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.

Morphological aspects and therapeutic options in melanoma: a narrative review of the past decade.

Melanoma is a malignant cancer of the skin, the incidence of which has been increasing year by year. This neoplasm has high aggressivity as well as the potential for invasion and metastases. Multiple factors related to the proliferation of this type of tumor have been identified, such as exposure to ultraviolet (UV) radiation and specific genetic backgrounds. From a histological and cytological point of view, the most common cells that are found in melanoma are epithelioid or spindle cells. To confirm the diagnosis and the melanocytic origin of the tumor, specific and sensitive markers are used. Also, observation of the behavior of this cancer, including its proliferative properties, has led to the development of multiple therapies, each of which is characteristic of the pathological stage at the time of diagnosis. While surgery is the most important therapeutic and curative option in cases of melanoma in situ, chemotherapy has been the main treatment for advanced stages of melanoma for many years. However, recently, targeted therapy and immunotherapy have changed the approach to treatment. At present, multiple studies are attempting to obtain further data about the tumor microenvironment and investigating how targeting particular molecules can change the prognosis of patients.

S100A8∕A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction.

Myocardial infarction (MI) leads to irreversible ischemic damage of the heart muscle and is the leading cause of heart failure. The ischemic cardiac injury triggers a potent local and systemic immune response. In the acute phase post-MI, neutrophils infiltrate the myocardium in large numbers and induce further cardiomyocyte death, expanding the infarcted area. The alarmin S100A8∕A9 is a proinflammatory mediator primarily produced by myeloid cells, with an emerging role in MI. We previously demonstrated that short-term inhibition of S100A8∕A9 during the inflammatory phase of the immune response to MI improves long-term cardiac function. In the present study, we investigated the effects of S100A8∕A9 blockade on myocardial inflammation and post-ischemic myocardial injury in a mouse model of coronary artery ligation. Immunohistochemical (IHC) staining revealed that the presence of S100A9 is strongly correlated with neutrophil infiltration in the myocardium on days 1 and 3 post-MI. A 3-day treatment with the S100A8∕A9 blocker ABR-238901 starting immediately after MI decreased the number of neutrophils and S100A9 presence in the myocardium and had a positive impact on cardiac damage, reducing infarction size. These findings promote S100A9 as an IHC biomarker of neutrophil infiltration and a promising immunomodulatory target to regulate neutrophil recruitment, reduce ischemic injury and promote long-term beneficial cardiac recovery after MI.

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.

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.

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.

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.

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.

CK 8∕18: the key to differentiating intracutaneous lesions with pagetoid features.

INTRODUCTION: Neoplasms with pagetoid features are a category of rare lesions defined by the presence of atypical cells at different levels of the epidermis. The most important diseases within this category are mammary Paget disease (MPD), extramammary Paget disease (EMPD), Bowen's disease, in situ melanoma, and pagetoid reticulosis. AIM: The aim of this analysis was to describe the importance of the cytokeratin 8∕18 (CK 8∕18) immunostaining in diagnosing MPD and EMPD and differentiating them from other lesions. MATERIALS AND METHODS: A retrospective study was employed, based on the histopathological and immunohistochemical (IHC) characteristics of 30 cases that presented pagetoid features. The cases were processed and analyzed at the Department of Pathology, Mures Clinical County Hospital, Târgu Mures, Romania, from 2017 to 2020. RESULTS: Five MPD cases, one EMPD case, one pagetoid reticulosis case, 10 Bowen's disease cases, and 13 in situ melanoma cases were collected. Under Hematoxylin-Eosin staining, cells presented pale cytoplasm in MPD, EMPD, and in 25% of the melanoma cases. Hyperchromasia with nuclear enlargement was seen in all cases. Immunostaining with CK 8∕18 was positive in all MPD and EMPD cases. Tests for CK7, p63, and CK AE1∕AE3 were positive in MPD, EMPD, and Bowen's cases. Tests for S100, SRY-box transcription factor 10 (SOX10), human melanoma black 45 (HMB45), and Melan A were positive in melanoma cases, while cluster of differentiation (CD)3, CD4, and CD8 tests were positive in the pagetoid reticulosis case. CONCLUSIONS: CK 8∕18 is an IHC marker that can help establish the diagnosis of MPD and EMPD and differentiate them from other pagetoid neoplasms, ensuring the proper diagnosis and prognosis are provided.

Neuroendocrine tumors (NETs) - experience of a single Center.

INTRODUCTION: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors arising from cells that are part of the diffuse neuroendocrine system. PATIENTS, MATERIALS AND METHODS: We conducted a retrospective study in which we included a number of 91 cases diagnosed with neuroendocrine tumors (NETs). Descriptive statistics was performed: number of cases based on location, distribution by gender (male∕female), distribution by age, and we also performed a morphological and immunohistochemical (IHC) study. RESULTS: The highest number of cases was found in lungs (60 cases). Tumors located on the skin, breast or bladder have been discovered, locations considered rare for this type of tumor. Of all cases diagnosed in the lungs, 59 were diagnosed as small cell carcinomas (SCCs) and only one case as NET. All surgical specimens were positive for chromogranin A (CgA), with a different expression for the other immunomarkers. For the lung biopsies, the most frequently IHC staining was CgA and cluster of differentiation 56 (CD56), with an increased positivity for the latter. CONCLUSIONS: CgA remains the most sensitive immunomarker in the diagnosis of NETs. CD56 is the most widely used immunomarker for diagnosing small cell lung tumors. Positive expression of thyroid transcription factor 1 (TTF1) immunomarker does not confirm pulmonary origin of SCCs.