Presence of Merkel cell polyomavirus DNA and large-T antigen in keratinocyte carcinomas and its correlation with immunohistochemical markers p16, p53 and ki67

Abstract Background Merkel cell polyomavirus (MCPyV), a human polyomavirus that is unequivocally linked to merkel cell carcinoma (MCC), has been found in association with keratinocytes carcinomas (KC), especially basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Nevertheless, there is scarce information about the possible involvement of MCPyV in the development of KC. Objectives To assess the presence of MCPyV DNA and Large-T Antigen (LT-Ag) via Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) in cases of KC, and to correlate its presence with immunohistochemical markers p16, p53, and ki67, tumor type and subtype, sun-exposed location, and epidemiological data. Methods The prevalence of MCPyV DNA, LT-Ag, and immunohistochemical markers p16, p53, and ki67 was assessed by PCR and Immunohistochemistry (IHC) in 127 cases of KC, these results were correlated with tumor type and subtype, sun-exposed location, and epidemiological data. Results The MCPyV DNA was detected in 42.57% (43 of 101) cases by PCR, the LT-Ag was detected in 16.4% (20 of 122) of cases, p16 in 81.5% (97 of 119), p53 in 66.4% (83 of 125), ki67 in 89% (73 of 82). No correlation between MCPyV LT-Ag and DNA confronted with tumor type, subtype, location site, and immunohistochemical markers was found. A single correlation between the MCPyV LT-Ag and cSCC tumors and peri-tumoral lymphocyte cells was noted. Study limitations Further steps need to be taken to better evaluate the MCPyV influence and its possible role in KC carcinogenesis, as the evaluation of the virus genome state, the gene sequence that encodes LT-Ag in the KC tumor cells, and in situ hybridization for viral DNA or RNA in these cells. Conclusions Despite the frequent detection of MCPyV in KC, the data available so far does not support the hypothesis of a causal relationship between them.

Metástasis cerebral múltiple de adenocarcinoma pancreático. Reporte de caso / Multiple Brain Metastases from Pancreatic Adenocarcinoma: A Case Report

Resumen Introducción: Las metástasis cerebrales son las lesiones malignas más comunes en el sistema nervioso central. Las metástasis cerebrales de cáncer pancreático son muy raras y con un pobre pronóstico. El objetivo del presente caso es describir una rara patología y el trabajo realizado para la atención del paciente. Reporte de caso: Hombre de 49 años con cambios de la personalidad, depresión y apatía. Cinco días previos a su ingreso se agregó a sus síntomas disartria, hemiparesia izquierda y desorientación, que progresó a un mayor deterioro del estado de alerta y que ameritó un manejo avanzado de la vía aérea. La tomografía de cráneo evidenció lesiones cerebrales quísticas. Se realizó una craniectomía descompresiva, así como drenaje y resección de lesión de mayor tamaño. El estudio de inmunohistoquímica reportó CK 19 en tumor cerebral, compatible con adenocarcinoma pancreático. Conclusiones: Se presentó un caso raro de metástasis cerebrales múltiples y sospecha de metástasis pulmonar, ambos secundarios a adenocarcinoma de páncreas primario. El paciente debutó con síntomas asociados a las lesiones cerebrales. La incidencia de metástasis cerebrales con un tumor primario pancreático es muy baja, y es un caso excepcional al debutar con síntomas neurológicos. La resección quirúrgica de la lesión cerebral tuvo un rol limitado en la mejoría clínica del paciente, ya que la progresión de la enfermedad fue rápida, pero útil para establecer la confirmación del diagnóstico mediante inmunohistoquímica. Al no contarse con pruebas de tamizaje para tumores pancreáticos, es difícil identificarlos en estadios tempranos y sin síntomas gastrointestinales presentes.

Abstract Introduction: Brain metastases are the most common malignant lesions in the central nervous system. Brain metastases from pancreatic cancer are very rare, with poor prognosis. The present paper aims to describe a rare pathology and the work carried out for the patient's care. Case report: 49-year-old man with personality changes, depression, and apathy. Five days before admission, he presented dysarthria, added left hemiparesis, and disorientation that progressed to sudden neurological deterioration that required advanced airway management. A computed tomography study was seen with cerebral cystic lesions. A decompressive craniectomy and drainage of the larger lesion was performed, with subsequent resection. The study protocol with immunohistochemistry reports CK 19, compatible with pancreatic adenocarcinoma. Conclusions: A rare case of multiple brain metastases and suspected lung metastasis, both secondary to primary pancreatic adenocarcinoma was presented. The patient began with symptoms associated with brain lesions. The incidence of brain metastases with a primary pancreatic tumor is very low, and this is an exceptional case when presenting with neurological symptoms. Surgical resection of the brain lesion had a limited role in the clinical improvement of the patient since the progression of the disease was rapid. Still, it was useful to establish a diagnosis by immunohistochemistry. Since there are no screening tests for pancreatic tumors, it is difficult to identify them in early stages and without gastrointestinal symptoms.

Elevada expressão de galectina-3 em cicatrizes excessivas: Um estudo piloto / Elevated expression of galectin-3 in excessive scars: A pilot study

Introdução: Cicatrizes hipertróficas e queloides são tipos de cicatrizes excessivas de cicatrização anormal da pele. Galectina-3 (gal-3) é uma proteína da família das lectinas capaz de identificar carboidratos, que podem se combinar e atuar em diversas moléculas. Na literatura, a ação da gal-3 como principal agente regulador da fibrogênese já foi descrita, sendo atualmente utilizada na terapia antifibrótica de diversos órgãos como pulmão e fígado. O objetivo deste estudo piloto foi mostrar resultados preliminares encontrados na expressão de gal-3 em cicatrizes exacerbadas. Método: Foram coletadas 20 amostras de biópsias de cicatrizes excessivas (16 queloides e 4 cicatrizes hipertróficas) e 9 amostras de cicatrizes normais de 22 mulheres e 7 homens. Essas amostras foram processadas para análise histopatológica de rotina por imuno-histoquímica para detectar gal-3. As células positivas para gal-3 foram quantificadas pelo método estereológico utilizando uma grade de 36 pontos. Resultados: A imuno-histoquímica mostrou alta expressão de gal-3 em células endoteliais e epiteliais de todas as amostras de cicatrizes, bem como expressão em células distribuídas pela derme. Maior expressão de gal-3 foi encontrada em amostras de queloides (28% de células positivas) em comparação com cicatrizes normais (18%) e hipertróficas (22%) (p=0,0075). Os resultados foram obtidos de um pequeno número de pacientes, por se tratar de um estudo piloto. Conclusão: Os dados sugerem que a gal-3 participa do processo de cicatrização e, devido à sua maior presença em amostras de queloides, pode ser um potencial biomarcador para formação de queloides e um alvo terapêutico promissor a ser explorado.

Introduction: Hypertrophic scars and keloids are types of excessive scars from abnormal skin healing. Galectin-3 (gal-3) is a protein from the lectin family capable of identifying carbohydrates, which can combine and act on different molecules. In the literature, the action of gal-3 as the main regulatory agent of fibrogenesis has already been described and is currently used in anti-fibrotic therapy for various organs such as the lung and liver. The objective of this pilot study was to show preliminary results found in the expression of gal-3 in exacerbated scars. Method: Twenty biopsy samples from excessive scars (16 keloids and 4 hypertrophic scars) and 9 samples from normal scars were collected from 22 women and 7 men. These samples were processed for routine histopathological analysis by immunohistochemistry to detect gal-3. Gal-3 positive cells were quantified by the stereological method using a 36-point grid. Results: Immunohistochemistry showed high expression of gal-3 in endothelial and epithelial cells of all scar samples, as well as expression in cells distributed throughout the dermis. Higher gal-3 expression was found in keloid samples (28% positive cells) compared to normal (18%) and hypertrophic (22%) scars (p=0.0075). The results were obtained from a small number of patients, as this was a pilot study. Conclusion: The data suggest that gal-3 participates in the healing process and, due to its greater presence in keloid samples, it may be a potential biomarker for keloid formation and a promising therapeutic target to be explored.

Comparative study of fine needle aspiration cytology and tru-cut biopsy in the diagnosis of breast lesions

Background: Breast carcinoma is one of the most researched cancers across the world. FNAC is often used as a first priority investigation in patients with breast lump. Tru-cut biopsy is useful in preoperative knowledge of prognostic parameters with the help of IHC markers ER, PR, Her2 neu. The technique is reliable, simple and reproducible which can be used even in resource poor countries like India. To analyze the sensitivity, specificity, positive predictive values and negative predictive values and the diagnostic accuracy (efficacy) of fine needle aspiration cytology and trucut biopsy. Methods: The study included 82 patients presenting with palpable breast lesions. All patients underwent FNAC followed by Tru-cut biopsy under ultrasound guidance. ER, PR, HER2 Neu, cytokeratin immunostaining was done in malignant cases. The data collected analysed statistically. Results: The sensitivity, specificity, PPV, NPV of FNAC were 96.61 %, 95.65 %, 98.28%, 90.91% respectively and that of trucut biopsy were 100%, 100%, 100%, and 100 % respectively. Conclusions: Out of total 82 patients, maximum no of cases (57) were duct carcinoma accounting 69.50% on FNAC and Tru-cut biopsy. IHC was done in all carcinomas. Maximum (46 cases) were luminal type. The present study emphasizes that tru-cut biopsy can serve as confirmative diagnostic tool over FNAC and provides information regarding prognostic factors and treatment modalities based on IHC markers.

Immunohistochemical expression of p53, ki-67, tenascin, and fibronectin in giant cell fibroma and traumatic fibroma of the oral mucosa

Objective: This study aimed to compare the immunoexpression of p53, ki-67, tenascin, and fibronectin between giant cell fibroma (GCF) and traumatic fibroma (TF), in order to explore a benign neoplastic or a reactive nature of GCF. Methods: A cross-sectional study was conducted. Samples of GCF and TF were retrieved from the files of Oral Pathology Service, matched by site and size. Immunohistochemistry for p53, ki-67, tenascin, and fibronectin was evaluated in the superficial and deep regions of the lesions using the Image J Software. The number of positive cells was determined for p53 and ki-67, and the positive area was established for tenascin and fibronectin. Statistical analysis was performed with Mann-Whitney and independent t-tests (p≤0.05).Results: Comparing to TF, GCF showed higher expression of p53 protein in superficial (p=0.009) and deep regions (p=0.027), as well as higher tenascin expression in deep regions (p=0.000). Ki-67 and fibronectin immunoexpression did not differ between GCF and TF (p>0.05). Conclusion: The results of the present study seem supportive of a benign neoplastic nature of GCF, rather than a reactive one, especially considering the p53 and tenascin expression. Further studies with larger samples and broader markers should confirm this hypothesis. (AU)

Diagnosis of HPV-associated oropharyngeal squamous cell carcinoma in a middle-income country: report of two new cases

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct subset characterized by better treatment responses and higher survival rates. Clinical and morphological aspects are crucial for diagnosis. Here we report two additional cases of HPV-associated OPSCC. Case 1: A 46-year-old male smoker and alcoholic presented with a 6 cm asymptomatic destructive ulcer involving multiple areas of the oropharynx. Microscopic analysis revealed non-keratinizing squamous cell carcinoma (SCC) with strong and diffuse cytoplasmatic and nuclear positivity for p16 in the tumor cells on IHC and ISH for HPV16/18 revealed the presence of viral DNA in a dot-like pattern. Case 2: A 53-year-old male smoker and alcoholic complained of dysphagia and exhibited erythematous areas in the uvula. Microscopically, a basaloid SCC was observed. Assessment of p16 expression showed diffuse moderate nuclear and cytoplasmatic positivity and ISH for DNA HPV16/18 also demonstrated dot-like signals. The present cases highlight the clinical and microscopical aspects of HPV-associated OPSCC. Pathologists and clinicians must remain vigilant in identifying HPV-associated OPSCC, even in cases where there is a history of alcohol and tobacco consumption. Assessment of p16 immunohistochemical patterns and ISH analysis are crucial to better understand the scenario of HPV-associated OPSCC in middle-income countries. (AU)

Clinicopathological and immunohistochemical study of canalicular adenoma

Objective: To evaluate the clinicopathological and immunohistochemical features of an original series of canalicular adenoma. Methods: Cases diagnosed as canalicular adenoma from a single center were retrospectively retrieved and clinical data collected from patients' charts. The histopathological features of all cases were reviewed and a large immunohistochemical panel carried out. Results: Eleven cases were collected, and no gender predilection was seen. A painless upper lip nodule was the most frequent clinical presentation. All cases presented the single-layer epithelial arrangement of tumor cells in a loose stroma. It was found an increased expression of low-weight cytokeratins, absence of myogenic markers, variable positivity for vimentin, S100 and GFAP, cytoplasmic and membrane reactivity for ß-catenin and a strong CD34 positivity, whereas no lymphatic vessel was identified using D2-40 antibody. Conclusion: Canalicular adenoma is composed of luminal epithelium with strong expression of low-weight cytokeratins, and peripheral expression of ß-catenin may be involved in the architectural maintenance of the tumor. (AU)

Mycobacterium tuberculosis bacilli in oral biopsies containing granulomatous inflammation with caseous necrosis

Objetive: This cross-sectional and retrospective study aimed to investigate the presence of Mycobacterium tuberculosis bacillus in formalin-fixed paraffin-embedded (FFPE) oral samples that contained granulomas with caseous necrosis. Methods: FFPE biopsies that showed granulomas with caseous necrosis, suggestive of the diagnosis of tuberculosis, were selected. M. tuberculosiswas searched by Ziehl-Neelsen staining (ZN), immunohistochemistry (IHC), nested-PCR, and GeneXpert® MTB/RIF assays. Results: Nine samples showing granulomas with caseous necrosis were selected. The study showed a male predominance, with a ratio of 2.5:1, with a mean age of 50 (19-89) years, and the tongue was the most affected anatomical site (n=4). The ZN technique did not detect bacilli in any sample, and IHC staining showed a coarse granular pattern staining, suggestive of M. tuberculosis, in three of them. Nested-PCR and the GeneXpert® MTB/RIF assays were positive in two and three of the samples, respectively. Conclusion: Molecular tests and IHC may be useful auxiliary methods for suspected cases of oral tuberculosis. (AU)

Assessing the diagnostic impact of P63, PSA and BCL-2 proteins in premalignant and malignant prostate tissues

Background: Prostate cancer (CaP) is increasingly becoming a major health issue affecting men as cancer-related fatalities are attributable to the condition. Immunohistochemistry (IHC) diagnostic criteria can help in gene-targeted therapy and help reduce its prevalence. This study is to assess the diagnostic impact of prostate-specific antigen (PSA), P63 and BCL-2 antibodies in CaP. Method: A case-controlled retrospective study was carried out on eighty (80) prostrate tissue blocks retrieved from the pathology archive of Ekiti State university teaching hospital Ado Ekiti. IHC analysis of the selected antibodies was carried out and also stained with haematoxylin and eosin (H and E) for second opinion and confirmation. Results: The study showed that all the CaP samples had 100% positivity with varying reactivity to the IHC biomarkers; PSA had 100% positivity and MPR of 94% due to its multiple weaknesses as a biomarker p63 is a basal cells marker. Conclusions: The expressions of these antibodies were observed in the progression of CaP. Although these markers are useful in predicting the progression from benign prostatic hyperplasia (BPH) to CaP, none of them can be utilised in isolation to a conclusion. Hence, they should be used in conjunction with one another to make up for their limitations. The immunohistochemical markers are beneficial in CaP diagnosis.

Exploring neuroendocrine carcinoma of the cervix: a case report and literature review

Neuroendocrine neoplasms (NENs) are rare, comprising less than 1% of cervical malignancies. Diagnosis and management of cervical neuroendocrine carcinoma (NEC) pose challenges due to its rarity and aggressive nature. Aim of the study was to highlight the importance of considering NEC in the differential diagnosis of cervical malignancies and underscore the potential benefits of comprehensive treatment approaches. We report a case of a 35-year-old woman presenting with post-coital bleeding, subsequently evaluated and diagnosed with NEC T1b1N0Mx following radical hysterectomy. Adjuvant chemoradiotherapy and chemotherapy led to one year of remission. Cervical NEC poses diagnostic and therapeutic challenges due to its rarity and aggressive nature. Despite multimodal treatment, prognosis remains poor, warranting further research and targeted therapies. The rarity of cervical NEC emphasizes the need for increased awareness among clinicians to facilitate early detection and appropriate management. Further studies are warranted to explore novel treatment modalities and improve outcomes for patients with this challenging malignancy.

Immunohistochemistry and next-generation sequencing for NTRK fusion detection in differentiated thyroid cancer of children, adolescents and young adults / Imunohistoquímica e sequenciamento nova geração para detecção de fusão NTRK em câncer diferenciado de tireoide em crianças, adolescentes e adultos jovens

INTRODUCTION: Pan-TRK immunohistochemistry staining can assess the protein expression from NTRK gene fusions. A little is known about its utility in differentiated thyroid cancer samples from children, adolescents, and young adults patients. Objective: Investigate pan-TRK immunohistochemistry sensitivity and specificity in differentiated thyroid cancer samples from children, adolescents, and young adults patients. METHODS: Tumor samples obtained from 79 children, adolescents, and young adults patients (age <21 years) diagnosed with differentiated thyroid cancer between January, 2010 and January, 2021 were retrospectively recruited from four health centers from state of Bahia e Paraíba, Brazil. NTRK gene fusion testing of all archival FFPE tumor samples: pan-TRK immunohistochemistry staining for TRKA, TRKB and TRKC protein expression were performed and then analyzed with RNA-based next-generation sequencing assay to confiC:\Users\yngrid.narciso\Desktop\CLIENTES\SITES\BJO\2024\5 - Maio\2024-05-02\siterm immunohistochemistry pan-TRK result and elucidate fusion partner. RESULTS: Pan-TRK immunohistochemistry: 3 of 79 cases had positive pan-TRK expression: next-generation sequencing; 4 were identified with NTRK gene fusion, pan-TRK immunohistochemistry was negative in all 4 NTRK next-generation sequencing-positive cases. 25 of 79 NTRK next-generation sequencing-negative control cases had concordant negative pan-TRK immunohistochemistry results. Therefore, our rate of false positive pan-TRK immunohistochemistry results was 3/25 (12%). The overall results for pan-TRK immunohistochemistry in our cohort of next-generation sequencing-negative cases was: (i) sensitivity (0%), (ii) specificity (96%), (iii) positive predictive value (94.7%), (iv) negative predictive value (91%). CONCLUSION: Pan-TRK immunohistochemistry was not a tissue-efficient screen for NTRK fusions in differentiated thyroid cancer from children, adolescents, and young adults patients. This is the largest cohort of from children, adolescents, and young adults differentiated thyroid cancer cases stained with pan-TRK immunohistochemistry, and it is the first to detail the sensitivity and specificity of pan-TRK immunohistochemistry regarding the data obtained by targeted RNA-based next-generation sequencing panel in differentiated thyroid cancer.

INTRODUÇÃO: A coloração imuno-histoquímica Pan-TRK pode avaliar a expressão proteica de fusões de genes NTRK. Pouco se sabe sobre sua utilidade em amostras diferenciadas de câncer de tireoide de crianças, adolescentes e adultos jovens. Objetivo: Investigar a sensibilidade e especificidade da imuno-histoquímica pan-TRK em amostras diferenciadas de câncer de tireoide de pacientes crianças, adolescentes e adultos jovens. MÉTODOS: Amostras tumorais obtidas de 79 pacientes crianças, adolescentes e adultos jovens (idade <21 anos) com diagnóstico de câncer diferenciado de tireoide entre janeiro de 2010 e janeiro de 2021 foram recrutadas, retrospectivamente, em quatro centros de saúde dos estados da Bahia e Paraíba, Brasil. Teste de fusão genética NTRK de todas as amostras de tumor FFPE arquivadas: coloração imuno-histoquímica pan-TRK para expressão da proteína TRKA, TRKB e TRKC foi realizada e depois analisada com ensaio de sequenciamento de próxima geração baseado em RNA, para confirmar o resultado imuno-histoquímico pan-TRK e elucidar o parceiro de fusão. RESULTADOS: Imunohistoquímica pan-TRK: 3 de 79 casos tiveram expressão pan-TRK positiva: sequenciamento de próxima geração; 4 foram identificados com fusão do gene NTRK, a imuno-histoquímica pan-TRK foi negativa em todos os 4 casos positivos para sequenciamento de próxima geração de NTRK. 25 dos 79 casos de controle negativo para sequenciamento de próxima geração de NTRK tiveram resultados de imuno-histoquímica pan-TRK negativos concordantes. Portanto, nossa taxa de resultados de imuno-histoquímica pan-TRK falsos positivos foi de 3/25 (12%). Os resultados gerais da imuno-histoquímica pan-TRK em nossa coorte de casos negativos para sequenciamento de próxima geração foram: (i) sensibilidade (0%), (ii) especificidade (96%), (iii) valor preditivo positivo (94,7%), (iv) valor preditivo negativo (91%). CONCLUSÃO: A imuno-histoquímica pan-TRK não foi uma triagem tecidualmente eficiente para fusões de NTRK em pacientes com câncer diferenciado de tireoide em crianças, adolescentes e adultos jovens. Esta é a maior coorte de casos de câncer diferenciado de tireoide de crianças, adolescentes e adultos jovens corados com imunohistoquímica pan-TRK, e é a primeira a detalhar a sensibilidade e especificidade da imunohistoquímica pan-TRK em relação aos dados obtidos por RNA direcionado baseado em um painel de sequenciamento de próxima geração no câncer diferenciado de tireoide.

Alpaca (Vicugna pacos) Skin Analyzed Under Architecture and Structure / Piel de Alpaca (Vicugna pacos) Analizada Bajo Arquitectura y Estructura

SUMMARY: This study evaluated the morphology of alpacas skin. Biopsies were collected and samples were fixed in 10 % neutral buffered formalin for histological procedures. The sections were stained with hematoxylin and eosin, picrosirius red and Masson's trichrome. Types I, III and IV collagen were analyzed by immunohistochemistry. The derma presented sebaceous and sweat glands, as well as follicular groups with medullated fibers. Type I and type IV collagen were observed at epidermis and dermis as well as in glandular structures and hair follicles. The collagen III, was observed only in dermis.

Este estudio evaluó la morfología de la piel de alpacas. Se recogieron biopsias y las muestras se fijaron en formalina tamponada neutra al 10 % para procedimientos histológicos. Las secciones se tiñeron con hematoxilina y eosina, rojo picrosirius y tricrómico de Masson. El colágeno tipo I, III y IV se analizó mediante inmunohistoquímica. La dermis presentó glándulas sebáceas y sudoríparas, así como grupos foliculares con fibras medulares. Se observó colágeno tipo I y tipo IV en la epidermis y la dermis, así como en estructuras glandulares y folículos pilosos. El colágeno III, se observó únicamente en la dermis.

Immunohistochemical expression of SNAIL and SLUG in endometrioid endometrial cancer and precursor lesions

Background: Endometrioid endometrial carcinoma is one of the most prevalent gynecologic cancers. The epithelial-mesenchymal transition is a multistep process involved in the development of cells that results in disappearance of intercellular adhesion in the epithelium and acquiring mesenchymal properties, hence influence cancer progression and metastasis. Loss of intercellular adhesion can be activated by different mechanisms, including transcriptional repression. However, the expression of transcriptional repressors in EEC and precursor lesions remain to be investigated. In the present study, we evaluated the immunohistochemical expression of proteins of transcriptional after repression snail and slug in EEC and its precursor lesions.Methods: It was a prospective nested case-control study on women from 35 to 70 years of age. Endometrial biopsies were obtained and processed for routine histological diagnosis. Immunohistochemical expression of snail and slug were evaluated.Results: A total of 39 EEC cases, 37 Endometrial hyperplasia and 19 normal controls were included in this study. Expression of snail was positive in 77% (30/39) and slug in 82% (32/39) of EEC cases while in precancer group snail was positive in 76% (28/37) and slug in 68% (25/37). In normal control snail was positive in 32% (6/19) and SLUG in 21% (4/19).Conclusion: Up-regulation of snail & slug observed in both precancer and cancer cases, suggesting their involvement from an early stage of carcinogenesis. Therefore therapies targeted at transcriptional repressors at an early stage of carcinogenesis, i.e., at precancerous lesions, could play a valuable role in reducing cancer progression and metastasis.

Nephroprotective effect of the methanolic fruit extract of Musa balbisiana Colla against carbon tetrachloride-induced toxicity in Swiss albino mice

Renal failure is the loss of renal functions owing to multiple factors, including oxidative stress, and it is a global concern, as it costs millions of lives every year. Carbon tetrachloride is a standard toxicant exploited to induce nephrotoxicity in experimental animals to study oxidative stress-related renal injury. This study was conducted to determine the nephroprotective activity of a methanolic extract derived from the unripe fruit pulp of Musa balbisiana Colla (MBME) in carbon tetrachloride-induced toxicity in Swiss albino mice. Multiple groups of mice were treated with a single dose of carbon tetrachloride (1-mg/kg body weight) intraperitoneally once in a week followed by oral administration of the methanolic fruit extract of M. balbisiana Colla (MBME) at two different doses (200 and 400 mg/kg body weight) consecutively for 28 days. Treatment with carbon tetrachloride reduced body weight along with enzymatic and non-enzymatic antioxidants in the renal tissue, elevated kidney weight, renal biomarkers, lipid peroxidation, IL-6, TNF-?, and TGF-? levels in the blood serum, impaired antioxidant system and up-regulated TGF-? expression in the kidney tissue, and brought histological changes in the architecture of renal tissues. Our data revealed that the oral administration of the methanolic fruit extract of M. balbisiana Colla (MBME) dose wisely restored kidney and body weight, renal biomarkers, enzymatic and non-enzymatic antioxidants in the renal tissue, reduced lipid peroxidation, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-?), and transforming growth factor-? (TGF-?) levels in the blood serum, re-established antioxidant system and down-regulated TGF-? expression in the kidney tissue, and re-established the architecture of renal tissues. Thus, this study reported the nephroprotective effects of methanolic fruit extract of M. balbisiana Colla (MBME) in carbon tetrachloride-induced toxicity in Swiss albino mice through possible antioxidant and anti-inflammatory activity.

CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration / CLCA1 se Expresa Deficientemente en el Adenocarcinoma de Estómago y se Correlaciona con la Infiltración Inmune

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.

El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.

A cutaneous malignant granular cell tumour: an uncommon entity with diagnostic challenge

Granular cell tumour (GCT) is rare and accounts for approximately 0.5% of all soft tissue tumours. The malignant GCT (MGCT) especially cutaneous malignant granular cell tumour is extremely rare constituting 1-2% of all granular cell tumours and mostly found in the subcutaneous soft tissues of lower exrtremities, especially thighs. The uncommon occurrence of cutaneous MGCT and their histopathological similarities with other entities make diagnosis difficult in some cases. Here we report a case of 36 years old male patient who presented with a mass in the skin of right lower abdominal wall which has been increased gradually over the last one year without pain. The size of the mass is approximately 6.5 cm in greatest dimension, firm in consistency with surface irregularity and ulceration diagnosed as malignant GCT at the histopathological examination showing focal ulceration and lined by keratinized stratified squamous epithelium revealing acanthosis and pseudoepitheliomatous hyperplasia. The dermis show neoplastic epithelioid cells arranged in sheets and nests with vesicular chromatin, conspicuous to prominent nucleoli, and abundant amount of fine granular eosinophillic cytoplasm. Mitosis is more than 2/10HP. Immunohistochemical stains for S-100, CD 68 and vimentin were positive in the lesional cells.

Tumor maligno de la vaina nerviosa periférica: reporte de un caso / Malignant peripheral nerve sheath tumor, a case report

Resumen El tumor maligno de la vaina nerviosa periférica (TMVNP) es un sarcoma de alto grado de malignidad. Es poco frecuente, agresivo y generalmente se localiza en tronco y miembros inferiores. Se presenta mayormente en pacientes con neurofibormatosis tipo 1, aunque no siempre se encuentra esta asociación. Este tumorcomparte características histológicas e inmunohistoquímicas con el melanoma, lo que puede dificultar el diagnóstico. Presentamos el caso de un paciente con TMVNP, en el cual los hallazgos histológicos iniciales condujeron a un diagnósticoerróneode melanoma.

Abstract Malignant peripheral nerve sheath tumor (MPNST) is a high-grade sarcoma. It is rare, aggressive and generally located on the trunk and lower limbs. It occurs in a high percentage of patients with neurofibormatosis type 1, although this association is not always found. This tumor shares histological and immunohistochemical characteristics with melanoma, which can make diagnosis difficult. We present the case of a patient with MPNST, in whom the initial histological findings led to an erroneous diagnosis of melanoma.

IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Schwannoma de colon derecho: a propósito de un caso / Schwannoma of the right colon: case report

RESUMEN El schwannoma de colon es una entidad sumamente rara que puede debutar como lesión subepitelial con signos ulcerativos de melena y anemia. El estudio de imágenes nos orienta a la localización mientras que la biopsia colonoscópica no es de ayuda. Muchas veces el diagnóstico y tratamiento se efectúa con la resección de la lesión en tanto que el diagnóstico final se realiza en el posoperatorio por histopatología y por la inmunohistoquímica, la cual muestra positividad intensa para S100 y vimentina en las células tumorales con un índice de proliferación KI67 menor al 1%, por lo que se concluye que se trata de una lesión benigna. Presentamos el siguiente caso por su dificultad diagnóstica pre e intraoperatoria, clínica inespecífica y diagnóstico definitivo por inmunohistoquímica.

ABSTRACT Colon schwannoma is an extremely rare entity that may debut as a subepithelial lesion with ulceration signs, such as melena and anemia. Imaging studies guide us to localization, while a colonoscopy biopsy is not helpful. Many times, the diagnosis and treatment are made with lesion resection, and the final diagnosis is postoperatively made with histopathology and immunohistochemistry, which shows intense positivity for S100 and vimentin in tumor cells with a KI67 proliferation index of less than 1%, therefore, it is concluded that this is a benign lesion. We present this case due to its pre- and intraoperative diagnostic difficulty, non-specific symptoms, and its definitive diagnosis that was achieved with immunohistochemistry.

Relationship between zinc finger protein A20, CTGF and FibroScan and fibrosis in chronic hepatitis B patients / 公共卫生与预防医学

Objective Studies on the expression and location of zinc finger protein A20 (A20) and connective tissue growth factor (CTGF) in liver tissues of patients with chronic hepatitis B were conducted, and the relationship between them and liver fibrosis was determined by FibroScan. Methods Studies on A20 and CTGF in liver tissues of 160 patients with chronic hepatitis B were conducted in accordance with the stage of pathological fibrosis and inflammation of the liver, and quantitative immunohistochemistry test was conducted, and statistical analysis was conducted by FibroScan. Results The expressions of A20 and CTGF in liver tissues increased with the aggravation of liver pathological fibrosis and inflammation, and there were significant differences between each stage and the control group (P0.05). There was positive correlation between liver A20 and CTGF, r=0.796 (P<0.05). Conclusions In patients with chronic hepatitis B, A20, CTGF and FibroScan are positively correlated with the degree of liver fibrosis, and A20 and CTGF are also positively correlated with the degree of liver inflammation, which can be used as indicators to evaluate the degree of liver inflammation and fibrosis, and further guide the anti-inflammatory and anti-fibrosis treatment of patients.