An incidentally diagnosed epithelioid trophoblastic tumor in hysterectomy.

Epithelioid trophoblastic tumor is a rare non-molar gestational trophoblastic disease. A 40-year-old multiparous woman was incidentally diagnosed with epithelioid trophoblastic tumor after hysterectomy. Hysterectomy specimen revealed multiple small, tan to yellow nodules measuring 0.3-0.8 cm just below the endometrium. In the microscopic examination uniform neoplastic cells with varying cellularity were accompanied by necrotic zones and eosinophilic hyaline material. Immunohistochemically neoplastic cells were diffusely stained with CK 7, inhibin-alpha, p63, hPL, and CD146. There was no staining with beta-HCG, SMA, PLAP, or h-caldesmon. Ki-67 proliferative index was approximately 10% and cyclin E was stained in approximately 10% of the neoplastic cells. Although immunohistochemical studies are helpful in classifying gestational trophoblastic lesions, borderline values can cause diagnostic confusion between neoplastic and reactive lesions, particularly in inadequate endometrial biopsies.

Preoperative serum leptin levels in patients with endometrial cancer and its correlation with prognostic variables.

PURPOSE OF INVESTIGATION: Since leptin is believed to be a key player in carcinogenesis, a study has been designed to investigate the relationship between leptin levels and endometrial cancer. METHODS: A study including 30 patients with endometrial cancer and 30 healthy controls was carried out between November 2008 and July 2009 in Hacettepe University Hospital. All patients with endometrial cancer underwent a complete surgical staging procedure including lymphadenectomy. Preoperative leptin levels of endometrial cancer patients and healthy controls were compared. The relationships between leptin levels and stage, grade, histological type and lymph node status of endometrial cancer cases were evaluated. RESULTS: The mean serum leptin levels were 16.9 ng/ml among endometrial cancer cases and 19.0 ng/ml among controls (p = 0.32). Of endometrial cancer cases, the mean leptin level was found to be 15.8 ng/ml for Stage I and 18.5 ng/ml for Stage II-IV disease (p = 0.34). The figure was 17.7 ng/ml for endometrioid and 13.2 ng/ml for non-endometrioid type of tumor (p = 0.24). The mean leptin levels of 16.3 ng/ml for grade 1 and 19.9 ng/ml for grade 2-3 tumors were observed (p = 0.07). The cases with positive and negative lymph nodes had leptin levels of 20.2 ng/ml and 16.1 ng/ml, respectively (p = 0.30). CONCLUSIONS: Serum leptin levels in endometrial cancer patients were similar to healthy controls. Leptin did not show any significant correlation with stage, grade, histological type and node metastases in endometrial cancer.

Distribution of human papillomavirus types in Turkish women.

PURPOSE OF INVESTIGATION: Since oncogenic types of human papillomavirus (HPV) are associated with a higher risk of cervical cancer and certain types can be controlled by a vaccine, a study has been performed to determine the HPV genotype distribution among Turkish women. METHODS: The study included patients with abnormal cytology or in the follow-up for cervical intraepithelial neoplasia between 2002 and 2009 at Hacettepe University Hospital. The results of 1797 consecutive cervical samples were analyzed retrospectively. INNO-LiPA HPV genotyping, HPV-Typing and Seeplex HPV 18-plex genotyping tests were used to determine the types of HPV. RESULTS: HPV was detected in 404 (22.4%) of 1797 samples studied. HPV DNA was identified in 194 cases by using HPV-Typing test but the specific genotype was not available. The most frequent genotype was HPV 16 which was observed in 103 cases (49.0%). CONCLUSION: HPV 16 was the most common genotype observed among Turkish women with abnormal cytology. It suggests that HPV vaccination may be useful for prevention of cervical cancer in this population.

Non-Hodgkin's lymphoma complicating pregnancy: a case report.

A 40-year-old, gravida 3, para 2 woman was initially referred to our department at 31 weeks' gestation complaining of fever, night sweats, malaise in association with jaundice and pancytopenia. Cesarean section with excisional iliac lymph node biopsy was carried out following a period of expectant management. An 1,840 g healthy male infant with an Apgar score of 9 at 34 weeks of gestation was delivered. Histologic examination of the excised lymph node revealed non-Hodgkin's lymphoma (Histiocyte and T cell predominant B cell lymphoma). The patient was evaluated to have Stage II B disease. A chemotherapy regimen of CHOP/Rituximab was instituted with successful maternal-fetal prognosis.

Clinical results of a split sample liquid-based cytology (ThinPrep) study of 4,322 patients in a Turkish institution.

PURPOSE: A prospective study was carried out to compare the efficacy of liquid-based cytology (ThinPrep) with the conventional Pap smear using a split-sample design in a Turkish university hospital outpatient gynecology clinic. METHODS: 4,322 consecutive patients were recruited for the study between 2002 and 2003. All the patients underwent conventional Pap tests followed by a ThinPrep test for screening of cervical cancer. The results were evaluated in terms of the Bethesda III classification. All the patients with abnormal tests underwent colposcopy and directed biopsy. RESULTS: While 2.3% of the specimens were unsatisfactory for evaluation in the conventional Pap test group, this rate was 1.7% for the ThinPrep group. Epithelial cell abnormalities were observed in 42 (1.0%) patients in the conventional Pap test group and in 36 (0.8%) patients in the ThinPrep group. ASCUS was observed in 26 patients in the conventional Pap test group whereas the ThinPrep group had 20 cases of ASCUS as the leading cause of abnormal cytology. Biopsy of these cases revealed CIN 1 in two CIN 2-3 in three and cervical/endometrial adenocarcinoma in three patients. The ThinPrep application led to diagnoses of one additional case of CIN 2-3 and one case of adenocarcinoma among the negative or unsatisfactory for evaluation categories of the conventional Pap test group. CONCLUSION: Despite an adverse bias introduced by the split-sample study design, application of ThinPrep showed an improved rate of specimen adequacy and increased sensitivity for more significant cervical precursor lesions over the conventional Pap test.

Management of ovarian dysgerminoma during a pregnancy complicated by preeclampsia; a case report.

A case of a 25-year-old primigravid woman at 31 weeks' gestation with the diagnosis of preeclampsia, malignant pelvic mass, fetal growth restriction and postpartum pulmonary thromboembolism is reported. Fertility preserving surgery for ovarian carcinoma following cesarean delivery was carried out. Final histopathology revealed Stage IC dysgerminoma. After eight months of initial surgery she became pregnant spontaneously. After two years of initial surgery she is still alive without any evidence of disease.

Reproductive tract pathology in asymptomatic women treated with tamoxifen.

PURPOSE: To determine the long-term effects of tamoxifen on the female reproductive tract in patients with breast cancer. METHODS: Forty-nine patients with breast cancer receiving tamoxifen longer than two years were analyzed. All the patients underwent pelvic examination, pap smear, transvaginal ultrasonography, serum CA 125 and dilatation and curettage. RESULTS: There were 16 patients with genital system pathology. Three of them had atypical Pap smears, one with cervical carcinoma and the other two with chronic cervicitis. Two significant ovarian pathologies were found. These were ovarian fibroma, and unilateral dermoid cyst. There were three patients with endometrial hyperplasia without atypia. Uterine myoma was encountered in seven of the cases. Only one patient had elevated CA 125 levels despite normal genital examination findings. CONCLUSION: Since no significant genital pathology attributable to tamoxifen therapy could be detected, the follow-up for gynecologic pathologies in breast cancer patients receiving tamoxifen therapy may be individualized.

Management of gestational trophoblastic diseases: subsequent pregnancy experience.

Patients with gestational trophoblastic disease (GTD) can usually achieve complete sustained remission while retaining their fertility even in the presence of wide-spread metastasis. Following complete and partial mole, our patients had 1,239 and 205 later pregnancies, respectively, which resulted in 68.6% and 74.1% term live births, respectively. Patients with either type of hydatidiform mole have, in general, a normal later pregnancy experience. After one molar pregnancy, the risk of a molar pregnancy in a later conception was about 1%. Our patients who received chemotherapy for persistent gestational trophoblastic tumor had 522 later pregnancies, which resulted in 358 (68.6%) term live births and only 10 (2.5%) major and minor congenital anomalies. Data from other centers involving 2,598 later pregnancies also indicate that after chemotherapy patients can generally anticipate a normal future reproductive outcome.

Expression of epidermal growth factor receptor-related family products in gestational trophoblastic diseases and normal placenta and its relationship with development of postmolar tumor.

OBJECTIVE: The goal of this work was to study the expression of epidermal growth factor receptor (EGFR) and c-erbB-3 and c-erbB-4 oncogenes in gestational trophoblastic diseases and normal first-trimester placenta. STUDY DESIGN: Paraffin sections of 16 cases of partial mole, 25 cases of complete mole, 10 cases of gestational choriocarcinoma, and 11 cases of therapeutic abortion were studied immunohistochemically for EGFR, c-erbB-3, and c-erbB-4 proteins. The presence of EGFR mRNA was studied using in situ hybridization. RESULTS: Staining for EGFR was detected immunohistochemically in all cell types in gestational trophoblastic diseases and normal placenta. In situ hybridization for EGFR mRNA correlated with immunostaining for EGFR in all tissues studied. All 10 cases of choriocarcinoma exhibited strong immunoreactivity for EGFR. The levels of expression of EGFR in choriocarcinoma and syncytiotrophoblasts and cytotrophoblasts in complete mole were significantly greater than those in syncytiotrophoblasts and cytotrophoblasts in both normal placenta and partial mole (P < 0.01, P < 0.01). Expression of c-erbB-3 did not significantly differ among placental and gestational trophoblastic disease tissues and trophoblastic cell types except for significantly increased expression in choriocarcinoma as compared with cytotrophoblasts of partial mole (P = 0.02). The placenta, complete and partial mole, and choriocarcinoma tissues demonstrated similar immunoreactivity for c-erbB-4. Strong immunostaining for EGFR (P = 0.02) and c-erbB-3 (P < 0.01) in extravillous trophoblasts of complete mole was found to be significantly correlated with the development of persistent postmolar gestational trophoblastic tumor. CONCLUSION: The EGFR-related family of oncogenes may be important in the pathogenesis of gestational trophoblastic diseases. The increased expression of EGFR and c-erbB-3 in complete mole may also influence the development of persistent gestational trophoblastic tumor.

Differential gene expression pattern between normal human trophoblast and choriocarcinoma cell lines: downregulation of heat shock protein-27 in choriocarcinoma in vitro and in vivo.

OBJECTIVE: Our purpose was to identify potential differences in gene expression between normal trophoblast and choriocarcinoma cells. METHODS: The Atlas human cDNA expression array hybridization technique was used to study the gene expression pattern in normal trophoblast and choriocarcinoma cell lines. Furthermore, to confirm heat shock protein-27 (Hsp-27) expression data, reverse transcriptase-PCR (RT-PCR), Western blot, and immunohistochemical analyses were used in vitro with cell lines and in vivo with paraffin sections. RESULTS: The expression of nine genes was strongly different comparing a normal trophoblast cell line with choriocarcinoma cells on the Atlas membranes. Compared to normal trophoblast cells, six genes were upregulated and three were downregulated in choriocarcinoma cells. Furthermore, the downregulation of Hsp-27 in choriocarcinoma cells was confirmed both in vitro with cell lines and in vivo with paraffin sections using RT-PCR, Western blot, and immunohistochemical techniques. CONCLUSION: cDNA expression array is a useful technique for identifying differentially expressed gene patterns in normal trophoblast and choriocarcinoma cells. The strong expression of Hsp-27 in placental villous trophoblast cells may play a role in trophoblast differentiation. The downregulation of Hsp-27 in choriocarcinoma may contribute to the extreme sensitivity of trophoblastic tumors to chemotherapy.

Outcome of pregnancies occurring within 1 year of hydatidiform mole.

OBJECTIVE: To determine the outcome of subsequent pregnancies in patients with partial or complete molar pregnancy who conceive before completing the recommended hCG follow-up of at least 6 months. METHODS: Retrospective record review of patients with partial or complete mole who conceived before the standard gonadotropin follow-up of 6 months was completed during 1980-1998. RESULTS: Sixty-seven patients with molar pregnancy who conceived before completion of hCG follow-up were identified. Thirty-five (52.2%) patients had a prior partial mole, and 32 (47.8%) had a prior complete mole. The mean interval from first achieving undetectable hCG level to new pregnancy was 3.1 and 3.4 months in patients with partial and complete mole, respectively. Eleven patients underwent elective termination, and 12 were lost to follow-up. Of the remaining 44 patients, 33 (75.0%) had live births, 10 had spontaneous abortions, and one had an ectopic pregnancy. A viable pregnancy outcome was achieved in 20 (83.3%) of 24 patients with partial mole and 13 (65.0%) of 20 patients with complete mole. None of the patients developed any evidence of postmolar persistent gestational trophoblastic tumor. None of the live births had any detectable fetal anomalies. CONCLUSION: The risk of persistent tumor is low and reproductive outcome is favorable once undetectable hCG levels are achieved. Pregnancies occurring before the completion of recommended hCG follow-up may be allowed to continue under careful surveillance.

Repetitive hydatidiform mole with different male partners.

OBJECTIVE: The aim of this study was to determine the role of parental factors that may relate to the pathogenesis of molar pregnancy. METHODS: A retrospective review of six patients who had a molar pregnancy with at least two different partners at New England Trophoblastic Disease Center between 1965 and March 1999 was performed. RESULTS: A total of 34 pregnancies with 20 different partners were observed in 6 patients. These pregnancies resulted in 15 (44.1%) hydatidiform moles, 8 (23.5%) term live births, 7 (20.6%) therapeutic abortions, 3 (8.8%) spontaneous abortions, and 1 preterm delivery. While 5 patients had a molar pregnancy with 2 different partners, 1 patient had a molar pregnancy with 3 different partners. Two patients developed persistent postmolar gestational trophoblastic tumor in 3 (20.0%) of the 15 episodes of molar pregnancy. Three of the male partners reported a total of 7 healthy children from prior relationships. CONCLUSION: The experience in these six patients suggests that a primary oocyte problem may contribute to the development of molar pregnancy.

Outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients with persistent gestational trophoblastic tumor.

OBJECTIVE: To determine the outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients treated with chemotherapy for gestational trophoblastic tumor. METHODS: Retrospective record review of patients with gestational trophoblastic tumor who conceived before standard hCG follow-up was completed during 1973-1998. RESULTS: Forty-three patients treated for gestational trophoblastic tumors conceived before human chorionic gonadotropin follow-up was completed. The antecedent pregnancy was complete mole in 31 (72.1%) and partial mole in 12 (27. 9%) patients. Of the 43 patients, 39 (90.7%) had stage I, 1 had stage II, and 3 had stage III disease. The mean interval from human chorionic gonadotropin remission to new pregnancy was 6.3 months (range 1-11 months). Ten patients underwent elective termination and four patients were lost to follow-up. Of the remaining 29 patients, 22 (75.9%) had term live births, 3 (10.3%) had preterm delivery, 3 had spontaneous abortion, and 1 (3.5%) had a repeat mole. Two cases of fetal anomalies were detected; one was inherited polydactyly and the other was hydronephrosis. One patient developed choriocarcinoma with lung involvement and underwent cesarean section at 28 weeks; a normal fetus was delivered and no choriocarcinoma was detected in the placenta. CONCLUSION: Pregnancies occurring in patients treated for gestational trophoblastic tumor before standard human chorionic gonadotropin follow-up is completed may continue under close clinical surveillance since the majority have a favorable outcome. However, patients should also be advised of the low but important risk of delayed diagnosis in case tumor relapse develops during early subsequent pregnancy.

p53 expression in ovarian carcinoma with regard to second-look findings.

Forty-eight (48) cases of ovarian carcinoma subjected to primary surgery and platinum based chemotherapy followed by second-look laparotomy (SLL) were analyzed with respect to p53 status. Overall aberrant p53 accumulation was observed in 20 (41.6%) out of 48 patients. While one out of 5 patients (20.0%) with stage I-II disease showed positive p53 staining, 19 out of 43 patients (44.1%) with stage III disease were found to be positive for p53. According to the histologic types, 41.9% of serous (13/31), 33.3% of endometrioid (2/6), 50.0% of transitional (2/4), 40.0% of mixed (2/5) and 50,0% of mucinous types of tumors showed abnormal expression of p53. p53 positivity was found in 12 (54.5%) out of 22 SLL(+) patients while only 8 (30.7%) were p53 positive out of 26 with SLL(-) patients. Cases with abnormal p53 accumulation tended to be SLL positive, however, the difference was not significant.

Skinning vulvectomy for the treatment of vulvar intraepithelial neoplasia 2-3: a study of 21 cases.

Twenty-one cases of patients with vulvar intraepithelial neoplasia (VIN) 2-3 were reviewed. The mean age at diagnosis was 45.4 years. All of the patients presented with vulvar pruritus. Five of the patients had hypertension, two had coronary heart disease and two had diabetes mellitus as complicating medical illnesses. None of the patients had history or evidence of vaginal intraepithelial neoplasia (VAIN) or cervical intraepithelial neoplasia (CIN), and only one patient had invasive cervical cancer at diagnosis. Provided the histology confirmed VIN, the patients were subjected to a skinning vulvectomy procedure. Of the patients, 15 (71.4%) had VIN 2, and the remaining 6 (28.6%) had VIN 3 at preoperative evaluation. Histologic analysis of skinning vulvectomy specimens revealed no evidence of neoplasia in three patients (14.2%). Multifocality was observed in only three patients (14.2%). The areas involved were the perineum in four patients, labia in 15 and clitoris in two patients. Associated vulvar pathologies were condyloma acuminata in one, squamous vulvar hyperplasia in three and lichen sclerosus with squamous hyperplasia in one patient. The complications of the procedure included febrile morbidity in three patients and minor wound break-down in one patient. None of the patients in this series experienced recurrence. Skinning vulvectomy seems to have a high success rate in treatment of VIN 2-3 with minimal postoperative complications and satisfactory cosmetic results. However, observation of only three patients with multifocal lesions as well as no patient with invasive cancer adds credence to an ablative procedure after appropriate evaluation under colposcopy.

Benign epithelial ovarian tumors.

Two hundred and twelve patients with benign epithelial ovarian tumors managed consecutively at Hacettepe University Hospital between 1974-1994 were analyzed retrospectively. Benign epithelial tumors constituted 9.5% (212/2216) of all ovarian tumors and 28.5% (212/743) of the primary epithelial ovarian tumors during the study period. Of the patients with benign epithelial tumors, 104 (49.0%) had serous, 94 (44.3%) had mucinous and the remaining 14 (6.7%) had Brenner tumors. The surgical procedures varied from cystectomy to total abdominal hysterectomy according to the age of the patient. Bilaterality was encountered in 12.8% of serous and 10.6% of mucinous tumors. Ovarian carcinoma occurred synchronously in two patients. In two patients, serous cystadenoma was detected in the preserved ovaries following 3 and 7 years of initial conservative surgery, respectively. Serous tumors were relatively more common constituting approximately one half of the cases. Most of the patients presented with an abdominopelvic mass.

nm23 expression in carcinoma of the uterine cervix.

To evaluate the significance of nm23 protein expression in cervical carcinoma, 83 patients with stage IB disease, treated primarily with surgery were studied immunohistochemically. Of the cases 57 were squamous carcinoma, 9 were adenocarcinoma, 14 were adenosquamous carcinoma and 3 were small-cell carcinoma. nm23 expression was positive in 63% of the cases. Although positive expression was more common in squamous and adenosquamous type tumors, negative expression was dominant in adenocarcinoma (P<0.05). When nm23 expression was compared with the clinicopathologic risk factors, there was no correlation of expression with the grade, deep invasion of the stroma, parametrial involvement and lymph node metastasis. But expression was inversely correlated with the number of metastatic lymph nodes (P<0.05). Although 3 or more lymph node metastases is a very poor prognostic sign, nm23 expression was not correlated either with recurrence or survival. Expression was negative in 77% of metastatic lymph nodes and in all of the recurrences. The predominance of negative expression in metastatic lymph nodes (P<0.05) and recurrences seems to be related to the aggressive behavior of the negative clone in the heterogeneous primary tumor.

Abnormal expression of cripto and p53 protein in endometrial carcinoma and its precursor lesions.

Many oncogenes and tumor suppressor genes are involved in multistep carcinogenesis. Cripto is an epidermal growth factor (EGF) related gene which shares homology with EGF and TGFalpha. The aim of this study was to evaluate the role of abnormal p53 and cripto oncogene expression in endometrial carcinogenesis and progression using a hyperplasia carcinoma sequence model. Ninety-six primary endometrial adenocarcinomas and 30 hyperplastic tissues of which 7 were atypical (AH), were immunohistochemically examined for the presence of cripto and abnormal p53 protein. Immunopositivity was compared in hyperplastic and carcinoma tissues and analysed for conventional clinicopathological prognostic variables such as grade, depth of myometrial invasion, lymphovascular invasion, lymph node metastases and clinical stage. Cripto immunoreactivity was strong in most cases of AH, and endometrial carcinomas revealed 71% overall and 41% strong positivity, while hyperplasias without atypia were weakly stained. There was no correlation between cripto expression and clinicopathological prognosticators. Abnormal p53 was not observed in hyperplasias but AH and carcinomas expressed 14% and 25% overall positivity, respectively. There was a statistically significant correlation between the stage of the disease and abnormal p53 accumulation. Our results suggest that both cripto and p53 may play a role in endometrial carcinogenesis while abnormal p53 expression is an important parameter for disease progression.

The clinical predictors of intrauterine fetal death.

Five hundred and thirteen (513) patients with intrauterine fetal death managed between 1983 and 1990 at Hacettepe University Hospital were analyzed retrospectively. Fetal death rate was 20.5/1,000 deliveries during the study period. The mean age of the mothers at diagnosis was 27.6 years. Of the 326 multigravida patients, 113 (34.6%) had a history of abortion and 113 had a history of previous intrauterine fetal death. The leading causes of intrauterine fetal death in this series were maternal hypertension in 167 patients (32.5%) followed by abruptio placentae in 38, Rh incompatibility in 30 and congenital anomalies in 30 patients. However, in 175 patients (34.1%), the cause of intrauterine fetal death could be explained. Three mothers were lost: one from pulmonary embolism complicating deep venous thrombosis, one from heart failure due to rheumatic disease, and one from cerebral injury following a traffic accident. The patients with a history of fetal demise should be managed under high risk category with close antepartum surveillance, especially in the last trimester, so as to reduce intrauterine fetal deaths which are mostly attributable to preventable causes.