Frequency and characteristics of endometrial carcinoma and atypical hyperplasia detected on routine infertility investigations in young women: a report of six cases.

Infertility patients are known to be at increased risk of endometrial carcinoma (EC) and atypical hyperplasia (AH). However, the incidence and clinical features of EC and AH in these patients remain to be clarified. In this study, we examined the rate at which a routine infertility workup revealed EC/AH and investigated the clinicopathological features of EC/AH detected in this way. Among patients diagnosed with EC or AH at the Jichi Medical University Hospital between the 10-year period from 1997 to 2006, six patients were referred from Tochigi Central Clinic, a specialized infertility facility. We report the clinicopathological features of these patients and calculate the incidence of EC/AH in patients who underwent infertility investigations at Tochigi Central Clinic. All six patients were younger than 40 and had early stage disease (final diagnosis: EC stage IA: 3, EC stage IB: 1, AH: 2). A total of 19 826 patients underwent routine infertility investigations at Tochigi Central Clinic during the same period. The incidence of EC/AH detected from these investigations was 0.03% (6/19 826) and that of EC was 0.02% (4/19 826): 5-10 times higher than the overall incidence in Japanese women of the same age. Routine infertility investigations may provide an opportunity to examine the corpus uteri of young women in whom examination is otherwise limited, contributing to the early detection of EC/AH.

Omental metastases in clinical stage I endometrioid adenocarcinoma.

The clinical benefit of an omentectomy in endometrioid adenocarcinoma is unclear. The objective of this study was to clarify the significance of an omentectomy performed for clinical stage I endometrioid adenocarcinoma. A prospective study was performed on 134 patients with clinical stage I endometrioid adenocarcinoma who underwent omentectomy in addition to a staging laparotomy between 1998 and 2004: simple total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection, and peritoneal cytology. The frequency and prognosis of omental metastases and their relationships with extrauterine spread to other sites were investigated. Omental metastasis was noted in four patients (3.0%). As for extrauterine spread, the positivity rate of lymph node metastases was 13/128 (10.2%), peritoneal cytology was 13/133 (9.8%), and adnexal metastases was 10/134 (7.5%). Omental metastases correlated with peritoneal cytology and adnexal metastases (P < 0.05 for both); however, two of the omental metastases-positive patients were peritoneal cytology negative. All omental metastases-positive patients died shortly after surgery, showing that their prognosis was poor. The omental metastases rate for clinical stage I endometrioid adenocarcinoma was lower than the positive rates for extrauterine spread to other sites; thus, the routine application of omentectomy as a part of a staging laparotomy may not be efficacious. However, omental metastases are a significant poor prognostic factor, and intraoperative examination of the omentum by close inspection and palpation as well as pathologic examination, if possible, may be indicated.

Long-term follow-up study of patients with phenylketonuria detected by the newborn screening programme in Japan.

The objective of this report is to determine the need for and value of the long-term follow-up study of phenylketonuria (PKU) patients detected by newborn screening (NBS) in Japan. NBS was started in 1977 and the nationwide follow-up study of the identified patients was introduced into the NBS system. Outcome data from the continuous follow-up study showed in 1993 that IQ of PKU patients was inversely correlated with blood phenylalanine levels. Accordingly, in 1995, new treatment guidelines were issued that involved more stringent restriction of phenylalanine levels. Follow-up data confirmed that mean blood phenylalanine levels decreased after the introduction of the new guidelines, which included the recommendation to start dietary treatment within 20 days postpartum. Follow-up data also confirmed that dietary treatment did in fact commence earlier after the guidelines were issued. The need for lifelong dietary treatment is a difficult issue and the number of patients who stop dietary treatment was found to increase gradually with age. At present 60% of PKU patients born between 1977 and 1981 have stopped their dietary restriction of phenylalanine. The data gained from NBS and the long-term follow-up study were found to be valuable for the improvement of blood phenylalanine levels for patients with PKU, indicating the need for parties responsible for NBS and the follow-up study of the identified patients to work cooperatively. Further, the evaluations of the effectiveness of the two initiatives as well as the treatment guidelines issued should be based on outcome data, which depend on the continuation of the follow-up study of patients with PKU.

Phase I trial of paclitaxel, doxorubicin, and carboplatin (TAC) for the treatment of endometrial cancer.

Doxorubicin, platinum compounds, and taxanes represent the chemotherapeutic agents with the greatest activity in endometrial cancer. We conducted an optimal-dose determination of combination chemotherapy consisting of paclitaxel (TXL), doxorubicin, and carboplatin (CBDCA) (TAC) in patients with endometrial cancer. Patients with epithelial endometrial cancer requiring adjuvant therapy were enrolled between June 2003 and March 2005. No patients had received prior radiotherapy, and only two patients had previously undergone chemotherapy. Doxorubicin was infused on day 1, and TXL followed by CBDCA was administered on day 2. The starting dose was doxorubicin 35 mg/m(2), TXL 120 mg/m(2), and CBDCA area under the curve (AUC). The dose of each agent was gradually escalated. Patients were scheduled to receive at least four cycles of therapy. If patients experienced grade 4 neutropenia or neutropenic fever with grade 3 neutropenia, they were permitted to be administered granulocyte colony-stimulating factor after the second course. Twenty-seven patients were enrolled. Although four patients out of 27 experienced dose-limiting toxicities, a maximum tolerated dose was not established at the final dose level. Five patients (three for recurrent and two for advanced) had measurable lesions. There were four responders (three for partial response and one for complete response) in our series. The recommended dose of TAC therapy for endometrial cancer was doxorubicin 45 mg/m(2) for day 1, TXL 150 mg/m(2) and CBDCA AUC 5 for day 2.

C-kit overexpression in neuroendocrine small cell carcinoma of the uterine cervix.

PURPOSE OF INVESTIGATION: Neuroendocrine small cell carcinoma of the uterine cervix (NESCC) grows aggressively, and is resistant to anticancer agents and radiation, having an extremely poor prognosis. The incidence of c-kit proto-oncogene overexpression is high in gastrointestinal stromal tumors (GISTs) and small cell lung cancer, and tyrosine kinase inhibitors have been used effectively to treat GISTs. Few studies have investigated whether c-kit is overexpressed in NESCC. To investigate whether NESCC can be a target for molecular targeted therapy with tyrosine kinase inhibitors, we examined the expression of c-kit in this tumor. METHODS: Twenty-one NESCCs were examined for c-kit expression by immunohistochemical staining using the labeled streptavidin-biotin complex (LSAB) method. The expression of c-kit was regarded as positive (overexpression) and negative when the membrane and cytoplasm of more or less than 25%, respectively, of tumor cells were stained. RESULTS: Nine NESCCs (43%) were c-kit-positive (overexpression). No difference in age or clinical stage was noted. No difference in prognosis was observed between the c-kit-positive and -negative patients. CONCLUSION: The incidence of c-kit overexpression was high in NESCC; therefore, the patients with this tumor may become a future target for molecular-targeted therapy with tyrosine kinase inhibitors.

High-grade endometrial stromal sarcoma after treatment with tamoxifen in a patient treated for breast cancer.

Tamoxifen has been widely used in breast cancer treatment. In recent years, the occurrence of uterine malignancies in patients receiving long-term tamoxifen therapy has attracted attention. Most of these malignancies are endometrial adenocarcinomas, but low-grade endometrial stromal sarcomas have occasionally been reported. Here we report a woman who developed a high-grade endometrial stromal sarcoma after receiving postmastectomy tamoxifen therapy. The patient underwent a left mastectomy at age 45 and subsequently received oral tamoxifen for 3 years. At age 51, she was diagnosed with endometrial stromal sarcoma, for which a radical hysterectomy was performed. High-grade endometrial stromal sarcoma was diagnosed by postoperative histologic examination. Immunostaining for the estrogen receptor was negative in sarcoma cells, but positive in the residual endometrial epithelium and the nucleus of adjacent stromal cells within the tumor. The patient has now survived disease-free for 37 months after surgery.

Chemosensitivity and p53-Bax pathway-mediated apoptosis in patients with uterine cervical cancer.

OBJECTIVES: To determine whether and how apoptosis through the p53-Bax pathway affects sensitivity to chemotherapy in cervical cancer. MATERIALS AND METHODS: Thirty patients with cervical squamous cell carcinoma, who had human papilloma virus (HPV) and underwent neoadjuvant chemotherapy, were entered in the present study. Tumor specimens were obtained before and after chemotherapy. HPV was detected by polymerase chain reaction. The expression of Ki-67, p53, Bax and Bcl-2 proteins was determined by immunohistochemical staining. Apoptotic cells were identified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling method. RESULTS: Of 30 patients, 18 responded to chemotherapy and 12 did not. The apoptotic index in tumors of responders was significantly higher than in non-responders after chemotherapy. The Ki-67 labeling index (LI) in responders was significantly higher than in non-responders before chemotherapy. Patients with tumors >33% of the LI, which was determined by a receiver operating characteristic curve, had a better survival rate. The incidence of p53 protein expression did not differ between responders and non-responders. After chemotherapy, the expression of Bax protein in responders was more frequent and Bcl-2 protein expression was less frequent than in non-responders. CONCLUSIONS: Chemosensitivity in cervical cancer may be associated with apoptosis via the p53-Bax pathway.

Problems with peritoneal cytology in second-look laparotomy performed in patients with epithelial ovarian carcinoma.

BACKGROUND: The recurrence rate of ovarian carcinoma is high even when a second-look laparotomy (SLL) is negative. In the current study, the accuracy of peritoneal cytology as an evaluation method of SLL was examined. METHODS: The positive SLL rate and the diagnostic accuracy of peritoneal cytology were evaluated in 101 patients with epithelial ovarian carcinoma. RESULTS: Twenty-three of the 101 patients (23%) were positive based on SLL. The factors considered to be high risk factors for a positive SLL were advanced disease (Stages III and IV by the International Federation of Gynecology and Obstetrics [FIGO] classification), serous adenocarcinoma, and maximum residual tumor > 2 cm after primary surgery (P < 0.05). Of the 23 patients found to be positive on SLL, peritoneal cytology was positive in 6 patients, in whom the percentage was low (26%). The remaining 17 patients (74%) demonstrated false-negative cytology. Of these 17 patients, the tumor tissues were found to be capsulated completely with connective tissues in all biopsy specimens from 9 patients (53%) and in all but 1 biopsy specimen in 6 patients (35%), together accounting for a capsulation rate of 88%. Conversely, clear exposure of the tumor tissues was observed in at least two biopsy specimens in those patients demonstrating positive cytology (P < 0.01). CONCLUSIONS: Peritoneal cytology in SLL was found to result in a high false-negative rate. One of the reasons for this was considered to be capsulation of the lesions with proliferated connective tissues, which may have been the result of by chemotherapy.

Establishment and characterization of a new cell line (SKS) from neuroendocrine small cell carcinoma of the uterine cervix and its chemosensitivity.

A new cell line (SKS) established from ascites of a patient with neuroendocrine small cell carcinoma of the uterine cervix had a good tumorigenicity and caused marked peritoneal dissemination, and was also highly sensitive to gemcitabine in an in vitro chemosensitivity test. SKS cells were small round cells with a high nuclear/cytoplasmic (N/C) ratio and grew into colony-like aggregates, forming spherical aggregates of floating cells. The population doubling time was 44 h. The number of chromosomes ranged from 50 to 56. On examination of the ultrastructure, membrane-bound dense-core neurosecretory-type granules were observed in the cytoplasm. Neuron-specific enolase (NSE) was immunocytochemically positive in the cytoplasm, and 9.3 ng/ml of NSE was detected in the cell culture supernatant. Human papillomavirus was not detected. In the p53 gene, a 3-bp deletion, AAC (Asn), was detected at codon 131 in exon 5. SKS exhibited good tumorigenicity, and the tumor doubling time was 11 days. Intraperitoneal injection of the cells caused peritoneal dissemination, and marked ascites formation was observed. SKS was highly sensitive to gemcitabine, and the 50% growth inhibitory concentration was 30 nM. SKS cells are useful as a model of neuroendocrine small cell carcinoma of the cervix, and chemotherapy using gemcitabine may possibly be effective in this malignancy.

Assisted reproductive technologies in conjunction with conservatively treated endometrial adenocarcinoma. A case report.

This case report illustrates the successful use of assisted reproductive technologies (ARTs) in a patient receiving conservative treatment for endometrial adenocarcinoma. A 31-year-old infertile woman, diagnosed as FIGO stage Ia endometrial adenocarcinoma (grade 1), received oral medroxyprogesterone acetate 400 mg/day for 12 weeks. Endometrial curettage was performed and the absence of endometrial carcinoma was confirmed. A single pregnancy was achieved with in vitro fertilization and embryo transfer. A healthy female infant was born via cesarean section at 42 weeks' gestation. The carcinoma has not recurred, and the patient now desires a second child. We conclude that ART combined with progesterone treatment might be a powerful option for the treatment of infertile patients with early stage, well-differentiated endometrial adenocarcinoma.

Neuroendocrine small cell carcinoma of the uterine cervix showing polypoid growth and complicated by pregnancy.

BACKGROUND: Neuroendocrine small cell carcinoma of the uterine cervix is an aggressive disease, and it rarely is complicated by pregnancy. CASE: A polypoid tumor was found in the uterine cervix in a 27-year-old Japanese woman at 27 weeks of gestation. No polyp had been detected at 14 weeks of gestation. The polyp was excised and diagnosed as neuroendocrine small cell carcinoma by histological examination, including Grimelius, neuron-specific enolase, and chromogranin staining. A healthy infant was born by cesarean section at 29 weeks of gestation: this was followed by radical hysterectomy with pelvic lymphadenectomy. After surgery, four cycles of combination chemotherapy with cisplatin and etoposide were administered, and the patient is disease-free as of 13 months after surgery. CONCLUSION: When a polypoid lesion is found, especially when it demonstrates rapid growth, it may be necessary to excise and histologically examine the polyp even during pregnancy.

Micrometastatic p53-positive cells in the lymph nodes of early stage epithelial ovarian cancer: prognostic significance.

We used immunohistochemical staining of p53 protein to detect micrometastasis in regional lymph nodes that were judged tumor-free by conventional histopathological methods in 58 patients with stage I or II (pT1 or 2, N0) epithelial ovarian cancer. Overexpression of p53 protein in the primary lesions of ovarian cancer was observed in 31 patients (53%), and p53 protein-positive cells were detected in the regional lymph nodes (micrometastasis-positive) in 19 of 31 patients with p53 protein overexpression (61%). In patients with micrometastasis, the prognosis was significantly poorer than that in those without micrometastasis (p < 0.05). Detection of micrometastasis of the regional lymph nodes of ovarian cancer by immunohistochemical staining of p53 protein may be useful in predicting the prognosis of patients with stage I or II epithelial ovarian cancer.

Are DNA mismatch repair deficiencies responsible for accumulation of genetic alterations in epithelial ovarian cancers?

To investigate the association of DNA mismatch repair deficiencies in the development and/or progression of epithelial ovarian cancers, the relationship between replication errors (RERs) and genetic alterations in three genes (p53, c-erbB2, K-ras) and loss of heterozygosity (LOH) on 6q27 was investigated in 70 patients with epithelial ovarian cancers. The presence of RERs was examined by PCR using five microsatellite markers. Mutations of p53 were analyzed by PCR-SSCP and sequencing. Amplification of c-erbB2 was analyzed by Southern blot hybridization. Point mutations of K-ras codon 12 were identified by PCR-PHFA, while 6q27LOH was examined by Southern blot hybridization. As a result, 18 of 70 patients with epithelial ovarian cancers (26%) were RER-positive and 52 patients (74%) were RER-negative. Tumors with two or three genetic alterations accounted for 28% and 33% of RER-positive tumors, respectively, and these were significantly more frequent than in the RER-negative tumors (17% and 6%, respectively)(P =.002). These results are consistent with mismatch repair deficiencies being involved in the development and/or progression of a proportion of epithelial ovarian cancers through accumulation of genetic alterations.

Primary malignant lymphoma of the uterine corpus diagnosed by endometrial cytology. A case report.

BACKGROUND: A relatively small number of cases of primary malignant lymphoma of the uterine corpus have been reported, and it is rare for cases to be preoperatively diagnosed by cytology. CASE: A 59-year-old female experienced abnormal uterine bleeding of two months' duration. Preoperative evaluation of endometrial cytology revealed malignant cells. These cells demonstrated a rather round or oval configuration, with a markedly increased nuclear/cytoplasmic ratio, and were isolated and scattered in an inflammatory background. The nuclei were round or oval, and macronucleoli were marked. The cytologic diagnosis was malignant lymphoma. Postoperative histologic evaluation verified the presence of a primary malignant lymphoma in the uterine corpus, with a B-cell phenotype. CONCLUSION: Preoperative endometrial cytology correctly demonstrated malignant lymphoma of the uterine corpus.

DNA replication error is frequent in ovarian granulosa cell tumors.

DNA replication errors (RER) have been detected in epithelial ovarian cancers, as well as in other human tumor types. These observations suggest that this genetic defect is present in ovarian granulosa cell tumors, and that a DNA mismatch repair deficiency may be involved in their development and/or progression. We therefore assayed tissue samples from 29 patients with granulosa cell tumors for RER, using polymerase chain reaction (PCR) and 5 microsatellite markers. The RER were observed at greater than or equal to 1 loci in 15 (58%) of 26 informative cases. The incidence of RER was unrelated to the patient's age or the histologic subtype or clinical stage of the tumors. The RER, however, were observed in 57% (8/14) of the informative patients with stage IA disease. These findings suggest that a DNA mismatch repair deficiency may contribute to the pathogenesis of ovarian granulosa cell tumors, and that this deficiency may be an early event in their development and/or progression.

Assessment of proliferation index with MIB-1 as a prognostic factor in radiation therapy for cervical cancer.

OBJECTIVES: The relationship between the expression of murine monoclonal antibody MIB-1, which reacts with Ki-67 nuclear antigen, a marker for proliferating cells, and the prognosis of stage IIIb cervical cancer after radiation therapy was analyzed. METHODS: A total of 67 patients with stage IIIb cervical cancer who had received radiation therapy were included in the retrospective study. The labeled streptavidin-biotin method was used for immunohistochemical staining of the MIB-1 protein. RESULTS: In 32 patients showing a high MIB-1 index (percentage of cells labeled with MIB-1 >/=26.4%), the cumulative 5- and 8-year survival rates were 75.8 and 61.5%, respectively, significantly better (P < 0.05) than those in 35 patients with a low MIB-1 index (<26.4%) (59.6 and 41.1%, respectively). Serum squamous cell carcinoma antigen levels, an index of the response to radiation therapy, decreased to

Lymph node metastasis in stage I epithelial ovarian cancer.

OBJECTIVES: A relatively high incidence of para-aortic and pelvic lymph node metastasis is found in epithelial ovarian cancer. This paper investigates the clinicomorphological features of intra-abdominal stage I epithelial ovarian cancer that may predict the occurrence of lymph node metastasis and the prognosis of patients in whom lymph node metastases are identified. METHODS: From November 1988 to December 1997 we performed systematic para-aortic and pelvic lymphadenectomy as primary surgery in 47 patients with intra-abdominal stage I epithelial ovarian cancer. The incidence of lymph node metastasis in these patients and the clinicomorphological features of the patients with lymph node involvement were examined. RESULTS: Five patients (10.6%) were metastasis positive (IC: four; IA: one), of whom four had serous adenocarcinoma. Serous adenocarcinoma was associated with a significantly higher incidence of metastases than other histological types (P < 0.05). The number of positive lymph nodes was one in four patients and two in one patient, and the metastatic sites ranged from the para-aortic to the suprainguinal lymph nodes. All five metastasis-positive patients were alive and disease free at the time of this report (survival 28-85 months: median 59 months). CONCLUSION: This clinical study suggests that serous adenocarcinoma carries a high risk of lymph node metastasis, requiring systematic lymphadenectomy for accurate staging in intra-abdominal stage I epithelial ovarian cancer.

Clinical significance of combined use of macrophage colony-stimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic teratoma of the ovary.

OBJECTIVES: Mature cystic teratoma of the ovary transforms into malignant tumors, mostly squamous cell carcinomas, at an incidence of approximately 2%. Preoperative diagnosis of squamous cell carcinoma arising in mature cystic teratoma of the ovary is a difficult task. The present study aims to assess whether combined use of two serum tumor markers, macrophage colony-stimulating factor (M-CSF) and squamous cell carcinoma antigen (SCC), is effective in preoperatively diagnosing squamous cell carcinoma arising in mature cystic teratoma of the ovary, distinguishing it from mature cystic teratoma without malignant transformation. METHODS: Serum levels of M-CSF and SCC were assayed using blood samples collected preoperatively from 31 patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary and 133 patients with mature cystic teratoma of the ovary without malignant transformation. RESULTS: In 22 of the 31 (71.0%) patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary, the serum M-CSF levels exceeded the upper limit of the normal level (1056 U/ml). This positive incidence of the elevated serum M-CSF levels was significantly higher compared with that (13.5%, 18/133) observed in patients with benign cystic teratoma of the ovary (P < 0.0001). Regarding the serum levels of SCC, 13 of 31 (41.9%) patients with malignant tumors showed positive values exceeding the cutoff value of 2.0 ng/ml. Again, this incidence of positive cases was significantly higher compared with that (15.0%, 20/133) observed in patients with benign tumors (P < 0.01). There was no correlation between the serum levels of M-CSF and SCC among patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary. Patients with malignant tumors testing positive for elevated M-CSF did not necessarily test positive for SCC. Patients with positive values for excess M-CSF and/or SCC constituted 87.1% of the total (27/31). Even when patients were restricted to those with stage I tumors, a value as high as 83.3% (15/18) was still obtained for those testing positive for elevated M-CSF and/or SCC. CONCLUSION: Serum M-CSF was proven to be useful as a tumor marker for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. Combined use of serum M-CSF and SCC as a marker seemed to be useful in the selective diagnosis of mature cystic teratoma of the ovary harboring malignant squamous carcinoma, discriminating it from that without malignant carcinoma.

Mutational analysis of transforming growth factor beta receptor type II and DNA mismatch repair genes in sporadic endometrial carcinomas with microsatellite instability.

To clarify how microsatellite instability (MI) is involved in carcinogenesis of sporadic endometrial carcinoma, we examined mutations of the transforming growth factor beta receptor type II (TGF beta RII) gene in 32 patients with MI-positive sporadic endometrial carcinoma. Moreover, mutations of 4 DNA mismatch repair (MMR) genes (hPMS1, hPMS2, hMLH1, hMSH2), which are considered to cause MI, were investigated as well. With respect to the TGF beta RII gene, mutations in the 10-bp polyadenine repeat sequence were observed in 7 of 29 informative cases (24%). Concerning MMR genes, a T to C point mutation at the -6 intronic splice acceptor site of exon 13 of hMSH2 was detected in 43% (6/14). However, there was no mutation in any exon of these 4 MMR genes. These results suggest that there is a carcinogenic mechanism via mutation of the TGF beta RII gene in some cases of MI-positive sporadic endometrial carcinoma. It seems unlikely that the unknown MMR genes are responsible for MI. The implication of the mutation at the intronic splice acceptor site in hMSH2 remains to be clarified.

A retrospective survey of clinical, pathologic, and prognostic features of adnexal masses operated on during pregnancy.

OBJECTIVES: To evaluate retrospective data concerning patients with adnexal masses that were managed surgically during pregnancy and their effect on fetal outcome. METHODS: Data were reviewed concerning pregnant women who required surgery at our hospital between 1980 and 1997 for an adnexal mass. RESULTS: In the past 19 years at our hospital a total of 69 Japanese women aged 28.5 +/- 3.4 years (including 2 women with twin pregnancies) were diagnosed with adnexal masses that required surgery. The masses (10.2 +/- 4.5 cm in the largest diameter) were removed at 13.9 +/- 3.7 weeks of gestation. The pathologic features of the 69 lesions were as follows: 33 mature cystic teratomas, 13 functional cysts, 8 mucinous cystadenomas, 6 endometriotic cysts, 4 paraovarian cysts, 3 serous cystadenomas, and 2 malignant neoplasms. Of the 60 patients for whom the outcome of pregnancy was available, 7 (12%) gave birth before 37 weeks of gestation, while 2 (3.3%) experienced spontaneous abortions. There were 3 perinatal deaths among the 60 infants. Two of these 3 infants died due to major anomalies. CONCLUSIONS: Although larger studies are required for confirmation, our results suggest that an adnexal mass might be associated with an adverse fetal outcome. Surgical intervention at < 24 weeks of gestation per se might not have been related to the adverse outcomes. We emphasize that surgical intervention during pregnancy can be avoided in patients who have ultrasonographically pathognomonic features of benign cystic teratomas, which are the most common neoplasms operated on during pregnancy.