Combining Molecular and Traditional Prognostic Factors: A Holistic Approach to Breast Cancer Prognostication.

Breast cancer is a heterogeneous disease with various morphologies and molecular features, and it is the second leading cause of cancer death in women in developed countries. According to the literature, we currently lack both prognostic biomarkers and therapeutic targets. The most important prognostic factors are disease stage and Nottingham grade. We conducted a retrospective analysis involving 273 patients with BC who underwent neoadjuvant therapy before proceeding to curative surgical treatment between 1 January 2014 and 31 December 2023. Pathological procedures were conducted at the Department of Pathology, Emergency County Hospital of Targu Mureș, Romania. A statistical analysis was performed. Regarding the relationship between Nottingham grade and Ki67, grade I was associated with a Ki67 of less than 14. The relationship between tumor grade and luminal was similar (p = 0.0001): Grade I was associated with luminal A. Regarding TNM stage, it was statistically significantly correlated with TILs (p = 0.01) and RCB (p = 0.0001). Stages III and IV were associated with a high RCB and poor prognosis. Regarding the prognostic value, Nottingham grade 3 and TNM stages III and IV were correlated with low overall survival and disease-free survival, with poor prognosis, and, among the molecular variables, RCB played the most important prognostic role.

Understanding the Pathophysiology of Preeclampsia: Exploring the Role of Antiphospholipid Antibodies and Future Directions.

Preeclampsia (PE) is a hypertensive disorder in pregnancy associated with significant fetal and maternal complications. Antiphospholipid syndrome (APS) is an acquired form of thrombophilia characterized by recurrent venous or arterial thrombosis and obstetric complications that significantly increases morbidity and mortality rates. While preeclampsia may not be the most prevalent obstetric complication in APS, it significantly impacts the long-term health of both mother and child. The treatment of preeclampsia in antiphospholipid syndrome is different from the treatment of preeclampsia as an independent disease. Despite current treatments involving anticoagulants, antiplatelet agents, and antihypertensive drugs, obstetric complications may persist, underscoring the need for cohesive management and effective treatments. The objective of our review is to briefly present knowledge about the physiopathology of preeclampsia and the role of antiphospholipid antibodies in this process. Based on the existing literature, our review aims to identify future directions in molecular pathology toward the discovery of biomarkers and targeted treatments. The application of multidisciplinary approaches and prognostic models, including new biomarkers, could be beneficial in the prediction of PE.

Shared Pathogenic and Therapeutic Characteristics of Endometriosis, Adenomyosis, and Endometrial Cancer: A Comprehensive Literature Review.

Endometriosis and adenomyosis behave similarly to cancer. No current treatments represent a cure, even if there are several options, including hormonal and surgical therapy. In advanced or recurrent pathologies, however, personalized treatment is necessary. We have found that due to the multiple common features, various therapeutic options have been used or studied for all three pathologies, with varying results. The objective of this review is to extract from the relevant literature the compounds that are used for endometriosis and adenomyosis characterized by malignant behavior, with some of these drugs being studied first in the treatment of endometrial cancer. Special attention is needed in the pathogenesis of these pathologies. Despite the multiple drugs that have been tested, only a few of them have been introduced into clinical practice. An unmet need is the cure of these diseases. Long-time treatment is necessary because symptoms persist, and surgery is often followed by postoperative recurrence. We emphasize the need for new, effective, long-term treatments based on pathogeny while considering their adverse effects.

The Early Hematological Profile and Its Variations: A Useful Tool in the Prediction of Intraventricular Hemorrhage in Extremely Preterm Infants.

Background and Objectives: The purpose of this study to investigate if the early variations in the hematological profile could be a useful tool in the prediction and evaluation of intraventricular hemorrhage. Materials and Methods: It is a retrospective study conducted between 1 January 2017 and 31 December 2022, in a tertiary academic center. In-born infants ≤ 28 weeks of gestation (n = 134) were enrolled. The study group of infants with all grades of IVH was further divided into mild IVH subgroups (grades 1 and 2) and severe IVH subgroups (grades 3 and 4); the control group included infants without IVH. Results: The prevalence of IVH was 35.8% (n = 48 of 134 infants-study group). We identified significantly lower median values of HGB (p = 0.0312) and HCT (p = 0.0172) in all grades of the IVH group at birth as compared with control, followed by a significantly higher drop in MCV (p = 0.0146) and MCH (p = 0.0002) in the fourth day of life. Conclusions: Extremely preterm infants with IVH may have lower HTC and HGB values at birth, together with a decrease in MCH and MCHC and increase in MPV. The predictive model based on logistic regression analysis could predict the probability of the occurrence of IVH according to their values.

Endometriosis and the Role of Pro-Inflammatory and Anti-Inflammatory Cytokines in Pathophysiology: A Narrative Review of the Literature.

Endometriosis is a chronic inflammatory disease, which explains the pain that such patients report. Currently, we are faced with ineffective, non-invasive diagnostic methods and treatments that come with multiple side effects and high recurrence rates for both the disease and pain. These are the reasons why we are exploring the possibility of the involvement of pro-inflammatory and anti-inflammatory molecules in the process of the appearance of endometriosis. Cytokines play an important role in the progression of endometriosis, influencing cell proliferation and differentiation. Pro-inflammatory molecules are found in intrafollicular fluid. They have an impact on the number of mature and optimal-quality oocytes. Endometriosis affects fertility, and the involvement of endometriosis in embryo transfer during in vitro fertilization (IVF) is being investigated in several studies. Furthermore, the reciprocal influence between anti-inflammatory and pro-inflammatory cytokines and their role in the pathogenesis of endometriosis has been assessed. Today, we can affirm that pro-inflammatory and anti-inflammatory cytokines play roles in survival, growth, differentiation, invasion, angiogenesis, and immune escape, which provides a perspective for approaching future clinical implications and can be used as biomarkers or therapy.

Human Placenta and Evolving Insights into Pathological Changes of Preeclampsia: A Comprehensive Review of the Last Decade.

The placenta, the foremost and multifaceted organ in fetal and maternal biology, is pivotal in facilitating optimal intrauterine fetal development. Remarkably, despite its paramount significance, the placenta remains enigmatic, meriting greater comprehension given its central influence on the health trajectories of both the fetus and the mother. Preeclampsia (PE) and intrauterine fetal growth restriction (IUGR), prevailing disorders of pregnancy, stem from compromised placental development. PE, characterized by heightened mortality and morbidity risks, afflicts 5-7% of global pregnancies, its etiology shrouded in ambiguity. Pertinent pathogenic hallmarks of PE encompass inadequate restructuring of uteroplacental spiral arteries, placental ischemia, and elevated levels of vascular endothelial growth factor receptor-1 (VEGFR-1), also recognized as soluble FMS-like tyrosine kinase-1 (sFlt-1). During gestation, the placental derivation of sFlt-1 accentuates its role as an inhibitory receptor binding to VEGF-A and placental growth factor (PlGF), curtailing target cell accessibility. This review expounds upon the placenta's defining cellular component of the trophoblast, elucidates the intricacies of PE pathogenesis, underscores the pivotal contribution of sFlt-1 to maternal pathology and fetal safeguarding, and surveys recent therapeutic strides witnessed in the past decade.

Exploring Patient Adherence to Post-Surgical Follow-Up in Pelvic Endometriosis.

Endometriosis is a significant cause of disability that affects 5-10% of reproductive-aged women. Laparoscopy with histological confirmation is the gold standard in establishing the diagnosis as therapeutic management surgery is addressed to a certain category of patients. The objective of this study was to assess patient adherence to follow-up after surgery for endometriosis as the primary endpoint, pain symptoms, quality of life, mental health, and fertility as the secondary endpoints. We have analyzed patients' adherence to follow-up after surgery for endometriosis after 1, 3, 5, and 7 years. Out of the 2538 total number of surgeries, 453 patients replied just to the first questionnaire (group A), 528 to the first and second (group B), and only 356 carried out the entire follow-up schedule. General health was significantly lower for group A (46.6 vs. 56.4) but with no statistical difference in the post-surgical improvement in both groups. Pain level score improvement was lower for group A (10.5 vs. 18.8), which is statistically significant. In this light, laparoscopy still remains the gold standard in diagnosis only. Furthermore, no malignancy was discovered. The mental component was improved by laparoscopy based on SF-36 in group B. Studies on patient preference for surgery versus alternative treatment are needed.

New Insights into Genetics of Endometriosis-A Comprehensive Literature Review.

This comprehensive review explores the genetic contributions to endometriosis and their potential impact on improving diagnostic techniques. The review begins by defining endometriosis and discussing its prevalence, emphasizing the need for a deeper understanding of the genetic basis of the condition. It highlights recent genome-wide association studies (GWAS) that have identified specific genetic variants associated with endometriosis, shedding light on the molecular pathways and mechanisms involved. The review addresses genetic heterogeneity across different populations and ethnicities, emphasizing the importance of considering population-specific markers in diagnostic approaches. It explores the diagnostic implications of genetic insights, including the potential use of genetic markers for precise and early detection, as well as risk prediction. The review also delves into the integration of genetic information with clinical parameters and imaging findings, and the exploration of multi-omics approaches for a comprehensive understanding of endometriosis. It discusses recent studies on genetic and epigenetic biomarkers, their potential as diagnostic tools, and the need for validation in independent cohorts. The review highlights the impact of new genomic technologies, such as next-generation sequencing, in improving diagnostic accuracy and personalized management. It identifies the challenges and future directions in translating genetic findings into diagnostic tools and emphasizes the transformative potential of genetic insights in endometriosis diagnosis. This review provides a roadmap for future research and underscores the significance of genetic insights in improving diagnostic precision and personalized care for individuals with endometriosis.

Adenomyosis and Its Possible Malignancy: A Review of the Literature.

Cancer arising from adenomyosis is very rare, with transformation occurring in only 1% of cases and in older individuals. Adenomyosis, endometriosis and cancers may share a common pathogenic mechanism that includes hormonal factors, genetic predisposition, growth factors, inflammation, immune system dysregulation, environmental factors and oxidative stress. Endometriosis and adenomyosis both exhibit malignant behaviour. The most common risk factor for malignant transformation is prolonged exposure to oestrogens. The golden standard for diagnosis is histopathology. Colman and Rosenthal emphasised the most important characteristics in adenomyosis-associated cancer. Kumar and Anderson emphasised the importance of demonstrating a transition between benign and malignant endometrial glands in cancer arising from adenomyosis. As it is very rare, it is difficult to standardize treatment. In this manuscript, we try to emphasize some aspects regarding the management strategy, as well as how heterogenous the studies from the literature are in terms of prognosis in both cancers that develop from adenomyosis or those that are only associated with adenomyosis. The pathogenic mechanisms of transformation remain unclear. As these types of cancer are so rare, there is no standardised treatment. A novel target in the diagnosis and treatment of gynaecological malignancies associated with adenomyosis is also being studied for the development of new therapeutic concepts.

Immature Teratoma: Diagnosis and Management-A Review of the Literature.

An immature teratoma is a germinal malignant tumor composed of three germ cell layers, occurring more frequently in young women. It is the second most frequent among the malignant germinal tumors after dysgerminoma, and it is the only neoplasm with germ cells that are histologically graded. Even if we do not have a consensus regarding its therapeutical management, it has a good prognosis, with an excellent overall survival rate and good fertility preservation. More studies are needed regarding the necessity of adjuvant chemotherapy in pediatric oncology, and because of chemotherapy's long-term adverse effects, surveillance or a targeted treatment is preferred, but the main therapy is fertility-sparing surgery. Special attention should be given to the genetic mapping of the histological pieces for patient risk stratification due to its value in prognosis and future treatment.

The Approach of Artificial Intelligence in Neuroendocrine Carcinomas of the Breast: A Next Step towards Precision Pathology?-A Case Report and Review of the Literature.

Primary neuroendocrine tumors (NETs) of the breast are considered a rare and undervalued subtype of breast carcinoma that occur mainly in postmenopausal women and are graded as G1 or G2 NETs or an invasive neuroendocrine carcinoma (NEC) (small cell or large cell). To establish a final diagnosis of breast carcinoma with neuroendocrine differentiation, it is essential to perform an immunohistochemical profile of the tumor, using antibodies against synaptophysin or chromogranin, as well as the MIB-1 proliferation index, one of the most controversial markers in breast pathology regarding its methodology in current clinical practice. A standardization error between institutions and pathologists regarding the evaluation of the MIB-1 proliferation index is present. Another challenge refers to the counting process of MIB-1's expressiveness, which is known as a time-consuming process. The involvement of AI (artificial intelligence) automated systems could be a solution for diagnosing early stages, as well. We present the case of a post-menopausal 79-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). The purpose of this paper is to expose the interpretation of MIB-1 expression in our patient' s case of breast neuroendocrine carcinoma, assisted by artificial intelligence (AI) software (HALO-IndicaLabs), and to analyze the associations between MIB-1 and common histopathological parameters.

Diagnosis and Management of Dysgerminomas with a Brief Summary of Primitive Germ Cell Tumors.

Dysgerminoma represents a rare malignant tumor composed of germ cells, originally from the embryonic gonads. Regarding its incidence, we do not have precise data due to its rarity. Dysgerminoma occurs at a fertile age. The preferred treatment is the surgical removal of the tumor succeeded by the preservation of fertility. Even if a multidisciplinary team, founded in 2009 by a gynecologist, an oncologist, a pediatric oncologist and a pediatric surgeon, under the guidance of the Malignant Germ Cell International Consortium (MaGIC), studies this type of tumor, issues still remain related to the lack of a randomized study and to both the management and understanding of the concept of OMGCTs (ovarian malignant germ cell tumors). The aim of this review is to present from the literature the various approaches for this type of tumor, and, regarding innovative therapies or possible prevention, which can be applied in clinical practice. Multidisciplinarity and treatment in reference centers have proven their usefulness as well.

An Interesting Image of Transmural Migration of a Levonorgestrel-Releasing Intrauterine Device (LNg-IUD).

Intrauterine devices (IUDs) are very common as a method of birth control. By adding progesterone (levonorgestrel), a decrease in the risk of complications has been documented, including the risk of perforation. Even though only a few complications have been described, adjacent organs may be involved in the case of migration-a life-threatening situation. A 45-year-old G4P2 woman was seen in our clinic for LNg-IUD removal, according to the medical instructions. Her main complaints were abdominal discomfort, low back pain, and recurrent menorrhagia. A "lost" IUD was initially suspected; the patient confirmed the detection and removal of the control strings, and a subsequent discussion related to delayed transmural migration of the IUD being followed. The ultrasonography revealed the migration of the IUD to the uterine cervix and size-decreased uterine fibroids, confirming the effectiveness of the LNg-IUD. The MRI and ultrasonography being useless, a subsequent X-ray and CT scan were requested, both confirming a myometrium-positioned IUD, adjacent to the serosa and lumbosacral plexus. Even though the IUD is considered a safe device with reversible effect, it can be associated with severe morbidity, with an ultrasound follow-up being required. For more precise detection of the IUD, we strongly recommend an X-ray or CT scan examination, followed by safe removal.

Oxidative-Stress Related Gene Polymorphism in Endometriosis-Associated Infertility.

Background and Objectives: Endometriosis is a benign inflammatory disease associated with infertility and chronic pelvic pain, estimated to affect 7−10% of reproductive-age women, with the possibility of malignant transformation. Recent studies focus on oxidative stress and genetic mutations as risk factors in the pathophysiology of endometriosis-associated infertility. Materials and Methods: This case-control study is the first in Eastern European women that aimed to investigate four genes' genetic polymorphisms that encode antioxidant enzymes involved in oxidative stress (glutathione peroxidase 1, GPX1 198Pro > Leu, catalase CAT-262C > T, glutathione S-transferase M1, and T1 null genotype) and their association with endometriosis-related infertility. We compared 103 patients with endometriosis-associated infertility with 102 post-partum women as the control group. Results: The endometriosis group had a mean age of 34.5 +/− 6.12 years, while the control group's mean age was 35.03 +/− 5.95 years. For CAT-262C > T polymorphism, the variant genotypes were significantly more frequent in the endometriosis group. Moreover, for the GPX1 198Pro > Leu, the endometriosis group had significantly more frequent CT and TT genotypes. The null genotype of GSTM1 was detected significantly higher in the endometriosis group. No significant differences were found in the frequency of GSTT1 between the two groups. This study suggests that GPX1 198Pro > Leu, CAT-262C > T, and GSTM1 polymorphisms may be risk factors and that the association between the GSTM1-GSTT1 null genotype may play a significant role in endometriosis-associated infertility. Moreover, this study suggests that the GSTT1 null genotype does not influence the disease. Visual identification of endometriotic lesions with microscopic confirmation is the accepted gold standard for diagnosing endometriosis, but general anesthesia and laparoscopy are required. Conclusions: In this regard, a panel of genetic or laboratory markers is needed for the early diagnostics of this prevalent disease, especially in the case of young patients with future pregnancy intention.

A Race against the Clock: A Case Report and Literature Review Concerning the Importance of ADAMTS13 Testing in Diagnosis and Management of Thrombotic Thrombocytopenic Purpura during Pregnancy.

Thrombocytopenic purpura (TTP) is a rare, potentially fatal pathology characterized by microangiopathic thrombotic syndrome and caused by an acute protease deficiency of von Willebrand factor, ADAMTS13. Moreover, ADAMTS13 deficiency promotes microthrombosis led by the persistence of ultra-large VWF multimers in the blood circulation. According to the few studies involving pregnant participants, the heterogeneity of manifestations has made this pathology difficult to diagnose, with an unexpected occurrence and increased risk of maternal and fetal morbidity and mortality. We reported on the case of a 28-year-old pregnant woman with an obstetric score of G2P0 who presented to the obstetrics and gynecology department of our clinic with the complaint of minimal vaginal bleeding. The evolution of our case was severe and life-threatening, a "race against the clock", with our goal being to emphasize the importance and difficulty of diagnosing TTP in the absence of specific symptomatology. We faced a lack of technological support for a correct and complete diagnosis, and the first manifestation of this disease was the intrauterine death of the fetus. After completing all the necessary procedures, the placental tissue was sent for further histopathological evaluation. We highlighted the importance of monitoring ADAMTS13 for relapses monthly, with prophylaxis being essential for maternal and fetal mortality and morbidity.

Atypical Polypoid Adenomyoma of the Vagina: Follow Up and Subsequent Evolution: A Case Report and Update.

Atypical polypoid adenomyoma (APA) is a rare tumor developed from a mix of cells of epithelial and mesenchymal origin. We present the case of an 84-year-old patient with atypical polypoid adenomyoma on the vaginal vault, after total hysterectomy with total adnexectomy for endometrial hyperplasia with atypia four years ago. Not following regular indicated gynecological appointments, the symptoms presented were vaginal bleeding and anemia. The importance of the case consists both in the unique way in which the adenomyoma appears on the vaginal vault and in the subsequent evolution of this pathology. After complete resection, it recurs in five months with a malignant transformation into carcinosarcoma. This fact shows that adenomas can turn not only into carcinomas but also the mesenchymal component can progress to sarcoma, a fact of exceptional rarity. Follow-up and accurate diagnosis are essential for proper management, which is a challenge anyway due to the lack of case studies.