Mucinous cystadenoma of the ovary with functioning stroma and virilization in pregnancy: a case report and review of the literature

Virilization caused by ovarian tumors with functioning stroma during pregnancy is extremely rare and has been reported in many ovarian tumors. In mucinous cystadenomas with maternal virilization during pregnancy the stromal cells responsible for the hormone secretion resemble lutein or Leydig cells and have been referred to as luteinized stromal cells. We present a case of a 30-year-old, gravida 2, para 1, woman who presented at approximately the 38th week of pregnancy with features of virilization. At the same time, a cesarean section was performed because of fetal distress and a male weighing 3,030 g without any gross abnormalities was delivered. A large tumor of the right ovary was detected and a right salpingo-oophorectomy was performed. Histopathologically, the tumor proved to be a benign mucinous cystadenoma. Masses typically resembling lutein stromal cells or Leydig cells of the testes or ovarian hilus were found in the wall of the cyst below the mucinous epithelium. No crystalloids of Reinke were identified. The stromal component of the tumor was characterized as functioning stroma with luteinized stromal cells. The glandular mucinous epithelium showed focal positivity for human chorionic gonadotrophin. The cytoplasm of the luteinized stromal cells reacted strongly and diffusely with antiserum for vimentin. Also, the cytoplasm of the luteinized stromal cells showed focal intense positivity for synaptophysin, and focal mild positivity for human chorionic gonadotrophin. Staining results for oestrogen and progesterone receptors were negative. In conclusion, we present an unusual case of clinical virilization during pregnancy associated with an ovarian mucinous cystadenoma with functioning stroma. The virilizing manifestations disappeared after removal of the ovarian neoplasm, supporting the perception that the functioning ovarian stroma was responsible for the androgen production.     

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.     

Benign mucinous cystadenoma with stromal luteinization responsible for maternal virilization and fetal intrauterine growth restriction

Virilization caused by ovarian tumors with functioning stroma during pregnancy is extremely rare and has been reported to be due to different types of ovarian tumors. In mucinous cystadenomas with maternal virilization during pregnancy, the stromal cells responsible for hormone secretion resemble lutein or Leydig cells and have been referred to as luteinized stromal cells. Here we present a rare case of mucinous cystadenoma accompanied by virilization, which was also the cause of fetal intrauterine growth restriction during pregnancy and discuss the mechanisms of hormone production in these tumors in the light of the literature.     

Primary retroperitoneal mucinous borderline tumor: a case report

BACKGROUND: Primary retroperitoneal mucinous borderline tumors are rare. These tumors can be present in women with otherwise normal pelvic anatomy. CASE: A 22-year-old woman with abdominal pain was found to have a large midline mass superior to the uterus with ascites. In surgery, a large mass was arising from the sigmoid mesentery. The pelvis was normal on inspection. Final pathology of the mass revealed borderline tumor (tumor of low malignant potential) and focus of ovarian tissue. CONCLUSION: This is a case report of primary retroperitoneal mucinous borderline tumor. The gynecologic oncologist should be aware of primary retroperitoneal tumors and the differential diagnosis.     

Ovarian mucinous cystadenocarcinoma with virilization

BACKGROUND: Ovarian neoplasms, other than sex cord--stromal tumors, are rare causes of hyperandrogenism. Only two cases of primary mucinous carcinomas associated with virilization have been reported. CASE: A 50-year-old female was referred to our clinic with a large pelvic mass. On examination she had significant facial hirsutism, clitoromegaly, and male pattern pubic hair growth. Serum levels of testosterone and dihydroepiandrosterone sulfate were elevated. A 30-cm, multilocular, solid and cystic, left ovarian mass was resected. Histology revealed moderately to poorly differentiated mucinous cystadenocarcinoma. The ovarian stroma contained florid proliferation of luteinized cells. The right ovary showed cortical stromal hyperplasia. Abnormal hormone values normalized 10 days postoperatively. CONCLUSION: We report a rare case of mucinous cystadenocarcinoma with virilization, review the literature, and discuss the mechanisms of hormone production by these tumors.     

Maternal virilization due to mucinous ovarian tumour: a case report

Virilization in pregnancy is rare and mostly due to luteoma or to hyper-reactio luteinalis. We present a rare case of a virilization borderline mucinous ovarian tumour on a gravida 1 patient. The tumour was responsible for a clinical hyperandrogenism and for an increased level of testosterone. This patient was treated by ovariectomy at 31 weeks of gestation. The surgery was completed one month after delivery. There was no fetal consequence and the clinical and biological signs of virilization totally disappeared after surgery.     

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.     

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.     

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.     

Neutral endopeptidase/CD10 expression in the stroma of epithelial ovarian carcinoma.

This study investigated the immunohistochemical expression and localization of neutral endopeptidase (NEP) (CD10), which plays a functional role by degrading bioactive peptides, in ovarian tumors. In normal ovaries and benign cystadenomas, NEP was not detected in any epithelial or stromal cells. In borderline tumors, NEP was detected in the stromal cells in 6 of 7 serous tumors, but not in those from mucinous tumors. In ovarian carcinomas, NEP in the stromal cells was observed in 13 of 20 serous, 8 of 10 endometrioid, and 7 of 10 clear-cell adenocarcinomas. NEP was weakly detected in only 1 of 9 mucinous adenocarcinomas. The staining intensity of stromal NEP was decreased in grades 2 and 3 serous carcinomas compared with that in grade 1 serous carcinomas. In conclusion, NEP was specifically expressed in the stroma of borderline and malignant ovarian tumors, but not in adenomas. Furthermore, stromal NEP was downregulated as the histological grade advanced. These results suggest that NEP may play a role in the regulation of neoplastic transformation and tumor differentiation in epithelial ovarian carcinomas.     

An ovarian steroid cell tumor with virilization and hypothyroidism: a case report

Steroid cell tumors are rare ovarian sex-cord stromal tumors with malignant potential. The majority of these tumors produce steroids with testosterone being the most common. The diagnosis of these rare tumors can be problematic especially in the case of a small nonpalpable ovarian tumor. A 41-year-old woman presented with the gradual onset of defeminization, mild hypothyroidism, and virilization. A physical examination revealed a relatively healthy woman with borderline hirsutism, clitoromegaly and adnexal fullness without a palpable tumor. Elevated serum levels of TSH and testosterone were found preoperatively. Five weeks after an oophorectomy, serum levels of TSH and testosterone returned to normal and menstruation returned. Nonpalpable virilizing ovarian steroid cell tumors may be difficult to diagnose. A careful study of the patient’s history, the development of defeminization followed by virilization, and a “characteristic” ultrasonogram, can be helpful for diagnosis. Hormonal studies including thyroid function should also be considered in an ovarian steroid cell tumor.     

286例妊娠合并卵巢肿瘤的临床分析

目的:探讨妊娠合并卵巢肿瘤的临床病程特点,以及相应的诊断和处理对母儿结局的影响。方法:回顾分析2003年3月至2010年12月在上海市第一妇婴保健院住院分娩的286例妊娠合并卵巢肿瘤患者的临床资料,分析比较诊断时孕周,妊娠期间卵巢肿瘤的特点、对妊娠结局影响、分娩方式,病理特点等,并对上述因素进行相关分析。结果:妊娠合并卵巢肿瘤的孕妇阴道分娩54例,剖宫产232例,剖宫产率81.12%;剖宫产获得的232例病理结果中,良性肿瘤227例,交界性肿瘤5例。良性肿瘤行卵巢肿瘤剥除术或患侧附件切除术,交界性肿瘤行患侧附件切除术或肿瘤减灭术;妊娠合并卵巢交界性肿瘤组新生儿体重及分娩孕周均明显低于妊娠合并卵巢良性肿瘤组(P<0.05)。结论:妊娠合并卵巢肿瘤以良性肿瘤最常见。因早期妊娠时缺乏典型的临床症状而不易早期诊断,故应加强孕前及早孕期间的检查;妊娠早期应行B超检查提高卵巢肿瘤检出率;剖宫产术中应仔细探查双侧附件,及时发现卵巢肿瘤;妊娠合并交界性肿瘤,由于终止妊娠时期早,故围产期母儿并发症较高,其处理原则需根据患者年龄、生育情况、组织类型、肿瘤期别、妊娠期限、胎儿成熟度评价等而异。     

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.     

Youngest Reported Patient Presenting with an Androgen Producing Sclerosing Stromal Ovarian Tumor

BackgroundSclerosing stromal tumors are extremely rare sex cord stromal tumors of the ovary, with approximately 100 cases reported since first described in 1973. These tumors present predominantly in the 2nd and 3rd decades of life, typically present with pelvic/abdominal pain and tenderness, mass, and/or abnormal menses, and with hormonal activity reported predominantly in postmenarchal females. Only 5 cases of these tumors have been reported in premenarchal girls, with age ranging from 7 months to 12 years. Only 2 demonstrated hormonal manifestations, with vaginal bleeding due to hyperestrogenism in the 7 month old, and virilization in an 11-year-old female.CaseWe report a 9-year-old female who was diagnosed with this ovarian tumor, and who presented with virilization.Summary and ConclusionThis report is remarkable as our patient not only was diagnosed with an ovarian tumor that is extremely rare in this age group but is the youngest reported patient with this tumor who presented with virilization.     

Serous and mucinous borderline tumors of the ovary: a clinicopathologic and DNA-ploidy study of 102 cases

One-hundred and two patients with epithelial borderline ovarian tumors treated at Tampere University Hospital between January 1965 and September 1991 were evaluated. There were 48 patients with serous tumors and 54 with mucinous tumors. Ninety-three (91%) patients had clinical stage I and nine had stage III disease. Abdominal hysterectomy and bilateral salpingo-oophorectomy were performed in 70% of the patients. Forty percent of those with serous and 20% with mucinous tumors were operated conservatively. After conservative surgery six patients had a total of 10 deliveries and none of these had a recurrence. Seven patients received chemotherapy, none had radiation therapy. An aneuploid DNA pattern was identified in 8.2% of 85 specimens studied and a high S-phase fraction was found in 8.6% of 81 specimens studied. DNA measurement failed to identify the malignantly behaving tumors. Elevated preoperative serum levels of CA125 were found in 10 (63%) out of 16 cases studied. All of them dropped postoperatively to normal. During the follow-up period (mean 11.6 years, range 4.5–29.7 years) 22 patients died but in 17 of them death was unrelated to ovarian tumor. The corrected (borderline malignancies related) 5-year survival rate was 100% in patients with serous tumor and 96% with mucinous tumor, 25-year survival rate was 97% and 91%, respectively. There was no difference between the serous and mucinous groups. Our results show that ovarian borderline tumors have a good prognosis. Quite conservative therapy is often enough, especially in low-stage disease in young women who want to retain their fertility.     

Cell proliferation activity unrelated to COX-2 expression in ovarian tumors

The objective of this study was to assess the expression of Cyclooxygenase-2 (COX-2) and cell proliferation activity (Ki67 expression) in benign, borderline, and malignant serous and mucinous ovarian tumors. Expression of COX-2 and Ki67 proteins were evaluated by immunohistochemistry, in paraffin-embedded sections of ovarian epithelial tumors. The study included 113 serous (67 benign, 15 borderline, and 31 malignant) and 85 mucinous (48 benign, 28 borderline, and 9 malignant) tumors, removed from women who underwent laparotomy between January 1997 and December 2003. From benign to malignant tumors, there was a progressive positive trend in COX-2 expression in both serous and mucinous tumors, more evident in mucinous ones (P < 0.001). Comparing histologic types, COX-2 expression was more prominent in serous than in mucinous benign tumors (P < 0.01), but this difference was not significant in the borderline (P= 0.11) or malignant categories (P= 0.71). There was a progressive Ki67 positivity in line with the tumor histologic gradient for both serous (P < 0.01) and mucinous lesions (P < 0.01), but this increasing expression did not correlate with COX-2 expression in the present series (P= 0.78). There was a higher COX-2 expression in serous ovarian adenomas than in mucinous ones. COX-2 positivity increases in line with the morphologic gradient, from benign to malignant in both histologic types, but it was more prominent in mucinous lesions, pointing to different oncogenic pathways related to different histologic types. A correlation between the expression of COX-2 and Ki67 was not found, suggesting that COX-2 may be required for carcinogenesis, but this pathway is not responsible for cell proliferation in ovarian tumors.     

青春期少女卵巢上皮性肿瘤的临床特点及治疗

目的探讨青春期少女卵巢上皮性肿瘤的临床特点及治疗方法。方法回顾性分析北京协和医院1983年1月-2002年10月间收治的全部13～19岁卵巢上皮性肿瘤患者29例。其中,良性肿瘤20例、交界性肿瘤4例、恶性肿瘤5例。结果患者平均年龄16．5岁,其中13-14岁3例(10％)、15．16岁9例(31％)、17-19岁17例(59％)。临床表现主要为腹痛、腹胀、下腹部巨大肿物。病理类型：黏液性肿瘤22例,浆液性肿瘤6例,子宫内膜样肿瘤1例。手术病理分期：交界性或恶性肿瘤患者9例中,Ⅰ期8例,Ⅲc期1例。治疗：良性肿瘤20例中,开腹行一侧附件切除术9例,腹腔镜下行卵巢囊肿剔除术11例;9例交界性或恶性肿瘤患者全部施行了肿瘤细胞减灭术和全面的分期手术,其中8例I期患者保留了生育功能,1例Ⅲc期患者未保留生育功能;5例恶性肿瘤患者中,4例接受了4-6个疗程以顺铂为主的化疗。随访期间良、恶性肿瘤无一例复发。结论青春期少女卵巢上皮性肿瘤的发生率随年龄的增长而增加;黏液性肿瘤是最常见的病理类型。对于多数良性肿瘤患者可以考虑腹腔镜下行肿瘤剔除术;对于交界性或恶性肿瘤患者应兼顾治愈肿瘤和保留生育功能,治疗方案应个体化。     

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.     

CA_(125)、CA_(19.9)、CEA在卵巢上皮性交界性肿瘤中的临床价值

目的 :探讨测定血清CA12 5、CA19.9、CEA在诊断卵巢上皮性交界性肿瘤中的临床价值。方法 :回顾分析卵巢交界性肿瘤 5 0例血清CA12 5、CA19.9、CEA水平与临床资料。结果 :浆液性及粘液性肿瘤中CA12 5的阳性率分别为 5 3.85 %和 60 % ,差异无显著性 (P >0 .0 5 ) ,临床分期晚者CA12 5阳性率有增高趋势 ;粘液性肿瘤中CA19.9的阳性率为 4 3.75 % ;CEA阳性率为 12 % ,仅见于粘液性或以粘液性为主的肿瘤中 ;与术前相比 ,术后CA12 5、CA19.9水平及阳性率均显著下降 (P <0 .0 5 )。结论 :CA12 5、CA19.9对卵巢上皮性交界性肿瘤的术前诊断及疗效监测有一定价值 ,CEA则在鉴别组织学类型中有一定价值。     

Ultrasound, physical examination, and CA 125 measurement for the detection of recurrence after conservative surgery for early borderline ovarian tumors

BACKGROUND: Borderline ovarian tumors often affect women of childbearing age and the prognosis is outstanding. Given the young age of several patients and the good prognosis, fertility-sparing surgery is considered adequate for stage I tumors. However, women treated conservatively have a relatively small but well-defined risk of recurrence and no study has specifically addressed the optimal follow-up technique. METHODS: From 1981 to 1997, 164 women underwent fertility-sparing surgery for stage I borderline ovarian tumor and were followed prospectively. After surgery all women underwent physical examination and ultrasound examination every 3 months for 2 years after first diagnosis and every 6 months thereafter. Measurement of serum CA 125 levels was planned every 6 months in patients with a serous tumor. RESULTS: With a median follow-up of 71, months 28 women treated with fertility-sparing surgery (28/164 = 17%) had either recurrence of borderline tumor (23) or recurrence with carcinoma. Complete details of follow-up procedures are available for 24 women and they represent the study population. An abnormal adnexal mass was detected in 18 of 19 women with recurrent borderline tumor. One patient had diagnosis due to persistent free fluid. All five women with invasive carcinoma had diagnosis of a complex adnexal mass. Gynecologic examination was suspicious (palpable mass) in 7 cases and obviously abnormal (large mass or nodules) in another 7. CA 125 serum levels were elevated in 8 cases. CONCLUSION: Transvaginal ultrasound is currently the most effective diagnostic technique for the follow-up of young patients treated conservatively for early borderline ovarian tumor.