Ichthyosis uteri associated with squamous cell carcinoma of the endometrium - a case report.

BACKGROUND: Ichthyosis uteri is an extremely rare condition in which the entire or extensive parts of endometrial lining are replaced by stratified squamous epithelium. Malignant potential of this entity is unclear and its association with dysplastic changes and primary squamous cell carcinoma of the endometrium and endometrial adenocarcinoma has been reported. However, lack of data makes difficult to interpret the significance of neoplasms arising from this condition. PATIENTS AND METHODS: We report a case of ichthyosis uteri associated with squamous cell carcinoma of the endometrium in a 62-year-old female who presented with postmenopausal bleeding and thin endometrium on ultrasound. RESULTS: Endometrial curettage was performed and revealed high grade squamous intraepithelial lesion. The patient underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy and bilateral pelvic lymph node dissection. Microscopic examination of sections revealed squamous cell cancer along with extensive replacement of the endometrial lining by stratified squamous epithelium, consistent with ichthyosis uteri. CONCLUSION: If ichthyosis uteri is suspected we recommend hysterectomy in order to rule out possibility of coexisting carcinoma. Also, thin endometrium in women with postmenopausal bleeding does not reliably exclude endometrial cancer.

Interleukin 10 rs1800896 and interleukin 1B rs16944 polymorphisms and the risk of cervical cancer.

BACKGROUND: The purpose of this study was to evaluate the relationships between interleukin 10 (IL10) (rs1800896) and interleukin 1B (IL1B) (rs16944) genetic polymorphisms and the risk for cervical cancer in a cohort of women from Croatia. METHODS: A case-control study of 81 patients with cervical cancer and 80 age-matched healthy controls was performed. We collected peripheral blood samples, extracted deoxiribonucleic acid (DNA), and analyzed two single-nucleotide polymorphisms (SNPs) rs1800896 and rs16944 using TaqMan assays (Fa. Thermo Fisher Scientific, Waltham, MA, USA) and real-time polymerase chain reaction (PCR). We investigated a possible association between two cytokine genetic polymorphisms and the occurrence of cervical cancer. RESULTS: Our results showed no significant difference in the frequency of IL10 (rs1800896) and IL1B (rs16944) genotypes between the patients and the controls (χ2 test, P < 0.05). CONCLUSION: In this study, no association was found between IL10 rs1800896 and IL1B rs16944 polymorphisms and cervical cancer development.

BENIGN MULTICYSTIC PERITONEAL MESOTHELIOMA MIMICKING GYNECOLOGIC PATHOLOGY.

Benign multicystic peritoneal mesothelioma is a rare pathology that arises from the abdominal peritoneum. It has an affinity to develop on the surfaces of pelvic viscera. It predominantly occurs in women of reproductive age. The most used form of treatment is complete surgical removal. We report a case of a a 21-year-old female patient who presented with unclear diffuse abdominal pain. Transvaginal ultrasound and magnetic resonance imaging of the abdomen and pelvis revealed multiple functional cysts in the projection of the right and left ovary and free fluid in the pouch of Douglas. Laparoscopy was performed and multicystic tumor with thin, smooth walls, filled with clear serous content was found in lesser pelvis spreading to the left paracolic region and under the spleen. The multicystic mass was removed. Histologic examination revealed cystic formations filled with mucous content and formed from connective tissue outside and single row epithelium-mesothelium inside. Definitive diagnosis was benign multicystic mesothelioma of the abdominal peritoneum. The patient was well at one year follow-up.

Premature rupture of the membranes at 16 weeks: report of a successful outcome of pregnancy and review of the literature.

Prelabor rupture of the fetal membranes (premature rupture of membranes, PROM) before or at the limit of fetal viability is condition associated with significant and serious pediatric morbidity and mortality. It is a rare problem, with an estimated incidence between 0.1 and 0.7%. Management of this condition is one of the most challenging clinical situations in obstetrics. We report the case of a pregnant woman presenting at 16 weeks gestation with ruptured membranes. The course of pregnancy was further complicated by complete placenta previa. Expectant management was undertaken, with term delivery and successful outcome of pregnancy. Expectant management is a reasonable approach in properly selected patients. Better understanding of the mechanisms of spontaneous membrane resealing is needed in order to improve poor outcomes. More published data and evidence are necessary to standardize treatment options for this rare condition.

Role of ganglioside biosynthesis genetic polymorphism in cervical cancer development.

Cervical cancer is the most common gynaecological cancer in women. Cell mediated immunity plays a significant role in the progression or regression of neoplastic cervical lesions caused by human papilloma virus infection. Engagement of antigen-specific T cell receptors is a prerequisite for T cell activation. The initial events of T cell activation involve the movement of the T cell receptor into specialised microdomains known as lipid rafts. Gangliosides play an active role in the formation, stabilisation and biological functions of lipid rafts. This study aims to determine whether polymorphisms in the genes involved in the biosynthesis of gangliosides represent risk a factor for cervical cancer.Taqman methods for single nucleotide polymorphism genotyping was used. All subjects carried the homozygous wild-type genotypes for all analysed genes (CC for gene B4GALT5, AA for gene ST3GAL5, AA for gene ST8SIA1 and CC for gene B4GALNT1). A χ2 test showed significant differences in genotype failure for B4GALT5 rs138960078 (χ2 = 32.02, df = 1, p = .001) and genotype failure for B4GALNT1 rs144643461 (χ2 = 41.03, df = 1, p = .001) between cervical cancer group and control group. Genotype failures were significantly more frequent in the cervical cancer group. Unknown adjacent SNPs to rs138960078 in gene B4GALT5 and rs144643461 in gene B4GALNT1 could be associated with cervical cancer development.IMPACT STATEMENTWhat is already known on this subject? Individual genetic factors play an important role in the pathogenesis of disease. In recent years, the different SNPs and their potential effects on CC risk have been extensively studied. A large number of single nucleotide genetic variants associated with cervical cancer have been identified.What do the results of this study add? Our results suggest the presence of unknown adjacent SNPs to rs138960078 in gene B4GALT5 and rs144643461 in gene B4GALNT1 that could be associated with cervical cancer development.What are the implications of these findings for clinical practice and/or further research? Better understanding of causal-consequence relationship between ganglioside biosynthesis and TCR mediated activation with consequently cervical cancer development is needed. Our research opens a new possibilities for identification of polymorphisms in the genes involved in the biosynthesis of gangliosides which can be a risk factor for cervical cancer development.

Proofs for implementation of higher HE4 and ROMA index cut-off values in ovarian cancer preoperative stratification.

This study aimed to identify and quantify the clinical significance of the HE4 and ROMA index in patients with an adnexal tumour. We recruited 159 women and the HE4 and CA125 were measured with an electrochemiluminescence immunoassay in the sera. We used the Kolmogorov-Smirnov test, Mann-Whitney's test and logistic regression to interpret the data. In the premenopausal group (n = 57), the ROC analysis (with cut-off: 86.1 pmol/L for HE4; 40.7 U/L for CA125 and 21.9% for ROMA) demonstrated the superior prognostic potential of those markers when the higher cut-offs used are compared to producers. The AUC for HE4/CA125/ROMA were 0.846/0.867/0.846, respectively. The HE4/ROMA showed 85.7% sensitivity and 94% specificity. In the postmenopausal group (n = 102), the ROC analysis cut-off values were: 99.8 pmol/L for HE4; 45.8 U/L for CA125 and 38.4% for ROMA. AUC for HE4/CA125/ROMA were 0.928/0.899/0.927, respectively. HE4 had an 86.1% sensitivity at 92.4% specificity, while ROMA showed an 88.9% sensitivity at a 90.9% specificity. Impact Statement What is already known on this subject? The incidence of ovarian cancer has been increasing, despite the improvement of diagnostic, operative and therapeutic procedures. As a part of the multiparametric approach, the HE4 and ROMA index improve the diagnostic sensitivity and specificity of CA125 in the detection of ovarian cancer. What the results of this study add? The evaluation of HE4 and ROMA efficacy in the preoperative stratification was made by logistic regression analysis. The better prognostic potential of ROMA index, in patients with present adnexal mass, was obtained using our higher cut-offs for the ROMA index (21.9% for premenopausal and 38.4% for postmenopausal) in comparison to the producer's (11.7% for premenopausal and 29.9% for postmenopausal). The HE4 and ROMA index had 14.29 +LR, 0.15 -LR, 67% PPV and 97.9% NPV in the premenopausal patients. In the postmenopausal group, the HE4 had 11.37 +LR, 0.15 -LR, 75.6% PPV and 92.4% NPV, the ROMA showed 9.78 +LR, 0.12 -LR, 91.2% PPV and 95.2% NPV. What the implications are of these findings for clinical practice and/or further research? Application of a higher cut-off for HE4/CA125/ROMA index can significantly reduce the percentage of FP and FN in the preoperative stratification of ovarian cancer and justify speculations about this subject in the future.

Apoptosis regulator Bcl-2 is an independent prognostic marker for worse overall survival in triple-negative breast cancer patients.

BACKGROUND: The objective of this study was to examine the prognostic significance of carbonic anhydrase IX (CAIX), an endogenous marker for tumor hypoxia; the cellular tumor antigen p53; and the apoptosis regulator Bcl-2, in triple-negative breast cancer (TNBC) patients. METHODS: Immunohistochemically determined expression of CAIX, p53, Bcl-2 and proliferation factor Ki-67, analyzed in 64 paraffin-embedded TNBC tissue samples, was used to assess their relation to clinicopathological variables and prognostic implications for overall survival (OS). RESULTS: Bcl-2 expression was negatively correlated with histological grade of tumor, while expression of p53 was positively correlated with the same clinical variable (p = 0.036 and p = 0.033, respectively). The p53 expression was also positively correlated with tumor size (p = 0.010). Survival analysis showed that patients with high Bcl-2 expression (above cutoff value determined by receiver operator characteristic [ROC] curve analysis) had shorter OS (p = 0.020). The same was observed for patients with tumors larger than 5 cm (p = 0.034) or positive lymph nodes (p = 0.004). Among all 3 examined markers, multivariate analysis showed that only Bcl-2 expression was a strong independent prognostic indicator for decreased OS (hazard ratio [HR] = 15.16, 95% confidence interval [95% CI], 2.881-79.727, p = 0.001). CONCLUSIONS: Elevated expression of Bcl-2 was an independent prognostic factor for poorer OS in TNBC and as such a significant marker for tumor aggressiveness.

MESONEPHRIC ADENOCARCINOMA OF ENDOCERVIX WITH LOBULAR MESONEPHRIC HYPERPLASIA: CASE REPORT.

Mesonephric adenocarcinoma is a rare variant of cervical adenocarcinoma. We present a case of mesonephric adenocarcinoma of endocervix with cervical and vaginal lobular mesonephric hyperplasia in a 57-year-old woman. Vaginal bleeding persisting for 12 months was the only symptom. Histopathologic findings and characteristic immunophenotype are crucial for the diagnosis. The tumor was composed of papillary formation with a central fi brovascular stroma, villoglandular and densely compact tubular structures containing intraluminal eosinophilic secretion, and coated with one or more rows of cylindrical atypical epithelial cells. There were 30 pathologic mitotic shapes found per 10 HPF. The tumor invaded nearly full-thickness of cervical stroma with positive lymphovascular space invasion and clear margins. The case demonstrated characteristic cytokeratin 7, vimentin and epithelial membrane antigen positivity and high Ki-67 proliferation index (60%). Estrogen receptors, progesterone receptors and carcinoembryonic antigen were negative. Intratubular lumen secretion was periodic acid-Schiff positive with periodic acid-Schiff negative carcinoma cells. Diff erential diagnoses include adenoma malignum, well-diff erentiated villoglandular adenocarcinoma, endometrioid adenocarcinoma, serous adenocarcinoma, mesonephric adenocarcinoma with a sarcomatous component, clear-cell carcinoma and mesonephric hyperplasia. Radical hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy was performed. Three years after the surgery, the patient remains well. There has not been any evidence of local or distant recurrence. There are no specific recommendations for the treatment of this rare disease. It remains uncertain whether surgical approach is sufficient or the treatment should include additional radio/chemotherapy.

Pneumothorax and Pneumomediastinum as a Rare Complication of Laparoscopic Surgery

Occurrence of bilateral pneumothorax, pneumomediastinum and subcutaneous emphysema during gynecologic laparoscopic procedure is very rare. We report a case of a 23-year-old woman who developed bilateral pneumothorax, pneumomediastinum and subcutaneous emphysema during laparoscopic ovarian cystectomy. Carbon dioxide extravasations outside the peritoneal cavity during laparoscopy may have fatal consequences. Careful monitoring, immediate diagnosis and proper treatment are crucial for patient safety.

THE RISK OF HYPERCOAGULABILITY IN OVARIAN HYPERSTIMULATION SYNDROME.

Ovarian hyperstimulation syndrome (OHSS) is a rare and potentially life-threatening complication of infertility treatment occurring during either the luteal phase or early pregnancy. An increasing number of thromboembolic complications associated with the increased use of assisted reproductive techniques have been reported in the literature. Identification of the risk factors is crucial for prevention of thromboembolic events in OHSS patients. Alterations in the hemostatic system cause hypercoagulability in women affected by severe OHSS. Coexistence of inherited hypercoagulable conditions increases the risk of thromboembolism. The role of clinical parameters that can help predict development of thrombosis is controversial. Patients with a personal or family history of thrombosis undergoing infertility treatment should be considered for thrombophilia screening, while routine examination of inherited thrombophilic mutations is not indicated in infertile patients. Antithrombotic primary prevention is not indicated in healthy women undergoing assisted reproductive procedures or in women with thrombophilia. Anticoagulant therapy is indicted if there is clinical evidence of thrombosis or laboratory evidence of hypercoagulability. In this review, the risks of hypercoagulability in the OHSS are discussed.

A correlation between the expression of estrogen receptors and progesterone receptors in cancer cells and in the myometrium and prognostic factors in endometrial cancer.

Endometrial cancer is the most common gynecological malignancy in Croatia. The aim of this study was to determine the immunohistochemical expression of estrogen receptors (ER) and progesterone receptors (PGR) in cancer cells and in the myometrium and to correlate it with prognostic factors of endometrial carcinoma. ER positivity in carcinoma cell nuclei was found in 42 cases (73.7%) and PGR positivity was found in 39 cases (68.4%). Loss of ER in carcinoma cell nuclei correlated with larger tumor size (p = 0.041), poor carcinoma differentiation (p = 0.012), a more aggressive histological type (p < 0.001), lymphovascular space invasion (p = 0.002) and a higher surgical stage (p = 0.037). Loss of PGR in carcinoma cell nuclei correlated with an increased age in patients (p = 0.009), poor tumor differentiation (p = 0.002), a more aggressive histological type (p < 0.001), lymphovascular space invasion (p = 0.002) and a higher surgical stage (p < 0.001). The lower expression of both receptors did not correlate with the depth of myometrial invasion. Regarding the status of receptors in the myometrium, loss of PGR in the myometrium correlated with a more aggressive histological type (p = 0.005) and a lack of ER in the myometrium tended to correlate with tumor growth (p = 0.059). In conclusion, the loss of both hormone receptors in carcinoma cells and loss of PGR in the myometrium was a predictor of a more aggressive type of endometrial cancer and a poor prognosis.

The level of serum pro-matrix metalloproteinase-2 as a prognostic factor in patients with invasive ductal breast cancer.

This paper analyses data of 150 female patients undergoing surgical treatment for invasive ductal breast cancer at the University Hospital for Tumors from January 2006 to January 2007. The control group consisted of 50 healthy women. The patients were classified into three groups, depending on their tumor differentiation, i.e. grade I, II and III tumor groups. Each group consisted of 50 patients. Traditional prognostic factors including: age, tumor size and differentiation grade, axillary lymph node status, presence of distant metastases, steroid receptor findings, vascular invasion of the primary tumor, presence of an extensive intraductal component (EIC) in the primary tumor, HER-2 protein expression were evaluated. Both the patients' and controls' serum levels of proMMP-2 (pro-matrix metalloproteinase-2) were assessed using the ELISA method. The aim of the study was to assess pathohistological prognostic factors and the level of serum proMMP-2 in the three patient groups and the controls, compare the relationship between the prognostic factors and the level of serum proMMP-2 in the patient groups, and upon the results, determine possible features of proMMP-2 as a prognostic factor in breast cancer patients. The study results showed no difference in proMMP-2 concentrations between the three patient groups and the controls. No statistically significant difference in the serum proMMP-2 concentration was found between the patient groups, although the grade III group values were the highest showing a trend toward statistical significance. Comparison of proMMP-2 and prognostic factors revealed a statistically significant correlation between proMMP-2 and age in patients with histologic grade I tumors. There was no statistically significant correlation between circulating proMMP-2 and other pathohistological prognostic factors.

Primary extragastrointestinal stromal tumor of the sigmoid mesocolon with metastatic spread to greater omentum: case report.

A 71-year-old female complained of abdominal pain, weight loss and abdominal distension. Gynecologic examination revealed a hardly movable, palpable mass in the lower abdomen, reaching the umbilicus. An abdominal ultrasound and computed tomography (CT) scan suggested a large abdominal mass with the possible origin in the left ovary and without significant lymph node enlargements. The patient subsequently underwent complete evacuation of tumor tissue, omentectomy and total abdominal hysterectomy and bilateral salpingo-ovariectomy. Immunohistochemical examination revealed strongly positive staining of tumor cells for CD117. The final pathologic diagnosis was a primary extragastrointestinal stromal tumor (EGIST) of the sigmoid mesocolon with omental metastasis. The differential diagnosis of the tumor presented in the lower abdomen should consider the EGIST as well.

Prognostic value of lymphovascular space invasion in endometrial cancer.

AIM: To evaluate the prognostic significance of lymphovascular space invasion (LVSI) in endometrial cancer (EC) patients. METHODS: A total of 73 patients who underwent surgery for endometrial cancer at the University Hospital for Tumors, Zagreb, Croatia and University Hospital Centre Split, Croatia, in the period from 1999 to 2008 were evaluated. RESULTS: Lymphovascular space invasion was identified in 58 cases (79.5%). Univariate analysis and multivariate analysis demonstrated a significant association between LVSI and EC recurrence (p=0.004; HR 0.241, CI 0.114-0.511). The median time from diagnosis to EC recurrence of patients with positive LVSI was 20 months, and the median time from diagnosis to EC recurrence of patients with negative LVSI was 86 months (relative risk of recurrence 0.24). CONCLUSION: Lymphovascular space invasion identified on routine haematoxylin and eosin stained sections, is a significant independent predictor of endometrial cancer recurrence.

An incidental finding of unicornuate uterus with unilateral ovarian agenesis during laparoscopy in patient who gave birth to eleven children: a case report.

Congenital uterine anomalies are often asymptomatic. They may present with infertility, recurrent miscarriage, preterm delivery, abnormal lie in pregnancy and other obstetric complications. We report the case of a 38-year old patient with unicornuate uterus without rudimentary horn and with unilateral left ovarian agenesis and unilateral left renal agenesis who gave birth to eleven children. Anomaly was incidentally diagnosed during laparoscopic sterilization.

Prognostic significance of matrix metalloproteinases 2 and 9 in endometrial cancer.

We investigated the prognostic significance of matrix metalloproteinases 2 (MMP 2) and 9 (MMP 9) in endometrial cancer (EC). The expression of MMP 2 and MMP 9 was analyzed immunohistochemically in 73 primary EC patients. In most cases, the gelatinases were predominantly localized to epithelial cell of tumor origin. In univariate analysis histological type, tumor grade, FIGO (1988) surgical stage and high stromal MMP 2 expression were identified as a significant determinant for EC recurrence, while epithelial MMP 2 expression and epithelial and stromal MMP 9 expression were not. Multivariate analysis revealed a subgroup of patient age > or = 63.6 years with endometrioid adenocarcinoma and papillary serous carcinoma, all FIGO (2009) stage I disease where strong staining of stromal MMP 2 increase risk of EC recurrence (p = 0.037).

Aggressive intestinal schwannoma malignum mimicking gynecological pathology - A case report.

Primary malignant schwannoma of the small and large intestine is an extremely rare disease. Therefore, we are going to report an aggressive multifocal malignant intestinal schwannoma in a 66-year old female patient, that was primarily diagnosed as the gynecological tumor that, even after the surgical treatment, had a very quickly recurrence. Small intestine tumors may show images similar to an adnexal tumor, so it is difficult to differentiate one from another prior to the surgery. The patient did not suffer from neurofibromatosis type 1 (NF-1), disease that increases occurrence of malignant schwannoma in comparison with general population. These tumors are often diagnosed late, and radical surgical intervention does not guarantee longer survival. After surgical removal of macroscopically visible tumor masses from this patient, tumor formation within one month after the operation had reached the sizes of 83x66 mm and 85x75 mm respectively, with the occurrence of metastases in the liver, and thereafter the patient died. In differential diagnosis of adnexal tumor small intestine tumor has to be considered, especially if nonspecific symptoms are present.