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.     

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 borderline mucinous tumor in a premenarchal girl: review on ovarian epithelial cancer in young girls.

Ovarian tumors constitute the most common gynecological neoplasms during childhood. Unlike in adult women, ovarian epithelial tumors are uncommon in young girls and extremely rare prior to menarche. To our knowledge this is the first report of a borderline malignant mucinous tumor of the ovary in a premenarchal girl. It was successfully treated by conservative surgery. In our review of ovarian neoplasms in girls under 20 years of age, epithelial tumors were found in 19.3%, with a malignancy rate of 15.9%. Of these malignant tumors, 39.4% were of the mucinous type and 30.3% were borderline malignant. The occurrence of such a tumor at this age underscores the possibility of malignant transformation of the ovarian epithelium even prior to menarche. Its mucinous nature confirms the predominance of the mucinous subgroup in young girls. Hypotheses on the origin of mucinous tumors are discussed.     

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.     

Epithelial ovarian tumors and CA125 in premenarchal girls

PURPOSE: This is a review of our 18-year experience with premenarchal girls with epithelial ovarian tumors. Special attention was focused on the predictive value of CA125 serum levels. METHODS: Analysis of premenarchal patients with resected or biopsied ovarian masses from 1988 to 2005 was performed. Patient age, clinical presentation, operative procedures, histologic type of tumor, treatment and outcome were obtained. RESULTS: Six premenarchal girls (aged from 6 to 14 years) were surgically treated for epithelial tumors, representing 13% of all ovarian tumors at this age. Histological findings revealed cystadenoma in four girls, one with a mucinous borderline tumor and one with undifferentiated carcinoma. Tumor volume was higher than 400 cm3 in four girls. Sensitivity, specificity and positive predictive value of CA125 level for ovarian malignant epithelial tumors were 0.50, 0.50, and 0.33, respectively. The premenarchal girl with undifferentiated carcinoma in Stage III died after six months in spite of chemotherapy. CONCLUSION: Ovarian epithelial tumors in premenarchal girls show important growth potential and a relatively high malignancy rate with great influence of borderline neoplasms. CA125 is a tumor marker with low sensitivity and specificity for detection of epithelial ovarian malignancy in this age group.     

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.     

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.     

An immunohistochemical study of the incidence and significance of C-erbB-2 oncoprotein overexpression in ovarian neoplasia

Abstract. Wilkinson N, Todd N, Buckley CH, Gusterson BA, Fox H. An immunohistochemical study of the incidence and significance of C-erb-B oncoprotein overexpression in ovarian neoplasia. Int J Gynecol Cancer 1991; 1 : 285–289.
An immunohistochemical study was made of overexpression of the c-erbB-2 oncogene product in benign, borderline and malignant epithelial neoplasms of the ovary. Positive staining was found only in 2 of 15 mucinous tumors of borderline malignancy and in 11 of 16 mucinous adenocarcinomas. Positive staining was not detected in serous or endometrioid tumors. Amongst the group of mucinous adenocarcinomas, no correlation could be found between overexpression of c-erbB-2 oncoprotein and tumor stage, tumor differentiation or patient survival. It is concluded that overexpression of c-erbB-2 oncoprotein is not an adverse prognostic factor in ovarian adenocarcinoma.     

Peripheral and ovarian venous concentrations of steroid and gonadotropin hormones in postmenopausal women with epithelial ovarian tumors

Peripheral serum concentrations of estrone (E1), estradiol (E2), testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), cortisol, prolactin, LH, and FSH were measured in 28 postmenopausal women with epithelial ovarian tumors (12 ovarian cancer, 5 borderline malignant, 11 benign neoplasms) and in 15 controls before bilateral salpingo-oophorectomy and 1 and 8 weeks postoperatively. The levels of these hormones were also measured in ovarian venous blood of 15 patients with ovarian tumors. E2 was significantly higher in the tumor group than in controls preoperatively and the levels of E1 and E2 decreased after radical operation. Hormone levels were similar in the benign and malignant tumor groups. Only DHEAS levels in peripheral serum were significantly lower in ovarian cancer patients than in the group with benign neoplasm. This was not the case in testosterone and androstenedione measurements. The measured levels of the hormones in ovarian venous blood were highest in mucinous ovarian tumors. E2 and testosterone levels were higher in mucinous ovarian tumors than in others. LH(hCG)-receptor levels were measured in 24 specimens and none of these showed detectable concentrations of LH(hCG) receptor. The results indicate that of all epithelial tumors mucinous ovarian tumors had hormonal activity most often, and malignancy had no effect on hormonal activity.     

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.     

An ovarian mucinous borderline tumour with mixed mural nodules

The occurrence of mural nodules in serous or mucinous ovarian tumours is not frequent. Mural nodule can be developed in benign, borderline or malignant tumours. They can be benign, malignant or mixed type. Thus the prognosis of the ovarian tumour can be dramatically modified by the presence if these nodules. Eighty-two cases of mural nodules were reported in the literature, among which we account four cases of mixed nodules type. We report an additional case of mixed type mural nodules of anaplastic carcinoma and sarcoma-like developed in an ovarian mucinous borderline tumour at a 60-year-old woman.We give details about the classification, the differential diagnosis and prognosis of theses nodules.     

卵巢粘液性上皮内癌12例报告

目的:探讨卵巢粘液性上皮内癌的诊断意义和临床特点。方法:回顾分析2001年以来北京协和医院收治的12例卵巢粘液性上皮内癌(组织学检查确诊)的病理及临床特点和预后,并复习文献进行讨论。结果:患者中位年龄40.0岁。肿瘤均为单侧,肿瘤最大直径的中位数19.0cm(8.0~55.0cm)。ⅠA期8例,ⅠC期4例。1例行肿物剔除术,5例行附件切除术,3例行全子宫加双附件切除术,3例行肿瘤细胞减灭术。平均随诊38.8个月,无1例复发或死亡。结论:卵巢粘液性上皮内癌属卵巢粘液性交界瘤范畴,可能是浸润癌的癌前病变。年轻患者可行保留生育功能手术,预后较好,与同期别的粘液性交界瘤相当。     

Elevated progesterone levels in serum and ovarian venous blood in patients with ovarian tumors

Peripheral serum concentrations of progesterone were measured in 27 postmenopausal women with malignant, borderline, or benign ovarian tumor and in 10 women without ovarian neoplasm. The progesterone levels were significantly higher in all ovarian tumor groups as compared with the controls. There was no difference between malignant and benign tumors. Patients with a tumor volume over 1 000 ml had higher progesterone levels than patients with smaller tumors, in both peripheral and ovarian venous blood. Mucinous ovarian tumors were associated with the highest progesterone levels, compared with other histologic types of ovarian tumor. The results indicate that mucinous ovarian tumors are able to secrete progesterone and that the stage of malignancy has no effect on this hormonal activity.     

卵巢上皮性肿瘤中黏蛋白MUC2和MUC5AC的表达及意义

目的 研究卵巢上皮性肿瘤中黏蛋白MUC2和MUCSAC的表达，探讨它们在卵巢上皮性肿瘤恶性进展中的作用及其临床意义。方法 采用免疫组化方法SP法检测20例良性、23例交界性和37例恶性卵巢上皮性肿瘤中黏蛋白MUC2和MUCSAC的表达。结果 黏蛋白MUC2和MUCSAC表达水平随卵巢黏液性肿瘤恶性程度的增加而表达增高。黏蛋白MUC2的表达与肿瘤的病理分级和临床分期密切相关，而黏蛋白MUCSAC与病理分级和临床分期无关。结论 卵巢黏液性肿瘤发生早期肿瘤细胞即有胃型和肠型的分化，并且随着肿瘤的恶性进展持续存在。检测黏蛋白MUC2的表达可作为预测卵巢癌预后的有价值的指标。。     

Pseudomyxoma peritonei et ovarii associated with sequential ovarian and appendicular tumors and acromegaly

Pseudomyxoma peritonei associated with highly differentiated mucinous, intestinal-type ovarian tumor is reported in a 46-year-old acromegalic patient. Five years after its discovery a second operation revealed a mucinous cystadenoma of the appendix. The coexistence of pseudomyxoma peritonei with ovarian and appendicular tumors is rare, raising questions about the primary was origin of the peritoneal tumor. In this case the primary was ovarian while the appendicular tumor occurred later. Since acromegaly is associated with a high risk for the development of colorectal tumors, it could also have elicited a similar response in the intestinal-type ovarian tumor and the appendicular neoplasm found in this patient. The role of appendectomy in the surgical treatment and staging of ovarian tumors is stressed.     

Ovarian epithelial tumors of borderline malignancy in Japan

Seventy-one cases of ovarian epithelial tumor of borderline malignancy have been surveyed from a clinicopathologic viewpoint. The majority of the borderline tumors (73.2%) were of the mucinous type, versus only 16.9% of the serous type. The other types--endometrioid (2.8%), Brenner (1.4%), and mixed type (5.6%)--were much rarer. Patients with mucinous tumors were significantly younger (mean age 42.6) than those with serous tumors (mean age 57.5) (P less than 0.01). Of patients with mucinous tumors, 64.2% were of reproductive age (15-45 years), compared with 17% of patients with serous tumors. Some 78.8% of mucinous and 83.3% of serous borderline tumors were FIGO stage I. Serous tumors were more frequently bilateral (66.7%) than mucinous tumors (9.8%). In mucinous borderline tumors, the extent of tumor spread at the first laparotomy had an intimate relationship to the prognosis, but in serous borderline tumors, it was insignificant. The survival rate of patients with mucinous borderline tumors was 69.3% at 5 years and 62.4% at 10 years (Kaplan-Meier method). Most patients with pseudomyxoma peritonei classified as borderline at the time of discovery died within 5 years of the operation. The prognosis of the serous type was extremely favorable. Criteria for borderline tumors of various cell types and differences in the clinicopathologic data of ovarian borderline tumors between Japan and other countries were discussed.     

卵巢上皮性肿瘤的临床病理特征及其细胞周期素D1和p53蛋白表达的研究

目的研究卵巢上皮性癌（卵巢癌）和交界性上皮性肿瘤的临床病理特征及其细胞周期素D1（cyclin D1）和p53蛋白表达的情况,探讨卵巢癌和交界性上皮性肿瘤在发病机制上的联系。方法分析45例卵巢癌（卵巢癌组）和54例卵巢交界性上皮性肿瘤（交界性肿瘤组）的临床病理资料,采用免疫组化法检测两组组织中cyclin D1、p53蛋白的表达情况,并分析其与临床病理特征的相关性。结果（1）临床病理特征：①年龄：交界性肿瘤组平均年龄为42．5岁（14～82岁）,中位数年龄41岁;卵巢癌组平均年龄为53．5岁（26～80岁）,中位数年龄51岁。②分期：按国际妇产科联盟（FIGO）分期标准,交界性肿瘤组Ⅰ期48例、Ⅱ期3例、Ⅲ期3例;卵巢癌组Ⅰ期6例、Ⅱ期8例、Ⅲ期26例、Ⅳ期5例。③病理类型：交界性肿瘤组以黏液型为主[占56％（30／54）],其次为浆液型[其中普通型11例,微乳头型5例;占30％（16／54）];卵巢癌组以浆液型（其中低度恶性19例,高度恶性3例）为主[占49％（22／45）]。④病理分化程度：卵巢癌组高分化5例,中分化17例,低分化或未分化23例。⑤预后：交界性肿瘤组5年生存率为98％,卵巢癌组为51％,两组比较,差异有统计学意义（P=0．000）。（2）cyclin D1和p53蛋白的表达及其与卵巢癌和交界性肿瘤临床病理特征的相关性：卵巢癌组cyclin D1和p53蛋白的阳性表达率分别为31％（14／45）和56％（25／45）,p53蛋白表达强度与病理分化程度呈正相关（r=0．320,P=0．032）;交界性肿瘤组cyclin D1和p53蛋白的阳性表达率分别为69％（37／54）和6％（3／54）。其中,普通型浆液性交界性肿瘤与高度恶性浆液性癌比较（两者cyclin D1蛋白阳性表达率分别为91％和26％,p53蛋白分别为0和58％）,差异有统计学意义（P〈O．01）;而微乳头型浆液性交界性肿瘤与低度恶性浆液癌比较（两者cyclin D1蛋白阳性表达率分别为3／5和2／3,p53蛋白分别为1／5和1／3）,差异则无统计学意义（P〉0．05）。结论cyclin D1蛋白的过度表达常见于卵巢浆液性交界性肿瘤及低度恶性浆液性癌组织中,而p53蛋白的过度表达更多见于高度恶性浆液性癌组织中。卵巢浆液性交界性肿瘤与高度恶性浆液性癌具有不同的发病机制,而微乳头型浆液性交界性肿瘤与低度恶性浆液性癌的关系可能更为密切。     

Carcinoembryonic antigen (CEA) and carbohydrate determinant 19-9 (CA 19-9) localization in 121 primary and metastatic ovarian tumors: an immunohistochemical study with the use of monoclonal antibodies

An immunoperoxidase study, using the Avidin-Biotin-Peroxidase complex method and the monoclonal antibodies, anti-carcinoembryonic antigen (CEA) and anti-carbohydrate determinant 19-9 (CA 19-9), was carried out on 108 common epithelial tumors of the ovary and 13 epithelial tumors metastatic to the ovary. Primary mucinous tumors were positive in 62% of the cases (benign, 15%; borderline, 80%; and carcinomatous, 100%) with anti-CEA. None of the serous tumors were positive with anti-CEA, but 27% (benign, 23%; borderline, 40%; and carcinomatous, 20%) were positive with anti-CA 19-9. With anti-CEA, 30% of the endometrioid carcinomas, 50% of the malignant mesodermal mixed tumors, 14% of the clear cell carcinomas, 36% of the Brenner tumors, and 83% of the metastatic carcinomas from the large intestine were positive. With anti-CA 19-9, 76% of the mucinous, 40% of the endometrioid, 25% of the malignant mesodermal mixed tumors, 57% of the clear cell carcinomas, 45% of the Brenner tumors, and all the metastatic carcinomas from the large intestine were positive. All the undifferentiated carcinomas were unreactive with both antibodies. Although neither CEA nor CA 19-9 is a specific marker for any type of ovarian tumor or for malignancy per se, the presence of the former antigen can be useful in differentiating serous from mucinous tumors. Moreover, demonstration of either antigen in a variety of tumors may indicate its potential value as a serum marker in monitoring the course of the patient.     

Malignant ovarian tumors associated with pregnancy: report of six cases

Six cases of pregnancy associated malignant ovarian tumors, four epithelial cancers, one immature teratoma and one metastatic cancer of colon origin, are reported. One patient with mucinous cystadenocarcinoma had a history of persistent ovarian tumor during her past three pregnancies. Another patient was found to have mucinous cystadenocarcinoma after an emergency operation for twisted ovarian tumor. Immature teratoma associated with pregnancy is very rare and our case seems to be the 8th reported such case.