Struma Ovarii during Pregnancy.

Struma ovarii is a rare type of ovarian teratoma primarily composed of over 50% thyroid tissue. Its occurrence is reported in 2-5% of all ovarian teratomas, with approximately 0.5% to 10% showing malignant transformation. Managing it during pregnancy poses significant challenges as pregnancy can promote the growth of malignant struma ovarii due to elevated levels of ovarian and pregnancy-related hormones, including estrogen, progesterone, and human chorionic gonadotrophin (hCG). Most ovarian tumors, including struma ovarii, are detected during routine ultrasonography in the first and second trimesters, often as acute emergencies. Diagnosis during pregnancy is rare, with some cases incidentally discovered during cesarean section when inspecting the adnexa for ovarian cysts. This review explores the diagnostic, management, and therapeutic approaches to struma ovarii during pregnancy.

A Prospective Study on the Progression, Recurrence, and Regression of Cervical Lesions: Assessing Various Screening Approaches.

(1) Background: The prediction of cervical lesion evolution is a challenge for clinicians. This prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors in the prediction of progression, regression, or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions who underwent follow-up in a private clinic. We calculated the predictive performance of individual tests (cervical cytology, HPV genotyping, CINtecPlus results, and clinical risk factors) or their combination in the prediction of cervical lesion progression, regression, and persistence; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model comprising a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least three clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesion regression or persistence was modest when using individual or combined tests; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

Prolapsed Atypical Polypoid Adenomyoma-A Case Report and Literature Review.

Atypical polypoid adenomyoma (APAM) is a rare polypoid benign tumor of the uterus that causes irregular vaginal bleeding in women of reproductive age. It has the potential for malignant transformation, but it does not metastasize. APAM may coexist with endometrial hyperplasia and adenocarcinoma, usually leading to misdiagnosis. Histopathologically, it is a biphasic tumor, represented by the endometrioid glands with a complex histoarchitecture, with sometimes squamous morular metaplasia or cytologic atypia, interspersed with a fibromyomatous stroma. This tumor has a high incidence of recurrence. We present a very rare case of a 21-year-old patient, a virgin, without a significant medical history, with a bleeding mass occupying the vagina. The mass was excised using forceps, scissors, and a suture of the visible pedicle. After a four-year follow-up and no additional medical treatment, no relapse was observed. Given the risk of recurrence and progression, APAM might be treated via a hysterectomy in patients with no desire for pregnancy. Due to a lower recurrence rate, the conservative treatment of atypical polypoid adenomyoma performed via an operative hysteroscopy represents the best choice. Previously diagnosed in hysterectomy specimens, with the introduction of better-performing indirect imaging techniques, adenomyosis is a clinical entity that has the possibility of being diagnosed in the presurgical stage.

The significance of immune microenvironment in patients with endometriosis.

Endometriosis represents an estrogen-dependent disease of the female reproductive system and intra- and extraperitoneal regions, with chronic feature. Currently, immune cells, such as macrophages and lymphocytes, are considered to play a pivotal role in angiogenesis and invasion of endometriotic cells through matrix remodeling. Additionally, various studies have revealed the role of E-cadherin, ß-catenin, along with steroid hormone receptors in endometriosis development. In this context, our study aimed to analyze the relationship between the cellular immune profile and E-cadherin, ß-catenin, estrogen receptor alpha (ERα), and progesterone receptor (PR) immunoexpression in endometriosis tissues, along with an analysis of the possible association between serological parameters and immunohistochemical (IHC) markers. The study included 53 patients diagnosed with ovarian or cutaneous abdominal wall endometriosis, which have been investigated by routine histology, immunohistochemistry, and serum analysis. The IHC exam showed an increased density of cluster of differentiation (CD)4+ T-cells, CD8+ T-cells, and CD68+ macrophages, along with variable increased expressions of E-cadherin, ß-catenin, ERα, and PR. Statistical analysis revealed an intense positive correlation between CD68 and PR expression (p<0.05), without any other statistically significant correlations between IHC markers or between IHC and serological markers. Our study supports that endometriosis is an immune-dependent disease characterized by an abnormal morphological profile of T-cells and macrophages in endometriotic implants. Our study provides additional data useful in the understanding the immune milieu of endometriosis in the context of its complex pathogenic molecular mechanism. Further research is needed to develop new immunological therapeutic approaches, like immune checkpoint inhibitors administration or T-cell-targeted immunotherapy in these patients.

Retained Placenta Percreta with Acquired Uterine Arteriovenous Malformation-Case Report and Short Review of the Literature.

Placenta accreta spectrum disorder (PAS) has an increased frequency due to the high number of cesarean sections. The abnormal placentation associated with a retained placenta can cause persistent uterine bleeding, with ultrasound Doppler examination being the main choice to assess the uterine hemorrhage. An acquired uterine arteriovenous malformation (AVM) may occur because of uterine trauma, spontaneous abortion, dilation and curettage, endometrial carcinoma or gestational trophoblastic disease. The treatment for abnormal placentation associated with AVM can be conservative, represented by methotrexate therapy, arterial embolization, uterine curettage, hysteroscopic loop resection or radical, which takes into consideration total hysterectomy. Therapeutic management always considers the degree of placental invasion, the patient hemodynamic state and fertility preservation. Considering the aspects described, we present a case of retained placenta percreta associated with acquired uterine AVM, with imagistic and clinical features suggestive of a gestational trophoblastic disease, successfully treated by hysterectomy, along with a small review of the literature, as only a few publications have reported a similar association of diagnostics and therapy.

The Interplay between Tumour Microenvironment Components in Malignant Melanoma.

Malignant melanoma has shown an increasing incidence during the last two decades, exhibiting a large spectrum of locations and clinicopathological characteristics. Although current histopathological, biochemical, immunohistochemical, and molecular methods provide a deep insight into its biological behaviour and outcome, melanoma is still an unpredictable disease, with poor outcome. This review of the literature is aimed at updating the knowledge regarding melanoma's clinicopathological and molecular hallmarks, including its heterogeneity and plasticity, involving cancer stem cells population. A special focus is given on the interplay between different cellular components and their secretion products in melanoma, considering its contribution to tumour progression, invasion, metastasis, recurrences, and resistance to classical therapy. Furthermore, the influences of the specific tumour microenvironment or "inflammasome", its association with adipose tissue products, including the release of "extracellular vesicles", and distinct microbiota are currently studied, considering their influences on diagnosis and prognosis. An insight into melanoma's particular features may reveal new molecular pathways which may be exploited in order to develop innovative therapeutic approaches or tailored therapy.

Spongiotic reaction patterns in autoimmune bullous dermatoses (Review).

Spongiosis or a spongiotic reaction pattern is the histological hallmark of intercellular epidermal edema, viewed as clear spaces within the epidermis. Although considered a histopathological term, spongiosis has clinical correlations, with the variable degrees of spongiotic reaction leading to different dermatological findings. This review aimed to highlight the spongiotic reactive patterns found in different autoimmune bullous dermatoses, considering the paucity of publications in this domain. The pathogenesis of spongiosis assumes the passage of extravasated edema fluid from the dermis into the epidermis, frequently accompanied by dermal inflammatory cells, and classification of the spongiotic reaction patterns, as well as their associated spongiotic dermatitis, take into consideration the type and distribution of these inflammatory cells. It is mandatory to consider different reactive processes, specific for other skin disorders, which act as simulants of different spongiotic patterns for the diagnosis. Considering the possible transient occurrence, the heterogeneity and non-specificity of the histopathological features of these diseases, the diagnosis is very complex, requiring clinicopathological correlations and additional analyses. A deep insight into spongiosis pathogeny may open the perspectives of a classification refinement of autoimmune bullous dermatoses.

BMI-1 Expression Heterogeneity in Endometriosis-Related and Non-Endometriotic Ovarian Carcinoma.

BMI-1 is a key component of stem cells, which are essential for normal organ development and cell phenotype maintenance. BMI-1 expression is deregulated in cancer, resulting in the alteration of chromatin and gene transcription repression. The cellular signaling pathway that governs BMI-1 action in the ovarian carcinogenesis sequences is incompletely deciphered. In this study, we set out to analyze the immunohistochemical (IHC) BMI-1 expression in two different groups: endometriosis-related ovarian carcinoma (EOC) and non-endometriotic ovarian carcinoma (NEOC), aiming to identify the differences in its tissue profile. METHODS: BMI-1 IHC expression has been individually quantified in epithelial and in stromal components by using adapted scores systems. Statistical analysis was performed to analyze the relationship between BMI-1 epithelial and stromal profile in each group and between groups and its correlation with classical clinicopathological characteristics. RESULTS: BMI-1 expression in epithelial tumor cells was mostly low or negative in the EOC group, and predominantly positive in the NEOC group. Moreover, the stromal BMI-1 expression was variable in the EOC group, whereas in the NEOC group, stromal BMI-1 expression was mainly strong. We noted statistically significant differences between the epithelial and stromal BMI-1 profiles in each group and between the two ovarian carcinoma (OC) groups. CONCLUSIONS: Our study provides solid evidence for a different BMI-1 expression in EOC and NEOC, corresponding to the differences in their etiopathogeny. The reported differences in the BMI-1 expression of EOC and NEOC need to be further validated in a larger and homogenous cohort of study.

Perirenal Adipose Tissue-Current Knowledge and Future Opportunities.

The perirenal adipose tissue (PRAT), a component of visceral adipose tissue, has been recently recognized as an important factor that contributes to the maintenance of the cardiovascular system and kidney homeostasis. PRAT is a complex microenvironment consisting of a mixture of white adipocytes and dormant and active brown adipocytes, associated with predipocytes, sympathetic nerve endings, vascular structures, and different types of inflammatory cells. In this review, we summarize the current knowledge about PRAT and discuss its role as a major contributing factor in the pathogenesis of hypertension, obesity, chronic renal diseases, and involvement in tumor progression. The new perspectives of PRAT as an endocrine organ and recent knowledge regarding the possible activation of dormant brown adipocytes are nowadays considered as new areas of research in obesity, in close correlation with renal and cardiovascular pathology. Supplementary PRAT complex intervention in tumor progression may reveal new pathways involved in carcinogenesis and, implicitly, may identify additional targets for tailored cancer therapy.

Thymolipoma - the frontier between hamartoma and neoplasia?

Thymolipoma is an uncommon benign thymus lesion, with a partially deciphered etiopathogeny, being most frequently diagnosed in young patients, regardless of gender. Incidentally diagnosed in asymptomatic patients, larger thymolipomas lead to symptoms related to neighboring mediastinal structures compression, with an intensity which is correlated with the mass size. Our review presents the main epidemiological, pathogenic, clinicopathological and morphological characteristics of this rare pathology. Sometimes, thymolipomas may be associated with paraneoplastic syndromes, which are alleviated by the mass complete surgical resection. Imagistics may orientate the diagnosis, which is certified by the microscopic examination of the resection specimens. Extensive thymectomy remains the current therapeutic option and new tools have been developed to increase the accuracy of the surgical procedure to avoid incidental lesions of the important elements of the anterior mediastinum. Although rare, thymolipomas should be considered in the differential diagnosis of mediastinal masses and of paraneoplastic syndromes.

Insights into molecular pathways of endometriosis and endometriosis-related ovarian carcinoma.

BACKGROUND: Endometriosis is a benign estrogen-dependent gynecological disease involving components of the female genital tract (uterus, Fallopian tubes, ovaries, large, round, and utero-sacral ligaments) and intra- and extraperitoneal regions. Since the moment of its etiopathogeny has been identified, the intrinsic capacity of endometriosis malignant transformation has been hypothesized. PATIENTS, MATERIALS AND METHODS: Our study included a total number of 50 patients diagnosed with endometriosis (31 cases) and endometriosis-related ovarian carcinoma (EOC) (19 cases). A clinicopathological and immunohistochemical study directed towards the detection of atypical transition lesions and the similitudes in epithelial-mesenchymal transition (EMT) phenomenon [E-cadherin∕ß-catenin∕cytokeratin 18 (CK18)], apoptosis [B-cell lymphoma 2 (Bcl-2)∕Bcl-2-associated X (Bax)], and hormonal dynamics mirrored by the immunoexpression of estrogen receptor (ER) and progesterone receptor (PR) in endometriosis and EOC glands and stroma has been performed. RESULTS: Our study showed a higher immunoexpression of CK18 and E-cadherin in endometriosis than in neoplastic counterparts, while ß-catenin had a stronger immunoexpression in tumors compared with endometriotic areas, with statistically significant differences between the studied groups. Bcl-2∕Bax higher rate in endometriosis had a statistically significant association to a more aggressive tumor behavior (p=0.020). ER immunoexpression was stronger in endometriosis, with less negative scores compared to EOC, while PR immunoexpression was stronger in endometriosis, with a lower percent of negative scores compared to EOC. PR immunostaining was correlated to ovarian location of endometriosis (p=0.004) and tumor grade of EOC (p=0.027). Stromal ER and PR immunoexpression has been significantly lower in endometriosis in comparison to tumor stroma (p=0.001) and PR stromal immunoexpression had been higher in more differentiated tumors compared to less differentiated types (p=0.005). CONCLUSIONS: Our study supports that endometriosis is a precursor of EOC by the identification and the coexistence of both lesions in the investigated cases, the identification of intermediate lesions, as well as the expression of EMT immunomarkers, along with apoptosis and steroid receptors immunoexpression.

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.

Perivascular adipose tissue in cardiovascular diseases-an update.

The perivascular adipose tissue (PVAT) has been recently recognized as an important factor in vascular biology, with implications in the pathogenesis of cardiovascular diseases. The cell types and the precursor cells of PVAT appear to be different according to their location, with the component cell type including white, brown, and beige adipocytes. PVAT releases a panel of adipokines and cytokines that maintain vascular homeostasis, but it also has the ability of intervention in the pathogenesis of the atherosclerotic plaques development and in the vascular tone modulation. In this review, we summarize the current knowledge and discuss the role of PVAT as a major contributing factor in the pathogenesis of ischemic coronary disease, hypertension, obesity, and diabetes mellitus. The new perspective of PVAT as an endocrine organ, along with the recent knowledge of the mechanisms involved in dysfunctional PVAT intervention in local vascular homeostasis perturbations, nowadays represent a new area of research in cardiovascular pathology, aiming to discover new therapeutic methods.

Ovarian hydatid cyst - systematic review of clinicopathological and immunohistochemical characteristics of an unusual entity.

Primary ovarian hydatid disease (HD) is a rare entity, produced by the larval stage of Echinococcus granulosus. HD commonly involves liver, lung, abdomen cavity, spleen and is unusually identified in pelvic organs. Based on our knowledge, the paper reviews 27 literature reports of ovarian HD, diagnosed during the last 20 years, providing a valuable database. Patients' ages ranged between 12-76 years, the gross appearance was that of 40-330 mm diameter hydatid cysts (HCs), 66.66% of them being primary. According to these reports, ovarian HD has non-specific clinical manifestations, such as abdominal or pelvic pain, nausea, dysmenorrhea or amenorrhea. The diagnosis may be achieved by abdominal ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI), serological exams, such as eosinophilia (in 10-30% of patients) or indirect hemagglutination and immunoglobulin (IgG) antibodies detection. Ovarian HC microscopic pattern is characterized by three layers: pericyst or adventitia (host origin), germinal layer (endocyst), and laminated membrane (ectocyst). The immunoreaction triggered by parasites is initially rich in macrophages and neutrophils, followed by eosinophils and lymphocytes, with numerous cluster of differentiation 8 (CD8)-positive T-cells in active lesions and progressive forms. Concomitant ovarian diseases are relatively rare, being represented by borderline tumors (n=2 cases), mucinous cystadenoma (n=1 case), hemorrhagic cyst (n=1 case), and serous adenocarcinoma (n=1 case). In conclusion, the ovarian location of HD should be considered in any differential diagnosis of a cystic lesion, while it does not exclude synchronous ovarian tumors. These cases reinforce the necessity of better measures of prophylaxis and screening of HD in endemic areas.

The endometrial regeneration frontiers: from mechanisms to applications in regenerative medicine.

The endometrium is a unique and remarkable tissue characterized by a constant regeneration activity and this has been speculative for scientists, regarding its mechanism, regulatory factors, and their significance for fertility and endometrial pathology. Relatively recent scientific progresses due to genomics, proteomics, and transcriptomics have changed the knowledge in respect with endometrial regeneration and uterine-derived diseases. Our review is designed to highlight the recent progresses in understanding the endometrial physiology and its alterations involvement in uterine-derived diseases, addressing the current paradigm regarding endometrial regeneration, based on endometrial regenerative cells. In an attempt to explain the complex process of endometrial regeneration, different mechanisms have been proposed during time, from proliferation of basal glandular cells, to mesenchymal-epithelial transition, and lately to differentiation of stromal cells, based on endometrial regenerative cells or stem cells. Their unlimited potential of reconstruction of any type of tissue has been demonstrated and is currently in different trial stages in cell-based therapies of regenerative medicine, opening promising perspectives in severe or lethal diseases, by exploitation of stem cells. Currently, beside uterine acquired diseases and infertility, endometrial stem cells have been tested in a large spectrum of clinical applications. The great potential of endometrial cells for cell therapies arise from their accessibility, completely xeno-free derivation, allogenic use, possibility of large-scale therapeutic doses production, safety, reproducibility, and chance to overcome the drawbacks associated with autologous therapies. In order to overcome hostile environment of an injured tissue, the association of endometrial stem cells with other cells or added medium opens the perspective of specific combination available as standardized therapeutic means in the next future.

Adipocytes spectrum - From homeostasia to obesity and its associated pathology.

Firstly identified by anatomists, the fat tissue is nowadays an area of intense research due to increased global prevalence of obesity and its associated diseases. Histologically, there are four types of fat tissue cells which are currently recognized (white, brown, beige, and perivascular adipocytes). Therefore, in this study we are reviewing the most recent data regarding the origin, structure, and molecular mechanisms involved in the development of adipocytes. White adipocytes can store triglycerides as a consequence of lipogenesis, under the regulation of growth hormone or leptin and adiponectin, and release fatty acids resulted from lipolysis, under the regulation of the sympathetic nervous system, glucocorticoids, TNF-α, insulin, and natriuretic peptides. Brown adipocytes possess a mitochondrial transmembrane protein thermogenin or UCP1 which allows heat generation. Recently, thermogenic, UCP positive adipocytes have been identified in the subcutaneous white adipose tissue and have been named beige adipocytes. The nature of these cells is still controversial, as current theories are suggesting their origin either by transdifferentiation of white adipocytes, or by differentiation from an own precursor cell. Perivascular adipocytes surround most of the arteries, exhibiting a supportive role and being involved in the maintenance of intravascular temperature. Thoracic perivascular adipocytes resemble brown adipocytes, while abdominal ones are more similar to white adipocytes and, consequently, are involved in obesity-induced inflammatory reactions. The factors involved in the regulation of adipose stem cells differentiation may represent potential pathways to inhibit or to divert adipogenesis. Several molecules, such as pro-adipogenic factors (FGF21, BMP7, BMP8b, and Cox-2), cell surface proteins or receptors (Asc-1, PAT2, P2RX5), and hypothalamic receptors (MC4R) have been identified as the most promising targets for the development of future therapies. Further investigations are necessary to complete the knowledge about adipose tissue and the development of a new generation of therapeutic tools based on molecular targets.

Clinicopathological significance and prognostic value of myoinvasive patterns in endometrial endometrioid carcinoma.

Endometrioid endometrial carcinoma has an overall good prognosis. However, variable five-year survival rates (92%-42%) have been reported in FIGO stage I, suggesting the involvement of other factors related to tumor biological behavior. These may be related to the role played by epithelial-mesenchymal transition (EMT) and cancer stem cells in endometrial carcinogenesis. In this context, our review highlights the prognostic significance of several types of myoinvasion in low grade, low stage endometrioid endometrial carcinoma, as a reflection of these molecular changes at the invasive front. According to recently introduced myoinvasive patterns, the diffusely infiltrating and microcystic, elongated, and fragmented (MELF) patterns show loss of hormone receptors, along with EMT and high expression of cancer stem cell markers, being associated with a poor prognosis. Additionally, MELF pattern exhibits a high incidence of lymphovascular invasion and lymph node metastases. Conversely, the broad front pattern has a good prognosis and a low expression of EMT and stem cells markers. Similarly, the adenomyosis (AM)-like and adenoma malignum patterns of invasion are associated to a favorable prognosis, but nevertheless, they raise diagnostic challenges. AM-like pattern must be differentiated from carcinoma invasion of AM foci, while adenoma malignum pattern creates difficulties in appreciating the depth of myoinvasion and requires differential diagnosis with other conditions. Another pattern expecting its validation and prognostic significance value is the nodular fasciitis-like stroma and large cystic growth pattern. In practice, the knowledge of these patterns of myoinvasion may be valuable for the correct assessment of stage, may improve prognosis evaluation and may help identify molecules for future targeted therapies.

Immunohistochemical significance of ER alpha, inhibin A, calretinin, and Ki67 expression in granulosa cell ovarian tumors.

Adult granulosa cell tumors (AGCTs) have a heterogeneous morphology and an unpredictable behavior, which can lead to a misinterpreted diagnosis. The aim of our study was to assess the immunoexpression of estrogen receptor (ER) alpha, Ki67, calretinin, and inhibin A in AGCTs, in order to evaluate their value in diagnosis and prognosis of this type of tumor. Immunohistochemical stainings for these markers were performed in 21 cases of AGCTs. The immunopositivity evaluation of calretinin and inhibin A was scored according to the percentage of staining intensity and the extent of positive cells, of ER alpha was scored based on the percentage of positive cells, and Ki67 score was recorded as the percentage of positively stained nuclei across the tumor, without taking in consideration the staining intensity. ER was positive in nine cases, Ki67 was expressed in 12 cases, calretinin showed positive immunoreactivity in 16 cases, and inhibin A was positive in 14 cases. Stromal cells presented also immunopositivity for inhibin A and calretinin in the negative cases. ER alpha and calretinin immunoexpression can help in identification of cell components of AGCT. Our results regarding Ki67 expression emphasize the potential utility of this marker in tumor behavior prediction. Inhibin A immunopositivity has an important value in AGCT diagnosis, in association to the other evaluated markers. Additional studies are needed to identify new specific and sensitive markers for AGCT or, at least, of a panel of markers which might contribute to a more accurate characterization of these tumors.

Intrapartum diagnostic of Roberts syndrome - case presentation.

Roberts syndrome is a rare disease, with multiple limb and skeletal abnormalities (called "pseudothalidomide disease"). There are only around 150 cases described in literature. We present a case of Roberts syndrome, diagnosed in moment of delivery, after a pregnancy without prenatal follow-up. The stillborn baby was naturally delivered by a 17-year-old primiparous woman at 38 weeks of amenorrhea. The pregnancy was not followed due to socioeconomic and family situation, and no prenatal ultrasound was performed. The male baby has 2650 g and presented several morphological abnormalities and tight double umbilical abdominal loop. The macroscopic evaluation showed: dolichocephaly, hypoplastic inferior maxilla with micrognathia, antimongoloid palpebral slant, pterygium colli, abnormal and lower implanted ears, superior limbs phocomelia, syndactyly at lower left limb and tetradactyly in all limbs, bilateral cryptorchidism, pancreatic aplasia. Roberts syndrome is a rare genetic disease with recessive autosomal transmission generated by mutations in ESCO2 gene, located on chromosome 8. The disease should be easy to diagnose by antenatal ultrasound examination, but in our case, the lack of prenatal follow-up determined the diagnostic at term. We believe consider this case is an argument towards introducing ultrasound-screening compulsory to all pregnancies. To identify a possible genetic mutation, further investigations of the parents are in progress, but classically the disease has a recessive autosomal transmission.

Matrix metalloproteinases involvement in pathologic conditions.

Matrix metalloproteinases (MMPs) have a great variability that provides a complex intervention in pathophysiological conditions. MMPs roles in pathology may be grouped into the following main types: (1) tissue destruction, as in cancer invasion and metastasis, rheumatoid arthritis, osteoarthritis, different types of ulcers, periodontal disease, brain injury and neuroinflammatory diseases; (2) fibrosis, as in liver cirrhosis, fibrotic lung disease, otosclerosis, atherosclerosis, and multiple sclerosis; (3) weakening of matrix, as in dilated cardiomyopathy, epidermolysis bullosa, aortic aneurysm and restenotic lesions. Recent data also adds new MMPs functions in angiogenesis and apoptosis. Interesting opposite intervention in escaping mechanisms vs. antitumor defensive mechanisms had been also reported. As MMP-7 is expressed by tumor cells of epithelial and mesenchymal origin, it may be used as a biological marker of an aggressive phenotype and as a target of therapeutic intervention. MMPs play a pivotal role in the pathogenesis of arthritis, atherosclerosis, pulmonary emphysema, and endometriosis. Although MMP involvement in pathology is more than simple excessive matrix degradation, or an imbalance between them and their specific tissular inhibitors (TIMPs), MMP inhibition may be of therapeutic benefit, so synthetic MMPs inhibitors had been developed and are currently under clinical testing.