies fron tumors metastatic to the ovaries. The simple algorithm proposed by Seidman and colleagues for assessment of ovarian mucinous tumors is helpful and can be applied to low-grade adenocarcinomas of other histological types.     

Ovarian metastasis of a primary renal cell carcinoma: case report and review of literature

Ovarian metastases from renal cell carcinoma (RCC) are very rare, with only 23 cases reported in the literature. We report a case of 54-year-old women who developed bilateral ovarian metastasis 39 months after diagnosis of clear cell carcinoma. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was carried out. Subsequently she was treated with sunitinib and her disease stabilized. She is still alive four years after diagnosis of the renal primary, and disease has stabilized on sunitinib. We conclude that, although rare, the possibility of metastatic RCC should be considered in the differential diagnosis of clear cell tumors of the ovary. Due to therapeutic and prognostic implications, it is very important to differentiate if the tumor is a primary ovarian tumor or a metastasis from a renal cell carcinoma. Early diagnosis of this rare metastatic tumor results in prompt treatment and prolonged patient survival.     

Ovarian mucinous cystic tumor of borderline malignancy with a mural nodule of anaplastic spindle cell carcinoma: a case report

Ovarian cystic tumors with a mural nodule are a rare entity. We report a case of a mural nodule of anaplastic spindle cell carcinoma in an ovarian mucinous cystic tumor of borderline malignancy. The patient was a 45-years-old Japanese woman who presented with an ovarian cyst. She suffered from mature cystic teratoma of both ovaries 9 years before the present history. Image analysis and laboratory data showing a high serum CA19-9 level suggested ovarian malignancy. She underwent bilateral salpingo-oophorectomy with hysterectomy and omentectomy. There was a mural nodule in the ovarian mucinous cystic lesion. Microscopically, the nodule was composed of spindle-shaped cells with severe nuclear atypia. Immunohistochemical analysis allowed the cells to be categorized as anaplastic spindle cell carcinoma. Fifteen months after the operation the patient is alive without any clinical findings of tumor recurrence. To the best of our knowledge in the English literature, this is the first report of a mural nodule of an anaplastic spindle cell carcinoma within an ovarian mucinous cystic borderline tumor harboring previously confirmed cystic teratoma.     

Aggressive behavior of stage I ovarian mucinous tumors lacking extensive infiltrative invasion: a report of four cases and review of the literature.

Previous studies have indicated that mucinous carcinomas of the ovary associated with extraovarian spread at the time of presentation or follow-up almost always have extensive infiltrative invasion within the primary tumor. We present four cases of stage I ovarian mucinous tumors that lacked extensive infiltrative invasion but were associated with an unexpectedly aggressive behavior. The patients were 18, 20, 41, and 45 years of age at presentation. All four of them presented with an abdominal mass or increased abdominal girth. The tumors were all stage Ia, 17 to 37 centimeters in maximal dimension, and typically multicystic with solid areas. The number of blocks per centimeter of tumor diameter was 0.65, 0.88, 0.92, and 1.0 in the four tumors, respectively, a degree of sampling within that recommended in previous studies. Clinical findings supported that they were primary tumors rather than metastatic from an occult primary tumor. On microscopic examination, the tumors all contained foci of intraepithelial carcinoma and foci of invasion as follows: expansile invasion only (two cases), expansile invasion and microinvasive carcinoma (one case), and microinvasive carcinoma only (one case). The expansile invasion was extensive in each of the three cases in which it was present. On follow-up, each patient experienced recurrent disease 7 months to 4.5 years after diagnosis, including hematogenous spread to lung and/or bone and liver in three patients. Three of four patients developed intraperitoneal spread. Three of four patients died of disease, and one patient is alive with persistent disease. Although ovarian mucinous tumors with only expansile invasion or only microinvasive carcinoma are usually associated with an excellent prognosis, this study indicates that these tumors can rarely behave in an aggressive fashion with hematogenous spread and a fatal outcome. Some of these tumors may have contained unsampled foci of infiltrative invasion. Although the optimum level of sampling in mucinous tumors remains to be determined, we recommend additional sampling of tumors in which the initial sections reveal intraepithelial carcinoma, microinvasive carcinoma, expansile invasion, or combinations thereof.     

Steroid receptors and ovarian tumors: variation within primary tumors and between primary tumors and metastases

Estrogen and progesterone receptors have been measured in primary and secondary ovarian carcinoma in eight patients, in bilateral ovarian tumors in 16 patients, and from multiple sites within the same tumor in 16 patients (12 primary and 4 secondary). In the majority of cases, metastatic tumors contained less receptors than their primary tumors. Marked variations in receptor content were noted within the same tumor and between bilateral tumors. This variation in receptor levels may explain the discrepancy between the presence of receptors and the response to hormonal treatment. Multiple sites of ovarian carcinoma need to be assayed for receptor content before a final decision can be made on receptor status.     

易与库肯勃瘤混淆的几类卵巢原发性肿瘤

库肯勃瘤是恶性程度极高的卵巢转移性肿瘤,早期即可有广泛的浸润和转移,预后不佳。临床上可见一些少见的卵巢原发性肿瘤,如卵巢印戒细胞间质瘤、硬化性间质瘤、黏液性类癌、透明细胞癌,在病理学上也可见特征化的印戒细胞,易与库肯勃瘤混淆。这需要在临床症状,体征,病理学,免疫组织学及影像学等多方面进行正确鉴别。库肯勃瘤的治疗方法主要为手术,故争取提高术前诊断准确率,对于提高患者的生存率有重要的意义。     

促排卵后快速进展的双侧卵巢库肯勃瘤一例报告并文献复习

报告1例37岁女性在促排卵治疗后5 d出现腹胀、腹水、双侧卵巢对称性多囊性增长,按照卵巢过度刺激综合征治疗近1个月无好转,双侧卵巢肿瘤由囊性变为囊实性。CT引导下卵巢肿瘤内部实性组织穿刺病理检查为腺癌,剖腹探查及病理证实为缩窄型结肠低分化腺癌及双侧卵巢库肯勃瘤（Krukenberg瘤）。患者术后接受了6个疗程奥沙利铂+贝伐珠单抗+卡培他滨化疗,现病情稳定。此例为在促排卵状态下,盆腔丰富的血供及淋巴循环促进了结肠癌来源的双侧卵巢Krukenberg瘤快速生长的病例,临床上较为罕见,结合文献复习辅助生殖技术对原发性卵巢恶性肿瘤的潜在致病风险及对转移性卵巢恶性肿瘤生长的影响。     

Immunohistochemistry as a tool in the differential diagnosis of ovarian tumors: an update.

Immunohistochemistry has become an important tool in the diagnosis of ovarian tumors. This article reviews the role of immunohistochemistry in the differential diagnosis of the three main categories of ovarian tumors, with emphasis on recently developed antibodies. In the surface epithelial stromal category the most common problem is its discernment from metastasis. The use of differential cytokeratins, primarily CK7 and CK20, as well as Cdx-2, beta-catenin, and P504S in differentiating between metastatic adenocarcinoma, particularly of colorectal origin, and primary ovarian carcinoma is discussed. Dpc4 may be useful in distinguishing pancreatic from ovarian mucinous carcinomas, because up to 55% of pancreatic carcinomas lack Dpc4 expression, whereas the differential expression of mucin genes may be helpful in distinguishing between primary ovarian mucinous and metastatic tumors. Urothelial markers (thrombomodulin and uroplakin III) and renal cell carcinoma markers (CD10 and renal cell carcinoma marker) can be helpful in the diagnosis of metastatic urothelial and renal cell tumors to the ovary. The roles of inhibin, calretinin, CD99, and other recently described markers in the diagnosis of sex cord-stromal tumors are reviewed. The uses of OCT-4 (POU5F1) (a new highly sensitive and specific marker of dysgerminoma and embryonal carcinoma), CD30, and c-kit are also discussed.     

Pancreatic tumor revealed by metastatic bilateral ovarian tumor with virilisation syndrome

We report a case of a 38-year-old patient presenting with both pancreatic and a bilateral ovarian tumor revealed by a virilization syndrome. Clinically, both tumors were conceivably distinct. However, on histological examination, they were found to be morphologically similar, with neuroendocrine features, suggesting that pancreatic tumor was a primitive neoplasm and the ovarian one a metastatic spread of that lesion. The virilization syndrome was due to the functional status of the ovarian tumors that was confirmed by immunohistochemical detection of inhibin.     

Current issues in the pathology of ovarian cancer

The majority of primary ovarian tumors are histologically classified as surface epithelial-stromal neoplasms. The malignant potential of such neoplasms may be categorized, on the basis of the extent of epithelial proliferation and stromal invasion, as benign, borderline or malignant. Recent efforts to further classify the malignant potential of such neoplasms have produced a new system for the histologic grading of ovarian carcinoma as well as new potential histologic predictors of behavior, including micropapillary morphology and stromal microinvasion in serous tumors. Among mucinous ovarian neoplasms, new criteria have been proposed to distinguish primary ovarian from metastatic carcinomas; the distinction may be difficult but has great clinical significance. The origin of ovarian mucinous tumors associated with pseudomyxoma peritonei has been reassessed. Finally, recent pathologic findings from prophylactic salpingo-oophorectomy specimens in patients with hereditary risks for ovarian carcinoma have highlighted the additional risk for fallopian tube carcinoma and primary peritoneal carcinoma. Special processing of the pathologic specimens is required to detect early and minimal neoplasia in this setting. These current issues in the pathology of ovarian carcinoma and their clinical significance form the basis of this review.     

Robotic-assisted laparoscopic cytoreductive surgery for lobular carcinoma of the breast metastatic to the ovaries

The first case of robotic-assisted laparoscopic cytoreductive surgery for a metastatic malignant ovarian tumor is described. A 65-year-old woman who was treated for breast cancer 13 years earlier presented with a deep venous thrombosis in the right leg and a pelvic mass. Imaging tests showed bilateral solid ovarian tumors and an enlarged lymph node at the level of the right common iliac vessels but no evidence of any other tumor metastases. The patient was offered and accepted to undergo a da Vinci robotic-assisted bilateral adnexectomy with hysterectomy and pelvic lymph node sampling. The surgery took 200 minutes, and the patient was discharged uneventfully on the third postoperative day. Histologic examination showed strongly estrogen receptor-positive metastatic lobular carcinoma of the breast in both ovaries and fallopian tubes. She was further treated with adjuvant exemestane and is currently doing well. It is possible to treat selected patients with malignant ovarian tumors by robotic-assisted laparoscopy.     

Carcinosarcoma-like mural nodule in intestinal-type mucinous ovarian of borderline malignancy: a case report

Epithelial ovarian tumors of borderline malignancy are tumors with histologic features and biologic behavior between benign and frankly malignant epithelial ovarian neoplasms. To date, we cannot accurately predict the patients who are prone to an aggressive course of disease. Here, we present a 35-year-old patient with carcinosarcoma-like mural nodule in intestinal-type mucinous ovarian tumor of borderline malignancy. Foci of intraepithelial carcinoma (about 10%) without stromal invasion are also noted. Total hysterectomy, bilateral salpingo-oophorectomy, appendectomy, and omentectomy were performed, and the frozen pathology during operation showed mucinous tumor of borderline malignancy of left ovary on April 18, 2002. The patient was followed at our outpatient department for 19 months after operation and was free of the disease without any adjuvant chemotherapy. It is difficult to determine whether intestinal-type borderline mucinous tumors with intraepithelial carcinoma are associated with a worse prognosis compared with those with epithelial atypia alone due to disparate results in the published literature. In contrast, most patients with mural nodules of anaplastic carcinoma have had a malignant, often rapid, course. However, too few cases of carcinosarcoma-like mural nodule in mucinous tumor have been published to warrant a conclusion regarding their prognosis.