H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma.

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.

Pathophysiology, Histopathology, and Differential Diagnostics of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma-An Update from the Pathologist's Point of View.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequently occurring non-melanocytic skin cancers. The objective of our study is to present the pathophysiology of BCC and cSCC and its direct relationship with the histopathological diagnostics and the differential diagnostics of these types of cancer, based on the morphological characteristics, immunohistochemical profile, and genetic alterations. The qualitative study was based on emphasizing the morphological characteristics and immunohistochemistry profiles of BCC and cSCC and the differential diagnostics based on the tissue samples from the Clinical Pathology Department of Mures Clinical County Hospital between 2020 and 2022. We analyzed the histopathological appearances and immunohistochemical profiles of BCC and cSCC in comparison with those of Bowen disease, keratoacanthoma, hyperkeratotic squamous papilloma, metatypical carcinoma, pilomatricoma, trichoblastoma, Merkel cell carcinoma, pleomorphic dermal sarcoma (PDS), and melanoma. Our study showed the importance of the correct histopathological diagnosis, which has a direct impact on the appropriate treatment and outcome for each patient. The study highlighted the histopathological and morphological characteristics of NMSCs and the precursor lesions in HE and the immunohistochemical profile for lesions that may make the differential diagnosis difficult to establish.

The Inflammatory Profile Correlates with COVID-19 Severity and Mortality in Cancer Patients.

BACKGROUND: The correlation of the inflammatory profile with the severity of the disease in neoplastic patients with SARS-CoV-2 infection was addressed. METHODS: A database of 1537 patients hospitalized in the pneumology department was analyzed. After applying the inclusion and exclusion criteria, 83 patients (67% males, 33% females) were included. RESULTS: Most of the analyzed patients were hospitalized with a moderate form of disease, explaining the significant percentage of 25% mortality. The frequency of the type of neoplasm was higher for lung cancer, followed by malignant colon tumor. We identified a significant association between the increased value of ferritin (p < 0.0001, OR = 22.31), fibrinogen (p = 0.009, OR = 13.41), and C-reactive protein (p = 0.01, OR = 7.65), respectively, and the level of severity of COVID-19. The results of the univariate logistic regression analysis for predicting the severity of the disease revealed that the increased values of ferritin (p = 0.001, OR = 22.31) and fibrinogen (p = 0.02, OR = 13.41) represent a risk for a serious negative prognosis of COVID-19. CONCLUSIONS: Our study demonstrated that the value of the analyzed inflammatory parameters increased in direct proportion to the severity of the disease and that higher values were associated with increased mortality in the study group.

Pulmonary Fibrosis Related to Amiodarone-Is It a Standard Pathophysiological Pattern? A Case-Based Literature Review.

Amiodarone hydrochloride is an antiarrhythmic drug, with proven efficacy in prevention and treatment of numerous arrhythmias, atrial fibrillation especially, or ventricular arrhythmias, with a long half-life (55-60 days). The increased risk of developing amiodarone-induced pulmonary fibrosis is directly related to the dose and the duration of the intake. Amiodarone-induced pulmonary toxicity is conditioned by dose, patient's age, and pre-existent pulmonary pathologies. The pattern for drug-induced lung injury may vary in many forms, but the amiodarone can cause polymorphous injuries such as diffuse alveolar damage, chronical interstitial pneumonia, organizing pneumonia, pulmonary hemorrhage, lung nodules or pleural disease. The pathological mechanism of pulmonary injury induced by amiodarone consists of the accumulation of phospholipid complexes in histocytes and type II pneumocytes. Differential diagnosis of pulmonary fibrosis induced by amiodarone is made mainly with idiopathic pulmonary fibrosis, left ventricular failure or infectious disease. Before starting treatment with amiodarone, patients should be informed of potential adverse effects and any new respiratory symptoms should promptly be reported to their family physician or attending physician. The assessment carried out at the initiation of amiodarone treatment should include at least chest X-ray and respiratory function tests and extrapulmonary evaluation.

Carotid Plaque Features and Inflammatory Biomarkers as Predictors of Restenosis and Mortality Following Carotid Endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is the first-line surgical intervention for cases of severe carotid stenoses. Unfortunately, the restenosis rate is high after CEA. This study aims to demonstrate the predictive role of carotid plaque features and inflammatory biomarkers (monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), Systemic Inflammation Response Index (SIRI), and Aggregate Index of Systemic Inflammation (AISI)) in carotid restenosis and mortality at 12 months following CEA. METHODS: The present study was designed as an observational, analytical, retrospective cohort study and included all patients over 18 years of age with a minimum of 70% carotid stenosis and surgical indications for CEA admitted to the Vascular Surgery Clinic, Emergency County Hospital of Targu Mures, Romania between 2018 and 2021. RESULTS: According to our results, the high pre-operative values of inflammatory biomarkers-MLR (OR: 10.37 and OR: 6.11; p < 0.001), NLR (OR: 34.22 and OR: 37.62; p < 0.001), PLR (OR: 12.02 and OR: 16.06; p < 0.001), SII (OR: 18.11 and OR: 31.70; p < 0.001), SIRI (OR: 16.64 and OR: 9.89; p < 0.001), and AISI (OR: 16.80 and OR: 8.24; p < 0.001)-are strong independent factors predicting the risk of 12-month restenosis and mortality following CEA. Moreover, unstable plaque (OR: 2.83, p < 0.001 and OR: 2.40, p = 0.04) and MI (OR: 3.16, p < 0.001 and OR: 2.83, p = 0.005) were independent predictors of all outcomes. Furthermore, AH (OR: 2.30; p = 0.006), AF (OR: 1.74; p = 0.02), tobacco (OR: 2.25; p < 0.001), obesity (OR: 1.90; p = 0.02), and thrombotic plaques (OR: 2.77; p < 0.001) were all independent predictors of restenosis, but not for mortality in all patients. In contrast, antiplatelet (OR: 0.46; p = 0.004), statin (OR: 0.59; p = 0.04), and ezetimibe (OR:0.45; p = 0.03) therapy were protective factors against restenosis, but not for mortality. CONCLUSIONS: Our data revealed that higher preoperative inflammatory biomarker values highly predict 12-month restenosis and mortality following CEA. Furthermore, age above 70, unstable plaque, cardiovascular disease, and dyslipidemia were risk factors for all outcomes. Additionally, AH, AF, smoking, and obesity were all independent predictors of restenosis but not of mortality in all patients. Antiplatelet and statin medication, on the other hand, were protective against restenosis but not against mortality.

Actualities in the Morphology and Immunohistochemistry of Cutaneous and Ocular Melanoma: What Lies Ahead? A Single-Centre Study.

Melanoma is the most aggressive melanocytic tumor whose incidence is continuously increasing worldwide. METHODS: We highlight the morphological, immunohistochemistry, and particularities of various melanoma types based on the cases diagnosed in our department from 2017 to 2021. RESULTS: We present 100 melanoma cases and one capsular nevus case. The most common type was nodular melanoma. The immunohistochemistry markers used were SRY-box transcription factor 10 (SOX10), S100 protein, human melanoma black 45 (HMB45), and melanoma antigen recognized by T cells 1 (Melan-A). Uveal melanoma and conjunctival melanoma represent particular tumors with independent prognostic factors. Uveal melanoma requires assessment of macrophages, microvascularisation, and mitoses. Sentinel lymph node metastases are essential targets that provide staging tools. Conjunctival melanoma and capsular nevi are diagnostic pitfalls. CONCLUSION: Melanoma can appear in various forms, and sometimes the diagnosis might be unclear. Today, immunohistochemistry remains the most important tool in confirming the diagnosis and prognosis for this type of neoplasia.

Scientific Research Directions on the Histopathology and Immunohistochemistry of the Cutaneous Squamous Cell Carcinoma: A Scientometric Study.

Introduction: Cutaneous squamous cell carcinoma (cSCC) is one of the most frequently occurring types of cancer in humans. Scientometric research is an innovative method for analyzing the research trends in various domains, with great implications in the field of medicine. Materials and Methods: We searched the Web of Science database with the following established query terms: "Squamous cell carcinoma", "skin", and "immunohistochemistry". After applying the inclusion and exclusion criteria, a total of 76 articles were selected. The present study aims to analyze, based on the frequency of use of keywords with scientometric algorithms and map-based distributions, the trends of the research concerning cSCCs in 2017-2022. Results: A graphical representation based on 11 scientometric maps presented the division of the keywords into seven clusters, from which seven categories of research interest were defined. The clusters represent a multidisciplinary approach to the diagnosis and treatment of cSCCs, cancer diagnostics, patient outcomes, histopathological importance, management of cSCCs, role of progression, and adequate treatment of and importance of immunohistochemistry for cSCCs. The distribution of the citations shows the importance of the available research on cSCCs by analyzing the first five most-cited articles included in our study in direct concordance with the seven defined clusters. Conclusion: The scientometric research method reveals the interest of research in the multidisciplinary approach used to obtain the best outcomes for the patient, including a targeted investigation, as well as diagnostic and treatment options. The trends in the research reveal that histopathological diagnostics and immunohistochemistry, combined with molecular techniques, are the most important tools used to establish a personalized diagnosis, thus increasing the quality of life and life expectancy for patients with cSCCs.

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.

An Up-to-Date Correlation of Epidemiological and Histopathological Characteristics of Basal Cell Carcinoma of the Skin in a County Hospital in Romania.

Background and Objectives: Basal carcinoma of the skin (BCC) is part of the nonmelanoma skin cancer (NMSC) family and is the most frequently occurring type of skin cancer in humans. A combination of clinical and histopathological approaches is necessary in order to establish the best treatment regime for patients who have been diagnosed with this type of cancer. The objective of the present study was to establish the statistical value of prediction for certain sociodemographic characteristics (age category and environment of origin) and histopathological parameters of the subjects that could be related to the incidence of diagnosis with certain histopathological subtypes of BCC. Materials and Methods: In order to verify the veracity of the established research hypotheses, we conducted a retrospective study based on the histopathological reports of 216 patients who were treated at the Pathology Department of Mureș Clinical County Hospital. Results: Cystic BCC is higher in patients who are older than 71 years of age, and the superficial multicentric and keratotic subtypes are more frequently diagnosed in urban areas. Patients who have been diagnosed with the superficial multicentric BCC subtype are not usually very old in contrast to the patients who tend to be diagnosed with the cystic BCC subtype. The nodular BCC subtype is positively associated with ulceration (p = 0.004); the superficial multicentric BCC subtype is positively associated with intra- and peritumoral inflammatory infiltrate (p = 0.022, p = 0.034) and negatively associated with ulceration (r = -0.218, p = 0.001). The infiltrative BCC subtype is positively associated with ulceration (p = 0.021), and the keratotic BCC subtype is positively associated with peritumoral inflammatory infiltrate (p = 0.02). Conclusions: Depending on each patient's epidemiological and sociodemographic data, a pattern can be established regarding the appropriate clinical and treatment approaches for that patient, which can be supported based on the implications of the histopathological diagnostic. This can lead to an improvement in the patient's quality of life and increased satisfaction with the provided medical services.

VISTA, PDL-L1, and BRAF-A Review of New and Old Markers in the Prognosis of Melanoma.

Melanoma is currently known as one of the most aggressive malignant tumors. The prognostic factors and particularities of this neoplasm are a persistent hot topic in the medical field. This review has multiple purposes. First, we aim to summarize the known data regarding the histological and immunohistochemical appearance of this versatile tumor and to look further into the analysis of several widely used prognostic markers, such as B-Raf proto-oncogene, serine/threonine kinase BRAF. The second purpose is to analyze the data on the new prognostic markers, V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) and Programmed death-ligand 1 (PD-L1). VISTA is a novel target that is considered to be highly important in determining the invasive potential and treatment response of a melanoma, and there are currently only a limited number of studies describing its role. PD-L1 is a marker with whose importance has been revealed in multiple types of malignancies, but its exact role regarding melanoma remains under investigation. In conclusion, the gathered data highlights the importance of correlations between these markers toward providing patients with a better outcome.

The Impact of and Adaptations Due to the COVID-19 Pandemic on the Histopathological Diagnosis of Skin Pathologies, Including Non-Melanocyte and Melanoma Skin Cancers-A Single-Center Study in Romania.

Background and Objectives: The COVID-19 pandemic has globally affected health systems and services. Non-melanoma skin cancers (NMSCs) are the most common malignancies around the world. This study aimed to analyze the differences in the benign and malignant histopathological diagnoses performed on radical excision skin tumors and skin biopsies in the dermatopathology ward in Mures Clinical County Hospital, Targu Mures, Romania, 1 year prior to and during the COVID-19 pandemic, to emphasize the changes in the diagnostic process as per the new regulations. Materials and Methods: A total of 1168 histopathological diagnoses were included in the study-302 from the COVID-19 period and 866 from the non-COVID-19 period-considering the number, type, and frequency of the histopathological diagnoses as variables to be analyzed. Results: In the COVID-19 period, out of the 55 NMSC and melanoma histopathological diagnoses, 50.9% (n = 28) were BCCs, 20% (n = 11) were SCCs, 10.9% (n = 6) were basosquamous cell carcinomas, and 18.18% (n = 10) were melanoma cases. Regarding the non-COVID-19 period, out of the 173 NMSC and melanoma histopathological diagnoses, 46.82% (n = 81) were BCCs, 22.54% (n = 39) were SCCs, 7.51% (n = 13) were basosquamous cell carcinomas, and 23.12% (n = 40) were melanoma cases. Conclusions: During the COVID-19 pandemic, a decrease in histopathological diagnoses at the dermatopathology ward in our hospital was observed, for both benign and malignant pathologies, especially for NMSCs and melanomas, compared to the same period 1 year prior to the pandemic.