O presente estudo teve como objetivo avaliar a qualidade da água e o grau de contaminação por metais na água, sedimento e peixes no trecho médio da Bacia do rio Doce, no Estado de Minas Gerais. Para tanto, em fevereiro e setembro de 2001, foram feitas análises físicas, químicas e biológicas de amostras de água e sedimento, testes de toxicidade e análises dos tecidos branquiais de peixes. As amostras de água apresentaram concentrações de amônio e fósforo total mais elevadas que o limite estabelecido pela resolução Conama 20/86 em todos os pontos e períodos de coleta. Maiores valores de condutividade elétrica e de compostos nitrogenados e fosfatados foram verificados no ribeirão Timotinho. Neste local, também foram encontradas as maiores concentrações de material em suspensão, carbono e fenóis totais. Em geral, as amostras de sedimento apresentaram baixos teores de matéria orgânica e maior porcentagem de areia dentre as frações granulométricas, tendo sido verificados os maiores valores de nitrogênio total e fósforo total nas amostras de sedimento do ribeirão Timotinho. As concentrações de metais na água estiveram geralmente acima dos limites máximos estabelecidos pela resolução CONAMA 20/86 para águas classe 2, sendo que os pontos de coleta no ribeirão Timotinho e rio Doce/Cenibra apresentaram concentrações muito acima do estabelecido para a maioria dos metais analisados, nos dois períodos de amostragem. Nas amostras de sedimento, as concentrações de Cr estiveram acima de valores encontrados em regiões não impactadas, em ambos os períodos de amostragem. Nos peixes também foram observadas elevadas concentrações de metais, sendo que Geophagus brasiliensis, Oligosarcus argenteus, Hoplias lacerdae e Loricariichthys castaneus; Leporinus sp e Geophagus brasiliensis apresentaram respectivamente níveis de Cr, Pb e Ni acima do permitido pela legislação, indicando processos de bioconcentração e bioacumulação. Os testes de toxicidade aguda e crônica com amostras de sedimento à Daphnia similis, Chironomus xanthus e Ceriodaphnia silvestrii mostraram maiores efeitos de toxicidade no ribeirão Timotinho e rio Doce/Cenibra. Além disso, foram também verificados efeitos de toxicidade crônica no ribeirão do Turvo, rio Matipó e reservatório de Guilmam-Amorim. As análises dos tecidos branquiais revelaram alterações histopatológicas em Tilapia rendalli (aneurismas) e Rhamdia quelen (fusão lamelar) coletados no ribeirão Timotinho e rio Doce/Cenibra, demonstrando que estas e outras espécies estão seriamente expostas à poluentes. / The present study aimed to evaluate water quality and metals contamination levels in water, sediment and fishes of different sampling sites in the middle Doce river basin in Minas Gerais State. Therefore, in February and September of 2001, physical, chemical and biological analyses of water and sediment samples, toxicity tests and branchial tissues analyses of fishes were carried out. The water samples showed higher ammonium and total phosphorus concentrations than the limit established by CONAMA 20/86 in all sites and sampling periods. Higher electric conductivity and nitrogenous and phosphorus compounds were found in Timotinho stream, where were also found the highest concentrations of suspended matter, carbon and total phenols. In general, the sediment samples presented low organic matter values and higher sand percentage among granulometric fractions, with higher values of total phosphorus and nitrogen being found at Timotinho stream. The concentrations of metals in water were generally above the maximum limit established by CONAMA 20/86 for class 2 waters, with much higher values being found at Timotinho stream and Doce river/Cenibra for most metals determined, in both sampling periods. In the sediment samples, the chromium concentrations were above the values found in unimpacted areas, in both sampling periods. High concentrations of metals were also detected in the fishes. Geophagus brasiliensis, Oligosarcus argenteus, Hoplias lacerdae e Loricariichthys castaneus; Leporinus sp and Geophagus brasiliensis respectively presented chromium, lead and nickel values above the established by legislation, indicating bioconcentration and bioaccumulation processes. The acute and chronic toxicity tests with sediment samples to Daphnia similis, Chironomus xanthus and Ceriodaphnia silvestrii showed more toxicity effects at Timotinho stream and Doce river/Cenibra. Moreover, chronic toxicity effects were also detected at Turvo stream, Matipó river and Guilmam-Amorim reservoir. The branchial tissues analyses revealed histopathological alterations in Tilapia rendalli (aneurisms) and Rhamdia quelen (lamellar fusion) collected at Timotinho stream and Doce river/Cenibra, demonstrating that these and other species are seriously exposed to pollutants.

In cancer diagnosis there is a goal of having the treatment being tailored to each patient. This in order to increase efficiency and reduce side effects. Using more data on each patient can help in achieving this. One such data source is histological images on tissues, such as lymph nodes. This report sets out to find a method in which such images on lymph nodes can be automatically segmented. This so that they can later be analysed and maybe tell in what stage a cancer is in. Such work is today done by hand, and this makes it a subjective process, that might differ between doctors and institutions. If there was a method done by a computer, the process would be replicable and objective. Also, a lot of time would be saved. The results show that such a method is reachable in this early stage of development. It is also quite efficient when segmenting the lymph node itself. The segmentation of smaller areas of the lymph nodes is not as efficient, but with further work in the area it might improve enough to be useful. Some issues are still had since the method relies in part on a person to decide a parameter in order to get a clean segmentation. The final conclusion is that one model is to prefer compared to the others and that further work on this might make it a useful tool in analysing histological images.

Subconcussive (SC) impacts have become a growing concern within the neuroscience community regarding the immediate and long-lasting effects of sports-related injuries. While a single low-level impact, i.e., a subconcussion, may not cause cerebral perturbations, it has been increasingly recognized that repeated SC exposure can induce deleterious effects. Therefore, determining the lower limits of systematic perturbation resulting from multiple SC impacts is of critical importance in expanding our understanding of cerebral vulnerability and recovery. Currently, there is a lack of correlation between a mild traumatic brain injury (mTBI) and repeated SC impacts with respect to injury biomechanics. Moreover, the cumulative threshold for repetitive low-level impacts is currently undefined. Thus, this research was designed to determine the pathophysiological differences between a single impact of an mTBI and repeated SC impacts with a subdivided cumulative kinetic energy of the single mTBI impact. In order to address this gap in knowledge, the present investigation employed a surgery-free, closed-head, weight drop injury device capable of producing repeatable, head impacts within a rat model. General locomotion and anxiety-like behavior were assessed using an Open Field Test and motor coordination dysfunction was measured using the rotarod assay. Neuroinflammation was measured using immunohistochemical assessment of astrogliosis (GFAP) and microgliosis (Iba-1) within the hippocampus. Additionally, immunohistochemical assessment of neuronal loss (NeuN) was measured within the hippocampus. To investigate the tolerance and the persistence of cerebral vulnerability following a single mTBI and repeated subconcussive impacts, measurement outcomes were assessed over two-time points (3- and 7-days) post final impact. Although injury groups were not statistically different from their associated sham groups with respect to behavioral outcomes; on average, RSC injury rats displayed a significant increase in anxious-like behavior after 7-days of recovery compared to the single mTBI group. From an inflammatory perspective, both mTBI and RSC injury groups led to extensive microgliosis in the gray matter following 3-days post-impact. Overall, this work’s findings do not provide evidence in support of the notion that repeated subconcussive impacts do result in behavioral disturbances and neuroinflammation, that do not manifest following a single mTBI of the same energy input.

Voiced communication plays a fundamental role in society. Voice research seeks to improve understanding of the fundamental physics governing voice production, with the eventual goal of improving methods to diagnose and treat voice disorders. For this thesis, three different aspects of voice production research were studied. First, porcine vocal fold medial surface geometry was determined, and the three-dimensional geometric distortion induced by freezing the larynx, especially in the region of the vocal folds, was quantified. It was found that porcine vocal folds are qualitatively geometrically similar to canine and human vocal folds, as well as commonly used models, and that freezing of tissue in the larynx causes distortion of around 5%. Second, a setup of multiple high-resolution cameras and a stereo-endoscopy system simultaneously recorded positions on the superior surface of synthetic, self-oscillating vocal fold models to estimate the error in the measurement of the three-dimensional location by the stereo-endoscopy system. The error was found to be low in the transverse plane, whereas the error was relatively large in the inferior-superior direction, suggesting that the stereo-endoscope is applicable for in vivo measurements of absolute distances of the glottis in the transverse plane such as glottal length, width, and area. Third, a function for strain-varying Poisson's ratio for silicone was developed from experimental data. It is anticipated that the findings herein can aid voice researchers as they study voice production, leading to improved voice care.

La pose d’implants mammaires est l’une des interventions chirurgicales les plus courantes en chirurgie plastique. Elle permet de reconstruire un sein après une mastectomie ou d’augmenter son volume pour améliorer le décolleté et la forme du sein. Depuis leur introduction dans les années 1960, les implants mammaires siliconés ont fait l’objet de multiples controverses et leur innocuité a pendant longtemps été questionnée. Ces dispositifs médicaux sont considérés comme sûr par la FDA mais ne sont pas pour autant exempts de complications. L’une d’entre elles, le silicone bleeding, se traduit par la migration de particules de silicone depuis le gel de l’implant vers la capsule péri-prothétique. Ces particules de silicone représentent une source potentielle d’inflammation chronique autour des implants mammaires dont les conséquences à long terme sur la santé des patientes ne sont pas claires. Bien que cette complication soit objectivée depuis les années 1970, il existe à l’heure actuelle peu de données sur la quantité de silicone qui est susceptible de migrer des implants mammaires. L’objectif principal de notre étude a été de quantifier les particules de silicone dans les capsules péri-prothétiques des implants mammaires en décrivant une nouvelle méthode de quantification basée sur une analyse histologique approfondie des spécimens de capsule. Les résultats préliminaires de notre étude ont permis de démontrer que des millions de particules de silicone peuvent diffuser dans la capsule péri-prothétique des implants mammaires siliconés et que l’ampleur du phénomène à tendance à croître avec la durée d’implantation. / The placement of breast implants is one of the most common surgical procedures in the field of plastic surgery. Although these medical devices are considered safe by the FDA, their use is not free of complications. One of these complications is silicone particle bleeding, or the migration of silicone particles from the breast implant into the peri-prosthetic capsule. These particles represent a potential source of chronic inflammation around breast implants, with unclear long-term consequences for patient health. Although this complication has been observed since the 1970s, there is currently very little data on the amount of silicone that is likely to migrate from breast implants. The primary objective of this study was to quantify silicone particles in the peri-prosthetic capsules of breast implants by describing a new method of quantification based on a thorough histological analysis of capsule specimens. Preliminary results of our study have shown that millions of silicone particles can diffuse into the periprosthetic capsule of silicone breast implants and that the amount of silicone particles tends to increase with the duration of implantation.

The purpose of this investigation was first, to make a histological and cytological study of the testis of male frogs, Rana pipiens, and to determine if there were tissue or cellular changes as well as physiological effects caused by fish pituitary-extract injections. Second, to determine if injections of fish pituitary extract into immature female white mice caused histological changes in the ovaries and uteri.

In der Humanmedizin wird zur Beurteilung der Magenschleimhautproben das aktualisierte Sydney-System nach STOLTE (1997) angewendet. Das Ziel war es herauszufinden, ob das histologische Grading System auch in der Veterinärmedizin, für die Beurteilung von Pferdemagenschleimhautpräparaten, genutzt werden kann und ob daraus neue Erkenntnisse erwachsen. Von 60 Pferden wurden direkt post mortem Schleimhautproben aus der Pars glandularis (Drüsenschleimhaut), im Bereich der großen Kurvatur und dem Pylorus, entnommen. Die Patienten wurden in 4 Gruppen, 10 operierte (Kolik)pferde, 36 Pferde mit Kolik und infauster Prognose, 6 Pferde mit hochgradigen Magenulzera und 8 Pferde, die nicht auf Grund einer Kolik euthanasiert wurden, eingeteilt. Die makroskopische Beurteilung der 60 Pferdemägen erfolgte nach MURRAY et al. (1989) und MACALLISTER et al. (1995). Die histopathologische Beurteilung erfolgt in der Humanmedizin anhand der Helicobacter-like-Organismen Dichte, dem Grad der chronischen Entzündung, der Aktivität der Gastritis, der Atrophie und der intestinalen Metaplasie. Nach diesen Beurteilungsvariablen wurden die 120 Proben aus den 60 Pferdemägen beurteilt. Die ätiologischen Diagnosen sind in der Humanmedizin das Ergebnis jahrzehntelanger Forschung. Beim Pferd liegen dagegen zur Ätiologie der Gastritis noch keine gesicherten Erkenntnisse vor. Beim Pferd gibt es bestimmte Gastritisformen, die denen des Menschen ähnlich sind. Doch können die morphologischen Befunde in der Veterinärmedizin, nach den jetzigen Erkenntnissen, keinen Ätiologien zugeordnet werden. Die ätiologischen Diagnosen in dieser veterinärmedizinischen Studie beruhen auf der Diagnostik am Menschen und wurden noch nicht auf ihre Richtigkeit beim Pferd überprüft. Von den 60 untersuchten Pferdemägen wiesen 31 makroskopisch Läsionen in der Magenschleimhaut auf. 20 Pferde mit Veränderungen hatten diese in der Pars glandularis. Bei 44 der Pferde bestätigt der histologische Befund, nach dem aktualisierten Sydney- System, das makroskopische Grading. 13 der Pferde hatten nach dem aktualisierten Sydney-System histologisch einen pathologischen Befund, obwohl makroskopisch die Schleimhaut keine Auffälligkeiten aufwies. Bei nur 3 von den 60 Pferden konnte der histologische den makroskopischen Befund nicht bestätigen. Ätiologisch wurde, nach humanmedizinischen Beurteilungskriterien, bei 18 Pferden im Bereich der großen Kurvatur der Pars glandularis und, oder im Bereich des Pylorus eine C-Gastritis (chemische Gastritis), bei 11 Pferden eine like B-Gastritis (bakterielle Gastritis ohne den Nachweis von Helicobacter-like-Organismen), 3 Pferden eine B-Gastritis (bakterielle Gastritis mit dem Nachweis von Helicobacter-like-Organismen) und bei 9 Pferden eine Sonderform der Gastritis diagnostiziert. 6 Pferde bekamen die Diagnose: zur Zeit nicht klassifizierbar und 7 Pferde die deskriptive Diagnose erosive oder ulzerative Gastritis gestellt. 24 Pferde hatten keinen pathologischen Befund in einem der oben genannten Bereiche der Schleimhaut. Die histopathologischen Befunde der Pferde mit einer like-B-Gastritis oder einer B-Gastritis entsprachen nach humanmedizinischen Gesichtspunkten dem Bild einer Helicobacter-pylori-Gastritis beim Menschen. Bandartige Anordnung der Lymphozyten in der Lamina propria mucosae und neutrophile Granulozyten in Verbindung mit einer Atrophie des Drüsenkörpers, intestinaler Metaplasie und Erosionen. Bei drei Pferden konnte in der Warthin–Starry-Färbung und in der IHC-Reaktion Helicobacter-like-Organismen nachgewiesen werden. Die Pylorusschleimhaut war doppelt so häufig, im Vergleich zur Drüsenschleimhaut der großen Kurvatur, von einer like-B-Gastritis oder B-Gastritis betroffen. Die histologische Auswertung von Magenschleimhautbioptaten, in dieser Studie nach dem aktualisierten Sydney-System aus der Humanmedizin, komplettiert die makroskopische (endoskopische) Diagnostik. Nach den Ergebnissen der vorliegenden Studie gehört in der Pferdemedizin zu jeder Gastroskopie die Bioptatentnahme. Das aktualisierte Sydney-System kann in Zukunft in der Veterinärmedizin als Arbeitsgrundlage für die weitere wissenschaftliche Forschung genutzt werden. / Stolte’s updated Sydney system is used in the field of human medicine for grading the gastric mucosa (STOLTE 1997). The goal of this study was to determine whether this system could also be applied for histological parameter grading in veterinary medicine, in order to gain new insights into medications for treating equine gastric mucosa. Post mortem biopsies of mucosa were taken from 60 equines along the greater curve and pylorus of the pars glandularis. The test animals were divided into four groups: 10 post-colic surgery equines, 36 with colic and an infaust prognosis, six with chronic EGUS (equine gastric ulcer syndrome), and eight equines not euthanized for reasons other than colic. Macroscopic grading of the 60 equine stomachs was performed in accordance with MURRAY et al. (1989) and MACALLISTER et al. (1995). In human medicine, histological scoring is based on the following five parameters: density of Helicobacter-like organisms, grade of the chronic inflammation, level of gastric activity, atrophy, and intestinal metaplasia. A total of 120 biopsies taken from the 60 equines were graded according to these parameters. Etiologic diagnoses for humans are the outcome of decades of research, but the etiology of equine gastritis lacks an equivalent foundation. Equines exhibit forms of gastritis similar to those in humans, but their morphology cannot be classified into any specific etiology. In this study, the etiological diagnoses were based on human diagnostics, but their validity for equines has yet to be substantiated. Of the 60 equine stomachs examined, 31 showed lesions in the gastric mucosa, while 20 of those with changes had lesions in the pars glandularis. Histological findings of 44 equines confirmed the macroscopic grading according to the updated Sydney system. Thirteen equines exhibited pathological findings based on the updated Sydney system histology, although no abnormalities were discovered in the macroscopic examination. The histological diagnosis did not confirm the macroscopic grading for only three of the 60 subjects. The following etiological findings were reached in terms of human medicine: 18 equines with type C gastritis (chemical gastritis) along the greater curve of the pars glandularis and/or pylorus, 11 equines with type B-like gastritis (bacterial gastritis without evidence of H-like organisms), three equines with type B gastritis (bacterial gastritis with evidence of H-like organisms), and nine with a special form of gastritis. Six of the equines could not be classified, while seven showed erosive gastritis or ulceration. A total of 24 equines exhibited no pathological findings along any of the above-mentioned mucosae. The histopathological findings of the equines with either type B-like gastritis or type B gastritis corresponded with H pylori gastritis seen in humans, as ligamental lymphocytes in the lamina propria mucosae and neutrophilic granulocytes associated with atrophy of the glandular corpus, intestinal metaplasia, and erosion. Warthin-Starry staining and the IHC reaction confirmed H-like organisms in three of the equines. The frequency of type B-like gastritis or type B gastritis was observed to be twice as high in the pylorus mucosa as along the glandular mucosa of the greater curve. This study has demonstrated that histological analysis of gastric mucosa biopsies graded according to the updated Sydney system for human medicine significantly complements veterinary gastroscopy, which should therefore always include a biopsy. The updated Sydney system can thus serve as a platform for future scientific research in the field of veterinary medicine.

<p>Увод: Пинеална жлезда је неуроендокрини, циркумвентрикуларни орган филогенетски пореклом органа вида. Калцификације пинеалне жлезде су чест налаз приликом радиолошких претрага, без још увек довољно доказа да ли су оне нормалан налаз. Магнетна резонанца описује три морфолошка типа пинеалне жлезде. Циљеви: Утврдити степен корелације морфолошких типова пинеалне жлезде утврђених патохистолошким налазом са налазом компјутеризоване томографије, као и степен корелације присуства калцификација у пинеалној жлезди утврђених патохистолошким налазом и налазом компјутеризоване томографије. Утврдити степен калцификације пинеалне жлезде патохистолошким налазом у зависности од старости. Материјал и методе: Макроскопском морфолошком и микроскопском, хистолошком анализом обухваћено је 111 изолованих пинеалних жлезди осoба оба пола, не млађих од 18 година од којих је 27 снимљено апаратом Somatom Sensation 64 са дебљинама реконструисаних пресека 5 и 1mm, а још 9 апаратом Somatom Emotion 16. Резултати: Постоји статистички значајна разлика у одређивању сва три дијаметра епифизе петомилиметарским реконструкцијама, и при утврђивању два дијаметра једномилиметарским реконструкцијама. Постоји статистички значајна разлика у утврђивању морфолошких типова хистолошком и методом компјутеризоване томографије. Присутна је позитивна корелација калцификованости жлезде одређене мерењем њене густине у Хаунсфилдовим јединицама и утврђене микроскопски. Калцификованост пинеалног паренхима не корелира старости. Закључак: Наша студија је показала да су једномилиметарске реконструкције тачније у одређивању дијаметара жлезде. Макроскопским и микроскопским мерењем утврђена су сва три типа пинеалне жлезде описана магнетнорезонантним осликавањем. Утврђена је статистички значајна повезаност густине пинеалне жлезде измерене у Хаунсфилдовим јединицама на једномилиметарским реконструкцијама и степена калцификованости израженог у процентима. Није утврђена повезаност калцификованости епифизе мерене микроскопски и старости.</p> / <p>Uvod: Pinealna žlezda je neuroendokrini, cirkumventrikularni organ filogenetski poreklom organa vida. Kalcifikacije pinealne žlezde su čest nalaz prilikom radioloških pretraga, bez još uvek dovoljno dokaza da li su one normalan nalaz. Magnetna rezonanca opisuje tri morfološka tipa pinealne žlezde. Ciljevi: Utvrditi stepen korelacije morfoloških tipova pinealne žlezde utvrđenih patohistološkim nalazom sa nalazom kompjuterizovane tomografije, kao i stepen korelacije prisustva kalcifikacija u pinealnoj žlezdi utvrđenih patohistološkim nalazom i nalazom kompjuterizovane tomografije. Utvrditi stepen kalcifikacije pinealne žlezde patohistološkim nalazom u zavisnosti od starosti. Materijal i metode: Makroskopskom morfološkom i mikroskopskom, histološkom analizom obuhvaćeno je 111 izolovanih pinealnih žlezdi osoba oba pola, ne mlađih od 18 godina od kojih je 27 snimljeno aparatom Somatom Sensation 64 sa debljinama rekonstruisanih preseka 5 i 1mm, a još 9 aparatom Somatom Emotion 16. Rezultati: Postoji statistički značajna razlika u određivanju sva tri dijametra epifize petomilimetarskim rekonstrukcijama, i pri utvrđivanju dva dijametra jednomilimetarskim rekonstrukcijama. Postoji statistički značajna razlika u utvrđivanju morfoloških tipova histološkom i metodom kompjuterizovane tomografije. Prisutna je pozitivna korelacija kalcifikovanosti žlezde određene merenjem njene gustine u Haunsfildovim jedinicama i utvrđene mikroskopski. Kalcifikovanost pinealnog parenhima ne korelira starosti. Zaključak: Naša studija je pokazala da su jednomilimetarske rekonstrukcije tačnije u određivanju dijametara žlezde. Makroskopskim i mikroskopskim merenjem utvrđena su sva tri tipa pinealne žlezde opisana magnetnorezonantnim oslikavanjem. Utvrđena je statistički značajna povezanost gustine pinealne žlezde izmerene u Haunsfildovim jedinicama na jednomilimetarskim rekonstrukcijama i stepena kalcifikovanosti izraženog u procentima. Nije utvrđena povezanost kalcifikovanosti epifize merene mikroskopski i starosti.</p> / <p>Introduction: Pineal gland is a small neuroendocrine, circumventricular organ wich evolved from the eye. Calcifications were incidentally discovered and frequently without a proof whether they were normal or abnormal. Magnetic resonance imaging describes three morphological types. Aim: To determine if there is a correlation between pineal gland morphology types and calcifications established with histology and with computed tomography (CT) and if there is the correlation between calcifications and age. Method of work and material: Macroscopic and mycroscopic analysis encounted 111 isolated pineal glands of both sexes, no younger than 18, from wich 27 was examed with Somatom Sensation 64 and 9 with Somatom Emotion 16 with 5mm and 1mm reformated pictures. Results: All three diameters measured on 5mm reformated pictures and two measured on 1mm reformated pictures differed statistically compared to diameters measured macroscopically. There was siginificant difference between morphological types established on computed tomography and macroscopically. Pineal gland calcifications measured microscopically and with CT correlated positivelly. Pineal gland calcifications were not dependant on the patients age. Conclusion: Allthough 1mm reformated pictures are more accurate than 5mm, the pineal gland morpholgy types determined macroscopically and with CT are not correlated. However, calcification measurement with CT correlates with the microscopic measurement. Calcifications measured microscopically are not correlated with age.</p>

OBJETIVOS: Avaliar características clínico-patológicas com ênfase na presença de variantes histológicas (VH) nos carcinomas uroteliais da bexiga e nas metástases linfonodais (ML). Caracterizar perfis imuno-histoquímicos relacionados aos subtipos moleculares e verificar suas associações clínico-patológicas. MÉTODOS: 183 carcinomas uroteliais de alto grau músculo-invasivos submetidos a cistectomia radical no Instituto do Câncer do Estado de São Paulo, HCFMUSP ou Hospital Alemão Oswaldo Cruz foram caracterizados quanto ao gênero, idade, tamanho, focalidade, configuração neoplásica, necrose, invasões angiolinfática e perineural, VH, carcinoma in situ, infiltrado inflamatório peri e intratumoral, estádio, margem cirúrgica, ML e VH na metástase. Resultados semi-quantitativos da pesquisa imuno-histoquímica (IH) de CK20 e GATA3 (associados ao subtipo luminal) e CK5, SALL4 e Vimentina (associados ao subtipo basal), que foi realizada em micromatrizes teciduais com abundante representação do tumor primário e das ML, tiveram valor de corte de 20%, definindo os casos em positivos e negativos. Casos negativos para CK20 ou GATA3 e positivos para CK5 foram agrupados no subtipo basal; casos positivos para CK20 ou GATA3 e negativos para CK5 agrupados no subtipo luminal e casos duplo positivos ou duplo negativos agrupados no subtipo indeterminado. As associações entre estes subtipos e as características clínico-patológicas foram realizadas através de testes qui-quadrado ou exato de Fisher para as variáveis categóricas. A comparação dos subtipos obtidos no centro do tumor e na ML foi realizada com testes de McNemar-Bowker e concordância pelo coeficiente Kappa. A análise de sobrevida foi realizada pelo método Kaplan-Meier e testes de Breslow. RESULTADOS: VH foram observadas em 116 (63,4%) casos e associadas a invasão linfovascular (p=0,043), VH na metástase (p < 0,001), pior sobrevida global (p=0,043). Havia 14 diferentes VH, a escamosa, mais comum, foi associada a tumores maiores (p=0,003); necrose (p=0,004); VH sarcomatoide (p=0,047), VH na metástase (p=0,003), sem impacto nas sobrevidas. VH micropapilífera, segunda mais observada, foi associada a invasão linfovascular (p=0,002); margem cirúrgica positiva (p=0,005); metástase linfonodal (p < 0,001), VH na metástase (p=0,007) e piores sobrevidas doença específica (p=0,016) e global (p=0,005). VHs foram observadas em 40,7% das metástases linfonodais, com apenas um caso discordante das VH observadas no tumor vesical. Nos dois perfis IH estabelecidos não houve impacto nas sobrevidas e o subtipo basal foi associado a tumores maiores (CK5/CK20 p=0,025; CK5/GATA3 p=0,006) e a variante escamosa (CK5/CK20 e CK5/GATA3 p < 0,001) e o subtipo luminal foi associado a variantes micropapilífera (CK5/CK20 e CK5/GATA3 p < 0,001) e plasmocitoide (CK5/CK20 p=0,003; CK5/GATA3 p=0,011). Foi moderado o grau de concordância do subtipo observado no centro comparado ao observado na ML (CK5/CK20 Kappa=0,57; CK5/GATA3 Kappa=0,48). CONCLUSÕES: A presença de VH nos carcinomas uroteliais da bexiga, além de acarretar heterogeneidade intratumoral, foi associada a características clínico-patológicas de agressividade, com impacto na sobrevida, sobretudo na variante micropapilífera. O perfil IH basal foi associado a tumores maiores com variante escamosa e o perfil IH luminal foi associado às variantes micropapilífera e plasmocitoide. Os perfis IHs não diferiram quanto às sobrevidas e houve moderada concordância com os perfis observados nas ML / OBJETIVES: Evaluate clinicopathological features emphasizing the presence of histological variants (HV) in bladder urothelial carcinomas and their lymph node metastasis (LNM). Characterize immunohistochemical profiles related to molecular subtypes and verify their clinicopathological associations. METHODS: 183 high-grade muscle-invasive urothelial carcinomas undergoing radical cystectomy at Instituto do Câncer do Estado de São Paulo, HCFMUSP or Hospital Alemão Oswaldo Cruz were classified according to gender, age, size, focality, neoplastic configuration, necrosis, lymphovascular and perineural invasion, HV, carcinoma in situ, peritumoral and intratumoral inflammatory infiltrate, stage, surgical margin, LNM and HV in metastasis. Semi-quantitative results of the immuhistochemical (IHC) studies for CK20 and GATA3 (associated with the luminal subtype) and CK5, SALL4 and Vimentin (associated with basal subtype), which were performed in tissue microarrays with abundant representation of the primary tumor and LNM, had a cutoff value of 20%, dividing cases into positive and negative. Negative cases for CK20 or GATA3 and positive for CK5 were grouped into the basal subtype; positive cases for CK20 or GATA3 and negative for CK5 were grouped into luminal subtype and double positive or double negative cases were grouped into the undetermined subtype. The associations between these subtypes and clinicopathological features were performed using chi-square or Fisher´s exact tests for the categorical variables. Comparison of the subtype obtained at the center of the tumor and LNM was performed using McNemar-Bowker test and agreement with Kappa coefficient. Survival analysis was performed using Kaplan-Meier method and Breslow tests. RESULTS: HV were observed in 116 (63.4%) cases and associated with lymphovascular invasion (p=0.043); HV in metastasis (p < 0.001), worse overall survival (p=0.043). There were 14 different HV, and squamous variant, the most common, was associated with larger tumors (p=0.003); necrosis (p=0.004), sarcomatoid variant (p=0,047), HV in metastasis (p=0.003), with no impact on survival. Micropapillary variant, the second most observed, was associated with lymphovascular invasion (p=0.002); positive surgical margin (p=0.005); LNM (p < 0.001); HV in metastasis (p=0.007) and worse disease-specific (p=0.016) an overall survival (p=0.005). HV were observed in 40.7% of the LNM, and only one case was discordant with HV observed in the bladder tumor. In both IHC profiles there was no impact on survival, and the basal subtype was associated with larger tumors (CK5/CK20 p=0.025; CK5/GATA3 p=0.006) and squamous variant (CK5/CK20 and CK5/GATA3 p < 0.001). Luminal subtype was associated with micropapillary variant (CK5/CK20 and CK5/GATA3 p < 0.001) and plasmacytoid variant (CK5/CK20 p=0.003; CK5/GATA3 p=0.011). There was moderate agreement between the subtype observed in the tumor center compared to that observed in LNM (CK5/CK20 Kappa=0.57; CK5/GATA3 Kappa=0.48). CONCLUSIONS: The presence of HV in bladder urothelial carcinomas, in addition to cause intratumoral heterogeneity, was associated with clinical and pathological characteristics of aggressiveness, with impact on survival, especially in the micropapillary variant. The basal IHC profile was associated with larger tumors and squamous variant, and the luminal IHC profile was associated with micropapillary and plasmacytoid variants. The IHC profiles did not differ on the survival rates and there was moderate agreement compared to the subtypes observed in LNM

Hemangiopericitomas (CHP) assim como schwanomas são neoplasias cutâneas de origem mesenquimal, sendo os hemangiopericitomas freqüentemente relatados em cães, ao contrário dos neurofibromas que são mais raros nos mesmos. Relata-se que o CHP origina-se de pericitos, ou células que se localizam ao redor de vasos sanguíneos. São observadas mais freqüentemente nos membros, como massas, bem circunscritas, firmes e grandes. Os hemangiopericitomas têm características histológicas comuns aos schwanomas (neurofibromas), sugerindo uma possível semelhante histogênese. Na realidade, na experiência deste Serviço de Anatomia Patológica, o diagnóstico diferencial entre hemangiopericitomas e neurofibromas apenas com base na morfologia é bastante difícil. O aspecto histopatológico do hemangiopericitoma e schwanoma correspondem à presença de agrupamentos celulares na forma de espiral pericapilar ou não respectivamente. Na tentativa de melhor caracterizar os hemangiopericitomas e distinguí-los de outros tumores mesenquimais, principalmente dos neurofibromas, propõe-se a caracterização histológica, epidemiológica e imunoistoquímica, dos hemangiopericitomas em animais da espécie canina. Com este, espera-se refinar o diagnóstico diferencial destes tumores, por tratar-se de neoplasias pouco e mal diagnosticadas devido à dificuldade de caracterizá-las morfologicamente. Procura-se estudar também, a proliferação celular nos três subtipos histológicos dos CHP e contagem dos critérios morfológicos de malignidade, correlacionando com o prognóstico clínico. Para isto, o presente estudo propôs realizar um levantamento criterioso dos casos de hemangiopericitomas e neurofibromas e/ou neurofibrossarcomas em cães nos Arquivos do Serviço de Necroscopia do Departamento de Patologia da Faculdade de Medicina veterinária e Zootecnia da Universidade de São Paulo (FMVZ/USP) durante o período de 1990 a 2003, reclassificando histologicamente estas neoplasias e graduando os subtipos dos CHP. Os resultados apontaram um total de 77 casos de CHP dos quais o subtipo perivascular correspondeu (35/77casos); o estoriforme (20/77) e o epitelióide (22/77).As conclusões da imunoistoquímica para tipo perivascular (HPV) revelam positividade de 100% para F8; 60% para S100; 100% para vimentina; 7% para GFAP e 0% para CD34 e citoqueratina. O tipo estoriforme (HES) revelou 70% de positividade para F8; 50% para S100; 100% para vimentina; 0% para citoqueratina e GFAP; 10% para CD34. Destaca-se para o epitelióide (HEP) 70% de positividade para o F8; 40 % para o S100; 90% para vimentina; 0% para citoqueratina; GFAP e CD34. A contagem estatística dos critérios de malignidade como PCNA (CL3); índice mitótico (CL1); índice apoptótico (CL4); células multinucleadas (CL0) revelaram nos subseqüentes (HPV, HE, HEP) subtipos de CHP, respectivamente: CL0 (6.135&plusmn;4.038; 5.067&plusmn;3.019; 11.217&plusmn;5.729); CL1 (6.155&plusmn;2.380; 7.545&plusmn;1.941; 12.540&plusmn;8.629); CL3 (30.042&plusmn;10.824; 39.1.22&plusmn;11.158; 41.945&plusmn;9.705); CL4 (1.153&plusmn;1.1443; 1.888&plusmn;1.988; 2.400&plusmn;1.648). O prognóstico clínico revelou 59% de taxa de recidiva para o tipo epitelióide. Assim, o presente estudo mostrou que os hemangiopericitomas devem ser graduados histologicamente por três subtipos dos quais o epitelióide parece ser o mais agressivo e o perivascular o mais incidente (45,5%) (35/77 casos) e que a imunoistoquímica pode ter papel importante na diferenciação entre os hemangiopericitomas e neurofibromas, devido à positividade e negatividade do Fator 8 respectivamente; no entanto não auxilia para distinção entre os subtipos dos CHP. Contudo o estabelecimento de critérios para diferenciar, graduar e caracterizar os CHP poderão ter implicações epidemiológicas, terapêuticas e prognósticas importantes como mostra o presente estudo / Haemangiopericytomas CHP like Schwanomas are cutaneous neoplasms of mesenchymal origin, frequently appearing in dogs, unlike neurofibromas, which are rare on the species. There are cases reported that CHP originates from pericytes, or cells located around blood vessels. They are observed more in limbs such as tissues, they are well defined, big and firm. Haemangiopericytomas have histologic characteristics common to schwanomas (neurofibromas), suggesting a possible similarity in histogenesis. In fact, at this service of Animal Pathology experience, the distinguishing final diagnosis between Haemangiopericytomas and neurofibromas, based only on morphology offers great difficulty. The hispathological aspects of the haemangiopericytons and of the schwanomas correspond to the presence or not (respectively) of spiral pericilar shape cell forms. Attempting to better identify and distinguish the haemangiopericytons from other mesenquimal tumors, mainly neurofiberns, the study indicates the histological, epidemiological and immunohistochemical characterization of Haemangiopericytomas in canine species. With this, it is expected to refine the distinguishing diagnosis of such tumors, for they are known to be neoplasms rarely and wrongly diagnosed due to difficulties to identify them morphologically. The work also studies cell proliferation at the three histological subtypes of CHP and the count for morphological malignity, correlating with the clinic prospect. In order to accomplish it, the work proposes a thoroughly case study of Haemangiopericytomas and neurofibromas and/or neurobrosarcomas in dogs; investigating on the archives of the Necrology Department of Pathology at the Veterinary Medical and Zoology at São Paulo University; from 1990 to 2003, to reclassify histologically these neoplasms and scale the subtypes of CHP. The results indicated a sum of 77 cases of CHP from which the subtype perivascular accounted for (35/77) cases; the storiform (20/77) and the epithelioid (22/77). The conclusions of immunohistochemical to perivascular type (HPV) reveal positiveness of 100% to F8; 60% to S100; 100% to vimentin; 7% to GFAP and 0% to CD34 and cytokeratin. The type estoriform (HES) revealed 70% positiveness to F8; 50% to S100; 100% to vimentin; 0% to cytokeratin and GFAP; 10% to CD34. Note that to epithelioid (HEP) 70% positiveness to F8; 40% to S100; 90% to vimentin; 0% to cytokeratin; GFAP and CD34. Statistical count of malignity criteria such as PCNA (CL3); miotic level (CL1); apoptotic level (CL4); multinucleous cells (CLO) reveal on subsequent (HPV, HE, HEP) subtypes of CHP, respectively: CLO (6.135 (6.135&plusmn;4.038; 5.067&plusmn;3.019; 11.217&plusmn;5.729); CL1 (6.155&plusmn;2.380; 7.545&plusmn;1.941; 12.540&plusmn;8.629); CL3 (30.042&plusmn;10.824; 39.1.22&plusmn;11.158; 41.945&plusmn;9.705); CL4 (1.153&plusmn;1.1443; 1.888&plusmn;1.988; 2.400&plusmn;1.648). The clinical prognostic revealed 59% receding rate to epithelioid. Therefore the study showed that Haemangiopericytomas must be histologically scaled by three subtypes of which the epithelioid appears to be the most AGGRESSIVE =INVASIVE) and perivascular the most incidental (45,5%) (35/77cases); immunohistochemical may have an important role on distinguishing between Haemangiopericytomas and neurofibrossarcomas due to positiveness and negativeness of Factor 8 respectively; notwithstanding it does not aid to distinguish between subtypes from CHP. Nevertheless, a criteria definition that enables to distinguish, scale and define CHP may have relevant epidemiologic, therapeutical and prognostical connotations as shown by the present study