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.     

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.     

Carcinoembryonic antigen in primary and metastatic ovarian tumors

The immunoperoxidase method and an absorbed monospecific commercial rabbit anti-CEA antiserum were used to detect CEA in 105 primary ovarian tumors and 12 metastatic ovarian adenocarcinomas of intestinal origin. Primary ovarian tumors showed CEA in foci of squamous differentiation in 9 out of 10 cases of endometrioid carcinomas and focally in areas of intestinal differentiation in 21 out of 28 mucinous tumors as well as 4 out of 5 Brenner tumors. All of the serous tumors, clear cell carcinomas, and undifferentiated carcinomas as well as 19 of the 22 mucinous tumors without intestinal differentiation lacked CEA. All metastatic ovarian adenocarcinomas showed characteristic diffuse staining of CEA. Differences in CEA staining were found to be useful for histological differentiation between primary ovarian cancers and metastatic ovarian adenocarcinomas of intestinal origin. Furthermore, these data might be helpful in the selection of patients for serial CEA evaluation.     

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.     

Intraoperative assessment of ovarian tumors: a 5-year review with assessment of discrepant diagnostic cases.

Frozen section is often requested in the intraoperative assessment of patients, presenting with ovarian masses, to provide guidance for appropriate surgical management. To assess the accuracy of frozen section and identify causes of diagnostic error, we reviewed 914 consecutive ovarian frozen sections performed over a 5-year period in 2 laboratories; one of which provides a general surgical pathology service and, the other, a specialist gynecologic pathology service. Cases, in which there were significant diagnostic discrepancies between the intraoperative and the final histological diagnoses, were reviewed. The series included 552 benign lesions (60.4%), 96 borderline (atypical proliferating) epithelial tumors (10.5%), and 266 malignancies (29.1%). The overall accuracy of frozen section diagnosis was 95.3%. There were 43 cases with diagnostic discrepancy; 20 (3.8% cases) of which were reported in the specialist laboratory and 23 (5.9% cases) in the general laboratory. Underdiagnosis of tumor type accounted for 32 of 43 discrepant cases and was most frequent in borderline mucinous tumors. The most common cause of overdiagnosis was the misinterpretation of serous cystadenofibroma as borderline serous tumor. Slide review of the 41 assessable cases indicated that sampling error, pathologist misinterpretation, and suboptimal slide preparations contributed to misdiagnoses in 17, 23, and 9 tumors, respectively (in 9 cases, 2 factors were contributory), whereas no specific error was identified in the remaining case. Technical factors and pathologist misinterpretation were more common in the general pathology laboratory. This study confirms that ovarian frozen section is a generally reliable technique, but there are problematic areas, particularly involving the assessment of borderline tumors.     

Metastatic tumors to the ovaries: a study of 170 cases in northern Thailand

Abstract.   Khunamornpong S, Suprasert P, Na Chiangmai W, Siriaunkgul S. Metastatic tumors to the ovaries: a study of 170 cases in northern Thailand. Int J Gynecol Cancer 2006; 16(Suppl. 1): 132–138.
The cases of malignant ovarian tumors treated at Chiang Mai University hospital between 1992 and 2003 were histologically reviewed. The medical records, the radiologic findings, and the follow-up outcome in the cases suspicious or diagnostic of metastases were reviewed to confirm the diagnosis and to determine the primary sites. Metastatic tumors accounted for 30% of malignant ovarian tumors. A total of 170 cases of metastatic tumors included 117 cases with nongynecologic origin and 53 cases with gynecologic origin. Nongynecologic metastatic tumors were from large intestine (31%), stomach (14%), intrahepatic bile duct (10%), breast (9%), extrahepatic bile duct/gallbladder (7%), appendix (5%), hematologic tumors (3%), others (4%), and unknown primary site (16%). Metastatic gynecologic tumors were from cervix (53%), corpus (34%), fallopian tube (11%), and gestational trophoblastic disease (2%). The proportion of metastatic tumors to malignant ovarian tumors in northern Thailand was comparable to those of the Western or Japanese studies. However, the distribution of the primary sites was different and was correlated with the cancer incidence in Thai women. The majority of mucin-producing adenocarcinomas involving the ovaries were metastatic tumors.     

The accuracy of frozen section diagnosis of ovarian tumors

We compared all frozen section examinations of ovarian tumors during a 6-year period in our institute with the final diagnosis from paraffin sections. In this period, 946 ovarian tumor specimens were removed for histologic assessment; 176 (18.6%) had frozen section examination. Final histological diagnosis was divided into benign (55.1%), borderline malignant (10.3%), and malignant (34.6%). Sensitivity of the frozen section method for malignant or borderline disease was 83.5% and specificity for a benign lesion, 92.8%. Predictive values and 95% confidence intervals were computed: 100% (93-100%) for malignancy, 62% (32-86%) for borderline malignancy, and 92% (85-96%) for a benign disease. Diagnostic problems occurred in large borderline tumors of mucinous cell type. Analysis of the 12 false negative diagnoses revealed that a sampling error was involved in 11 cases. A judgment error was made in the only false positive and in 1 out of 12 false negative frozen section diagnoses. It is concluded that when surgeons and pathologists are aware of the limitations of frozen section diagnosis of ovarian tumors, peroperative histologic examination can be worthwhile and prevent under- and overtreatment of gynecologic patients.     

Accuracy of frozen section diagnosis in borderline ovarian malignancy

This study was conducted to determine the accuracy of frozen section diagnosis in borderline ovarian tumors. Thirty-three patients were evaluated on the basis of frozen sections between February 1992 and December 1997. Frozen section diagnosis and final diagnosis were divided into three categories: for frozen section diagnosis: 1 = benign, 2 = borderline, 3 = 'at least' borderline, and for final diagnosis: 1 = benign, 2 = borderline, 3 = cancer. Three patients with a benign diagnosis according to their frozen sections were reclassified as borderline in the final diagnosis and all of them were of the mucinous type. The frozen section diagnosis of tumors of borderline malignancy was inaccurate in 3 of 23 patients. Four of 7 patients with at least borderline according to their frozen section diagnosis had invasive cancer at the final diagnosis. The correlation between frozen section diagnosis and final pathological examination was 72.7% (24/33). We found 9% (2/22) inaccurate results in the serous type and 36.6% (4/11) in the mucinous type. The sensitivity and specificity of frozen section diagnosis were found to be 86.95 and 57.14%, respectively. We concluded that frozen section evaluation in identifying a borderline ovarian malignancy is accurate enough to exclude the presence of a benign pathology.     

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.     

K-ras gene point mutations and p21ras immunostaining in human ovarian tumors

It is well recognized that genetic alterations within oncogenes, tumor suppressor genes, DNA mismatch repair and excision repair genes contribute to tumorigenesis within the human ovary. This study was undertaken to screen for the existence of K-ras gene point mutations in paraffin-embedded slides randomly selected from benign and malignant ovarian tumors applying the PCR-RFLP technique. Expression of p21ras was also assessed in 30 primary ovarian adenocarcinomas immunohistochemically. K-ras codon 12 point mutations occurred in nine of 40 (22.5%) cases. They were not identified in two benign mucinous cystadenomas, but in one out of two (50%) mucinous tumors of LMP (low malignant potential), in five out of 30 (17%) ovarian adenocarcinomas, and in one case of adenocarcinoma metastatic to the ovary. K-ras activation was also detected in one out of four (25%) sex cord-stromal cell tumors (folliculoma), and in one dysgerminoma. None of these tumors exhibited K-ras codon 13 point mutations. Gene alterations were more frequently found in mucinous than in non-mucinous (30% vs 10%) tumors, although the difference did not reach significance (p > 0.05). The frequency of K-ras point mutations was correlated neither with clinical nor with pathological variables of cancer. Cytoplasmic p21ras was expressed in all adenocarcinomas negative for K-ras point mutations, whereas one of five (20%) K-ras-positive tumors exhibited lack of immunoreactivity. In conclusion, these findings confirm the role of K-ras activation in mucinous ovarian tumors. p21ras expression is not necessarily associated with K-ras gene alterations in human ovarian adenocarcinomas.     

Primary Appendiceal Malignancy Mimicking Advanced Stage Ovarian Carcinoma: A Case Series

Background. Primary appendiceal malignancy metastatic to the ovaries is a rare condition that may mimic late stage ovarian cancer. This condition is rarely diagnosed preoperatively.Cases. Three patients referred to our institution from 1994 to 1999 for presumed late stage ovarian cancer were found to have primary appendiceal adenocarcinoma, adenocarcinoid, and mucinous cystadenocarcinoma metastatic to the ovaries at laparotomy. We describe the clinical course of these patients and review the relevant literature.Conclusion. It is important for the gynecologic oncologist to be aware of the clinicopathological features and surgical management of these malignancies, as the incidence, prognosis, and recommended treatment vary with histological subtype.     

The accuracy of frozen section (intraoperative consultation) in the diagnosis of ovarian masses

OBJECTIVE: Frozen section is an important and helpful adjunct in the intraoperative diagnosis of ovarian tumors. This retrospective study was undertaken to determine the accuracy of frozen section diagnosis of ovarian masses and the reasons of discordance. METHODS: From January 1995 to December 2003, 1494 ovarian specimens were received for histopathological evaluation, and 617 of them were submitted for frozen section examination. RESULTS.: The final paraffin section diagnoses of these 617 cases were a nonneoplastic lesion in 18.3% of the cases, benign tumor in 56.1%, borderline tumor in 6.2%, and malignant tumor in 19.4%. The overall accuracy was 97%. Twenty-one cases were incorrectly diagnosed by frozen section. All of them were false negatives. There were no deferred cases. The majority of the cases of disagreement were mucinous and borderline tumors. The sensitivity for benign, borderline, and malignant tumors were 100%, 87%, and 87%, respectively. The specificity for benign tumors was 97%; for borderline tumors 98%; and for malignant tumors 100%. CONCLUSION: Our data confirm that frozen section diagnosis is a reliable method for the surgical management of patients with an ovarian mass. However, diagnostic problems can occur in mucinous and borderline tumors during frozen section examination. The clinicians and pathologists must be aware of the pitfalls of this method; therefore, a good communication established between them is necessary to obtain more accurate results and to minimize the number of deferred cases.     

Metastatic duodenal carcinoma simulating primary mucinous tumor of the ovary

Case report We report a case of metastatic duodenal carcinoma simulating a primary ovarian mucinous tumor, occurring in a 53-year-old woman who had undergone pancreatoduodenectomy for duodenal adenocarcinoma approximately 18 months previously. The surgically removed bilateral ovaries revealed multicystic tumors. Histological examination showed they closely mimicked primary ovarian mucinous tumors. Immunohistochemical examination using cytokeratin 7 and 20, and CA125 indicated that the bilateral ovarian tumors were metastasis from duodenal carcinoma.Conclusions Duodenal carcinoma can be a rare primary focus of metastatic tumor simulating primary ovarian neoplasm.     

Four synchronous female genital malignancies: the ovary,cervix, endometrium and fallopian tube

Objective To present a unique case of a 63 year-old woman with coexistent adenocarcinoma of the ovary, endometrium, cervix and fallopian tube. Materials and methods A case report from a tertiary health center. Results A woman presenting with postmenopausal bleeding and abdominal distantion was assessed by endometrial biopsy and explorative surgery. The frozen section of the mass on the right adnex revealed malign mucinous carcinoma of the ovary. As usual, optimal debulking was performed as initial surgical staging procedure of ovarian cancer. The microscopic examination of the right ovary revealed a typical mucinous cystadenocarcinoma. Furthermore, the focal endometrial irregularity at the left uterine cornus turned out to be a well differentiated endometrial carcinoma of the endometrioid type with <1/3 myometrial invasion. The pale infiltrative lesion in the cervix also turned out to be an adenocarcinoma of the endocervical type with deep stromal invasion and areas of diffuse glandular dysplasia and in-situ glandular neoplasia at the periphery. Besides, several sections from the left fallopian tube uncovered diffuse dysplasia in the lining epithelium and a focus of adenocarcinoma with papillary and cribriform pattern. Discussion When compared with patients having metastatic lesions, most synchronous female malignancies are accompanied with early stage and low-grade with a more favorable prognosis. However, there is paucity of data for the exact criterion to distinguish primary tumors from metastatic lesions. In such cases, the validity of immunohistochemical and cloning studies are not clear.     

Two Concurrent Cancers in a 19-Year-Old Patient: Yolk Sac Ovarian Tumor and Metastatic Gastrointestinal Tract Malignancy—Case Report

BackgroundTwo concurrent malignancies present in a young person is an extremely rare condition. Diagnoses of gastric cancer primarily concern older patients. There are very few reports of concomitant Krukenberg tumor and germ-cell ovarian malignancy.CaseA 19-year-old girl was admitted to the gynecologic oncology department with symptoms of advanced malignancy. Radiological imaging revealed disseminated neoplastic disease with bulky adnexal tumors. Cytoreductive surgery was performed, achieving no visible disease (T = 0 cm). The final pathology report confirmed metastatic mixed adenoneuroendocrine carcinoma (MANEC) in both ovaries, originating from the gastrointestinal tract. Moreover, the primary germ cell yolk sac tumor was found in the left ovary.ConclusionIn cases of concomitant gastric and ovarian tumors, metastatic disease (Krukenberg tumor) should be considered in the differential diagnosis. This concerns even adolescent patients. In particular cases, including tumors with germ cell components, primary debulking surgery is crucial for prognosis.     

Hypoxic status in ovarian serous and mucinous tumors: relationship between histological characteristics and HIF-1α/GLUT-1 expression

Material and methods We analyzed the expression of hypoxia inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) by immunohistochemistry in ovarian serous and mucinous tumors from the point view of the histological characteristics and acquisition of malignancy. A total of 102 ovarian tumors were examined, composed of 31 adenomas (serous 17 and mucinous 14), 32 borderline tumors (serous 13 and mucinous 19), and 39 adenocarcinomas (serous 21 and mucinous 18). Results The overall positive ratios were as follows: HIF-1α, 74% of adenomas, 91% of borderline tumors, and 100% of adenocarcinomas; and GLUT-1, 68% of adenomas, 95% of borderline tumors, and 100% of adenocarcinomas. Comparing serous tumors and mucinous tumors, there was no significant difference in the positive ratios of HIF-1α and GLUT-1 of adenomas, borderline tumors, and adenocarcinomas. However, both markers were more strongly expressed in serous adenocarcinomas (HIF-1α, 3 + 100%; GLUT-1, 3 + 76%) than in mucinous adenocarcinomas (HIF-1α, 3 + 61%; GLUT-1, 3 + 28%). The results of immunoblotting and mRNA expression level analyses corresponded with those of immunohistochemical expression profiles. DNA binding assay also demonstrated that HIF-1 is more commonly activated in serous adenocarcinomas than in mucinous adenocarcinomas. Conclusion HIF-1α and GLUT-1 expressions seemed to be coordinated to adapt ovarian tumor cells into hypoxic conditions in close association with the acquisition of malignancy. We consider that the relatively strong expression of both markers in serous tumors compared with mucinous tumors is related to the difference in their histological characteristics.     

Appendiceal tumors in patients undergoing primary surgery for mucinous ovarian tumors in a tertiary hospital,in Southern Thailand

ObjectiveTo evaluate the prevalence of appendiceal tumors in patients diagnosed with mucinous ovarian tumors and to determine factors associated with coexisting appendiceal tumors.Materials and methodsRetrospective review of all patients who were diagnosed with mucinous ovarian tumors and underwent an appendectomy during surgery between January 2002 and June 2017 was performed. Univariate and multivariate logistic regression analyses were used to identify risk factors for coexisting appendiceal tumors.ResultsA total of 303 patients with mucinous ovarian tumors who underwent appendectomy were identified, including 77 (25.4%) mucinous cystadenoma and 226 (74.6%) mucinous borderline tumor or carcinoma. Twenty-one (6.9%) had coexisting appendiceal tumors including 8 that were primary appendiceal mucinous adenocarcinomas, 6 low-grade appendiceal mucinous neoplasms, 6 secondary appendiceal metastasis from the ovary, and one hyperplastic polyp. None of mucinous cystadenoma had coexisting appendiceal tumors. Multivariate analysis revealed advanced age ≥50 years, previous rupture of ovarian tumors, abdominal extension of tumors, and grossly abnormal appendix were independent factors for coexisting appendiceal tumors.ConclusionPrevalence of coexisting appendiceal tumors in mucinous ovarian tumors was not uncommon. The risk factors were grossly abnormal appendix, abdominal extension of tumor, previous rupture of ovarian tumors, and advanced age.     

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.