Programmed death-ligand expression and lymph node involvement in penile squamous cell carcinoma.

PURPOSE: Our objective was to investigate the association between programmed death-ligand (PD-L1) immunoexpression measured as a combined positive score and clinical outcomes in penile SqCC. MATERIALS AND METHODS: We retrospectively reviewed all penile SqCC cases diagnosed in our institution between 2018 and 2023. PD-L1 immunohistochemistry was performed as a qualitative assay. Immunoexpression in both tumor and immune cells equal or superior to 1 was considered positive. RESULTS: A total of 34 patients with conventional penile SqCC were included. Eleven cases were HPV-associated (32.4%). Twelve cases were PD-L1 CPS < 1 and twenty-two were PD-L1 CPS ≥ 1. Nine cases (32.4%) were PD-L1 CPS ≥ 1 and p16 positive, but this did not translate in worse clinicopathological features. Larger tumors (3.0 cm in PD-L1 CPS ≥ 1 vs 2.5 cm in PD-L1 CPS < 1; p = 0.662), vascular invasion (36.4% in PD-L1 CPS ≥ 1 vs. 25.0% in PD-L1 CPS < 1; p = 0.705) and perineural invasion (40.9% in PD-L1 CPS≥1 vs. 16.7% in PD-L1 CPS < 1; p = 0.252) were associated with PD-L1 expression. Among the high-risk features, only lymph node involvement had statistical significance, with 14 out of 22 PD-L1 CPS ≥ 1 patients (63.6%) having lymph node metastases when lymphadenectomy was performed (p = 0.031). With a median follow-up of 16 months (IQR 27.5), PD-L1 CPS ≥ 1 patients had worse overall survival (53.4 months vs 75.9 months), but no statistical significance could be inferred (p = 0.188). CONCLUSIONS: It is noteworthy the clinical significance of lymph node involvement in PD-L1 CPS ≥ 1 cases and a trend towards worse overall survival in this group of patients.

Morphological characteristics and distribution identification of telocytes in Tibetan sheep testis and epididymis.

Telocytes (TCs) are a type of stromal cell discovered in the various organs of different animals and have many potential functions, including angiogenesis, signalling, and substance transport. However, the TCs have not been detected in the testis or epididymis of Tibetan sheep. This study investigated the position, characteristics, and distribution of TCs in the testis and epididymis of Tibetan sheep using transmission electron microscopy (TEM), toluidine blue staining, immunohistochemistry, and double immunofluorescence to elucidate their possible functions. TEM revealed that TCs were often found near basement membranes and capillaries and were characterised by large nuclei, elongated cytoplasmic protrusions, and many secretory vesicles. We also observed via toluidine staining that TCs were present near basement membrane and interstitial capillaries. Immunohistochemistry and double immunofluorescence revealed the positive expression of CD117, vimentin, platelet derived growth factor receptor α(PDGFRα), PDGFRα + CD117, and PDGFRα + vimentin in TCs. Additionally, we inferred that TCs participates in the formation of the blood-testis and blood-epididymis barriers, as well as in material transport and a stable microenvironment. This study presents the first evidence of the presence of TCs near the basement membrane and blood vessels in the testis and epididymis of Tibetan sheep. These findings provide new insights into the function of TCs in the reproductive systems of plateau animals.

PD-L1 immunohistochemical expression considering HPV status in oropharyngeal squamous cell carcinoma.

This systematic review aims to determine whether the presence of human papillomavirus (HPV) influences the immunohistochemical expression of programmed cell death-1 ligand (PD-L1) in oropharyngeal squamous cell carcinoma (OPSCC). PD-L1 immunohistochemical expression varies in OPSCC, and the presence of HPV is a plausible explanation for this variability. Comprehending these findings is crucial, as high PD-L1 expression in the tumor microenvironment of OPSCC can help identify patient subgroups that could be suitable for immunotherapy. Therefore, a systematic review was conducted following PRISMA guidelines (CRD42023437800). An electronic literature search was performed without time or language restrictions. The search included PubMed/MEDLINE, Embase, Scopus, Web of Science, https://clinictrials.gov, and relevant journals. A meta-analysis was performed using RStudio. Fourteen studies involving 1,629 participants were included. The sample consisted predominantly of males (81.26%) with a mean age of 58.3 years. Concerning clinical and pathological characteristics, the most frequently described anatomical location was the tonsils (68.54%), and most participants were either current or former smokers (78%) and alcohol users (79%). Advanced TNM IV was the most common stage. Regarding histopathological characteristics, HPV 16 was the only type mentioned, and half of the cases were detected through immunohistochemistry. The SP142 clone (35.7%) and the pattern of membrane immunostaining in tumor cells (71%) were the most commonly employed methods. The most prevalent findings were positive expression of PD-L1 (64.28%) and negative HPV status (57.14%). The association between PD-L1 positivity and HPV positivity (78.57%) was confirmed by meta-analysis. The conclusion was that HPV-positive status has an impact on immunohistochemical expression of PD-L1 in OPSCC.

Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC.

This study presents an observational, cross-sectional analysis of 64 patients diagnosed with small cell lung cancer (SCLC) at a reference laboratory for thoracic pathology between 2022 and 2024. The primary objective was to evaluate the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers such as Chromogranin, and Synaptophysin, utilizing both traditional immunohistochemistry and digital pathology tools. Patients were primarily older adults, with a median age of over 71, and most biopsies were obtained from lung parenchyma. Immunohistochemistry (IHC) was performed using specific monoclonal antibodies, with DLL3 showing variable expression across the samples. Notably, DLL3 was expressed in 72.3% of the cases, with varied intensities and a semi-quantitative H-score applied for more nuanced analysis. ASCL1 was expressed in 97% of cases, with the majority considered low-expressors. Only 11% had high expression. TTF-1, traditionally not a conventional marker for the diagnosis of SCLC, was positive in half of the cases, suggesting its potential as a biomarker. The study underscores the significant variability in the expression of neuroendocrine markers in SCLC, with implications for both diagnosis and potential therapeutic targeting. DLL3, particularly, shows promise as a therapeutic target due to its high expression rate in the cohort. The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches. The findings emphasize the need for further research into the role of these markers in the management and treatment of SCLC, considering the poor prognosis and high mortality rate observed in the cohort.

Cluster classification of a Brazilian gastric cancer cohort reveals remarkable populational differences in normal p53 rate.

BACKGROUND: Queiroz et al. showed that the application of cluster methodology for classifying gastric cancer is suitable and efficient within a Brazilian cohort, which is known for its population heterogeneity. The study highlighted the potential utilization of this method within public health services due to its low-cost, presenting a viable means to improve the diagnosis and prognosis of gastric cancer. BACKGROUND: Our Brazilian cohort with gastric cancer has a distinct distribution between mutated and normal p53. BACKGROUND: New genetic marker-based classifications improve gastric cancer diagnosis accuracy. BACKGROUND: Machine learning integration enhances predictive value in gastric cancer diagnosis. BACKGROUND: Molecular biomarkers complement clinical decisions, advancing personalized medicine. OBJECTIVE: Gastric adenocarcinoma remains an aggressive disease with a poor prognosis, as evidenced by a 5-year survival rate of approximately 31%. The histological classifications already proposed do not accurately reflect the high biological heterogeneity of this neoplasm, particularly in diverse populations, and new classification systems using genetic markers have recently been proposed. Following these newly proposed models, we aimed to assess the cluster distribution in a Brazilian cohort. Furthermore, we evaluated whether the inclusion of other clinical and histological parameters could enhance the predictive value. METHODS: We used a previously described four-immunohistochemistry/EBER-ISH marker to classify a cohort of 30 Brazilian patients with gastric adenocarcinoma into five different clusters and compared the distribution with other genetically diverse populations. Furthermore, we used artificial intelligence methods to evaluate whether other clinical and pathological parameters could improve the results of the methodology. RESULTS: Disclosing the genetic variability between populations, we observed a more balanced distribution of the aberrant/normal p53 ratio (0.6) between patients negative for the other markers tested, unlike previous studies with Asian and North American populations. In addition, decision tree analysis reinforced the efficiency of these new classifications, as the stratification accuracy was not altered with or without additional data. CONCLUSION: Our study underscores the importance of local research in characterizing diverse populations and highlights the complementary role of molecular biomarkers in personalized medicine for gastric adenocarcinoma, enhancing diagnostic accuracy and potentially improving survival rates.

PRAME expression in fibrosarcomatous dermatofibrosarcoma protuberans.

PRAME (PReferentially expressed Antigen in MElanoma) was first identified as a malignant melanoma-specific antigen. Recently, a few cases of fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP) were shown to have positivity for PRAME, while conventional dermatofibrosarcoma protuberans (C-DFSP) was negative. Because PRAME may be of diagnostic utility in FS-DFSP and is raising expectations as a new immunotherapy target, we examined the positivity of PRAME in FS-DFSP. Twenty-one cases of FS-DFSP and age/sex/location-matched cases of C-DFSP as a control group were examined by immunohistochemistry for CD34 and PRAME. The results were then evaluated by H-score, which was objectively and semi-quantitatively calculated using the open-source bioimaging analysis software QuPath. The results revealed that the PRAME H-score in FS-DFSP was significantly higher than that in C-DFSP (p = 0.0137). As for CD34, the H-score in FS-DFSP was significantly lower than that in C-DFSP (p < 0.001). Using these two immunohistochemical analyses in combination, the sensitivity and specificity for the diagnosis of FS-DFSP were 86% and 90%, respectively. Double staining of CD34 and PRAME revealed that PRAME-positive and CD34-positive areas did not overlap. This is the largest study to examine PRAME expression in FS-DFSP, and it confirmed the usefulness of PRAME in diagnosing this condition.

Spitz melanoma with MAP3K8::ABLIM1 rearrangement: a case report with review of the literature.

BACKGROUND: Spitz tumors are relatively uncommon melanocytic lesions, typically affecting a relatively younger population but can be encountered at any age. They are characterized by a proliferation of melanocytes with epithelioid and/or spindled cytomorphology features, and interpretation is often challenging. The majority of these tumors are driven by kinase fusions or HRAS mutations. MAP3K8 fusions, although rare, are characteristic genomic events in Spitz tumors, especially in more atypical or malignant lesions. CASE PRESENTATION: Here, we present the case of a 43-year-old woman with a clinically cystic mass in her right groin, histologically characterized as a spindle and epithelioid cell malignant tumor. Immunohistochemistry revealed diffuse expression of S100 protein, tyrosinase and SOX10, patchy weak PRAME, HMB45 and Melan-A reactivity, and negative staining for BRAF V600E. Next-generation sequencing analysis revealed the presence of a MAP3K8::ABLIM1 fusion gene, as well as GRIN2A and TERT promoter mutations. The morphology, immunohistochemistry and molecular analysis confirmed Spitz melanoma with molecular features suggesting a worse prognosis. CONCLUSION: This case introduces a novel fusion partner of MAP3K8 in the context of Spitz melanoma and expands the morphologic and molecular spectrum of Spitz melanoma.

Clinicopathological characteristics and prognosis of combined hepatocellular cholangiocarcinoma.

There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

Overexpression of TPD52L2 in HNSCC: prognostic significance and correlation with immune infiltrates.

BACKGROUND: Evidence has been presented that the tumor protein D52 (TPD52) family plays a critical role in tumor development and progression. As a member of the TPD52 family, the changes in TPD52L2 gene status are instrumental in kinds of cancer development. However, its effects on patient prognosis and immune infiltration in Head and Neck Squamous Carcinoma (HNSCC) are still poorly understood. METHODS: The Tumor Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and c-BioPortal database was used to explore the expression pattern, prognostic value, and variation of gene status in HNSCC. The LinkedOmics database was used to obtain the co-expression genes of TPD52L2 and identify the diagnostic value of TPD52L2 in HNSCC. The correlations between TPD52L2 expression and six main types of immune cell infiltrations and immune signatures were explored using Tumor Immune Estimation Resource (TIMER). The correlation between TPD52L2 expression and immune checkpoint genes (ICGs) was analyzed by TCGA database. Immunohistochemistry (IHC) was performed to validate the expression of three ICGs (PDL1, PDL2, EGFR) and TPD52L2 using 5 paired HNSCC and normal head and neck tissues. Polymerase Chain Reaction (PCR) and Western Blot (WB) of HNSCC and normal head and neck cell lines were performed to verify the high level of TPD52L2 mRNA and protein expression. protein expression of TPD52L2 in pan-cancer was also validated using UALCAN. RESULTS: TPD52L2 was overexpressed in tumor tissues, and it predicted worse survival status in HNSCC. ROC analysis suggested that TPD52L2 had a diagnostic value. Multivariate Cox analysis identified TPD52L2 as an independent negative prognostic marker of overall survival. Functional network analysis suggested that TPD52L2 was associated with immune-related signaling pathways, cell migration pathways, and cancer-related pathways. High expression of TPD52L2 was associated with a more mutant frequency of TP53. Notably, we found that the expression of TPD52L2 was closely negatively correlated with the infiltration levels of 15 types of immune cells and positively correlated with several immune markers. PCR, WB experiments, and UALCAN database verified the high level of TPD52L2 mRNA and protein expression. CONCLUSION: TPD52L2 is upregulated in HNSCC, which is an independent factor for adverse prognosis prediction. It probably plays a role in the negative regulation of immune cell infiltration. TPD52L2 might be a promising prognostic biomarker and therapeutic target in HNSCC.

Mitochondrial Pyruvate Carrier 1 as a Novel Prognostic Biomarker in Non-Small Cell Lung Cancer.

BACKGROUND: Abnormal mitochondrial pyruvate carrier 1 (MPC1) expression plays a key role in tumor metabolic reprogramming and progression. Understanding its significance in non-small cell lung cancer (NSCLC) is crucial for identifying therapeutic targets. METHODS: TIMER 2.0 was utilized to assess the expression of MPC1 in both normal and cancer tissues in pan-cancer. Overall survival (OS) differences between high and low MPC1 expression were analyzed in NSCLC using the Cancer Genome Atlas (TCGA) datasets. We also examined the expression of MPC1 in NSCLC cell lines using western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). In addition, the tissue samples and clinical information of 80 patients with NSCLC from our hospital were collected. Immunohistochemistry (IHC) was used to assess MPC1 expression, and OS was evaluated using Kaplan-Meier curves and the log-rank test. Univariate and multivariate Cox regression analyses were conducted to evaluate the prognostic values of the clinical characteristics and MPC1expression. RESULTS: Analysis of public databases suggested that MPC1 was downregulated in NSCLC compared to that in normal lung tissue and predicted poor prognosis. In addition, the expression of MPC1 in NSCLC cell lines was lower than that in human bronchial epithelial (HBE) cells at both protein and mRNA levels. Further clinical analysis suggested that MPC1 expression was correlated with age, tumor T stage, and TNM stage. Kaplan-Meier analysis revealed that NSCLC patients with high MPC1 expression had a better prognosis, particularly in lung adenocarcinoma (LUAD), whereas no survival benefit was observed in lung squamous cell carcinoma (LUSC). Univariate and multivariate analyses suggested that MPC1 was an independent prognostic factor for patients with NSCLC. CONCLUSIONS: MPC1 is poorly expressed in NSCLC, particularly in LUAD, which predicts a poor prognosis and may serve as an independent prognostic factor. Further studies on MPC1 may reveal new targets for the treatment of NSCLC.

Surrogate Immunohistochemical Markers of Proliferation and Embryonic Stem Cells in Distinguishing Ameloblastoma from Ameloblastic Carcinoma.

PURPOSE: The current study aimed to investigate the use of surrogate immunohistochemical (IHC) markers of proliferation and stem cells to distinguish ameloblastoma (AB) from ameloblastic carcinoma (AC). METHODS: The study assessed a total of 29 ACs, 6 ABs that transformed into ACs, and a control cohort of 20 ABs. The demographics and clinicopathologic details of the included cases of AC were recorded. The Ki-67 proliferation index was scored through automated methods with the QuPath open-source software platform. For SOX2, OCT4 and Glypican-3 IHC, each case was scored using a proportion of positivity score combined with an intensity score to produce a total score. RESULTS: All cases of AC showed a relatively high median proliferation index of 41.7%, with statistically significant higher scores compared to ABs. ABs that transformed into ACs had similar median proliferation scores to the control cohort of ABs. Most cases of AC showed some degree of SOX2 expression, with 58.6% showing high expression. OCT4 expression was not seen in any case of AC. GPC-3 expression in ACs was limited, with high expression in 17.2% of ACs. Primary ACs showed higher median proliferation scores and degrees of SOX2 and GPC-3 expression than secondary cases. Regarding SOX2, OCT4 and GPC-3 IHC expression, no statistically significant differences existed between the cohort of ABs and ACs. CONCLUSION: Ki-67 IHC as a proliferation marker, particularly when assessed via automated methods, was helpful in distinguishing AC from AB cases. In contrast to other studies, surrogate IHC markers of embryonic stem cells, SOX2, OCT4 and GPC-3, were unreliable in distinguishing the two entities.

Expression of Types I and III Collagens and Ultrastructure of the Extracellular Matrix in Rectal Adenocarcinoma of Different Differentiation Degree after Neoadjuvant Radiation Therapy.

The structural organization of the extracellular matrix of rectal adenocarcinoma of different differentiation degrees without and after neoadjuvant radiation therapy was studied on postoperative material using immunohistochemistry and electron microscopy. The differences in the expression of types I and III collagens, as well as in the ultrastructural organization of the extracellular matrix of rectal adenocarcinoma of different differentiation degrees without and after neoadjuvant radiation therapy were revealed. We observed high expression of collagen I and wide channels in the collagen matrix in the central areas of the well differentiated adenocarcinomas without neoadjuvant radiation therapy and in poorly differentiated adenocarcinomas after neoadjuvant radiation therapy, which can be associated with metastasis and poor prognosis for the patients.

Comparison of B-cell lymphoma 2 (BCL-2) expression in disordered proliferative endometrium and simple endometrial hyperplasia.

BACKGROUND AND OBJECTIVE: B-cell lymphoma-2 (BCL-2) is an anti-apoptotic protein that may play a role in disordered proliferative endometrium (DPE) and endometrial hyperplasia (EH). Several studies have investigated BCL-2 expression in normal, hyperplastic endometrium and endometrial adenocarcinoma, with conflicting results. Therefore, the present study aimed to compare the expression of BCL-2 in disordered proliferative endometrium and simple EH. METHODS: In this cross-sectional study, 63 DPE and 67 SEH samples from patients referred to Mostafa Khomeini Hospital between 2017 and 2022 were immunohistochemically stained by BCL-2 antibody. BCL-2 expression in each sample was reported as negative, weak positive, and strong positive. The findings were analyzed using SPSS version 16 software. RESULTS: Negative, weakly positive, and strongly positive BCL-2 expression was observed in 55.6%, 38.1%, and 6.3% of DPE samples, and 61.2%, 31.3%, and 7.5% of SEH samples, respectively, which does not show a statistically significant difference (p=0.718). There was no relationship between the age of patients and BCL-2 expression in any of the two groups of DPE and SEH (p=0.378 and p=0.178, respectively). CONCLUSION: BCL-2 expression is observed with a relatively similar frequency in DPE and SEH samples, and it is probably under the control of oestrogen hormone as the main factor involved in the pathogenesis of these lesions.

Immunohistochemical evaluation of cyclin D1 and p63 in odontogenic keratocyst and unicystic ameloblastoma.

INTRODUCTION: Odontogenic keratocyst (OKC) and unicystic ameloblastoma (UA) are lesions of odontogenic origin. Both lesions are morphologically cysts. However, they are classified as developmental cysts and epithelial odontogenic tumours, respectively. Cyclin D1 (CCD1) dysregulation is associated with oncogenic activity and malignancies, while tumour protein p63 (p63) alterations are associated with tumourigenesis. AIM: To evaluate and compare the protein expression of CCD1 and p63 in sporadic OKC (OKC-sp), syndromic OKC (OKC-sy), and UA. MATERIAL AND METHODS: 45 cases from the Anatomical Pathology Department, Faculty of Dentistry, University of Chile were analysed and divided into groups: OKC-sp (n=15), OKC-sy (n=15) and UA (n=15), the latter categorised into intraluminal and/or luminal (n=7) and mural (n=8). Immunohistochemical staining for CCD1 and p63 proteins was performed from paraffin-embedded sections. Statistical analysis included the Shapiro-Wilk test, one-way ANOVA with Tukey's multiple comparisons, and Spearman's correlation coefficient (p<0.05). RESULTS: There was an involvement mainly in women in the mandibular area, and a high frequency of jaw expansion, especially in the mural UA. P63 protein expression was higher than CCD1 in all cystic lesions, particularly in mural UA (p<0.001). No correlation was found between CCD1 and p63 expression. CONCLUSION: P63 may serve as a valuable marker for evaluating cell proliferative activity in odontogenic cystic lesions, providing insights into the aggressive behaviour of mural UA.

[A 49-year-old woman with long-standing urinary symptoms. Histological and immunohistochemical study of a case of bladder mullerianosis]. / Mujer de 49 años con clínica urinaria de larga evolución. Estudio histológico e inmunohistoquímico de un caso de mullerianosis vesical.

Bladder müllerianosis is defined by the presence of Müllerian epithelium (endometrial, endocervical or endosalpinx) in the bladder. It is a rare benign disease that affects women and presents a non-specific clinical presentation that poses a broad differential diagnosis. We present the case of a 49-year-old woman who presented with recurrent urinary tract infections, urinary discomfort and abdominal pain. The approach is carried out by ultrasound and urethrocystoscopy that reveal the presence of a 5mm polypoid lesion that is removed. The histological study revealed bladder müllerianosis together with the complementary finding of glandular cystitis and cystic cystitis.

Immunohistochemical examination of immunoreactivity of transient receptor potential melastatin 2, glutathione peroxidase 4 and spexin in lichen planus.

BACKROUND: In this study, we aimed to investigate the potential contributions to the disease by examining the immunoreactivities of SPX in LP-affected skin tissue using immunohistochemical methods, in light of its recent prominence as a molecule related to diabetes mellitus, along with apoptosis and ferroptosis mediated by GPX4 and TRPM2 channels facilitating oxidative stress-induced cell death. OBJECTIVE: This research explored the immunohistochemical expressions of TRPM2, GPX4, and SPX in Lichen Planus (LP) patients compared to healthy individuals. MATERIALS AND METHODS: Forty skin samples were collected, split equally between LP patients and healthy controls, excluding those with other conditions. Samples underwent immunohistochemical staining for TRPM2, SPX, and GPX4, using secondary antibodies and chromogens AEC or DAB. Histoscores were calculated based on staining diffusiveness and severity. Statistical analyses were performed with SPSS 22.0, using t-tests and ANOVA, with significance set at p < 0.05. RESULTS: There were no demographic differences between groups (p > 0.05). LP patients showed significantly lower TRPM2 and GPX4 histoscores and higher SPX histoscores compared to controls (TRPM2 and GPX4: p < 0.001, SPX: p < 0.001). Gender and age did not affect histoscores significantly. CONCLUSIONS: Findings suggest TRPM2, GPX4, and SPX play roles in LP pathogenesis, indicating a need for further molecular studies to clarify their involvement. This contributes to understanding LP beyond the traditional apoptosis perspective.

Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.

PURPOSE: Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. METHODS: We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. RESULTS: Fifteen lesions (3-42 mm) were identified, predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AML contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four AL contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included ulceration, thrombosis, inflammation, myxoid change, senescent nuclei, and extramedullary hematopoiesis; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin, desmin, and/or caldesmon) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. CONCLUSION: Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AML. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.

Amelioration of nephrotoxicity by targeting ferroptosis: role of NCOA4, IREB2, and SLC7a11 signaling.

Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms that disrupt iron homeostasis and lead to ferroptosis are yet to be elucidated. In this study, we aimed to investigate the involvement of nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor that mediates ferroptosis and autophagic degradation of ferritin in nephrotoxicity. Adult male Sprague-Dawley rats were randomly-assigned to four groups: control group, cisplatin (Cis)-treated group, deferiprone (DEF)-treated group, and Cis+DEF co-treated group. Serum, urine, and kidneys were isolated to perform biochemical, morphometric, and immunohistochemical analysis. Iron accumulation was found to predispose to ferroptotic damage of the renal tubular cells. Treatment with deferiprone highlights the role of ferroptosis in nephrotoxicity. Upregulation of NCOA4 in parallel with low ferritin level in renal tissue seems to participate in iron-induced ferroptosis. This study indicated that ferroptosis may participate in cisplatin-induced tubular cell death and nephrotoxicity through iron-mediated lipid peroxidation. Iron dyshomeostasis could be attributed to NCOA4-mediated ferritin degradation.

Segmental histomorphometry of the porcine ureter for use as a vascular xenograft.

PURPOSE: To histologically quantify the different tissues that make up the porcine ureter, (epithelial, connective, and muscular tissue) in the three segments labelled: cranial, middle and caudal, in order to identify the segment most compatible for use as a vascular graft. METHODS: Fifteen porcine ureters were collected, divided into the three segments, and the samples were stained with hematoxylin and eosin, picrosirius red and Weigert's resorcin-fuchsin. The immunohistochemistry technique was applied for alpha-smooth muscle actin. Collagen fibers, muscle, epithelium, and elastic fibers tissue were quantified, in the entire ureter, and divided into hemispheres, comparing the different segments. RESULTS: When comparing hemisphere segments, significant differences were observed (p < 0.01) for collagen and muscle tissue, with the cranial segment presenting the greatest amount of these components when compared to the middle and caudal. No significant difference was observed between the segments when comparing the entire ureters. CONCLUSIONS: After comparing the segments by hemisphere, the cranial segment presented a slight advantage for use as a vascular graft due to presenting greater collagen fiber content.

Leishmania infantum infection in European badgers (Meles meles) from northeastern Spain: a histopathological and immunohistochemical investigation.

The European badger (Meles meles) is a common mustelid species known as a significant reservoir for various human and animal diseases. Studies investigating Leishmania infection in European badgers across Mediterranean regions have yielded inconsistent findings. In Spain, results are particularly controversial: some studies confirm the presence of Leishmania in badgers, while others do not. Our study aimed to conduct a retrospective histopathological and immunohistochemical analysis to detect Leishmania in tissues of nine European badgers from northeastern Spain, a region previously unevaluated for Leishmania infection in this species. Microscopic examination revealed lesions indicative of leishmaniosis in the lymph nodes and spleens of six badgers. In one of them, Leishmania-like structures were identified in multiple organs and confirmed via immunohistochemistry. Parasites were detected in the lymph nodes, spleen, adrenal glands, and pancreas. The parasite load was high in the adrenal glands, moderate in the lymph nodes and spleen, and low in the pancreas. No parasites were found in other examined organs. This finding represents a frequency of 11.11% (1/9) of Leishmania infection among the badgers we studied. Further investigation of wildlife and atypical reservoirs can enhance our understanding of the pathogenesis of this significant zoonotic disease.