Células gigantes en lepra lepromatosa: dermatitis difusa con células gigantes exuberantes de tipo cuerpo extraño en lepra lepromatosa tratada / Giant cells lepromatous leprosy: Diffuse dermatitis with exuberant foreign body giant cells in treated lepromatous leprosy

Resumen Los pacientes con lepra lepromatosa que han recibido tratamiento durante años, usualmente requieren seguimiento con biopsias de piel para detectar lesiones persistentes o si la baciloscopia es positiva, incluso si los valores son menores que los iniciales. Se presenta el caso de una mujer de 48 años de edad con lepra lepromatosa de 15 años de evolución, índice bacilar de 4 en el extendido directo y en la biopsia, que recibió tratamiento con múltiples medicamentos durante 32 meses, aunque lo recomendado por la Organización Mundial de la Salud (OMS) es una duración de 12 meses. Se tomó una biopsia de piel para determinar si la enfermedad estaba activa. Se observó inflamación dérmica difusa con numerosas células gigantes de tipo cuerpo extraño y macrófagos vacuolados (células de Virchow). Estas células, CD68 positivas, contenían material granular ácido-alcohol resistente positivo con inmunohistoquímica para BCG. Se encontraron bacilos fragmentados y el índice bacilar fue de 2. Se interpretó como una forma residual de lepra lepromatosa y se concluyó que la paciente no requería prolongar el tratamiento con múltiples medicamentos. Este perfil histológico se ha observado en casos similares, pero sin datos clínicos estas biopsias representan un reto diagnóstico. La acumulación de lípidos en estas células gigantes se debe a la destrucción bacilar y a la fusión de macrófagos vacuolados. Se revisó el papel de los lípidos del bacilo y del huésped en la patogenia de la lepra lepromatosa. En estos casos, no es necesario extender los 12 meses de tratamiento con múltiples medicamentos recomendados por la OMS. En el seguimiento de los pacientes, se recomienda contar con los hallazgos clínicos, la baciloscopia, la biopsia anual de piel y los títulos IgM antiglucolípido fenólico.

Abstract Patients with lepromatous leprosy that have received treatment for many years usually get follow up biopsies for persistent skin lesions or positive bacilloscopy even if the values are lower than in the initial bacilloscopy. We report the case of a 48-year old woman with long-standing lepromatous leprosy of 15 years of evolution, with a bacterial index of 4 in the direct smear and the initial skin biopsy. The patient was treated with multidrug therapy for 32 months although the treatment recommended by the World Health Organization (WHO) is only for 12 months. A skin biopsy was taken to determine if there was an active disease. We observed a diffuse dermal inflammation with numerous foreign body giant cells and vacuolated macrophages (Virchow´s cells). These cells contained granular acid-fast material that was also positive with immunohistochemistry for BCG. There were fragmented bacilli and the BI was 2. These cells were also strongly positive for CD68. The biopsy was interpreted as a residual form of lepromatous leprosy that did not require further multidrug therapy. We have observed similar histological profiles in several cases. The lack of clinical data makes it a histological challenge. The accumulation of lipids in these giant cells is due to bacillary destruction and fusion of vacuolated macrophages. We discuss here the role of bacillary and host lipids in the pathogenesis of lepromatous leprosy. We concluded that there was no need to extend the 12-month multidrug therapy recommended by WHO. Clinical findings, bacilloscopy, annual skin biopsy, and anti-phenolic glycolipid-I IgM titers are recommended procedures for the follow-up of these patients.

[Artigo Parcialmente Retratado] Prevalência da infecção por Helicobacter pylori em pacientes dispépticos e associação com fatores de riscos clínicos para o desenvolvimento de adenocarcinoma gástrico / [article partial retraction] prevalence of helicobacter pylori infection in dyspeptic patients and its association with clinical risk factors for developing gastric adenocarcinoma

ABSTRACT BACKGROUND: In Brazil, particularly in the underdeveloped localities, the prevalence of Helicobacter pylori (H. pylori) infections can range up to 90%. These rates are higher in older individuals and vary by country region. H. pylori infections are linked to the development of gastric pathologies, namely mild to moderate gastritis, gastroenteritis, peptic ulcer, intestinal metaplasia, and gastric cancer. In 1994, this organism was classified by the International Agency for Research on Cancer (IARC) as pertaining to the Group 1 carcinogen for gastric adenocarcinoma etiology. Gastric cancer represents a significant public health problem, being the fourth most common malignant tumor and the second largest cause of cancer-related deaths. OBJECTIVE: To investigate the prevalence of H. pylori infection in dyspeptic patients and determine the link between clinical risk factors and gastric adenocarcinoma diagnosis. METHODS: Polymerase chain reaction (PCR) analysis was employed for molecular diagnosis of gastric tissue biopsies collected from 113 dyspeptic patients at the University Hospital of Federal University of Goiás. Molecular analyses allowed the identification of H. pylori infections. Furthermore, histopathological examinations were performed to determine the clinical risks of developing gastric malignancies. RESULTS: The test results identified 69 individuals older than 44 years, from 75 (66.4%) positive H. pylori infection samples. The prevalence of gastric adenocarcinoma in this study was 1.3%. Among the infected patients, six (8.2%) had high risk, and 67 (91.8%) had a low risk of developing gastric cancer (P<0.05). CONCLUSION: This study shows a high prevalence of H. pylori infection and identifies its contribution to gastric inflammations, which in the long term are manifested in high-risk clinical factors for the development of gastric adenocarcinoma.

RESUMO CONTEXTO: No Brasil, particularmente nas áreas mais pobres, a prevalência da infecção por Helicobacter pylori pode variar até 90%. Esses índices aumentam com o envelhecimento da população e são distintos entre as diferentes regiões do país. Podendo manifestar diferentes sintomatologias, essa infecção está diretamente relacionada com o desenvolvimento de patologias gástricas como gastrite leve a moderada, gastroenterites, úlcera péptica, metaplasia intestinal e principalmente, o câncer gástrico. Em 1994 a bactéria foi categorizada pela International Agency for Research on Cancer (IARC) como carcinógeno do Grupo 1 para adenocarcinoma gástrico, tipo de câncer que representa um importante problema de saúde pública, sendo o quarto tumor maligno mais comum e a segunda maior causa de mortes por câncer no mundo. OBJETIVO: Analisar a prevalência da bactéria em pacientes dispépticos e avaliar a associação de fatores de risco clínicos para desenvolvimento de adenocarcinoma gástrico. MÉTODOS: Biópsias de tecido gástrico coletadas de 113 pacientes dispépticos, atendidos no Hospital das Clínicas da Universidade Federal de Goiás, foram submetidas a diagnóstico molecular por meio de Reação em Cadeia da Polimerase, para identificação da infecção por Helicobacter pylori, e exame histopatológico, para avaliar o risco clínico de desenvolvimento de adenocarcinoma gástrico. RESULTADOS: Foram diagnosticadas 75 (66,4%) amostras positivas para infecção por Helicobacter pylori, sendo 69 indivíduos maiores de 44 anos de idade. A prevalência do adenocarcinoma gástrico nesse estudo foi de 1,3% e dentre os pacientes positivos para a infecção bacteriana seis (8,2%) possuem alto risco e 67 (91,8%) baixo risco de desenvolver esse tipo de câncer (P<0,05). CONCLUSÃO: Esse estudo mostra uma alta prevalência da infecção por H. pylori na população estudada e identifica sua intrínseca contribuição para inflamações gástricas, que a longo prazo se manifestam em fatores clínicos de alto risco para o desenvolvimento de adenocarcinoma gástrico.

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects

Abstract: The aim of this study was to evaluate macrophage M1 and M2 subpopulations in radicular cysts (RCs) and periapical granulomas (PGs) and relate them to clinical and morphological aspects. M1 macrophages were evaluated by the percentage of CD68 immunostaining associated with the inflammatory cytokine TNF-α, and M2 macrophages, by its specific CD163 antibody. The CD68+/CD163+ ratio was adopted to distinguish between the two macrophage subpopulations. Clinical, radiographic, symptomatology, treatment, and morphological parameters of lesions were collected and a significance level of p = 0.05 was adopted for statistical analysis. The results showed that the CD68+/CD163+ ratio was higher in the RCs (median = 1.22, p = 0.002), and the highest TNF-α immunostaining scores were found in RCs (p = 0.018); in PGs, the CD68+/CD163+ ratio was lower and associated with a greater CD163+ immunostaining (median = 1.02, p <0.001). The TNF-α in cyst epithelium had a score of 3 in 10 cases and predominance of M1 macrophages by CD68+/CD163+ (median = 2.23). In addition, CD68+ cells had higher percentage of immunostaining in smaller RCs (p = 0.034). Our findings suggest that increased CD68 immunostaining associated with TNF-α cytokine in RCs results in a greater differentiation of the M1 phenotype. The higher CD163 immunostaining in PGs results in greater differentiation of the M2 phenotype. Therefore, the inflammatory state promoted by M1 macrophages is related to growth and progression of RCs; on the other hand, the immunomodulatory state of M2 macrophages is related to maintenance of PGs.

Immunoexpression of vascular endothelial growth factor, beta-cell lymphoma 2 and cluster of differentiation 68 in cerebellar tissue of rats treated with Ganoderma lucidum / Inmunoexpresión del factor de crecimiento endotelial vascular, linfoma de células beta 2 y grupo de diferenciación 68 en tejido cerebeloso de ratas tratadas con Ganoderma lucidum

Traumatic brain injury (TBI) can potentially lead to hemorrhages in all areas of the skull, which can damage cells and nerve connections. This study aims to investigate the protective effects of Ganoderma lucidum polysaccharides (GLPS) as a antioxidant on cerebellar cell tissues after traumatic brain injury in rats. Sprague Dawley rats were subjected to TBI with a weight-drop device using 300 g1m weight-height impact. The groups are consisted of control, trauma, and trauma+Ganoderma lucidum groups. At seven days post-brain injury, experimental rats were decapitated after intraperitoneal administration of ketamine HCL (0.15 ml/100 g body weight). Cereballar samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) activity. Significant improvement was observed in cells and vascular structures of Ganoderma lucidum treated groups when compared to untreated groups. It is believed that Ganoderma lucidum may have an effect on the progression of traumatic brain injury. Ganoderma lucidum application may affect angiogenetic development in blood vessel endothelial cells, decrease inflammatory cell accumulation by affecting cytokine mechanism and may create apoptotic nerve cells and neuroprotective mechanism in glial cells.

La lesión cerebral traumática (LCT) puede provocar hemorragias en todas las áreas del cráneo, lo que puede dañar las células y las conexiones nerviosas. Este estudio tuvo como objetivo investigar los efectos protectores de los polisacáridos de Ganoderma lucidum (GLPS) como antioxidante en los tejidos de las células del cerebelo después de la lesión cerebral traumática en ratas. Ratas Sprague Dawley fueron sometidas a TBI con un dispositivo de caída de peso usando un impacto de peso de 300 g-1 m. Se formaron los siguientes grupos: control, trauma y trauma + Ganoderma lucidum. Siete días después de la lesión cerebral, las ratas experimentales fueron decapitadas después de la administración intraperitoneal de ketamina HCL (0,15 ml / 100 g de peso corporal). Se tomaron muestras cerebrales para el examen histológico y para la determinación de niveles de malondialdehído (MDA) y glutatión (GSH) y actividad de mieloperoxidasa (MPO). Se observó una mejora significativa en las células y las estructuras vasculares de los grupos tratados con Ganoderma lucidum en comparación con los grupos no tratados. Durante el estudio se observó que Ganoderma lucidum puede tener un efecto sobre la progresión de la lesión cerebral traumática. La aplicación de Ganoderma lucidum puede afectar el desarrollo angiogénico en las células endoteliales de los vasos sanguíneos, disminuir la acumulación de células inflamatorias al afectar el mecanismo de las citocinas y puede crear células nerviosas apoptóticas y un mecanismo neuroprotector en las células gliales.

Histological variability and the importance of clinicopathological correlation in cutaneous Rosai-Dorfman disease

Abstract: Rosai-Dorfman disease is a benign histiocytic proliferative disorder of unknown etiology. The disease mainly affects lymph node tissue, although it is rarely confined to the skin. Here, we describe a 53-year-old woman with purely cutaneous Rosai-Dorfman disease. The patient presented with a large pigmented plaque on her left leg, and sparse erythematous papules on her face and arms. A complete clinical response was achieved with thalidomide, followed by recurrence at the initial site one year later. The histological examination displayed the typical features of Rosai-Dorfman disease in the recent lesions but not in the older lesions. In the setting of no lymphadenopathy, the histopathological features of Rosai-Dorfman disease are commonly misinterpreted. Therefore, awareness of the histological aspects present at different stages, not always featuring the hallmark microscopic signs of Rosai-Dorfman disease, is particularly important for a correct diagnosis of this rare disorder.

Inflammatory response of human dental pulp to at-home and in-office tooth bleaching

ABSTRACT Tooth bleaching is a technique of choice to obtain a harmonious smile, but bleaching agents may damage the dental pulp. Objective: This study evaluated the inflammatory responses of human dental pulp after the use of two bleaching techniques. Material and Methods: Pulp samples were collected from human third molars extracted for orthodontic reasons and divided into three groups: control - no tooth bleaching (CG) (n=7); at-home bleaching with 15% carbamide peroxide (AH) (n = 10), and in-office bleaching with 38% hydrogen peroxide (IO) (n=12). Pulps were removed and stained with hematoxylin-eosin for microscopic analysis of inflammation intensity, collagen degradation, and pulp tissue organization. Immunohistochemistry was used to detect mast cells (tryptase+), blood vessels (CD31+), and macrophages (CD68+). Chi-square, Kruskal-Wallis, and Mann Whitney tests were used for statistical analysis. The level of significance was set at p<.05. Results: The inflammation intensity and the number of macrophages were significantly greater in IO than in AH and CG (p<0.05). The results of CD31+ (blood vessels per mm2) were similar in CG (61.39±20.03), AH (52.29±27.62), and IO (57.43±8.69) groups (p>0.05). No mast cells were found in the pulp samples analyzed. Conclusion: In-office bleaching with 38% hydrogen peroxide resulted in more intense inflammation, higher macrophages migration, and greater pulp damage then at-home bleaching with 15% carbamide peroxide, however, these bleaching techniques did not induce migration of mast cells and increased the number of blood vessels.

Three days of intermittent stretching after muscle disuse alters the proteins involved in force transmission in muscle fibers in weanling rats

The aim of this study was to determine the effects of intermittent passive manual stretching on various proteins involved in force transmission in skeletal muscle. Female Wistar weanling rats were randomly assigned to 5 groups: 2 control groups containing 21- and 30-day-old rats that received neither immobilization nor stretching, and 3 test groups that received 1) passive stretching over 3 days, 2) immobilization for 7 days and then passive stretching over 3 days, or 3) immobilization for 7 days. Maximal plantar flexion in the right hind limb was imposed, and the stretching protocol of 10 repetitions of 30 s stretches was applied. The soleus muscles were harvested and processed for HE and picrosirius staining; immunohistochemical analysis of collagen types I, III, IV, desmin, and vimentin; and immunofluorescence labeling of dystrophin and CD68. The numbers of desmin- and vimentin-positive cells were significantly decreased compared with those in the control following immobilization, regardless of whether stretching was applied (P<0.05). In addition, the semi-quantitative analysis showed that collagen type I was increased and type IV was decreased in the immobilized animals, regardless of whether the stretching protocol was applied. In conclusion, the largest changes in response to stretching were observed in muscles that had been previously immobilized, and the stretching protocol applied here did not mitigate the immobilization-induced muscle changes. Muscle disuse adversely affected several proteins involved in the transmission of forces between the intracellular and extracellular compartments. Thus, the 3-day rehabilitation period tested here did not provide sufficient time for the muscles to recover from the disuse maladaptations in animals undergoing postnatal development.

Tumor-associated macrophages (TAMs): clinical-pathological parameters in squamous cell carcinomas of the lower lip

Abstract The objective of this study was to analyze the presence of tumor-associated macrophage (TAM) subpopulations M1 and M2 in squamous cell carcinoma of the lower lip (SCCLL) by immunohistochemitry, and to evaluate the possible role of these subtypes in the development of regional lymph node metastasis and their association with clinical and pathological parameters. Forty-two cases of SCCLL were divided into two groups (21 with and 21 without regional lymph node metastasis). The histopathological grade of malignancy was determined and the material was submitted to double staining with anti-CD68/anti-CD163 and anti-CD68/anti-HLA-DR monoclonal antibodies. The results were analyzed statistically using the Wilcoxon signed-rank and Spearman correlation tests. The M1 and M2 subpopulations were observed in all cases studied. No significant difference was observed between the quantities of M1 and M2 TAMs regarding tumor size (p > 0.05). A significantly larger number of M2 compared to M1 TAMs was observed in tumors without regional lymph node metastasis, tumors in early stages, and low-grade tumors (p < 0.05). No significant difference between the numbers of M1 and M2 TAMs was observed in tumors with regional lymph node metastasis, tumors in advanced stages, and high-grade tumors (p > 0.05). There was a positive weak correlation between M1 and M2 TAMs (r = 0.361; p = 0.019). The results suggest a more important role of M2 TAMs in early stages than advanced stages of lip carcinogenesis. The progression of SCCLL does not seem to be related to an imbalance of macrophage polarization in the microenvironment of these tumors.

Expression of VEGF and CD68 in the placenta of gestational diabetic mothers (immunohistochemistry and ultrastructural study) / Expresión de VEGF y CD68 en la placenta de madres diabéticas gestacionales (estudio inmunohistoquímico y ultraestructural)

Placental angiogenesis, is essential for embryonic and fetal development. In this study, 18 gestational diabetes mellitus and 22 control pregnancies were included. Gestational diabetes mellitus (GDM) groups compared to the control group significantly higher values were detected (p<0.01). The following histological results were assessed; villous immaturity, chorangiosis, presence of, sncytial knots,mononuclear cell infiltration ischemia and fibrinoid necrosis. To evaluate and compare the placental histology of normal and GDM pregnancies. placentas of pregnant women with gestational diabetes also in terms of angiogenesis and macrophages and ultratructural revealed by examining the possible relationship between fetal complications were investigated.

La angiogénesis de la placenta es esencial para el desarrollo embrionario y fetal. En este estudio, se incluyeron 18 casos de diabetes mellitus gestacional (DMG) y 22 embarazos de control. En grupos los de DMG en comparación con el control, se detectaron valores significativamente mayores (p<0,01) en los siguientes parámetros histológicos que fueron evaluados: inmadurez vellosa, chorangiosis, presencia de nodos sincicial, infiltración celular isquémica mononuclear y necrosis fibrinoide. La investigación de las placentas de mujeres con DMG, reveló mediante el examen en términos de angiogénesis, macrófagos y ultraestructural, la posible relación entre las complicaciones fetales.

T-cell/myeloid mixed-phenotype acute leukemia with monocytic differentiation and isolated 17p deletion

Mixed phenotype acute leukemia is a rare subtype of leukemia that probably arises from a hematopoietic pluripotent stem cell. The co-expression of two of myeloid, B- or T-lymphoid antigens is the hallmark of this disease. Herein, the case of a 28-year-old female patient is reported who presented with hemoglobin of 5.8 g/dL, white blood cell count of 138 × 109/L and platelet count of 12 × 109/L. The differential count of peripheral blood revealed 96% of blasts. Moreover, the patient presented with lymphadenopathy, splenomegaly and bone marrow infiltration by monocytoid blasts characterized as 7% positivity by Sudan Black cytochemical staining. Immunophenotyping revealed the involvement of blasts of both T- and monocytic lineages. The cytogenetic analysis showed an isolated 17p deletion. Thus, the diagnosis of T-cell/myeloid mixed phenotype acute leukemia was made with two particular rare features, that is, the monocytic differentiation and the 17p deletion as unique cytogenetic abnormalities. The possibility of concomitant expressions of T-cell and monocytic differentiation antigens in the same blast population is hard to explain using the classical model of hematopoiesis. However, recent studies have suggested that myeloid potential persists even when the lineage branches segregate toward B- and T-cells. The role of an isolated 17p deletion in the pathogenesis of this condition is unclear. At present, the patient is in complete remission after an allogeneic stem cell transplantation procedure...

Case for diagnosis / Caso para diagnostico

Granular cell tumor is a rare benign neoplasm of neural origin. We report the case of a female patient, 27 years old presenting a brown-red nodule in the right arm, which pathological examination showed to be formed by polygonal cells with eosinophilic granular cytoplasm and immunohistochemistry positive for S100 protein and CD68. Granular cell tumor is usually solitary and in half the cases located in the head and neck areas, 30% of these in the tongue. It is most frequent between the third and fifth decades of life in women and people of African-American ethnicity. Its origination is controversial, including the possible origins in muscle, fibroblasts, neural crest, neural sheath or histiocytes. The positivity for S-100 and CD68 suggest the neural origin.

O tumor de células granulares é uma neoplasia benigna rara, de origem neural. Relatamos caso de paciente feminina, 27 anos, com nódulo de superfície acastanhada no braço direito, cujo exame anatomopatológico evidenciou densa proliferação de células, com amplo citoplasma contendo grânulos eosinofílicos, e imuno-histoquímica positiva para proteínas S100 e CD68. O tumor de células granulares é geralmente solitário e, em metade dos casos, localiza-se em cabeça e pescoço, dos quais 23% na língua. É mais frequente entre a terceira e a quinta décadas de vida, em mulheres e pessoas de etnia negra. A positividade para S-100 e CD68 favorece origem neural.

Tumor-Infiltrating Macrophage and Microvessel Density in Oral Squamous Cell Carcinoma

Tumor-associated macrophages (TAM) are the main cellular component in stroma of many tumors and participate in tumor angiogenesis. The aim of present study was to compare the microvascular density (MVD) and infiltrating macrophage density (IMD) in oral squamous cell carcinomas (OSCCs) with different histological grades. A histomorphometric analysis was performed after immunohistochemistry using antibodies such as von-Willebrand factor and CD68. A significant difference in MVD was found between well and moderately differentiated OSCCs (p<0.05). TAM were largely present in all studied tumors and the IMD was not different among OSCCs with different histological grades (p=0.381). Significant correlation between MVD and IMD was not observed (p=0.870). In conclusion, these results suggest that TAM and angiogenesis have an influence at different histological grades of OSCC. However, the lack of correlation between MVD and IMD could suggest that angiogenesis does not depend on the number of macrophages present in OSCC, but their predominant phenotype. Further studies involving distinct phenotypes of macrophages should be done to better understand the influence of TAM on the tumor angiogenesis.

Macrófagos associados a tumores (MAT) representam o componente principal do estroma de muitos tumores, além de participar da angiogênese tumoral. Este estudo comparou a microdensidade vascular (MDV) e densidade de macrófagos infiltrando o tumor (DMIT) em carcinoma escamocelular da boca (CEC) com diferentes graus histológicos de malignidade. Análise histomorfométrica foi empregada após técnica imuno-histoquímica para os anticorpos fator von-Willebrand e CD68. Uma diferença significante entre MDV e carcinomas bem e moderadamente diferenciados foi observada (p<0,05). MAT estavam fortemente presentes em todos os tumores estudados e a DMIT não foi diferente entre os diferentes graus histológicos de malignidade do CEC (p=0,381). Correlação significante entre MDV e DMIT não foi observada (p=0,870). Em conclusão, os resultados desse estudo sugerem a influência de MAT e angiogênese nos diferentes graus histológicos de malignidade do CEC. Entretanto, a ausência de correlação entre MDV e DMIT sugere que a angiogênese não depende do número de macrófagos presentes neste tipo de câncer, mas do fenótipo predominante. Outros estudos devem ser realizados a fim de contribuir para melhor compreensão da participação de MAT na angiogênese tumoral.

Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis

Disseminated leishmaniasis (DL) differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules) in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW)-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics). Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.

S100, CD68, and MHC class II molecule expression in cervical high- and low-grade HPV-induced lesions / Expressão de S100, CD68 e moléculas de MHC classe II em lesões cervicais de alto e baixo grau induzidas por HPV

INTRODUCTION: Some human papillomavirus (HPV) types are involved in malignant processes in the cervical epithelium, with 99 percent of cases attributed to oncogenic HPV infection. This study aimed to detect S100, CD68, and major histocompatibility complex class II (MHC-II) molecules in cervical uterine epithelial samples in patients with high- and low-grade lesions induced by HPV. METHODS: Fifty-eight samples from patients who were confirmed positive or negative for high-risk oncogenic HPV DNA, had histopathological diagnosis of cervical intraepithelial neoplasia (CIN) of grades I, II, or III, or were negative for intraepithelial lesion or malignancy were subjected to immunohistochemistry reaction to S100 protein, CD68, and MHC-II (HLA-DR alpha chain). RESULTS: The presence of MHC-II predominated in samples exhibiting histopathological alterations (p < 0.05). S100 detection was more numerous in carcinoma samples (CIN III) (75 percent). Presence of this protein correlated significantly (p < 0.05) with histopathological findings and viral load. CONCLUSIONS: A small expression of CD68 was observed, which may be explained by the observation in our study having been made on random microscopic fields and not on specific areas. The findings, such as the presence of S100 protein and MHC-II expression in samples with histological alterations, could suggest that the immune system fails to control HPV replication at the early stages of infection. Further studies with larger prospective data are necessary to confirm this result.

INTRODUÇÃO: Alguns tipos de papilomavirus humano (HPV) estão envolvidos em processos malignos no epitélio cervical, com 99 por cento dos casos atribuídos à infecção por HPV oncogênico. O objetivo deste estudo foi detectar a proteína S100, CD68 e moléculas de MHC-II (complexo principal de histocompatibilidade classe II) em amostras de epitélio cervical uterino, de pacientes com lesões de alto e baixo grau induzidas pelo HPV. MÉTODOS: Cinquenta e oito amostras de pacientes positivos ou negativos, confirmados, para DNA de HPV de alto ou baixo risco oncogênico, e que tiveram diagnóstico histopatológico de neoplasia intraepithelial cervical (NIC) de graus I, II ou III ou foram negativas para lesão intraepithelial e malignidade (NILM), foram submetidas à reação de imunohistoquímica (IHQ) para proteína S100, CD68 e MHC-II (HLA-DR cadeia alfa). RESULTADOS: A presença da molécula MHC-II predominou em amostras exibindo alterações histopatológicas (p < 0,05). A detecção de S100+ foi mais numerosa em amostras com carcinoma (NIC III) (75 por cento). A presença dessa proteína correlacionou-se significantemente (p < 0,05) com achados histopatológicos e a carga viral. CONCLUSÕES: Pequena expressão CD68+ foi observada, uma possível explicação seria que em nosso estudo as observações foram feitas em campo microscópicos aleatórios e não em áreas específicas. Os achados como a presença de S100 e a expressão de MHC-II, em amostras com alterações histológicas, podem sugerir que o sistema imune falha em controlar a replicação do HPV nas fases iniciais da infecção. Maiores estudos, com mais dados prospectivos, são necessários para confirmar esses resultados.

Caso para diagnóstico / Case for diagnosis

Relatamos um caso de histiocitose cefálica benigna em uma criança do sexo masculino, de um ano e três meses de idade que desenvolveu múltiplas pápulas na região malar bilateralmente, sem outros comemorativos associados. A histopatologia caracterizou-se pelo padrão derme papilar, com imuno-histoquímica negativa para S100 e CD1a, e positiva para CD68, ficando assim estabelecido o diagnóstico desta histiocitose não- Langerhans, baseado nos aspectos clínicos, histopatológicos e imuno-histoquímicos característicos.

The present paper reports a case of benign cephalic histiocytosis in a 15-month baby boy, who developed multiple papules bilaterally in the malar region with no other associated manifestations. Histopathology revealed a papillary dermal pattern, while immunohistochemistry was negative for S100 and CD1a and positive for CD68. Therefore, diagnosis was established as non-Langerhans cell histiocytosis, based on the clinical, histopathological and immunohistochemical features present.

Immunoarchitectural characterization of a human skin model reconstructed in vitro / Caracterização morfológica e imunoistoquímica de um modelo de pele humana reconstruída in vitro

CONTEXT AND OBJECTIVE: Over the last few years, different models for human skin equivalent reconstructed in vitro (HSERIV) have been reported for clinical usage and applications in research for the pharmaceutical industry. Before release for routine use as human skin replacements, HSERIV models need to be tested regarding their similarity with in vivo skin, using morphological (architectural) and immunohistochemical (functional) analyses. A model for HSERIV has been developed in our hospital, and our aim here was to further characterize its immunoarchitectural features by comparing them with human skin, before it can be tested for clinical use, e.g. for severe burns or wounds, whenever ancillary methods are not indicated. DESIGN AND SETTING: Experimental laboratory study, in the Skin Cell Culture Laboratory, School of Medical Sciences, Universidade Estadual de Campinas. METHODS: Histological sections were stained with hematoxylin-eosin, Masson's trichrome for collagen fibers, periodic acid-Schiff reagent for basement membrane and glycogen, Weigert-Van Gieson for elastic fibers and Fontana-Masson for melanocytes. Immunohistochemistry was used to localize cytokeratins (broad spectrum of molecular weight, AE1/AE3), high molecular weight cytokeratins (34βE12), low molecular weight cytokeratins (35βH11), cytokeratins 7 and 20, vimentin, S-100 protein (for melanocytic and dendritic cells), CD68 (KP1, histiocytes) and CD34 (QBend, endothelium). RESULTS: Histology revealed satisfactory similarity between HSERIV and in vivo skin. Immunohistochemical analysis on HSERIV demonstrated that the marker pattern was similar to what is generally present in human skin in vivo. CONCLUSION: HSERIV is morphologically and functionally compatible with human skin observed in vivo.

CONTEXTO E OBJETIVO: Nos últimos anos, diferentes modelos de pele humana reconstruída in vitro (PHRIV) foram descritos para uso clínico e aplicações em pesquisa na indústria farmacêutica. Antes de serem liberados para uso rotineiro como substitutos de pele humana, os modelos de PHRIV necessitam de testes (estudos) comparativos com a pele humana in vivo, por meio de análises morfológica (arquitetural) e imunoistoquímica (funcional). O objetivo deste trabalho é estudar as características imunoistoquímicas de um modelo de PHRIV desenvolvido em nosso serviço, comparando-as com a pele humana, para que esse modelo de PHRIV possa vir a ser testado clinicamente em casos de queimaduras e ulcerações de pele nos quais métodos tradicionais de tratamento não estejam indicados. TIPO DE ESTUDO E LOCAL: Estudo experimental laboratorial realizado no Laboratório de Cultura de Células da Pele da Faculdade de Ciências Médicas da Universidade Estadual de Campinas (FCM/Unicamp), Campinas, São Paulo, Brasil. MÉTODOS: Cortes histológicos foram corados com hematoxilina-eosina, tricrômio de Masson para fibras colágenas, ácido periódico-reagente de Schiff para membrana basal e glicogênio, Weigert-Van Gieson para fibras elásticas e Fontana-Masson para melanócitos. Estudo imunoistoquímico foi realizado para identificar citoqueratinas de amplo espectro de pesos moleculares (AE1/AE3), citoqueratinas de alto peso molecular (34βE12), citoqueratinas de baixo peso molecular (35βH11), citoqueratinas 7 e 20, vimentina, proteína S-100 (para melanócitos e células dendríticas), CD68 (KP1, histiócitos) e CD34 (QBend, endotélio). RESULTADOS: A histologia revelou similaridade satisfatória entre PHRIV e a pele in vivo. O estudo imunoistoquímico da PHRIV demonstrou padrão semelhante de marcadores usualmente presentes na pele humana in vivo. CONCLUSÃO: A PHRIV estudada é morfológica e funcionalmente compatível com a pele humana observada in vivo.

Immunohistochemical evaluation of the inflammatory response in periodontal disease

In order to contribute to the knowledge of the pathogenesis of periodontal disease, an immunohistochemical analysis of the density of inflammatory mononucleated cells and the number of dendritic cells was performed using anti-CD4, anti-CD20, anti-CD25, anti-CD68 and anti-protein S-100 antibodies in 17 cases of chronic gingivitis (CG) and 25 of chronic periodontitis (CP). The CD4+ and CD68+ cells exhibited a diffuse distribution in the connective tissue. CD20+ cell distribution was predominantly in groups and the CD25+ cells exhibited a diffuse or focal distribution. The S-100+ cells were identified in the epithelium and the lamina propria, exhibiting distinct morphology and number. The statistical analysis showed no significant differences (p>0.05) between CG and CP regarding the density of the CD4+ and CD20+ cells and the number of S-100+ cells. However, significant differences (p<0.05) were found between the groups in the density of CD25+ and CD68+ cells . The density of macrophages was greater in CG and the level of cellular activation of the lymphocyte infiltrate was greater in CP. No differences were detected between the aforementioned conditions regarding the density of the T and B lymphocytes and to the number of the dendritic cells.

Com o objetivo de contribuir para um melhor entendimento na etiopatogenia da doença periodontal, um análise imuno-histoquímica da densidade das células inflamatórias mononucleares e da quantidade das células dendríticas foi realizada utilizando os anticorpos anti-CD4, anti-CD20, anti-CD25, anti-CD68 and anti-proteína S-100 em 17 casos de gengivite crônica (GC) e 25 casos de periodontite crônica (PC). As células CD4+ e CD68+ exibiram distribuição difusa no tecido conjuntivo, enquanto que a distribuição das células CD20+ foi predominantemente em grupos, e as CD25+ exibiram distribuição ora difusa ora focal. As células S-100+ foram identificadas no epitélio e na lamina própria, exibindo morfologia e números distintos. A análise estatística não demonstrou diferenças estatisticamente significativas em relação a densidade das células CD4+ e CD20+ e no número de células S-100+ entre os casos de CG e PC. Entretanto, houve diferenças em relação a densidade das células CD25+ e CD68+ entre os grupos (p<0,05). A densidade dos macrófagos foi maior em GC e o nível de ativação celular do infiltrado linfocítico foi maior em PC, não havendo diferenças em relação a densidade de linfócitos T e B, bem como no número de células dendríticas entre as condições anteriormente mencionadas.