New approaches in ovarian cancer based on genetics and carcinogenesis hypotheses (Review).

Ovarian cancer is the leading cause of death among gynecological malignancies and its incidence is rising in the last decades especially in developed countries. High-grade serous ovarian cancer (HGSOC) represents 70% of ovarian cancers. Oral contraceptive use and salpingo-oophorectomy or salpingectomy are well known protective factors against development of ovarian cancer. Identification of specific mutations associated with a high risk of developing ovarian cancer, especially BRCA1/2 mutation and TP53 mutations, has paved the way for implementation of new strategies for early diagnosis and therapy. Hereditary forms of ovarian cancer account for 5-10% and have BRCA1/2 gene mutations or TP53 mutations. BRCA1/2 gene mutations appear in 22% of HGSOC and are associated with the defective homologous repair (HR)/DNA repair pathway. Genetic testing in ovarian cancer is important for risk assessment and therapeutic options. Although 'universal genetic testing' is not recommended yet, the procedure remains highly recommended in women with high risk. Genes involved in the development of ovarian cancer as TP53 may be targeted by gene therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors may enhance the cytotoxic effect of DNA-damaging chemotherapy, and induce synthetic lethality in cases with BRCA1/2 mutations. Other strategies are designed to target pathways driven by various gene mutations, including the use of tyrosine kinase inhibitors in low-grade serous ovarian cancer (LGSOC), or the use of drugs, which target growth factors, or epigenetic events including methylation, and acetylation of genes. The tubal involvement in ovarian carcinogenesis provides an important tool for the clinician to implement risk-reducing strategies including salpingo-oophorectomy or salpingectomy in high-risk cases at appropriate ages.

Follicle-stimulating hormone receptor gene polymorphisms of ovarian reserve markers in Romanian population.

Association between phenotype and follicle-stimulating hormone (FSH) receptor and FSH beta chain genotype was evaluated in women with ovarian dysfunction. FSH receptor gene single nucleotide polymorphisms (SNPs) were analyzed by restricted fragment length polymorphism (RFLP) technique. Three groups were analyzed: two groups formed of poor responders (women with ovarian dysfunctions caused by endometriosis and patients who underwent ovarian stimulation protocols) and a third good responders group (normal-ovulatory women who gave birth to naturally conceived children). A higher average level of basal FSH values were found in mutants in the A919G/Ala307Thr/rs6165 or A2039G/Asn680Ser/rs6166 tests (7.16±1.09; P=0.659). Anti-mullerian hormone (AMH) below 1.2 ng/ml was associated with a higher frequency of mutations: 33.3% A919G/Ala307Thr and A2039G/Asn680Ser (P=0.137) and also in 66.6% FSH receptor less frequent polymorphism (c.-29G>A) rs 1394205 (P=0.522). The age, day 3 FSH, and AMH levels are widely used to investigate female infertility. However, we have not yet found the ideal biomarker to determine the best outcome and treatment plan for our patients. We cconsider that genetic markers will become the future in the personalization of controlled ovarian stimulation treatment in the upcoming period.

Rare retroperitoneal conditions that mimic uterine myoma.

The most frequent tumoral condition of the uterus is represented by uterine myoma. The diagnosis, in most cases, is established by clinical examination and ultrasound scan. Nevertheless, there are rare cases, in which the surgical findings reveal a retroperitoneal tumor instead of a uterine myoma. These could be represented by schwannomas or Castleman disease. The schwannomas are rarely malignant and arise from the Schwann cells of nerve fibers. These tumors are frequently found at the level of the head, neck and mediastinum and rarely in the pelvis. Generally, schwannomas localized at retroperitoneal level are asymptomatic and with a very slow growth rate. The treatment consists in complete surgical resection. The recurrence rate is low and, generally, the prognosis is good. The Castleman disease is considered a rare entity, but it should be always taken into consideration when it comes to a differential diagnosis in a young patient who presents a retroperitoneal mass at imagery exams. The condition affects the lymphatic system and is characterized by a hyperplasia of the lymph nodes, sometimes associated with herpes virus infection. The clinical picture is often non-specific; the pain may be the only symptom. The imaging methods are not always conclusive for the final positive diagnosis and the histopathological examination is always necessary. Pelvic Castleman disease can be misdiagnosed as myoma or an adnexal tumor. In this article, we review the present knowledge regarding the pathogenesis, pathology and management of these rare retroperitoneal tumors. Both conditions, when located in pelvis must be taken into consideration in the differential diagnosis of uterine myomas, especially in the pedunculated form.

Abdominal wall endometriosis versus desmoid tumor - a challenging differential diagnosis.

AIM: Abdominal wall endometriosis (AWE) in young women, with previous gynecological abdominal surgery, is the first condition considered by many practitioners when a tumor in the region of the scar appears. AWE seems to be caused by an iatrogenic transfer of endometrial cells at the level of the scar. The onset of the disease may be late in many cases. Despite the fact that the disease could be totally asymptomatic, there are certain risk factors that can be identified during the anamnesis, such as: heredity, menarche at the age of >14 years, menstrual cycle <27 days, delayed menopause, excessive alcohol and caffeine consumption. Suggestive signs include cyclic or continuous abdominal pain caused by a palpable abdominal wall mass with a maximum tenderness in the region of the surgical scar. The differential diagnosis is complex and rare entities like desmoid tumors (DTs) must be taken into consideration. Desmoid tumor, or the so-called aggressive fibromatosis (AF), is a rare fibroblastic proliferation. This tumor can develop in any muscular aponeurotic structure of the body and is considered benign but with a high recurrence rate. DTs can cause local infiltration, subsequently producing certain levels of deformity and potential obstruction of vital structures and organs. The differential diagnosis is challenging in this situations, the imagery exams are useful, especially in detecting the precise location of the tumor. The histological examination of the tumor can state the final and precise diagnosis.

Morphological and histopathological changes in placentas of pregnancies with intrauterine growth restriction.

AIM: The definition of fetal growth restriction (FGR) refers to the incapability of a fetus to achieve the appropriate estimated growth, with expected fetal weight below the 10th percentile calculated for its gestational age. Placental factors and hypoxemia are considered to be essential elements with influence on intrauterine growth restriction (IUGR) and fetal death. The purpose of the present study was to investigate the macroscopic and microscopic pathological findings regarding the placentas in pregnancies complicated by influence on IUGR. PATIENTS, MATERIALS AND METHODS: Our study included 42 third-trimester pregnant patients admitted to the Cuza Voda Hospital of Obstetrics and Gynecology, Iasi, Romania, in the last three years. Soon after delivery, the 42 placentas were collected and analyzed; 32 placentas came from cases previously diagnosed with influence on IUGR and were included in our study group. Ten other placentas included in the control group were selected from uncomplicated pregnancies. Standard Hematoxylin-Eosin (HE) staining method, as well as Periodic Acid-Schiff (PAS) staining, and immunohistochemical techniques for cluster of differentiation 31 (CD31) and collagen IV were used in order to highlight the morphological features of the studied placentas. RESULTS: Our study revealed that reduced placental dimensions and eccentric umbilical cord insertion are correlated with the birthweight of the fetuses with IUGR (p<0.05). The most common histological finding in our study group was placental infarction later correlated with IUGR, but a certain causality could not be demonstrated, as this finding was also present in normal pregnancies. Other histopathological findings were also present in the influence on IUGR group, such as fibrin deposits, diffuse calcification, chronic villitis, avascular chronical villi, with no significant statistical correlations. CD31 was strongly immunoexpressed in the villous endothelial cells. Collagen IV presented a strong immunoreaction in the basement membrane and mesenchyme of the placental villi. CONCLUSIONS: Our study revealed a correlation between the dimensions of the diameters and volume of the maternal placenta and the presence of influence on IUGR. Moreover, it confirms the available data suggesting that the place of insertion of the umbilical cord is correlated with the weight of the fetus. Further studies with extended panel antibodies are needed in order to determine and complete the role of these morphological changes in the development of influence on IUGR.