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.     

Malign mural nodules associated with serous ovarian tumor of borderline malignancy: a case report and literature review

Background  

Cystic tumors of ovary, whether benign, borderline, or malignant may be associated with mural nodule of various types, including sarcomas, sarcoma-like mural nodules (SLMN), and foci of anaplastic carcinoma. Cases of serous borderline ovarian tumor with mural nodules of mixed type are very rare.     

Biological relevance of E-cadherin-catenin complex proteins in primary epithelial ovarian tumours

This study analysed the biological relevance of E-cadherin, alpha-catenin, beta-catenin and gamma-catenin immunoexpression pattern (reduced vs. preserved phenotype) in epithelial ovarian tumours. Immunohistochemistry was used to evaluate the expression of these proteins in 154 epithelial ovarian tumours, consisting of 17 benign, 33 borderline and 104 malignant tumours. In borderline tumours, the immunoexpression pattern of E-cadherin (p = 0.014) and alpha-catenin (p = 0.030) associated with histological type. In malignant tumours, the immunoexpression pattern of E-cadherin was related with histological type (p = 0.001). The immunoexpression pattern of beta-catenin associated with histological type and tumour differentiation (p = 0.005, p = 0.025, respectively). The preserved phenotype of E-cadherin was most frequently observed in mucinous tumours, whereas reduced E-cadherin was most frequently observed in serous tumours. The preserved phenotype of beta-catenin associated with endometrioid carcinomas, while reduced beta-catenin associated with poorly differentiated serous and clear cell carcinomas. Although the reduced phenotype was the most frequent immunoexpression observed for all proteins of the E-cadherin-catenin complex in epithelial ovarian tumours, only beta-catenin showed a significant difference between benign, borderline and malignant tumours (p = 0.045), since borderline and malignant tumours most frequently showed the reduced phenotype. The immunohistochemical profile of beta-catenin was shown to be of biological relevance: reduced beta-catenin was correlated with loss of tumour differentiation and serous carcinomas that are known to depict aggressive biological behaviour in epithelial ovarian tumours.     

Pathology of borderline (low malignant potential) ovarian tumours

Recent studies suggest that the borderline group of ovarian tumours can be subclassified into benign and malignant neoplasms. The survival for patients with serous borderline tumours confined to the ovaries is virtually 100%. Patients with serous borderline tumours with invasive peritoneal implants, and with micropapillary serous carcinomas (a distinctive neoplasm previously included in the borderline category), have a 30-40% mortality rate and therefore these tumours are classified as carcinomas. After these neoplasms are excluded, the remaining advanced stage serous borderline tumours (those with non-invasive implants) have a survival rate of nearly 100% and should be considered benign. Similarly, nearly all mucinous borderline tumours reported to display aggressive behaviour have been associated with pseudomyxoma peritonei, a condition now known to be of appendiceal origin. The remaining mucinous borderline tumours are always confined to the ovaries and have a benign behaviour. Since borderline tumours can now be classified into benign and malignant types, the category has no further utility.     

Developments in the pathology of ovarian tumours

The understanding of the pathogenesis and pathology of ovarian tumours is constantly evolving. Dominant themes in recent studies of ovarian tumours include prognostic features in borderline tumours, molecular events in the pathogenesis of ovarian tumours, the assessment of tumour features that may have prognostic or treatment implications, and the development of techniques that may enhance diagnostic accuracy. The literature has been reviewed with an aim to identifying those studies that can potentially impact practice and improve patient care. The most noteworthy developments include: the understanding that so-called 'tumours of low malignant potential' are virtually always benign, and that one can identify those rare cases with malignant potential; the importance of the recognition of micropapillary serous carcinomas; an improved understanding of early invasive carcinomas and their impact on screening practices; an understanding of the association of endometriosis with ovarian cancer; further awareness of factors in ovarian tumours that influence prognosis, such as refinements in grading and molecular markers such as P27; and refinements in diagnosis so as to distinguish primary from metastatic cancer and benign lesions from malignant tumours more effectively.     

Tumor de Brenner benigno asociado a tumor mucinoso borderline de ovario en paciente postmenopáusica

Brenner tumour is an uncommon neoplasm of the ovary of uncertain origin and often asymptomatic. Diagnostic is complex, without specific ultrasound patterns. It has been associated with mucinous tumours with different potential for malignancy, and it is possible to find malignant or borderline components that determine the treatment. For its differential diagnosis immunohistochemical study is essential, which shows, according to various studies, a clonal origin of Brenner and mucinous tumour. This is a case report of a Brenner tumour associated with a mucinous tumour, which in a definitive study showed to be associated with a borderline ovarian tumour component.     

p63 expression in epithelial ovarian tumors

Ovarian cancer is a highly lethal disease and its underlying biology is poorly understood. The p63 is a homologue gene of the tumor suppressor p53. p63 appears to be important for the development and differentiation of reproductive epithelium and interacts with p53 in human tumorigenesis. This study presents the immunoexpression of the p63 in benign and malignant epithelial ovarian tumors. We evaluated the p63 immunoexpression in 91 ovarian benign cystadenomas (29 mucinous and 62 serous) and in 29 ovarian malignant tumors (3 mucinous borderline, 3 serous borderline, 17 serous carcinomas, 2 endometrioid, 2 undifferentiated, 1 mucinous, and 1 clear-cell carcinoma) using a monoclonal antibody clone 4A4 (1:200), which recognizes all p63 variants. The tumors were considered p63 positive if 5% or more cells presented nuclear immunostaining. We observed 85.7% of positivity in benign tumors, 50% in borderline tumors, and 8.7% in invasive ovarian cancer (P < .0001). The benign serous cystadenomas were positive in 91.9% of cases and benign mucinous cystadenomas in 72.4% (P= .02). These data suggests an important role of p63 in the control of ovarian epithelium behavior. The p63 may be involved in the development of benign and malignant epithelial ovarian tumors.     

k-ras mutation may be an early event in mucinous ovarian tumorigenesis.

We explored the possible pathogenetic pathway for mucinous ovarian tumorigenesis by examining the k-ras mutational patterns in ovarian mucinous tumors (OMTs) with benign, borderline, and invasive epithelium in which the different types of mucinous epithelium are in close proximity. Sixteen patients with ovarian mucinous borderline tumors (OMBTs) and 4 patients with grade 1 ovarian mucinous adenocarcinomas (OMCs) were selected for the presence of a single histologic section which contained a clear "transition" zone from benign mucinous epithelium to borderline mucinous epithelium, and in four cases, to invasive epithelium. A PixCell II Laser Capture Microscope was used to microdissect and retrieve benign, borderline, and invasive epithelium separately from the 20 OMTs. Normal ovarian stroma from the same histologic section in each case was also microdissected and retrieved for use as a control. k-ras mutations were detected in these samples by PCR-SSCP analysis followed by direct PCR cycle sequencing. k-ras mutations were found in 8/16 (50%) of the OMBTs and 2/4 (50%) of the grade 1 OMCs. In 6 of these 10 cases (4 in OMBTs, 2 in grade 1 OMCs), the same k-ras mutation was found in both the benign and borderline (and invasive) regions. In 3 cases in which k-ras mutations were identified, the mutation was found in either the benign or borderline tissue samples alone, and in one case, two distinct mutations were found. No k-ras mutations were identified in the normal ovarian stroma. The presence of a k-ras mutation in adjacent benign and borderline regions of a single OMT may suggest a progression in the development of OMTs from benign to borderline and grade 1 OMCs. k-ras mutations, when they occur, are likely early genetic changes but may not alone be sufficient for malignant transformation of ovarian epithelium.     

Clinical characteristics and prognosis of mucinous tumors of the ovary

OBJECTIVE: Ovarian mucinous tumors consist of benign, borderline, and carcinomatous tumor, but the clinical characteristics of these 3 types have not been investigated in detail. In this study, we compared the clinical characteristics and prognosis among these 3 types of mucinous tumors. METHODS: One hundred sixty-one patients with mucinous cystadenocarcinoma and 143 patients with mucinous borderline tumor were registered between 1986 and 2003. All patients were reviewed by two pathologists, then the mixed type and cases showing other organized malignant tumors were excluded from this study. Patients with mucinous carcinoma staged Ib or more were treated postoperatively with 6 cycles of platinum-based chemotherapy. Survival probability was analyzed by the Kaplan-Meier method and differences in survival rates were calculated using log-rank test. RESULTS: Mean patient ages were 43.9, 44.7, and 49.7 years in patients with benign, borderline, carcinomatous tumor, respectively. The ratio of early stage (I, II) to advanced stage (III, IV) was significantly lower in carcinoma than in borderline tumor. The levels of tumor markers tended to increase with the level of malignancy. CA72-4 is the most useful discriminating marker according to ROC analysis. In borderline tumor, 5 patients died of disease, and all of these patients had stage III disease with residual tumor after the initial surgery. Patients with borderline tumor showed significantly better prognosis than those with carcinoma; however, there were no significant differences in prognosis between borderline tumor and carcinoma in patients with stage III tumor or residual tumor. CONCLUSIONS: In mucinous tumors, measurement of CA72-4 is recommended to distinguish malignant from benign tumors. Even in borderline tumor, patients with residual tumor showed a poorer prognosis than carcinoma, suggesting that complete resection is necessary for a good prognosis.     

Mucinous tumors of the ovary: analysis of 38 cases.

Ovarian mucinous tumors stem from ovarian surface epithelium and are divided into benign, borderline and malignant. It is difficult to differentiate borderline and malignant mucinous tumors. Thirty-eight cases of ovarian mucinous tumors which were diagnosed at the Pathology Department of Dicle University Medical Faculty were reviewed. Of these, 18 (47.3%), six (15.7%) and 14 (36.8%) were benign, borderline and malignant, respectively. The patients' ages ranged from 18 to 67 (average 44.5) years. Bilaterality was detected in 1/18 (5.5%), 0/6 and 4/14 (28.5%) of benign, borderline and malignant mucinous tumors, respectively. Mean tumor size was 26.4 cm. Microscopically, there was no stratification in the benign tumors. The borderline tumors had papillary infoldings and 2-3 layers of atypical epithelial cells but no invasion of the stroma. Malignant tumors had four or more layers of atypical epithelial cells and stromal invasion.     

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.     

Free Communications

Ovarian-type mucinous tumours occur very rarely in the retroperitoneum. We present a case of primary retroperitoneal mucinous tumour of borderline malignancy in a 58-year-old woman, detected as an incidental finding. The patient presented with acute renal failure, investigation for which revealed a complex pelvic mass initially thought to be in the right adnexa and consistent with an ovarian neoplasm. Surgical findings revealed a 130-mm, right-sided non-communicating retroperitoneal pelvic mass, posterior to the appendix, which was completely resected. Both ovaries were normal. Macroscopically, it was a multi-loculated cystic structure with a smooth external surface containing clear and mucinous fluid. Microscopic examination showed a mucinous tumour of borderline malignancy. The literature contains approximately nine other cases of primary mucinous retroperitoneal tumour of borderline malignancy. These cases have occurred in women aged 36–60 years. Most patients were asymptomatic and the mass was detected as an incidental finding. The patients have been followed up for up to 6 to 18 months and, to date, none have recurred. There are limitations to pre-operative radiological imaging. A definitive diagnosis can only be made after complete surgical excision and histological examination, having excluded retroperitoneal involvement by mucinous tumours from sites such the ovaries, bowel, appendix and pancreas.     

Mucinous borderline tumours of the ovary and the appendix: A retrospective study and overview of the literature

Objectives

Appendectomy is often recommended in patients with mucinous borderline ovarian tumours (mBOTs) based on studies suggesting that metastatic disease from a primary appendiceal tumour can mimic mBOT. The present study assessed the incidence of mucinous neoplasms in the appendix associated with the presence of mBOT.

Methods

A retrospective cohort study was performed in two university hospitals in the Netherlands between 1990 and 2011. All patients with mBOT and/or a mucinous appendiceal tumour were included.

Results

Of 127 patients included, 98 had a primary mBOT and 29 had a primary mucinous appendiceal tumour.In patients with a mBOT, the appendix was either removed at prior surgery (4%), resected as part of the staging procedure showing no pathological abnormalities (13%), described as normal and not resected (58%), or not described and not resected (25%). During a median follow-up period of 5 years (range 2–23), two patients developed a recurrence in which the appendix was not involved.In all patients with a primary mucinous tumour of the appendix, the appendix appeared abnormal at the time of surgery. Eight of these patients (28%) were diagnosed with invasive ovarian metastases.A review of the literature including the cases from this study identified 510 mucinous ovarian tumours with borderline features and 214 associated appendectomies, of which 4 (1.9%) contained a primary appendiceal malignancy.

Conclusions

A thorough inspection of the appendix should be performed in patients with a mucinous ovarian tumour with borderline features. An appendectomy should only be performed when the appendix is macroscopically abnormal.     

Immunohistological demonstration of peptide hormones and serotonin in ovarian mucinous and endometrioid tumors with argyrophil cells

The localization of peptide hormones and serotonin in ovarian mucinous and endometrioid tumors with argyrophil cells was examined by immunohistochemistry. All of the 15 mucinous tumors had argyrophil cells which resemble the enterochromaffin cells seen in the gastrointestinal tract, and peptide hormones such as gastrin and somatostatin were found in 3 of 5 benign, in 3 of 5 borderline, and in all of 5 malignant tumors. Serotonin was found in 4 benign, 3 borderline and 2 malignant tumors. Of 19 endometrioid adenocarcinomas, type I argyrophil cells which resemble enterochromaffin cells were found in 4 tumors, type II argyrophil cells which contain argyrophil granules mainly in the apical portion or throughout the whole cytoplasm were found in 14, and mixed type cells were found in one. Somatostatin-positive cells were found only in type I cells of a tumor with mixed type argyrophil cells. Serotonin-positive cells were found in 3 tumors containing type I cells. The results obtained were discussed in the comparison with those of cervical and endometrial adenocarcinomas of the uterus. In conclusion, the present study suggests that type I or similar argyrophil cells in ovarian tumors may have endocrine activity.     

Mucinous cystadenocarcinoma of the retroperitoneum: a light and electron microscopic study

A large, ovarian-type, retroperitoneal cystic tumor existing in the presence of normal ovaries was studied morphologically by light and electron microscopy. The cyst was monolocular, having several papillary nodules which measured 0.2-2.0 cm in diameter, and protruded into the lumen. Histologically, most of the tumor wall was covered by mesothelium-like cells which showed signs of differentiation into either a benign endocervical type mucinous epithelium or a mucinous epithelium of borderline malignancy, particularly around the nodules. The papillary nodules themselves had the histological features of a well-differentiated mucinous adenocarcinoma. These light and electron microscopic features resembled those of ovarian mucinous tumors. Histogenetically, the tumor appeared to be derived from a mesothelial inclusion cyst; some of the mesothelium being transformed by metaplastic change into the endocervical type mucinous epithelium and undergoing further transformation into either the mucinous epithelium of borderline malignancy or the well-differentiated mucinous adenocarcinoma by some unknown factors.     

Pre and Intraoperative Diagnosis of Ovarian Tumours: How Accurate Are We?

Summary: In the assessment of malignant potential of ovarian tumours, frozen section has been found to be accurate in 97.1% (168 of 173) of cases. The positive predictive value of frozen section in the diagnosis of a malignant lesion was 100% (34 of 34). Errors were mainly made in the diagnosis of borderline tumours with a predictive value of 87.5% (7 of 8). The negative predictive value was 98.4% (127 of 129). Frozen section however, was less accurate in the diagnosis of specific histological type with an accuracy rate of 91.9% (159 of 173). Macroscopic features were found to be useful in the intraoperative prediction of malignant potential. Completely cystic tumours were benign in 96.4% (108 of 167) of cases. Solid/cystic tumours were malignant in 69% (27 of 38) of cases. Completely solid tumours were malignant in 56% (9 of 16) of cases. Frozen section in completely cystic tumours only marginally improved the clinical macroscopic diagnosis of malignancy. The sensitivity and specificity of ultrasound scan in the diagnosis of malignant/borderline tumours were 82% and 86% respectively. The false negative rate of 7% makes laparoscopic excision of unsuspected malignant ovarian cyst a significant possibility. The predictive value of ultrasound scan in the diagnosis of malignant ovarian tumour was 62% (26 of 42). In the preoperative assessment of malignant potential of ovarian tumours, this study shows that ultrasound scan has a high false positive and a significant false negative rate. Careful intraoperative assessment of gross features and the use of frozen section especially in those with solid/cystic and solid tumours will help achieve a high accuracy rate in the assessment of ovarian tumours.     

Ovarian mucinous cystadenoma with a mural nodule of osteosarcoma: A case report

ObjectiveOsteosarcoma as a mural nodule in the ovary is extremely rare. We aimed to describe a case of a mural nodule with features of an osteosarcoma arising in an ovarian mucinous cystadenoma.Case reportThe 65-year-old woman presented with progressive abdominal swelling and poor intake. Image studies showed a huge (diameter, >30 cm) intra-abdominal multiloculated cystic lesion, suspected to be an ovarian tumor. She underwent unilateral salpingo-oophorectomy with no postoperative adjuvant therapy. She was disease-free at 16-month follow-up.ConclusionOsteosarcoma presenting as a primary ovarian neoplasm is rare, either as a pure osteosarcoma or arising from a teratoma. However, two osteosarcoma cases occurring arising from a mural nodule in an ovarian mucinous neoplasm have been reported. There is no consensus regarding the treatment strategy for osteosarcomatous mural nodules in mucinous tumors because of its rarity. More case studies are needed before its pathogenesis can be fully understood.     

Adnexal Torsion Due to Borderline Mucinous Tumor of the Gonad in a Prepubertal Girl with Mixed Gonadal Dysgenesis (45,X/46,XY) and a Turner Phenotype

BackgroundTurner syndrome (TS) is a sex chromosome condition characterized by complete or partial loss of the X chromosome. Patients with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype are predisposed to gonadoblastoma with malignant transformation.CaseWe present the case of a TS patient with 45,X/46,XY with 2 episodes of left adnexal torsion (AT). Biopsies during detorsion showed benign mucinous cystadenoma. Pathology following bilateral gonadectomy revealed a left gonad with mucinous borderline tumor and right gonad with gonadoblastoma, both of which have malignant potential.Summary and ConclusionGonadectomy is recommended in XY gonadal dysgenesis to decrease risk of malignant transformation from gonadoblastoma. Although rare in pediatric patients, ovarian malignancies have been identified among AT cases. To our knowledge, we present the first case of AT due to borderline ovarian mucinous tumor of the ovary and contralateral gonadoblastoma in a patient with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype.     

Periodic acid-Schiff stain as a prognostic indicator in serous and mucinous ovarian tumors

The prognostic significance of periodic acid-Schiff (PAS) stain in 112 serous: 43 benign, 25 borderline and 44 malignant cystadenomas: and in 106 mucinous: 60 benign, 32 borderline and 14 malignant cystadenomas of the ovary were investigated. The amount of positively stained mucin was estimated morphometrically. The outcome of most patients with benign or borderline lesion was good. One patient with benign mucinous cystadenoma died, however, of pseudomyxoma peritonei and another patient with borderline mucinous cystadenoma died of peritoneal carcinosis. Other patients were alive and free of the disease after a follow-up of 1-14 years, or had died of causes unrelated to the ovarian disease. Abundant PAS positive mucin predicted a longer survival both in serous and in mucinous malignant tumors. The 5-year survivals for the serous cystadenocarcinomas with and without PAS positive mucin were 21% and 13%, respectively (not statistically significant). For mucinous cystadenocarcinomas with mucin value over and below the median, the 5-year survival rates were 57% and 14%, respectively (P less than 0.10). High PAS positivity in both serous and mucinous cystadenocarcinomas clearly indicated better prognosis, although statistical significance was not achieved. Thus, further studies are needed for final evaluation of the prognostic significance of the PAS stain in these ovarian tumors.