Metastatic malignant ovarian melanoma--a case report.

BACKGROUND: Malignant melanomas of the female reproductive system are rare. These are biologically highly aggressive tumors with poor prognosis. Preoperative establishment of the diagnosis is practically impossible. Therapeutic approach and treatment of patients with metastatic ovarian melanoma are highly dependent on precise histological analysis. CASE REPORT: A woman aged 48 was admitted to the clinic for occasional pains in the lower abdomen and suspected myomatous changes of the uterus. The patient underwent surgery for melanoma on her right arm five years ago. Classic hysterectomy with bilateral adnexectomy with infracolic omentectomy and selective iliac lymphadenectomy were performed. Macroscopic examination revealed an oval tumefaction on the left ovary sized 12.5 x 10 x 3.5 cm of solid structure. Tumor tissue was yellowish-brown colored, of solid structure and mostly localized subcortically with central edema. Microscopic examination showed positive reaction for HMB-45, anti-Melan-A and S-100 protein, but negative immunoreactivity for estrogen and progesterone receptors. Malignant disease caused death after a 4-year follow-up period following gynecological operation. CONCLUSION: The previous diagnosis of skin melanoma is also indicative of metastatic ovarian tumor, while immunohistochemical analyses confirmed the histopathological diagnosis.

Reliability and relationship of colposcopical, cytological and histopathological findings in the diagnostic process.

BACKGROUND/AIM: The question about the accuracy of cytology and colposcopy is more and more asked due to false positive and negative findings on the basis of which the decision on biopsy is made. The aim of this study was to examine reliability of biopsies based only on abnormal colposcopical findings, before receiving the results of Papanicolaou (PA) smear, by comparing findings of colposcopical, cytological and histopathological (HP) examinations as well as determining validity of these diagnostic methods. METHODS: The study involved all patients who had their regular colposcopical and cytological examinations in the outpatient department during a two-year period (2009-2010) in the Clinic for Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade. The material for HP examination was obtained by colposcopically directed biopsy, due to abnormal colposcopical findings and without waiting for PA smear results. The data obtained by these methods were statistically analyzed and compared. Furthermore, validity of colposcopical and cytological examinations was assessed. Results. Out of 127 patients highly significantly more patients had more malignant cervical changes on colposcopical exam compared to HP (p = 0.000), and cytological exam (p = 0.000). Highly significantly more patients had more malignant cervical changes on PA smear than HP exam (p = 0.000), unless when findings were assessed in the widest sense of benign and malignant changes when there were no significant differences in these findings (p = 0.450). Sensitivity of colposcopy as a diagnostic method was 87.5%, specificity 24.14%, positive predictive value (+PV) was 34.65% and negative predictive value (-PV) 80.77%. Sensitivity of PA smear as a diagnostic method was 62.5%, specificity 87.36%, +PV was 69.44%, and -PV 83.52%. CONCLUSION: Regarding the results of our study it is best to make a decision on treatment according to findings of all the three methods. Cytological analysis is more reliable than colposcopical examination. Therefore, it is advisable that following abnormal colposcopical findings, PA smear should always be taken and only after receiving the results further diagnostics can be planned (biopsy and HP). A final decision on the therapy has to be made based on HP findings which are the only method that can give the ultimate reliable diagnosis of cervical changes.

The utility of human epididymal protein 4, cancer antigen 125, and risk for malignancy algorithm in ovarian cancer and endometriosis.

BACKGROUND: In women with pelvic mass, cancer antigen 125 (CA125) had not achieved satisfactory sensitivity and specificity in the detection of ovarian cancer, particularly in patients with underlying endometriosis. The aim of this study was to determine the diagnostic potential of human epididymal protein 4 (HE4), the combination of HE4+CA125, and the Risk of Ovarian Malignancy Algorithm (ROMA) for patients with pelvic mass, particularly in differentiating endometriosis from carcinoma. METHODS: A prospective cross-sectional study was conducted at the Clinic for Gynecology and Obstetrics, Clinical Center of Serbia. Serum samples were obtained preoperatively from 108 women undergoing surgery for pelvic mass; 29 of them had ovarian carcinoma, and 79 had a nonmalignant ovarian disease (39 with benign tumor, 20 with endometriosis, 20 healthy controls). Sera were analyzed for the levels of HE4 and CA125 and were then compared with the final pathologic results. The diagnostic performance of HE4 and CA125 was estimated using receiver operating characteristic curve and area under the receiver operating characteristic curve. RESULTS: The level of HE4 and CA125 was significantly higher among the patients with malignant tumors, compared with patients with nonmalignant disease. At the predefined specificity of 95%, HE4 and CA125 showed sensitivity of 65.5% and 58.6%, respectively, whereas the combination of HE4+CA125 reached 68.9% at the same specificity. Importantly, the level of HE4 did not differ significantly between the patients with endometriosis and with other nonmalignant diseases (which was not the case with CA125). Risk of Ovarian Malignancy Algorithm classified 96% of benign premenopausal cases as at low risk for ovarian cancer. CONCLUSIONS: HE4 showed satisfactory capability of distinguishing endometriosis from ovarian cancer, which CA125 lacked. The Risk of Ovarian Malignancy Algorithm score proved to be useful in excluding malignant diagnosis in premenopausal women.

Evaluation of adnexal masses: correlation between clinical, ultrasound and histopathological findings.

BACKGROUND/AIM: Concerning the growth of ovarian carcinoma incidence and bad prognosis for malignant forms, early and precise diagnostics is gaining in importance as a condition for precise and appropriate therapy for ovarian tumor masses. The aim of this study was to analyze pre- and postoperative findings of patients with adnexal masses in order to identify factors which could predict the nature and stage of the tumor prior to surgery. METHODS: All patients with adnexal masses who were treated in a 6-month period in the Institute of Obstetrics and Gynecology, Clinical Center of Serbia, (IOG, CCS), Belgrade, had their epidemiologic and gynecologic anamnesis and standard laboratory analyses taken prior to surgery. Also, clinical and ultrasonographic check up of pelvic organs was performed, as well as calculation of body mass index (BMI) and risk of malignancy index (RMI). After surgery we analyzed histopathological (HP) findings of tumors as a mean of final diagnosis and staging. For statistical analysis, we used SPSS 15 program. RESULTS: Throughout a 6-month period, we examined 81 patients with adnexal masses treated in the IOG CCS. HP findings showed that there were significantly more benign (n = 51) than malignant (n = 30) tumors in all the patients (Chi2 = 5.512). The patients with malignant HP findings were significantly older than those with benign adnexal masses (t = 3.362; p = 0.001). Significantly more patients with malignant HP findings were in menopause (p = 0.034). BMI values were highly significantly higher in the patients with malignant adnexal tumors (t = 3.421; p = 0.001). There was a statistically significant positive correlation between HP categories (benign, malignant) and RMI categories (low, intermediate and high risk) of all the patients (high risk, more malignant HP) (Ro(xy) = 0.428; df = 78; p = 0.000). CONCLUSION: . Patients in menopause, especially older ones, with high BMI and RMI should immediately be referred to a tertiary level institution, where appropriate surgery could be performed.

Evaluation of the risk malignancy index diagnostic value in patients with adnexal masses.

BACKGROUND/AIM: Ovarian cancer is the leading cause of death from gynecologic malignancies. Risk of malignancy index (RMI) is recommended in assessment of patients with adnexal masses. The aim of this study was to verify the effectiveness of the RMI in the discrimination between benign lesions and malignant adnexal masses in clinical practice. METHODS: Ultrasounds were performed for all the patients and menopausal status, CA125 level and calculated RMI were defined. All the patients were divided into 3 groups depending on RMI (< 25, 25-200, > 200). After operations all adnexal masses were analyzed histopathologically (HP) and then sensitivity, specificity and predictive value of RMI were calculated. RESULTS: Out of a total of 81 patients involved benign tumor had 51 (62.96%) and malignant 30 (37.04%) of the patients. The average value of CA125 in the group of patients with benign adnexal masses was 68.3 U/mL and in the group of patients with malignant adnexal masses it was 581.95 U/mL. In the group of patients with benign adnexal masses the average RMI was 284.9 and in the group of patients with malignant adnexal masses RMI was 469.2. All the results showed a positive correlation between both HP categories and RMI categories. The more malignant HP result produced higher RMI and the cut off value was RMI = 200. Sensitivity of RMI w as 83.33%, specificity was 94.12%, positive predictive value was 89.29% and negative predictive value was 90.57%. CONCLUSION: Our study showed that RMI is very reliable in differentiation benign from malignant adnexal masses.

Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT.

OBJECTIVES: Congenital anomalies of the kidney and urinary tract (CAKUT) are common causes of chronic renal failure in children. The angiotensin II receptor type 2 (AT2R) is one of proposed candidate genes for CAKUT, but the expression was never explored in humans. The aim was to establish the AT2R gene expression in human CAKUT concerning -1332A/G polymorphism, which might affect alternative splicing. DESIGN AND METHODS: Forty-eight patients with CAKUT constitute the basis of this study. Genotyping for -1332A/G, RT-PCR for AT2R gene expression and confirmation sequencing were performed. RESULTS: The expression of Ex 1/2/3 and Ex 1/3 transcript splice variants of the AT2R mRNA were detected in human CAKUT tissue. The pattern was observed independently of A to G transition. CONCLUSIONS: The expression of AT2R mRNA in human CAKUT was established for the first time and was not affected by -1332A/G polymorphism in children with CAKUT.

Simultaneous determination of cefotaxime and desacetylcefotaxime in real urine sample using voltammetric and high-performance liquid chromatographic methods.

Two rapid, accurate and sensitive methods are developed and validated for the quantitative simultaneous determination of cefotaxime (CFX) and its active metabolite desacetylcefotaxime (DCFX) in urine. Based on the previous results which showed the four electron reduction of CFX at approximately -0.5 V, and the new findings that DCFX reduction occurred at more positive potential (-0.23 V), the new adsorptive stripping differential pulse voltammetric (AdSDPV) method was developed for determination of CFX in the presence of DCFX. Linear responses were observed over a wide concentration range (0.07-0.52 microg/ml for CFX and 0.22-1.3 microg/ml for DCFX) in urine. The second assay involves subsequent separation on a reversed-phase HPLC column, with ultraviolet detection at 262 nm. Retention times were 4.057 and 1.960 min for CFX and DCFX, respectively. Linear responses were observed over a wide range, 0.55-6.60 microg/ml for CFX and 1.10-11.00 microg/ml for DCFX, in urine. The statistical evaluation for both methods was examined by means of within-day repeatability (n=5) and day-to-day precision (n=3) and was found to be satisfactory with high accuracy and precision.

Atypical proliferating mucinous tumors of gigantic dimensions.

UNLABELLED: BACKGROUND; Ovarian tumors of low malignant potential (LMP) are also known as atypically proliferating tumors. Ovarian tumors of LPM account for approximately 15% of all epithelial ovarian cancers. Mean age of occurrence is 40 years and they are 15-20 cm in diameter. CASE REPORT: A 32-year-old female patient was hospitalized as an urgent case with a large tumor mass that filled the entire abdomen. Cyst was 100 x 70 cm dimensions belonging to the right ovary and filled with 18 liters of content. Right adnexectomy, resection of the second ovary, as well as biopsy of the omentum were performed. Lymphadenectomy of the right iliac and obturator area was also performed. After receiving definitive histopathological results it was decided to perform a radical reoperation. On the 10th postoperative day relaparotomy, total hysterectomy and left adnexectomy were performed. The patient was released on the 6th postoperative day. She used to come to regular examinations up to date. CONCLUSION: This case is a proof that LMP tumors have low malignant potential, they grow slowly and can reach great proportions.

[Analysis of loss of heterozygosity of the tumor suppressor genes p53 and BRCA1 in ovarial carcinomas].

BACKGROUND/AIM: Among the genes involved in ovarian carcinogenesis, there has been increased interest in tumor-suppressor genes p53 and BRCA1. Both of the genes make control of cell cycle, DNA repair and apoptosis. The p53 is a "genome guardian" inactivated in more than 50% of human cancers, while BRCA1 mutations are found mostly in breast and ovarian cancer. The aim of this investigation was to establish the frequency of loss of heterozygosity (LOH) in the regions of the genes p53 and BRCA1 in ovarian carcinomas, and to analyze the association of LOH with the disease stage and prognosis. METHODS: We analyzed 20 patients with a confirmed diagnosis of epithelilal ovarian carcinoma. DNA for molecular-genetic analysis was extracted from the tumor tissue and blood as normal tissue of each person. Microsatellite markers of the regions of genes p53 and BRCA1 were amplified by PCR method. The determination of allelic status of microsatellites and detection of LOH was performed after PAA gel electroforesis. RESULTS: Both of the analyzed microsatellite markers were informative in 13/20 (65%) cases. In the region of gene p53, LOH was established in 4/13 (30.7%) tumors. One of them had histological gradus G1, one had gradus G2, and two of them had gradus G3, while all were with the International Federation of Gynecology and Obstetrics (FIGO) IIIc stage. In the region of gene BRCA1, LOH was detected in 5/13 (38.5%) tumors. Four of them had histological gradus G2, and one had gradus G3, while by the (FIGO) classification one was with stage Ib, one was with stage IIIb, while the three were with stage IlIc. LOH in both of the analyzed regions was detected in one tumor (7.70), with histological gradus G3 and the FIGO IIIc stage. CONCLUSION: The frequency of LOH in epthelial ovarian carcinomas was 30.7% and 38.5% for p53 and BRCA1 gene regions, respectively. Most of tumors with LOH had histological gradus G2 or G3, and the clinical FIGO stage IIIc, suggesting the association of this occurrence with a later phase of the disease.

Krukenberg tumor in pregnancy. The lethal outcome.

Krukenberg tumor refers to gastrointestinal cancer metastatic to the ovaries and its prognosis is uniformly poor. This case report concerns a 38-year-old pregnant woman suffering from abdominal pain and iterative vomiting episodes. She presented with a large abdominopelvic tumor. Because of suspected ovarian torsion, we performed urgent surgery. At laparotomy, bilateral ovarian tumors, ascites and gastric cancer located at the cardia and the lesser curvature invading the serosa were identified. We performed right ovariectomy, resection of the left ovary, and gastric biopsy. Histological examination of the specimen yielded diagnosis of Krukenberg tumor. Ten days later the patient underwent an elective Cesarean section in the 25th gestational week because of fetal asphyxia and very poor maternal life prognosis. We performed Cesarean delivery and extracted a vital female newborn of 31 cm, 600 g, Ap score 3, with virilization. Few days later the baby died at the intensive care unit. Two weeks later the mother died because of pulmonary failure.

[Methods of screening for endometrial cancer].

One of the established strategies for combating cancer is screening the asymptomatic population for premalignant conditions and early-stage disease. The prevalence of endometrial cancer in asymptomatic women is low and the overall prognosis is good because women present in early stage with abnormal bleeding. For all these reasons, screening for endometrial cancer is not recommended in general population. However, screening in high risk population will be very important in the future.

[Screening methods for malignant ovarian tumors in adult women].

Ovarian cancer is associated with high mortality rate which has improved a little despite therapeutic advances. It causes more deaths than combined cervical and uterine cancer. High mortality is believed to be a direct result of already advanced stage at the time of diagnosis. Survival is excellent in case of early stage disease but poor in late stage disease, regardless of histology. The goal of screening for ovarian cancer is restricted to detection of asymptomatic early stage disease, as precursor lesions of ovarian cancer have not been identified. At present, there is no reliable method of ovarian cancer screening which has been shown to reduce mortality from ovarian cancer. Therefore, routine screening of women in general population can not be currently advised. Screening should be limited to high-risk population and subjects participating in research projects as long as the results of current studies are available.

[Ovarian cancer after in vitro fertilization]. / Karcinom jajnika nakon fertilizacije in vitro.

There is serious concern about cancer risk in women undergoing ovarian stimulation treatment for infertility and longterm safety of these procedures. Association between fertility drugs and ovarian cancer is still controversial. A 30-year-old woman was referred to our institution with the initial diagnosis of an adnexal tumor after in vitro fertilization. Her history revealed adnexectomy for mucinous cystadenofibroma of the left ovary eight years ago, and cystectomy due to cystadenoma of the right ovary three years ago. At admission, the most remarkable findings were high temperature and elevated white blood cell count and erythrocyte sedimentation rate. Broad spectrum antibiotic treatment was initiated. Six days after admission, the patient was feverish, with temperature up to 38 degrees C, and evident signs of the acute abdomen. Immediate laparotomy was performed and multilocular right adnexal tumor 150x130x100 millimeters in size was identified. The right salpingo-oophorectomy was carried out. Pathological diagnosis was mucinous ovarian adenocarcinoma. Eighteen days later, radical surgery was performed. After the surgery, chemotherapy was applied. There is an urgent need for clear interpretation of the association between fertility drugs and subsequent higher ovarian cancer risk. Lacking conclusive evidence, an increased risk of ovarian cancer has been reported and more recently disputed. Higher ovarian cancer risk may be serious and even life-threatening complication for women undergoing ovarian stimulation.

Hysterectomy for Treatment of CIN.

The objective of this investigation was to determine the percentage of microinvasive and invasive cancers found when CIN 3 was treated by hysterectomy. The postoperative histologic findings of all patients with CIN 3 treated by conization or hysterectomy were analyzed. In 295 patients treated by conization, 14 (4.75%) microinvasive and 11 (3.73%) invasive cancers were found. Histologic analysis of 106 hysterectomy specimens revealed microinvasive carcinoma in 11 (10.38%) and invasive carcinoma in 17 (16.04%) cases. The finding of unexpected invasive cervical cancer in hysterectomy specimens seems significantly higher compared with conization. One must be cautious to avoid hysterectomy as the primary mode of treatment for women with coincident uterine pathology, postmenopausal women, or those who do not desire further reproduction. Hysterectomy as a mode of treatment for CIN 3 should be performed only if the existence of invasive cancer was excluded with certainty.