Malignant mixed Müllerian tumor with small cell neuroendocrine differentiation: a case report and review of the literature.

INTRODUCTION: Small cell neuroendocrine differentiation (NE) in malignant mixed Müllerian tumors (MMMTs) is a rare and unusual occurrence with very few previously reported cases. There is no consensus regarding its diagnosis, classification, and optimal treatment options. CASE: The authors report a patient with endometrial MMMT and NE differentiation who initially received comprehensive surgery followed by adjuvant chemotherapy containing cisplatin and etoposide. She further underwent metastasectomy and received carboplatin and paclitaxel for the relapse. She is still alive 12 months after the diagnosis. The authors performed a review of literature in order to characterize the clinical phenotype. These patients have a very aggressive disease. Median life expectancy seems to be less than a year. CONCLUSIONS: It is reasonable to perform comprehensive staging surgery followed by adjuvant chemotherapy irrespective to stage of the disease.

Apoptosis and expression of Bcl-2, Bax, p53, caspase-3, and Fas, Fas ligand in placentas complicated by preeclampsia.

AIM: To determine whether preeclampsia is associated with an increase in placental apoptosis and altered expression of mediators of apoptosis such as Fas, Fas ligand, caspase-3, p53, Bcl-2 and Bax. METHODS: Placental samples obtained from 20 women with preeclampsia and 14 normal women were analyzed using the Klenow, Frag-EL DNA fragmentation detection kit for apoptosis. Expression of Fas, Fas ligand, caspase-3, p53 Bcl-2, and Bax was assessed using immunohistochemistry. RESULTS: The median percentage of apoptotic nuclei in trophoblasts was significantly higher for the preeclampsia group than for the controls (6.9 vs 0.25; p =.001). Fas ligand expression was significantly higher in the decidua among the subjects with preeclampsia compared with controls (1.2 vs 0; p = .023). Otherwise no difference was observed in the expression of Bax , Bcl-2, p53, caspase-3, and Fas between groups. CONCLUSION: Increased apoptosis in preeclampsia may not be associated with significant alterations in Fas, Fas ligand, caspase-3, p53, Bcl-2 and Bax expression.

Effect of intratumoral lymphocyte density on the disease-free survival and overall survival in malignant epithelial tumors of the ovary.

Malignant epithelial ovarian tumors are the fifth most common cancer of females which has the highest mortality rate among gynecological malignancies. Tumor-specific or related antigens that induce an immune response have been defined in tumors. Intratumoral T lymphocytes recognize these antigens and induce a cytolytic activity. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor expressed in many tumors. In this study, we studied the relation between clinicopathological findings and intratumoral T lymphocyte and VEGF expressions in malignant epithelial ovarian tumors. The presence of VEGF in ovarian surface epithelial carcinomas and CD3, CD4 and CD8 antibodies in tumor-infiltrated lymphocytes were investigated in 63 cases with an immunohistochemical method. Positive-stained intratumoral lymphocytes were graded on a scale of 0 to 3 (0 --> 0, +1 --> < or = 5, +2 --> 6-19, +3 --> > or = 20). VEGF was assessed according to the staining intensity (0: negative, +1: weak, +2: moderate, +3: strong). CD3 positivity was observed in intratumoral lymphocytes in all cases while only CD4 and CD8 positivities were observed in 30% and 80%, respectively. VEGF was positive in 73% of the cases. No significant relation was observed between VEGF expression and presence of intratumoral T lymphocyte and clinicopathological parameters. Moreover, they did not have any significant effect on disease-free survival and overall survival.

Expression of c-erbB-2 and p53 in breast carcinoma patients: comparison with traditional prognostic factors and survival.

We aimed to determine the correlations between standard clinicopathological factors and expression of c-erbB-2 and p53 proteins, and to investigate the significance of these variables in relapse and disease-free survival (DFS) in breast carcinoma patients. Data from 200 patients who had undergone mastectomy for breast carcinoma were evaluated. Significant correlations were found between c-erbB-2 positivity and high histological grade (grade 3) tumour, p53 positivity and high grade tumour, and age < 60 years and oestrogen receptor negativity. Twenty-six patients (13%) developed a recurrence. Disease relapse was more frequent in patients who had axillary lymph node (ALN) metastasis, high grade tumour, c-erbB-2 positivity and p53 positivity; these variables were also associated with a shorter DFS. The effects of ALN metastasis and p53 positivity were significant. In conclusion, ALN metastasis and p53 positivity were important factors for predicting disease relapse in mastectomy-treated breast carcinoma patients; other clinicopathological criteria and c-erbB-2 positivity were not predictive.

The effect of platinum-based combination chemotherapy on the lymph nodes in advanced-stage epithelial ovarian cancer: does it decrease the incidence of lymph node involvement?

This paper aims to determine the impact of platinum-based combination chemotherapy on the lymph nodes in advanced-stage epithelial ovarian carcinoma. From 1997 to 2000, the patients in whom we performed lymphadenectomy before (group A) or after chemotherapy (group B) in the Department of Obstetrics and Gynecology, Akdeniz University School of Medicine were enrolled in this study. A total of 47 cases were included in the study. Twenty five cases had lymphadenectomy during the initial laparatomy and 22 cases during second-look procedures. Lymph node metastasis was detected in 14 (56%) patients in group A and in 10 (45.4%) cases in group B (P > 0.05). Platinum-based combination chemotherapy does not decrease significantly the incidence of involved lymph nodes in advanced-stage epithelial ovarian carcinoma.

Proliferating cell nuclear antigen (PCNA) and Ki-67 in epithelial ovarian tumours: correlation with DNA flow cytometric analysis.

AIMS: The aim of the present retrospective study was to evaluate the prognostic significance of Ki-67 and Proliferating cell nuclear antigen (PCNA) immunostaining and DNA content measured by flow cytometry (FCM) in epithelial ovarian tumours. Further, we compared these variables with histopathologic features and each other. METHODS: We used immunohistochemical methods on paraffin embedded tissue sections of 67 surgically resected epithelial ovarian neoplasms, diagnosed between 1987-1998, (benign serous n=12, benign mucinous n= 15, borderline mucinous n=3, malignant serous n= 15, malignant mucinous n=8, malignant endometrioid n=10, clear cell n=3 and malignant Brenner n= 1) for the presence of PCNA and Ki-67 reactivity. Samples from malignant and borderline tumours were also examined for DNA ploidy and S-phase fraction (SPF) by flow cytometry. Five malignant tumours were excluded because there was not sufficient tissue for flow cytometric analysis. CONCLUSION: There was no significant correlation between DNA ploidy, SPFs derived from FCM analysis, and proliferative activity, determined by PCNA and Ki-67 and the known histopathologic parameters of prognostic significance in ovarian epithelial malignancies.

Predictors of distant metastasis at presentation in breast cancer: a study also evaluating associations among common biological indicators.

BACKGROUND: To investigate the correlation among some of the commonly used clinical, pathological factors and newer biological indicators, and to identify the independent predictors of distant metastasis at presentation in patients with breast cancer. METHODS: The pathological specimens from 73 patients with breast cancer were retrospectively evaluated by immunohistochemistry. Data on 13 biological indicators; ER, PR, P53, c-erbB-2, PCNA, CEA, Ki-67, Vimentin, Ulex, Nm23, Cathepsin D, Factor VIII, PS2 together with clinical and pathological factors were collected. RESULTS: A number of highly significant correlations were found among the biological indicators studied. By logistic regression analysis, the predictors of distant metastasis at presentation in univariate tests were tumor diameter, number of lymph nodes involved, P53, c-erbB-2 and grade. In multivariate analysis, tumor diameter (P = 0.042, HR: 1.88(1.02-3.44)), c-erbB-2 expression (P=0.035, HR: 18.20 (1.23-268.66)) and grade (P=0.010, HR: 8.05(1.66-39.00)) retained their significance. CONCLUSION: Our findings show that inactivation of suppressor genes, expression of oncogenes, loss of differentiation, augmentation of proliferative activity, metastatic potential, angiogenesis and hormone receptor status are all interrelated facets of breast cancer pathogenesis. Patients with tumors overexpressing c-erbB-2 or with bigger or higher-grade tumors probably need to be more carefully evaluated for the presence of distant metastasis, thus be better staged, at presentation. This may be a new reason to test c-erbB-2 routinely in all patients with breast cancer in addition to its well-known prognostic and predictive uses.

Proliferating activity in differential diagnosis of benign phyllodes tumor and cellular fibroadenomas: is it helpful?

Benign phyllodes tumors and fibroadenomas are two types of fibroepithelial tumors of breast that are usually difficult to differentiate. The purpose of this study is to evaluate the proliferative activity of these tumors and to find out if it helps in differential diagnosis. Thirty-one benign phyllodes tumors and twelve cellular fibroadenomas were retrieved from the archives of Pathology Department of Akdeniz University, School of Medicine. Proliferating activity of epithelial and stromal cells were evaluated by using labeling index (LI) of proliferating cell nuclear antigen (PCNA) and Ki-67 antigen by immunohistochemistry. The results were compared with other clinicopathologic findings. There was not any significant difference between the proliferating activity of phyllodes tumor and cellular fibroadenomas. Mean LI of PCNA was 28.01 (+/-22.85) in stromal cells and 56.57 (+/-30.98) in epithelial cells of phyllodes tumor where it was 28.92 (+/-24.02) and 62.53 (+/-32.56) in fibroadenomas. Ki-67 indices were 0.05 (+/-0.19) in stromal cells, 2.65 (+/-12.53) in epithelial cells of phyllodes tumors and 0.0 (+/-0) in stromal cells, 0.43 (+/-0.63) in epithelial cells of fibroadenomas. There was no correlation between the diameter of tumors and proliferating activity in both groups. Proliferating activity, determined by immunohistochemistry with PCNA and Ki-67 antibodies did not reveal significant difference between phyllodes tumor and fibroadenoma.

Drug resistance in epithelial ovarian cancer: P-glycoprotein and glutation S-transferase. Can they play an important role in detecting response to platinum-based chemotherapy as a first-line therapy.

OBJECTIVE: Drug resistance is important for the treatment of ovarian cancer. P-glycoprotein and glutation S-transferase as resistance markers play an important role in the effectivity of chemotherapeutical agents. The role of P-glycoprotein and glutation S-transferase in the treatment of epithelial ovarian cancer is not well understood. We investigated the relation between P-glycoprotein and glutation S-transferase level for response to platinum-based chemotherapy in epithelial ovarian cancer. MATERIAL AND METHODS: We reviewed 30 cases diagnosed as epithelial ovarian cancer and treated with platinum-based chemotherapy in the Department of Obstetrics and Gynecology, Akdeniz University School of Medicine. The material was attained from initial parafin-embeded blocks stained for P-glycoprotein and glutation S-transferase. The cases that were diagnosed and treated before attending our clinic were not enrolled in the study. RESULTS: Mean age was 58.2 (25-70) and mean gravida 4.1 (0-10). Twenty-four patients (80%) were glutation S-transferase positive. Three cases (10%) out of 30 had positive reaction for P-glycoprotein. No difference was revealed regarding chemotherapy response rate among the cases showing glutation S-transferase positivity and P-glycoprotein negativity. CONCLUSION: Detection of glutation S-transferase and P-glycoprotein levels in epithelial ovarian cancer tissue is not important for response to platinum-based chemotherapy as a first line.

Benign persistent papular acantholytic and dyskeratotic eruption of the vulva: a case report.

We report a case of 44-year-old woman with persistent pruritic papules on the left and right labium majus of the vulva. Histopathologic examination of the vulvar biopsy specimen revealed a suprabasal separation of the epidermis with acantholysis and dyskeratosis.

The utilization of immunohistochemical prognostic factor in endometrial adenocarcinoma: is it cost effective?

This study investigated the relation between immunohistochemical prognostic factors and clinical stage and histopathological grade in endometrial adenocarcinoma. Twenty-seven patients with a mean age of 61 (38-74), who underwent radical surgery due to endometrial adenocarcinoma in our hospital between 1983-1998, were re-evaluated. For clinical staging FIGO criteria were used. Histopathological differentiation of the tumor was graded as good (grade 1), moderate (grade 2), and poor (grade 3). Estrogen and progesterone receptors, c-erb B2, UEA 1, Ki-67, PCNA and p53 were studied as immunohistochemical prognostic factors. There were no patients in stages IA and IIIB. Among the prognostic factors, PCNA was the most significantly stained marker, followed by c-erb B2, estrogen and progesterone receptors, regardless of the clinical stage and histopathological grade of the tumor. The least positivity was achieved with Ki-67. There was no significant difference when each prognostic factor was analysed with respect to clinical stage and histopathological grade. In our study no significant relation was found between the prognostic factors and the clinical stage and histopathological differentiation of the tumor. Therefore the cost effectiveness of the utilization of these factors should be reconsidered.

Immunohistochemical staining properties of PCNA, Ki-67, p53, beta-hCG and HPL in trophoblastic disease.

OBJECTIVE: In this study proliferating markers PCNA (proliferating cell nuclear antigen) Ki-67 and mutation of supressor gene p53 were investigated in gestational trophoblastic disease (GTL). These markers were tested by using immunostaining with beta subunits of human chorionic gonadotropin (hCG) and human placental lactogen (HPL). MATERIAL AND METHODS: Twenty curetting samples, 20 spontaneous abortions, 16 hydatidiform moles and two choriocarcinomas were studied and compared. Hydatidiform moles were subdivided into 10 complete and six partial moles by using flow cytometry analysis. All slides were stained with PCNA, Ki-67, p53, hCG, and HPL immunohistochemically. PCNA and Ki-67 stained slides were studied quantitatively to determine the PCNA and Ki-67 index. Other slides that were stained with p53, hCG, HPL were evaluated according to staining percentage and intensity. Staining properties of all groups were compared with each other. Variance analysis and the Mann Whitney U test were used for statistical analysis. Choriocarcinomas were not included in the statistical analysis. Ki-67 and the PCNA index in two choriocarcinoma cases found 81.4% and 41%, and 44% and 64%, respectively. One case was stained in 70% with (++) intensity by p53. While both were stained in 80% with (++) intensity by hCG, one was stained in 30% field (+) intensity by HPL. RESULTS: The four groups of complete and incomplete diagnosed hydatiform moles, spontaneous abortions and retention curettage were matched in pairs and evaluated according to the PCNA index. This index showed significant differences among the groups. The differences among the Ki-67 index, p53, hCG and HPL staining properties were not statistically significant. CONCLUSION: Our findings showed that PCNA is a significant and useful marker for trophoblastic diseases and can be used as a prognostic factor.

Primary pure choriocarcinoma of the ovary in reproductive ages: a case report.

Choriocarcinoma is an aggressive tumor with cyto- and syncytiotrophoblastic cells. It arises gestationally or nongestationally. Nongestational choriocarcinoma of the ovary can be pure or mixed with other germ cell tumors. Pure type is less frequent than mixed type and the diagnosis of nongestational choriocarcinoma of the ovary is very difficult in the reproductive period. A case of a 20-year-old woman with pure choriocarcinoma of the ovary is presented with a review of the literature and discussion of its origin.

A case of thoraco-omphalo-ischiopagus bipus conjoined twins.

A case of thoraco-omphalo-ischiopagus bipus conjoined twins is reported. The twins shared a common lower chest and abdominal wall, a single pelvis and two lower extremities. Our initial approach was to determine the detailed anatomy of the viscera and then to outline a surgical plan. However, the twins' general condition gradually deteriorated, and the approach was not completely realized despite maximal supportive therapy for cardiorespiratory failure. After the death of the twins, it was detected that they had a single pericardial cavity, and shared an abdominal aorta and vena cava. Furthermore the right twin had Bochdalek hernia and left ventricular hypoplasia. Consequently, such cardiovascular pathologies, coupled with major additional anomalies, may threaten the twins' life. Therefore further management plans are required considering urgent surgical correction of the life-threatening anomalies before the definitive procedure.

Acute respiratory distress due to malignant schwannoma. A case report.

A 13-year-old boy with acute respiratory distress due to a malignant schwannoma located in the neck, is reported. This case suggested that malignant schwannoma in the neck can lead to airway obstruction.