Deep learning for Alzheimer's disease: Mapping large-scale histological tau protein for neuroimaging biomarker validation.

Abnormal tau inclusions are hallmarks of Alzheimer's disease and predictors of clinical decline. Several tau PET tracers are available for neurodegenerative disease research, opening avenues for molecular diagnosis in vivo. However, few have been approved for clinical use. Understanding the neurobiological basis of PET signal validation remains problematic because it requires a large-scale, voxel-to-voxel correlation between PET and (immuno) histological signals. Large dimensionality of whole human brains, tissue deformation impacting co-registration, and computing requirements to process terabytes of information preclude proper validation. We developed a computational pipeline to identify and segment particles of interest in billion-pixel digital pathology images to generate quantitative, 3D density maps. The proposed convolutional neural network for immunohistochemistry samples, IHCNet, is at the pipeline's core. We have successfully processed and immunostained over 500 slides from two whole human brains with three phospho-tau antibodies (AT100, AT8, and MC1), spanning several terabytes of images. Our artificial neural network estimated tau inclusion from brain images, which performs with ROC AUC of 0.87, 0.85, and 0.91 for AT100, AT8, and MC1, respectively. Introspection studies further assessed the ability of our trained model to learn tau-related features. We present an end-to-end pipeline to create terabytes-large 3D tau inclusion density maps co-registered to MRI as a means to facilitate validation of PET tracers.

Smartphone adapter time trial analysis: A low-cost, time-efficient method to disseminate quality photomicrographs at the microscope.

BACKGROUND: Within the field of pathology there is a need for a uniform low-cost option for securing high-quality photomicrographs. Advances in smartphone photography and 3D-printing technology allow for custom adapters to be designed for the purpose of photomicrograph capture. METHODS: Photomicrograph acquisition was performed using four core modalities: a novel 3D-printed smartphone-to-microscope adapter, freehand smartphone-to-microscope technique, a commercial adaptor (LabCam Pro), and a microscope-mounted digital camera. Eight skin diagnoses were photographed using each of the modalities and time to image capture was measured. The photomicrographs were blindly reviewed by two academic dermatopathologists and one pathologist using a side-by-side comparison technique to determine the image quality. Cost assessments were evaluated by obtaining free pricing information on manufacturer websites. RESULTS: The 3D-printed adapter was the most efficient method of capturing a high-quality photomicrograph in addition to being budget neutral. The microscope-mounted camera produced the highest quality photomicrographs followed by the 3D-printed adapter. CONCLUSIONS: The 3D-printed smartphone-to-microscope adapter offers a low-cost, time-efficient method of capturing high-quality photomicrographs.

Estudo da correlação das proteínas INGs com a P53 em lesões odontogênicas epiteliais benignas / Study of the correlation of INGs proteins with P53 in benign epithelial odontogenic lesions

As proteínas INGs (inhibitor of growth gene) desempenham papel de supressoras tumorais e podem agir por vias dependentes, ou independentes, da p53 na sinalização do ciclo celular e da apoptose. Este trabalho investigou, por meio de imuno-histoquímica, a correlação entre a expressão das proteínas INGs e a expressão da proteína p53 em ceratocistos odontogênicos (20), TOAs (20) e ameloblastomas sólidos (20). Os espécimes foram submetidos à marcação utilizando os anticorpos anti-Ing3, anti-Ing4, anti-Ing5 e anti-p53. Foi realizada análise quantitativa levando-se em consideração a localização citoplasmática e/ou nuclear para as proteínas INGs e a localização nuclear para a proteína p53. A análise da imunoexpressão das proteínas ING1 e ING2 foi realizada em um estudo prévio e os resultados foram considerados apenas para a análise de correlação com as proteínas estudadas neste estudo. Os dados foram analisados pelo Statistical Package for Social Sciences para Windows (SPSS versão 22.0; IBM, USA). Para a comparação da imunoexpressão entre os grupos de lesões foi utilizado o teste de Kruskal Wallis, e para a investigação das correlações foi utilizado o teste de Spearman. Foram considerados significativos os valores de p ≤ 0.05. O presente estudo evidenciou redução da expressão nuclear e citoplasmática das proteínas ING3, ING4 e ING5 em ceratocistos odontogênicos (COs) e ameloblastomas (AMBs). Além disso, em alguns casos, a perda da expressão nuclear das INGs esteve negativamente correlacionada à expressão da proteína p53. As análises de correlação entre as proteínas INGs indicam a existência de mecanismos compensatórios entre as proteínas INGs em folículos dentários (FDs) e tumores odontogênicos adenomatoides (TOAs), estes mecanismos parecem ser menos evidentes em COs e AMBs. Observou-se redução na expressão da proteína ING3 em AMBs (p=0,003); redução na expressão da proteína ING4, tanto em AMBs (p=0,02) quanto em COs (p=0,001); e uma redução da expressão nuclear da proteína ING5 nos COs (p=0,09) e nos AMBs (p=0,012). Foram evidenciadas correlações positivas entre a expressão nuclear da p53 com a expressão citoplasma/núcleo da proteína ING1 (r=0,603; p=0,05) em COs, e com a expressão citoplasma/ núcleo das proteínas ING3 (r=0,475; p=0,034) e ING4 (r=0,448; p=0,047) em AMBs. Por fim, os resultados deste estudo sugerem que a redução na expressão nuclear das proteínas INGs pode ser um evento envolvido na etiopatogênese de lesões odontogênicas mais agressivas, e que a redução da expressão nuclear/citoplasmática das proteínas INGs não está relacionada ao aumento expressão da p53 em COs e AMBs, o que sugere que a expressão destas proteínas deve resultar em alterações funcionais de maneira independente da p53 em lesões odontogênicas (AU).

INGs (inhibitor of growth gene) proteins play a role of tumor suppressors and can act via p53-dependent or independent pathways in signaling cell cycle and apoptosis. The aim of this study is to evaluate correlation between expression of proteins of ING proteins and expression of protein p53 in dental follicles (DF), odontogenic keratocysts (OK), adenomatoid odontogenic tumors (AOT) and solid ameloblastomas (AMBs). The sample was intentional and non-probabilistic, consisting of 20 cases of solid AMBs, 20 cases of AOT, 20 cases of OKs and 10 samples of DFs. The specimens were subjected to immunohistochemical method, using antibodies anti-Ing3, anti-Ing4, anti-Ing5 and antip53. Quantitative analysis was performed taking into account cytoplasmic and / or nuclear location for ING proteins and nuclear location for the p53 protein. The analysis of ING1 and ING2 immunoexpressions was performed in a previous study and the results were considered only for the correlation analysis. Data were analyzed by Statistical Package for Social Sciences for Windows (SPSS version 22.0; IBM, USA). Kruskal Wallis test was used to compare the immunoexpression between the groups of lesions, and Spearman test was used to investigate correlations. Values of p ≤ 0.05 were considered significant. This study showed a reduction in nuclear and cytoplasmic expression of ING3, ING4 and ING5 in odontogenic keratocysts (OKs) and ameloblastomas (AMBs). In addition, in some cases, loss of INGs nuclear expression was negatively correlated with p53 expression. Correlation analyzes may indicate existence of compensatory mechanisms between all the ING proteins in dental follicles (FDs) and adenomatoid odontogenic tumors (TOAs). These mechanisms seem to be less evident in COs and AMBs. The results of this study showed a reduction in ING3 expression in AMBs (p = 0.003); a reduction in ING4 expression, in OKs (p = 0.02) and in AMBs (p = 0.001); and a reduction in ING5 nuclear expression, also in OK (p = 0.09) and in AMBs (p = 0.012). Positive correlations were found between p53 nuclear expression with ING1 cytoplasm / nucleus expression (r = 0.603; p = 0.05) in OKs, and with ING3 cytoplasm / nucleus expression (r = 0.475; p = 0.034) and also ING4 cytoplasm / nucleus expression (r = 0.448; p = 0.047) in AMBs. Finally, this study suggests that reduction in the expression of INGs proteins seems to be an event that occurred in etiopathogenesis of more aggressive odontogenic lesions. Futhermore, nuclear / cytoplasmic expression of INGs proteins is not related to increase in p53 expression in OKs and AMBs, which indicates that loss of expression of these proteins may results in functional changes independently of p53 (AU).

El dializador en el año 2017: mucho más que una membrana / The dialyser in the year 2017: much more than a membrane

No disponible

Cisto tireoglosso em assoalho bucal ­ relato de caso / Thyroglossal cyst in the buccal floor ­ case report

Cisto do Ducto Tireoglosso é a mais comum das patologias congênitas de linha média. Sua origem ocorre a partir da permanência de remanescentes epiteliais do trato tireoglosso durante o período embrionário. A localização mais comum do cisto é na linha média (ou ligeiramente fora da linha média) entre a tireóide e o osso hioide ou logo abaixo do osso hioide. Pode haver o desenvolvimento dos cistos em qualquer idade, porém há um maior índice de diagnósticos entre 10 e 20 anos. Um cisto tireloglosso pode se desenvolver em qualquer lugar ao longo de um ducto tireoglosso, embora cistos dentro da língua ou no chão da boca sejam raros. A localização ectópica, principalmente em assoalho bucal, é pouco citada na literatura. O procedimento cirúrgico de Sistrunk é indicado como o tratamento de escolha para a remoção do cisto, apresentando um baixo índice de recorrência. O presente trabalho teve como objetivo realizar uma breve revisão de literatura sobre o Cisto do Ducto Tireoglosso e relatar um caso clinico atípico de cisto do ducto tireoglosso localizado em assoalho bucal (AU).

Thyroglossal duct cyst is the most common of midline congenital pathologies. Its origin occurs due to the presence of epithelial remnants in the thyroglossal duct during the embryological formation. The most common location of a thyroglossal cyst is the midline (or slightly off midline), between the thyroid and the hyoid bone or just below the hyoid bone. These cysts can appear at any age, however there are greater number of cases reported between ten and twenty years old. A thyroglossal cyst can develop anywhere along a thyroglossal duct, although cysts within the tongue or in the floor of the mouth are rare. The ectopic localization, mainly in the buccal floor, is little mentioned in literature. Sistrunk surgical procedure is accepted as the operation of choice for thyroglossal duct cysts, with a lower recurrence rate. This report aims to present a brief review of literature on Thyroglossal Duct Cyst and reports an atypical clinical case of thyroglossal duct cyst located in the buccal floor (AU).

Planos conjugados y sistema de iluminación de Köhler en microscopía óptica / Conjugate planes and Köhler illumination in optical microscopy

Un adecuado conocimiento y comprensión del concepto de planos conjugados es de capital importancia en la utilización del microscopio por cuanto que desde hace ya bastante tiempo el diseño de los microscopios se basa en la correcta situación de sus dos conjuntos de planos conjugados. En 1893 August Köhler publicó el trabajo «Un nuevo sistema de iluminación en microfotografía» donde dio a conocer los fundamentos básicos de una técnica de iluminación que actualmente lleva su nombre. El conocimiento y aplicación de los principios del sistema de iluminación de Köhler constituye el elemento de mayor importancia en el correcto manejo de un microscopio. Dichos principios no siempre son bien conocidos y comprendidos por los usuarios del microscopio constituyendo una fuente frecuente de errores en microscopía, particularmente en microfotografía. En este artículo revisamos los principios básicos del concepto de planos conjugados y del sistema de iluminación de Köhler (AU)

Adequate knowledge and understanding of the concept of conjugate planes is of paramount importance in the use of the microscope and for a long time microscope design was based on the correct location of the two sets of conjugate planes. In 1893 August Köhler published the article «A new illumination system in microphotography» in which he introduced the basics of an illumination technique that now bears his name. The knowledge and application of the principles of the Köhler illumination system is the most important element in the proper handling of a microscope. These principles are not always well known or understood by the users of microscopes, frequently leading to errors in microscopy, particularly in photomicrography. This article reviews the basic principles of the concept of conjugate planes and Köhler illumination system (AU)

Expressão imuno-histoquímica do ativador de plasminogênio do tipo uroquinase e seu receptor em carcinoma epidermoide de língua oral e sua relação com parâmetros clínico-patológicos / Immunohistochemical expression of plasminogen activator of the urokinase type and its receptor in squamous cell carcinoma of tongue and their relationship with clinicopathological parameters

O carcinoma epidermoide oral (CEO) é a neoplasia maligna mais comum da cavidade oral, apresentando uma alta taxa de mortalidade. Devido a isto, a descoberta de biomarcadores que facilitem a compreensão do comportamento biológico desse tumor e aprimorem o tratamento é necessário. O ativador de plasminogênio do tipo uroquinase (uPA) e o seu receptor, uPAR, têm se destacado por atuarem na proteólise de estruturas da membrana basal e matriz extracelular, facilitando a invasão tumoral. O presente estudo se propôs a avaliar a imunoexpressão dessas proteínas em 46 casos de carcinoma epidermoide de língua oral (CELO). Esses resultados foram relacionados com a presença de metástase, estadiamento clínico TNM, recidiva locoregional, desfecho da lesão e gradação histológica de malignidade. A imunomarcação de cada caso foi avaliada semiquantitativamente, tanto no front de invasão como no centro do tumor, na qual foram atribuídos os escores: 0 (0% de células positivas), 1(1-10% de células positivas), 2 (11-50% de células positivas), 3 (mais de 50% de células positivas). A expressão do uPA foi observada em 93,5% dos casos no front de invasão, com predomínio do escore 2 (34,8%), e em 67,9% dos casos no centro do tumor, com predomínio do escore 1 (32,6%). De modo geral, os parâmetros clínicos não exerceram influência na imunoexpressão do uPA. Em relação à gradação histológica, foi observada uma maior expressão de uPA nos casos de alto grau de malignidade em relação aos de baixo grau de malignidade (p=0,05). Quando analisado em relação aos parâmetros morfológicos, foi identificado uma maior expressão do uPA nos casos de pior padrão de invasão (p=0,03).

A expressão do uPAR foi observada em 73,9% dos casos no front de invasão, com predomínio do escore 1 (45,65%), e em 47,5% dos casos no centro do tumor, com predomínio do escore 0 (54,35%). Embora não tenham sido observadas significâncias estatísticas em relação à metástase linfonodal, estadiamento clínico TNM, desfecho e gradação histológica, houve uma maior expressão do uPAR nos casos com recidiva locoregional em relação aos sem recidiva (p=0,04). Em relação à análise da localização tumoral, foi observada uma maior expressão de uPA e uPAR no front de invasão em relação ao centro do tumor (p<0,001). Na correlação entre uPA e uPAR, não foi observada significância estatística. Com base nestes resultados, sugere-se que o uPA e uPAR estejam envolvidos na progressão do CELO, atuando principalmente na região mais profunda do tumor. (AU)

Squamous cell carcinoma (SCC ) is the most common malignancy of the oral cavity (OSCC), with a high mortality rate. Due to this, the discovery of biomarkers that facilitate the understanding of the biological behavior of the tumor and improve treatment is necessary. Urokinase type plasminogen activator (uPA) and its receptor, uPAR, are responsible for the proteolysis of structures of the basement membrana and extracellular matrix, facilitating tumor invasion. This study aims to assess the immuno expression of these proteins in 46 cases of squamous cell carcinoma of the oral tongue (OTSCC). These results were related to the presence of metastasis, clinical TNM staging, locoregional recurrence, outcome of the lesion and histological grading. Immunostaining of each case was evaluated semiquantitatively, in the front of invasion and center of the tumor, in which scores were assigned: 0 (0% of positive cells), 1 (1-10% of positive cells), 2 (11 -50% positive cells) and 3 (more than 50% positive cells). The expression of uPA was observed in 93.5% (n=43) of the cases in the front of invasion, with predominance of score 2 (n=16; 34.8%) and in 67.9% (n=31) of the cases in the center of the tumor, with predominance of score 1 (n=15; 32.6%). Overall, the immunoexpression of uPA was not associated with clinical parameters. Regarding the malignant histological grading, a higher expression of uPA was observed in cases of high-grade malignancy comp ared to low-grade malignancy (p=0.05).

Regarding the morphological parameters, increased expression of uPA was observed in the worst mode of invasion (p=0.03 ). The expression of uPAR was observed in 73.9% of cases in the front of invasion, with a predominance of score 1 (n=21; 45.6 %), and in 47.5% (n=21) of the cases in the center of the tumor, with a predominance of score 0 (n=25; 54.4%). Although no statistical differences were observed in relation to lymph node metastasis, clinical TNM staging, outcome, and histological grading, there was a higher expression of uPAR in cases with locoregional recurrence (p=0.04). Regarding the tumor intra -localization, it was observed an increased expression of uPA and uPAR at the front of invasion in relation to the center of the tumor (p<0.001). Regarding the correlation between uPA and uPAR, there was no statistical sign ificance. Based on these results, it is suggested that uPA and uPAR are involved in the progression of CELO, mainly in the deeper region of the tumor. (AU)

Avaliação imunoistoquímica de CD34 e triptase em cistos odontogênicos radiculares e cistos dentígeros inflamados / Immunohistochemical evaluation of CD34 and tryptase in root odontogenic cysts and inflamed dentigerous cysts

Dentre os cistos odontogênicos comumente encontrados na prática clínica odontológica, os cistos radiculares (CRs) e os cistos dentígeros (CDs) representam conjuntamente os mais frequentes cistos dos ossos gnáticos. Os cistos odontogênicos possuem origem inflamatória ou de desenvolvimento. No entanto, alterações inflamatórias secundárias podem ser vistas nos últimos. Alguns estudos têm identificado os mastócitos nessas lesões císticas e sua possível relação com a angiogênese. Nesta perspectiva, a presente pesquisa objetivou avaliar e comparar a expressão imunoistoquímica do CD34 e da triptase em CDs inflamados e CRs e verificar se os mastócitos influenciam na angiogênese destas lesões. Para tanto, foram selecionados 20 casos de CDs inflamados e 20 casos de CRs para serem submetidos à análise morfológica e imunoistoquímica. A imunomarcação de cada caso foi avaliada de forma quantitativa. Após a identificação das áreas de maior imunorreatividade, foram analisadas a densidade microvascular (DMV), a área microvascular (AMV) e o perímetro microvascular (PMV) mensurados através da imunoexpressão do CD34 e a densidade dos mastócitos (DMC) mensurada por meio da imunoexpressão da triptase, realizadas nas mesmas áreas dos consecutivos campos representativos de cada caso.

A análise estatística foi realizada através dos testes de Mann-Whitney, Qui-quadrado de Pearson, Exato de Fisher e Correlação de Spearman (r), com nível de significância estabelecido em 5% (p < 0,05). Os resultados demonstram diferenças estatisticamente significativas entre as lesões císticas supracitadas em relação à avaliação da DMC (p < 0,001). Além disso, a análise da DMV revelou diferenças estatisticamente significativas entre as lesões císticas (p = 0,007) e também no que se refere à intensidade do infiltrado inflamatório (p = 0,021). Por fim, observou-se nos casos de CDs inflamados, moderada correlação positiva entre a DMC e a AMV (r = 0,660; p = 0,002), assim como moderada correlação positiva entre a DMC e o PMV (r = 0,634; p = 0,003). Face ao exposto, pode-se concluir que os mastócitos participam em diferentes etapas da angiogênese associada à inflamação dos CRs e CDs. (AU)

Among the odontogenic cysts commonly found in dental clinical practice, radicular cysts (RCs) and dentigerous cysts (DCs) together represent the most common cysts of gnathic bones. Odontogenic cysts feature inflammatory or developmental origin. However, secondary inflammatory changes can be seen in the latest. Some studies have identified mast cells in these cystic lesions and its possible relation to angiogenesis. From this perspective, the present study aimed to evaluate and compare the immunohistochemical expression of CD34 and tryptase in inflamed RCs and DCs and to verify if mast cells influence the angiogenesis of these lesions. For this purpose, we selected 20 cases of inflamed DCs and 20 cases of RCs to undergo morphological and immunohistochemical analysis. Immunostaining of each case was evaluated quantitatively. After identifying the areas of greatest immunoreactivity, we analyzed microvessel density (MVD), microvessel area (MVA) and microvascular perimeter (MVP), measured by CD34 immunostaining, and the density of mast cells (DMC), measured by tryptase immunostaining, which were held in the same representative areas of consecutive fields for each case. Statistical analysis was performed using the Mann-Whitney, Chi-square and Fisher's exact tests, and Spearman's correlation (r). Significance level was set at 5% (p < 0.05). The results showed statistically significant differences between the abovementioned cystic lesions regarding DMC evaluation, being higher in CR (p < 0.001). Furthermore, MVD analysis revealed statistically significant differences between cystic lesions (p = 0.007) being greater in CR and also in regard to intensity of the inflammatory infiltrate with a predominance of lesions classified as intense infiltration (p = 0.021). Finally, we observed in cases of inflamed DCs, moderate positive correlation between DMC and MVA (r = 0.660; p = 0.002) and moderate positive correlation between DMC and MVP (r = 0.634; p = 0.003). Given the above, it can be concluded that mast cells participate in different stages of inflammation-associated angiogenesis in RCs and DCs. (AU)

Técnica de electrólisis para el estudio histopatológico de stents coronarios / Electrolysis technique for the histopathological study of stented coronaries

Introducción. El uso generalizado de stents coronarios para el tratamiento de la cardiopatía isquémica hace que con frecuencia se encuentren en los corazones de autopsia. Al ser metálicos, las coronarias no pueden procesarse de forma convencional y su estudio requiere la extracción manual previa, o la inclusión en resinas sintéticas, que es un método caro y lento. En 2009, Bradshaw et al. describieron un método para la disolución de stents mediante electrólisis. El objetivo de este trabajo es presentar esta técnica y los resultados obtenidos en nuestro laboratorio. Material y método. Se requiere fuente de alimentación para crear un campo eléctrico, vaso de precipitados con solución electrolítica, cables eléctricos, anilla metálica, tapadera, muelle de acero inoxidable y grasa industrial. La técnica se basa en una reacción electroquímica, de manera que se crea una corriente eléctrica continua en una solución salina entre un metal (stent) más electropositivo que se oxida (se disuelve) y un metal (anilla) más electronegativo que se reduce. Tras la disolución del stent la coronaria se secciona e incluye en parafina. Hemos estudiado 60 segmentos coronarios con stents de 54 corazones. Resultados. La disolución del metal se ha conseguido en todos los casos excepto en uno. En 54 se observó neoíntima con orificios vacíos dejados por el metal; en 6 se observó la impronta dejada por el stent en la íntima y en 3 de estos, trombosis oclusiva. Conclusión. La electrólisis de stents coronarios es una técnica sencilla, económica y segura accesible a cualquier laboratorio de Anatomía Patológica (AU)

Introduction. Coronary stenting for the treatment of ischemic heart disease is widespread and thus stents are frequently found in hearts at autopsy. Conventional methods of histological preparation cannot be used in stented coronaries and embedding in synthetic resins is required, which is expensive and time-consuming. In 2009, Bradshaw et al. described a method to dissolve metallic stents by electrolysis. The aim of this work is to present this method and the results obtained in our laboratory. Material and method. A power supply, a beaker with electrolytic solution, electrical wires, a metal ring, a stopper, a stainless steel spring and industrial grease are required. The method is based on an electrochemical reaction so that an electric current is created in a saline solution between a more electropositive metal (stent), which is oxidized (dissolves), and a more electronegative metal (ring), which is reduced. After dissolution the stented coronary is cut and embedded in paraffin. We have studied 60 stented coronaries from 54 hearts. Results. Metal dissolution was accomplished in all cases but one. In 54 a neointima was observed with empty holes left by the metal; in six, the stent imprint was observed in the intima and 3 showed occlusive thrombus. Conclusion. Stented coronary electrolysis is a simple, cheap and safe technique accessible to any Pathology Laboratory (AU)

A Scalable and Modular Dome Illumination System for Scientific Microphotography on a Budget.

A scalable and modular LED illumination dome for microscopic scientific photography is described and illustrated, and methods for constructing such a dome are detailed. Dome illumination for insect specimens has become standard practice across the field of insect systematics, but many dome designs remain expensive and inflexible with respect to new LED technology. Further, a one-size-fits-all dome cannot accommodate the large breadth of insect size encountered in nature, forcing the photographer to adapt, in some cases, to a less than ideal dome design. The dome described here is scalable, as it is based on a isodecahedron, and the template for the dome is available as a downloaded file from the internet that can be printed on any printer, on the photographer's choice of media. As a result, a photographer can afford, using this design, to produce a series of domes of various sizes and materials, and LED ring lights of various sizes and color temperatures, depending on the need.

Nora's lemsion of the anterior Maxilla: a rare case report and literature review

Bizarre parosteal osteochondromatous proliferation (BPOP), or eponymically Nora's lesion, is a rare growing, to a certain extent, exophytic lesion usually emanating from the periosteum or its adjacent layers. BPOP is idiopathically painful. Given its cartilage-producing nature and pain, BPOP is viewed with great suspicion. Regular post-surgical radiographs and clinical follow-up are mandatory. In the gnathic bones, the lesion is extremely rare. To the author's best knowledge, this paper reports the sophomoric appearance of BPOP in the anterior maxilla, in an adult female (AU)

La proliferación paraosteal osteocondromatosa bizarra (PPOB), o lesión de Nora según su epónimo, es un crecimiento inusual, exofítico, que procede del periostio o sus capas adyacentes. La PPOB es idiopáticamente dolorosa. Dada su naturaleza cartilaginosa y el dolor que la acompaña, la PPOB resulta una lesión sospechosa. Son obligatorios el estudio radiológico y seguimiento clínico postquirúrgicos. En los huesos maxilares, esta lesión es extremadamente infrecuente. En lo que conoce el autor, este artículo es la primera descripción de la PPOB de maxilar, en una mujer adulta (AU)

Retinoblastoma en un adolescente. Hallazgos clinicopatológicos poco frecuentes / Retinoblastoma in the adolescent. Unusual clinical and histopathology findings

CASO CLÍNICO: Hombre de 17 años, con un tumor intraocular izquierdo de 2 años de evolución y pérdida visual progresiva. Presentó rotura escleral durante la enucleación. Microscópicamente, las tinciones de H-E, PAS e inmunohistoquímica (NSE, GAFP, SYN, y CD99) demostraron un tumor maligno de células pequeñas, redondas y azules, con necrosis, apoptosis e invasión al nervio óptico, cuerpo ciliar, coroides, cámara anterior y esclerótica. La SYN resultó positiva y el CD99 negativo en células neoplásicas, confirmándose un retinoblastoma pobremente diferenciado. Discusión: El retinoblastoma es el tumor intraocular maligno primario más frecuente en niños, aunque ocasionalmente afecta a otros grupos de edad. La inmunohistoquímica es obligada en los retinoblastomas pobremente diferenciados

CASE REPORT: A 17-year- old male with 2 years history of an intraocular mass and progressive visual loss of the left eye. Spontaneous sclera rupture occurred during enucleation. Microscopic evaluation with H-E, PAS and immunohistochemistry (NSE, GAFP, SYN, CD99) revealed a small blue round cell malignant neoplasm with extensive necrosis and apoptosis. The optic nerve, ciliary body, choroid, anterior chamber, and sclera were infiltrated. SYN was positive and CD99 was negative in neoplastic cells, consistent with a poorly differentiated retinoblastoma. DISCUSSION: Retinoblastoma is the most frequent primary intraocular malignant tumour in childhood, but occasionally older patients can be affected. Immunohistochemistry is mandatory in poorly differentiated retinoblastomas

Characterization of muscle alteration in oral submucous fibrosis-seeking new evidence

BACKGROUND: The aim of the study was to assess the progression of Oral Submucous Fibrosis (OSF) by investigating the correlation between clinical mouth opening and muscle-epithelial distance in tissue sections. Characterization of changes involving muscle was ascertained. MATERIAL AND METHODS: 50 cases and 10 controls were included in this case-control study. Interincisal mouth opening was measured and classified according to Lai et al as Group A (more than 35 mm), Group B (30 to 35 mm), Group C (20 to 30 mm), Group D (less than 20 mm). Histopathological sections were graded as very early, early, moderately advanced, advanced OSF. Muscle-epithelial distance was calculated using image analysis software. The four most common degenerative changes observed in muscles, namely fragmentation, highly eosinophilic areas with loss of striations, nucleus internalization and multiple pyknotic nuclei were also assessed. RESULTS: Comparisons of muscle-epithelial distance were made between the clinical and histopathological groups to those of controls. The mean muscle-epithelial distance was: Group A-626.8±309.36 μm, B-827.5±549.72 μm, C-673.2 ± 321.93 μm, D-439.9 ± 173.84μm, Controls-1222.19 ± 441.7μm. Post-hoc Bonferroni Test revealed a statistically significant reduction in the muscle-epithelial distance in Group C (p-value = 0.001) and D (p-value = 0.001) as compared to controls. The mean muscle-epithelial distance in very early, early, moderately advanced and advanced OSF was 732.73 ± 232.81 μm, 726.54 ± 361.63 μm, 548.36 ± 273.13 and 172.40±58.41 μm respectively. Highly significant difference in muscle-epithelial distance was seen between controls as compared to early (p-value = 0.002), moderately advanced (p-value = 0.001) and advanced OSF (p-value = 0.001. Fragmentation and highly eosinophilic areas were invariably noticed in advanced OSF. Multiple pyknotic nuclei were variable with no specificity. CONCLUSIONS: Reduction in muscle-epithelial distance may prove to be a significant predictor of OSF progression. Degenerative changes must be noted while observing OSF cases, irrespective of the histopathological grade

PALM and STORM: Into large fields and high-throughput microscopy with sCMOS detectors.

Single Molecule Localization Microscopy (SMLM) techniques such as Photo-Activation Localization Microscopy (PALM) and Stochastic Optical Reconstruction Microscopy (STORM) enable fluorescence microscopy super-resolution: the overcoming of the resolution barrier imposed by the diffraction of light. These techniques are based on acquiring hundreds or thousands of images of single molecules, locating them and reconstructing a higher-resolution image from the high-precision localizations. These methods generally imply a considerable trade-off between imaging speed and resolution, limiting their applicability to high-throughput workflows. Recent advancements in scientific Complementary Metal-Oxide Semiconductor (sCMOS) camera sensors and localization algorithms reduce the temporal requirements for SMLM, pushing it toward high-throughput microscopy. Here we outline the decisions researchers face when considering how to adapt hardware on a new system for sCMOS sensors with high-throughput in mind.

Evaluación sistemática de la biopsia de médula ósea en casos de sospecha de mielofibrosis primaria. Propuesta de informe diagnóstico estandarizado. Consenso de expertos de las SEAP/SEHH / Systematic evaluation and standardised reporting of cases with suspicion of primary myelofibrosis. Consensus of SEAP/SEHH hematopathology experts

Se ha elaborado un consenso aplicando la metodología Delphi para acordar cuál debe ser la sistemática de evaluación e información de las biopsias de médula ósea en las neoplasias mieloproliferativas crónicas, especialmente en casos de mielofibrosis primaria (MFP). Un panel de 10 expertos hematopatólogos ha elaborado un cuestionario que se ha remitido a 37 hematopatólogos con preguntas acerca de los datos clínicos, analíticos y moleculares a conocer en la fase pre-analítica, parámetros histopatológicos a evaluar y contenido del informe diagnóstico final. Se realizaron 2 rondas buscando un consenso mínimo del 70% para los parámetros imprescindibles y recomendables. A partir de los resultados del consenso se elabora y propone un prototipo de informe histopatológico para informar de manera homogénea y reproducible los casos de MFP (AU)

A consensus based on Delphi methodology was developed to produce a guide for the evaluation and reporting of bone marrow biopsies in patients with a clinical suspicion of myeloproliferative neoplasm with fibrosis. Ten expert haematopathologists formulated a questionnaire including: clinical and laboratory data required before regarding a biopsy suspicious for primary myelofibrosis (PMF), descriptive aspects to be reported and the main histopathological differential diagnoses to be considered. It was circulated among 37 hematopathologists and consensus was defined when more than 70% of the experts "strongly agreed" or "agreed" after two rounds. The recommendations gave rise to a proposal for a standardized diagnostic report form to aid in the diagnostic workup and homogeneous reporting of cases with a clinical suspicion of PMF (AU)