Immunohistochemical expression of markers Ki-67, neun, synaptophysin, p53 and HER2 in medulloblastoma and its correlation with clinicopathological parameters.

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5%), >20% of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40%) and 8 (20%) cases, respectively. P53 was positive in 18 (45%) cases, with 11 (61%) weakly positive and 7 (39%) strongly positive. HER2 was positive in 23 (57.5%) of the samples and did not show statistical association with survival (p=0.07).

Immunoexpression of endoglin in brain metastasis secondary to malignant melanoma: evaluation of angiogenesis and comparison with brain metastasis secondary to breast and lung carcinomas.

Brain metastases are linked to poor prognosis. After carcinomas of the lung and breast, malignant melanomas (MM) are the next type of neoplasm with the higher metastatic dissemination involving the central nervous system and that has the worst prognosis after metastasis has been diagnosed. Angiogenesis has been linked to tumor growth and metastasis. Among the immunomarkers of angiogenesis, endoglin (CD105) is the most specific antibody, since it is a marker for tumor endothelium, and expression of CD105 has been observed to be associated with prognosis in several types of tumor, which is not always observed in melanomas. This study investigated angiogenesis in brain metastasis secondary to malignant melanomas and compared these with brain metastasis secondary to carcinomas of the lung and breast, through expression of CD105 (endoglin). The study investigated 93 cases of brain metastasis secondary to MM (33) and carcinomas of the lung (31) and breast (29), assessing endoglin immunoexpression, number of microvessels and diameter of tumor vessels. Tumor microvessels were counted using a modified version of the Chalkley technique. The observed difference between MM and breast carcinoma was statistically significant (P = 0.026). The difference between MM and lung carcinoma was not significant (P = 0.218). Vascular diameter observation revealed no statistical difference between the vascular size of neoplastic vessels in MM and in breast and lung carcinomas. Of the tumors investigated here, malignant melanomas were shown to have the lowest number of microvessels and had intermediate tumor vessel diameter as compared to carcinomas of the lungs and breast. Such results were not expected to be found in neoplasms such as melanomas that, besides presenting high dissemination capacity, have a high index of hemorrhage secondary to brain metastasis.

Expression of nestin and vimentin in gliomatosis cerebri.

Gliomatosis cerebri (GC) is a rare form of CNS neoplasia in which there is diffuse involvement of the nervous tissue with or without the presence of tumor mass. The origin of the tumor is unknown, nor whether it represents a disease with diffuse onset or infiltration from a neoplastic focus. Here we studied the histopathologic characteristics of 6 cases with a diagnosis of GC and performed an immunohistochemical analysis using glial fibrillary acidic protein (GFAP), synaptophysin, nestin and vimentin. Most tumor cells were negative for GFAP, even though there were foci of positivity for this marker in all cases. We detected the presence of many positive cells for nestin and vimentin in all studied samples. The presence of these cells may indicate origin of the tumor from undifferentiated cells with a high degree of mobility.

[Immunohistochemistry in oligodendrogliomas]. / Imunoistoquímica em oligodendrogliomas.

Oligodendrogliomas (OL) are neuroepithelial tumors characterized by the presence of uniformly round nuclei with a clear cytoplasm around it. These features can also be seen in central neurocytomas, DNTs and clear cell ependymomas. Immunohistochemistry with glial and neuronal markers may be helpful in differential diagnosis. The aim of this study was to determine the glial and neuronal differentiation in 42 specimens of otherwise typical OL using immunohistochemical techniques. Ten cases showed anaplastic characteristics. Thirty-three samples (78.5%) were positive to GFAP with few cells stained in ten cases and many positive cells in six. Twelve cases (28.5%) were focally positive to NSE and/or synaptophysin showing neuronal differentiation. Thirty-four cases (80.9%) expressed S-100. In conclusion, glial proteins may be present focally in OL due to presence of mature reactive astrocytes or transitional forms between astrocytes and oligodendrocytes. Focal areas of neuronal differentiation can also be found in typical OL. The widespread staining with neuronal marker suggests central neurocytoma, but this diagnosis should not be done with small amount of tissue.

Evaluation of the expression of C-kit (CD117) in ependymomas and oligodendrogliomas.

C-kit is a proto-oncogene located on the long arm of chromosome 4. Its product, CD117, is a specific immunohistochemical (IHQ) marker that is associated with response to a potent tyrosine kinase inhibitor therapy with STI-571 (Gleevec®) in chronic myelogenous leukemia and GISTs. In our study, we aimed to evaluate the expression of CD117 in glial tumors as this finding may guide therapeutic approaches for these brain tumors. Ependymomas and oligodendrogliomas, in formalin fixed and paraffin embedded blocks were assayed for CD117 immunoreactivity using anti-c-kit (CD117, DAKO). GISTs were used as positive control. We observed immunoreactivity of CD117 protein in 25.5% of tumors in both histological types. In oligodendrogliomas, there was an association between older age at diagnosis and positivity for CD117 (P=0.039). In addition, we observed an association between higher tumor grade (grade III) and positivity for CD117 (P=0.007). No clinical association was observed in ependymomas (P>0.05). This study encourages further investigations, considering that CD117 may be a possible oncogenic factor in some glial tumors. In this case, tumors that express this marker may eventually benefit from a therapy with selective inhibitors of receptor kinases.

Determination of cell proliferation using Mcm2 antigen and evaluation of apoptosis and TGF-beta1 expression in GH-secreting or clinically nonfunctioning pituitary adenomas.

Pituitary adenomas (PA) occasionally show aggressive behavior, with invasion of the surrounding tissues. The identification of markers able to recognize aggressive PA in early stages remains a challenge. We aimed to determine the expression of a new cell proliferation marker, Mcm2, and the presence of apoptosis in PA, and to evaluate the association of clinicopathological features with the apoptotic and proliferative indices. Additionally, the TGF-beta1 expression, an inducer of apoptosis, was determined. The proliferative index was determined in GH-secreting or clinically nonfunctioning PA using immunohistochemical (IH) methods for Mcm2 and Ki-67 antigens. The apoptosis was assessed by the TUNEL method and the TGF-beta1 expression by IH. A significant positive correlation was found between log Mcm2 index and log Ki-67 index (p < 0.001). Mcm2 and Ki-67 detected a similar number of proliferating cells. Mcm2 index showed a significant association with tumor extension (p = 0.02), but not with tumor invasion. Apoptosis was detected in 17% of the adenomas, with a maximum apoptotic index of 0.77%. Immunoreactivity to TGF-beta1 was observed in 77% of the adenomas, showing an association with tumor extension. We concluded that, in this sample, Mcm2 was similar to Ki-67 in the identification of the proliferating cells and that apoptosis was rare.

[Orbito-sphenoidal expansive processes: an anatomopathological study of 82 cases]. / Processos expansivos orbitoesfenoidais: estudo anatomopatológico de 82 casos.

PURPOSE: To describe the orbito-sphenoidal expansive processes diagnosed at the Anatomo-Pathological Laboratory of the Fundação Faculdade Federal de Ciências Médicas de Porto Alegre - Complexo Hospitalar Santa Casa de Porto Alegre during a period of 15 years, evaluating their relative frequencies among other tumoral processes. METHODS: We performed a statistical analysis of all orbital tumors with anatomicopathological diagnosis from January 1968 to December 1982, comparing the frequency of orbital tumors with the total number of tumors diagnosed at this Laboratory in a period of 5 years. RESULTS: Eighty-two cases were diagnosed of expansive processes involving the orbit in 15 years - 20.7% of the total (17 cases) affecting children (up to 14 years-old) and the remaining 79.3% (65 cases) affecting adults. Children presented more frequently optic nerve gliomas (4 of 6 cases 66.6%), retinoblastomas (4 cases - 100%) and rhabdomyosarcomas (3 of 4 cases - 75%). Less frequent diseases in children were optic nerve meningioma, neurofibroma, inflammatory pseudotumor, chronic dacryoadenitis, neuroma and chronic inflammatory process. The adult population presented more cases of basal cell carcinomas (18 cases), squamous cell carciomas (12 cases), meningiomas (10 cases), choroidal malignant melanoma (3 cases) and lacrimal gland tumors (7 cases). Tumors originated from bone or vascular structures, pseudo-tumors, and intraorbital epidermic cysts were also diagnosed, among others. Of a sum of 2,639 tumors diagnosed at this Laboratory in the time period of 5 years (1976 to 1980), there were 22 cases of orbital tumors, reaching a total of 0.8% of all cases. CONCLUSIONS: The anatomicopathological study of these processes is somehow important to diagnose and to establish an adequate therapy. The incidence of the expansive processes involving the orbit allows an epidemiological characterization of the different medical services responsible for the treatment of eye diseases. Despite its lower frequencies when compared to the diagnosis from other branches of Anatomical Pathology, Eye pathology has developed considerably over the past few years, contributing to more accurate diagnosis and to a better understanding of mechanisms responsible for these processes.

Processos expansivos orbitoesfenoidais: estudo anatomopatológico de 82 casos / Orbito-sphenoidal expansive processes: an anatomopathological study of 82 cases

OBJETIVO: Descrever os processos expansivos orbitoesfenoidais diagnosticados no Laboratório de Anatomia Patológica da Fundação Faculdade Federal de Ciências Médicas de Porto Alegre - Complexo Hospitalar Santa Casa de Porto Alegre durante o período de 15 anos, avaliando sua frequência relativa aos demais processos tumorais. MÉTODOS: Foi realizado levantamento estatístico de todos os tumores de órbita com diagnóstico anatomopatológico durante o período de janeiro de 1968 a dezembro de 1982, e correlacionada a frequência de tumores de órbita com o número total de tumores diagnosticados neste Laboratório por um período de 5 anos. RESULTADOS: Foram diagnosticados 82 casos de processos expansivos que acometiam a órbita no período estudado, sendo 20,7 por cento do total (17 casos) em crianças (até 14 anos) e os 79,3 por cento restantes (65 casos) em adultos. As crianças apresentaram mais frequentemente gliomas de nervo óptico (4 de 6 casos - 66,6 por cento), retinoblastomas (4 casos - 100 por cento) e rabdomiossarcomas (3 de 4 casos - 75 por cento). Outros diagnósticos menos frequentes em crianças foram meningioma do nervo óptico, neurofibroma, pseudotumor inflamatório, dacrioadenite crônica, neuroma e processo inflamatório crônico. Já a população adulta apresentou maior incidência de carcinomas basocelulares (18 casos), carcinomas epidermóides (12 casos), meningiomas (10 casos), melanomas malignos de coróide (3 casos) e tumores de glândula lacrimal (7 casos). Tumores derivados de estruturas ósseas ou vasculares, pseudotumores e cistos epidermóides intraorbitários foram também diagnosticados, entre outros. De um total de 2.639 tumores diagnosticados neste Laboratório no período de 5 anos (1976 a 1980), foram encontrados 22 tumores orbitários, perfazendo 0,8 por cento do total de casos. CONCLUSÕES: O estudo anatomopatológico destes processos é de fundamental importância para o diagnóstico e para o estabelecimento de terapêuticas adequadas. As ...

PURPOSE: To describe the orbito-sphenoidal expansive processes diagnosed at the Anatomo-Pathological Laboratory of the Fundação Faculdade Federal de Ciências Médicas de Porto Alegre - Complexo Hospitalar Santa Casa de Porto Alegre during a period of 15 years, evaluating their relative frequencies among other tumoral processes. METHODS: We performed a statistical analysis of all orbital tumors with anatomicopathological diagnosis from January 1968 to December 1982, comparing the frequency of orbital tumors with the total number of tumors diagnosed at this Laboratory in a period of 5 years. RESULTS: Eighty-two cases were diagnosed of expansive processes involving the orbit in 15 years - 20.7 percent of the total (17 cases) affecting children (up to 14 years-old) and the remaining 79.3 percent (65 cases) affecting adults. Children presented more frequently optic nerve gliomas (4 of 6 cases 66.6 percent), retinoblastomas (4 cases - 100 percent) and rhabdomiosarcomas (3 of 4 cases - 75 percent). Less frequent diseases in children were optic nerve meningioma, neurofibroma, inflammatory pseudotumor, chronic dacryoadenitis, neuroma and chronic inflammatory process. The adult population presented more cases of basal cell carcinomas (18 cases), squamous cell carciomas (12 cases), meningiomas (10 cases), choroidal malignant melanoma (3 cases) and lacrimal gland tumors (7 cases). Tumors originated from bone or vascular structures, pseudo-tumors, and intraorbital epidermic cysts were also diagnosed, among others. Of a sum of 2,639 tumors diagnosed at this Laboratory in the time period of 5 years (1976 to 1980), there were 22 cases of orbital tumors, reaching a total of 0.8 percent of all cases. CONCLUSIONS: The anatomicopathological study of these processes is somehow important to diagnose and to establish an adequate therapy. The incidence of the expansive processes involving the orbit allows an epidemiological characterization of the different medical ...

Immunohistochemical expression of markers Ki-67, neun, synaptophysin, p53 and HER2 in medulloblastoma and its correlation with clinicopathological parameters / Expressão imunoistoquímica dos marcadores Ki-67, neun, sinaptofisina, p53 e HER2 em meduloblastoma e sua correlação com os parâmetros clínico-patológicos

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5 percent), >20 percent of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40 percent) and 8 (20 percent) cases, respectively. P53 was positive in 18 (45 percent) cases, with 11 (61 percent) weakly positive and 7 (39 percent) strongly positive. HER2 was positive in 23 (57.5 percent) of the samples and did not show statistical association with survival (p=0.07).

Meduloblastoma (MB) é o tumor maligno encefálico mais freqüente na infância. dentre as alterações encontradas estão: a presença das oncoproteínas p53 e HER2, elevado índice mitótico e presença de diferenciação neuronal. o objetivo deste estudo foi determinar a expressão imunoistoquímica (IMQ) dos marcadores Ki-67, NeuN, sinaptofisina, HER2 e p53 em 40 amostras de MB, correlacionando-as com parâmetros clinicopatológicos e com a sobrevida. Vinte e nove pacientes (72,5 por cento) apresentaram 20 por cento ou mais das células positivas para Ki-67. os pacientes do sexo masculino apresentaram maior expressão do Ki-67 (p=0,02) e também menor sobrevida (p=0,002). NeuN e sinaptofisina foram negativos em 16 (40 por cento) e 8 (20 por cento) casos, respectivamente. P53 foi positivo em 18 (45 por cento) casos, sendo 11 (61 por cento) fracamente positivos e 7 (39 por cento) fortemente positivos. HER2 foi positivo em 23 (57,5 por cento) das amostras e não demonstrou associação estatística com a sobrevida (p=0.07).

Imunoistoquímica em oligodendrogliomas / Immunohistochemstry in oligodendrogliomas

Os oligodendrogliomas (OL) são tumores gliais caracterizados histologicamente pela presença de núcleo redondo e homogêneo com halo claro perinuclear. A diferenciação microscópica desses tumores com neurocitoma central, DNT e algumas vezes com ependimoma de células claras pode ser difícil. O estudo imunoistoquímico com marcadores glial e neuronal tem sido utilizado e pode auxiliar no diagnóstico diferencial. O objetivo do presente estudo foi determinar a diferenciação neuronal e glial por meio de técnica imunoistoquímica utilizando anticorpos de rotina em tumores com características microscópicas de OL. Foram estudados 42 pacientes com idade entre 4 e 60 anos. Dez apresentavam sinais de maior malignidade (anaplásico). Trinta e três casos (78,5%) mostraram positividade para GFAP, sendo em 10 focal e 6 casos com expressão intensa. Doze casos (28,5%) apresentaram positividade para NSE e/ou sinaptofisina, demonstrando alguma diferenciação neuronal, principalmente focal. Trinta e quatro casos (80,9%) foram positivos para S-100 e três casos (7,1%) foram positivos focalmente para NeuN. Concluimos que áreas focais de diferenciação neuronal e/ou glial podem estar presente em OL típicos e, portanto, é necessário cautela no diagnóstico diferencial em amostras pequenas de tumor. A positividade difusa para marcadores neuronais deve sugerir o diagnóstico de neurocitoma central.

Expression of nestin and vimentin in gliomatosis cerebri / Expressão de nestina e vimentina na gliomatosis cerebri

Gliomatosis cerebri (GC) is a rare form of CNS neoplasia in which there is diffuse involvement of the nervous tissue with or without the presence of tumor mass. The origin of the tumor is unknown, nor whether it represents a disease with diffuse onset or infiltration from a neoplastic focus. Here we studied the histopathologic characteristics of 6 cases with a diagnosis of GC and performed an immunohistochemical analysis using glial fibrillary acidic protein (GFAP), synaptophysin, nestin and vimentin. Most tumor cells were negative for GFAP, even though there were foci of positivity for this marker in all cases. We detected the presence of many positive cells for nestin and vimentin in all studied samples. The presence of these cells may indicate origin of the tumor from undifferentiated cells with a high degree of mobility.

A gliomatosis cerebri (GC) é uma forma rara de neoplasia do sistema nervoso central em que existe o envolvimento difuso do tecido nervoso com ou sem a presença de massa tumoral. A origem do tumor é incerta, bem como se representa uma doença de início difuso ou uma infiltração a partir de um foco de neoplasia. Foram estudadas as características histopatológicas de seis casos com diagnóstico de GC e realizada imuno-histoquímica utilizando-se GFAP, sinaptofisina, nestina e vimentina. A maioria das células tumorais mostrou-se negativa para GFAP, apesar de existirem focos de positividade para este marcador em todos os casos. Observamos muitas células positivas para nestina e para vimentina em todas as amostras estudadas. Estas células poderiam indicar a origem do tumor em células multipotenciais com alto grau de mobilidade.

Meningiomas and hormonal receptors: immunohistochemical study in typical and non-typical tumors

The authors assessed 116 cases of meningiomas classified as typical, atypical and anaplastic and they used an immunohistochemical technique for estrogen and progesterone receptors attempting to determine if there is any difference between typical and non-typical tumors in relation to hormone receptors. The immunohistochemical technique to estrogen receptors was negative in all meningiomas studied. Progesterone receptors were detected in 58.3 percent of typical, and in 48.2 percent of non-typical meningiomas. This difference was not statistically significant. However, individually considering the criteria used for selection of non-typical tumours, those that concurrently displayed brain invasion and increased mitotic activity or necrosis, as well as the summation of those three features, were predominantly negative for progesterone receptors (respectively p=0.038; p=0.001; and p=0.044). The authors conclude that estrogen receptors were not present in meningiomas; that progesterone receptors in isolation are not enough to predict a higher tumoral malignancy but can be useful associated with other histological features.

Encefalite neo-natal pelo vírus do Herpes simplex: diagnóstico imuno-histoquímico de um caso / Neonatal encephalitis due to Herpes simplex: immunohistochemical study of a case

Os autores relatam o caso de recém-nascido do sexo feminino com crises convulsivas e lesöes vesiculosas no nariz e lábio inferior, desde o quinto dia de vida. O exame do LCR mostrou alteraçöes compatíveis a encefalite. Houve deterioraçäo do quadro neurológico e respiratório, com morte da paciente. A autópsia paracial do crânio revelou cérebro edemaciado com área necro-hemorrágica envolvendo ambos os lobos temporais. O exame histopatológico revelou encefalite necro-hemorrágica, sem a presença de inclusöes intranucleares. O exame imuno-histoquímico, realizado pela técnica da avidina-biotina-peroxidase utilizando anticorpos policlonais contra vírus Herpes simplex tipo 1 e tipo 2, mostrou-se positivo em numerosas células neuronais, astrocíticas e, principalmente, oligodendrogliais para o anticorpo contra o vírus Herpes simples tipo 2

Neuropatologia das epilepsias de difícil controle: estudo de 300 casos consecutivos / Neuropathology of hard control epilepsy: study of 300 consecutive cases

Fazemos uma análise das alterações neuropatológicas encontradas em 300 casos consecutivos de cirurgia da epilepsia realizadas durante período de 6 anos. O material foi predominantemente de lobo temporal (70,33 por cento), sendo a esclerose hipocampal o diagnóstico mais frequente (44 por cento), seguido das neoplasias (15 por cento) e dos distúrbios da migração neuronal (10 por cento). Os tumores mais frequentes foram o ganglioglioma (42,22 por cento) e tumor neuroepitelial disembrioplástico (20 por cento). Segue revisão dos diagnósticos mais comuns em epilepsia baseados nessa série e relatados na literatura.

Carcinoide originado em teratoma ovariano benigno / Carcinoid originated on benign ovarian teratoma

Paciente de 58 anos de idade apresenta sindrome carcinoide e processo expansivo de ovario. Este foi ressecado cirurgicamente e o exame anatomopatologico revelou tratar-se de teratoma cistico benigno, com tumor carcinoide. O exame imuno-histoquimico foi positivo para os anticorpos contra a enolase neuronio-especifica e serotonina, confirmando o diagnostico. Assinala-se a raridade deste tipo de tumor e seu prognostico favoravel

Meningeomas: aspectos histopatológicos e recidiva / Meningiomas: histopathological aspects and recurrence

Os autores realizaram a avaliaçäo de 246 casos de meningeomas que foram classificados como típico, atípico, anaplásico e papilar segundo critérios previamente definidos. Entre os critérios utilizados para definiçäo de tumores näo típicos, a invasao do sistema nervoso central predominou em 62,3 por cento dos casos. Os meningeomas foram típicos em 75,22 por cento dos casos, atípicos em 19,1 por cento, anaplásicos em 5,68 por cento. Houve recidiva em 3,78 por cento dos meningeomas típicos, em 42,55 por cento dos atípicos e 45,45 por cento dos anaplásicos. Os autores concluem que os critérios utilizados para definiçao de típicos e näo típicos foram adequados para predizer maior chance de recidiva tumoral.

Gangliosidose GM1, tipo 1 / Gangliosidosis GM1, type 1

As autoras fazem uma revisäo sobre a doença de Norman-Landing, enfatizando os progressos no conhecimento, especialmente quanto aos aspectos genéticos, clínicos e de diagnóstico