Diagnostic yield and safety of transbronchial lung cryobiopsy and surgical lung biopsy in interstitial lung diseases: a systematic review and meta-analysis.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly being used as an alternative to video-assisted thoracoscopic surgery (VATS) biopsy to establish the histopathologic pattern in interstitial lung disease (ILD). METHODS: A systematic literature search of the PubMed and Embase databases, from October 2010 to October 2020, was conducted to identify studies that reported on diagnostic yield or safety of VATS or TBLC in the diagnosis of ILD. RESULTS: 43 studies were included. 23 evaluated the diagnostic yield of TBLC after multidisciplinary discussion, with a pooled diagnostic yield of 76.8% (95% confidence interval (CI) 70.6-82.1), rising to 80.7% in centres that performed ≥70 TBLC. 10 studies assessed the use of VATS and the pooled diagnostic yield was 93.5% (95% CI 88.3-96.5). In TBLC, pooled incidences of complications were 9.9% (95% CI 6.8-14.3) for significant bleeding (6.9% for centres with ≥70 TBLC), 5.6% (95% CI 3.8-8.2) for pneumothorax treated with a chest tube and 1.4% (95% CI 0.9-2.2) for acute exacerbation of ILD after TBLC. The mortality rates were 0.6% and 1.7% for TBLC and VATS, respectively. CONCLUSIONS: TBLC has a fairly good diagnostic yield, an acceptable safety profile and a lower mortality rate than VATS. The best results are obtained from more experienced centres.

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.

Effect of N-acetylcysteine on vasospasm in subarachnoid hemorrhage / Efeito da N-acetilcisteína sobre o vasoespasmo na hemorragia subaracnóidea

Vasospasm remains an extremely serious complication that affects patients presenting with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms. The current therapeutic armamentarium is still insufficient in many cases, and the search for new therapies is necessary. In this study, we evaluated the effect of N-acetylcysteine (NAC) on cerebral arterial vasospasm using an experimental model. Twenty-four wistar rats were divided into 4 groups: [1] Control, [2] SAH, [3] SAH+NAC and [4] SAH+Placebo. The experimental model employed double subarachnoid injections of autologous blood. The proposed dose of NAC was 250 mg/kg intraperitoneally per day. We analyzed the inner area of the basilar artery to assess the action of NAC. The experimental model proved to be very adequate, with a mortality rate of 4 percent. The inner area of the basilar artery in the SAH group showed significant difference to the control group (p=0.009). The use of NAC significantly reduced vasospasm as compared to the untreated group (p=0.048) and established no significant difference to the control group (p=0.098). There was no significant improvement with the administration of placebo (p=0.97). The model of the dual hemorrhage proved to be very useful for vasospasm simulation, with overall low mortality. The administration of NAC significantly reduced vasospasm resulting from SAH, and may represent a new therapeutic alternative.

O vasoespasmo arterial encefálico continua sendo uma complicação extremamente grave que acomete pacientes com hemorragia subaracnóidea (HSA) por ruptura de aneurismas. O arsenal terapêutico atual ainda, em muitos casos, é insuficiente e a busca de novas alternativas terapêuticas torna-se necessária. Neste estudo, avaliamos a ação da N-acetilcisteína (NAC) sobre o vasoespasmo arterial encefálico em um modelo experimental. Foram utilizados 24 ratos wistar divididos em 4 grupos: [1] Controle, [2] HSA, [3] HSA+NAC e [4] HSA+Placebo. O modelo experimental utilizado foi o da dupla injeção subaracnóidea de sangue autólogo. A dose proposta da NAC foi de 250 mg/kg/dia por via intraperitoneal. Foi analisada a área interna da artéria basilar para avaliação da ação da NAC. O modelo experimental mostrou-se excelente com mortalidade de 4 por cento. A mensuração da área interna da artéria basilar do grupo HSA demonstrou diminuição significativa em relação ao grupo controle (p=0,009). A administração da NAC reduziu significativamente o vasoespasmo em relação ao grupo não tratado (p=0,048) e estabeleceu diferença não significativa em relação ao grupo controle (p=0,098). Não houve melhora significativa com administração de placebo (P=0,97). O modelo da dupla hemorragia mostrou-se bastante útil para reprodução do vasoespasmo, com baixos índices de mortalidade. A administração da NAC diminuiu significativamente o vasoespasmo decorrente da HSA, podendo representar uma nova alternativa terapêutica.

Peritumoral brain edema in intracranial meningiomas.

Occurrence of peritumoral brain edema (PBE) in meningiomas has been associated with several factors in recent years, although its pathophysiological mechanism has not yet been fully elucidated. The aim of this study was to analyze the correlation between the presence / degree of PBE and factors such as gender, age, size and histological subtype of tumor. We analyzed the MRI images of 74 patients operated on Hospital Beneficência Portuguesa de Porto Alegre for the presence / degree of PBE and data was statistically correlated with the parameters of the patient. PBE was present in 70.1% of patients. Tumors with higher volume had more PBE. Tumors of the olfactory groove showed more PBE than sphenoid wing and parassagittal tumors. Transitional subtype showed more PBE than fibroblastic and meningothelial subtypes.

Peritumoral brain edema in intracranial meningiomas / Edema peritumoral em meningiomas intracranianos

Occurrence of peritumoral brain edema (PBE) in meningiomas has been associated with several factors in recent years, although its pathophysiological mechanism has not yet been fully elucidated. The aim of this study was to analyze the correlation between the presence / degree of PBE and factors such as gender, age, size and histological subtype of tumor. We analyzed the MRI images of 74 patients operated on Hospital Beneficência Portuguesa de Porto Alegre for the presence / degree of PBE and data was statistically correlated with the parameters of the patient. PBE was present in 70.1 percent of patients. Tumors with higher volume had more PBE. Tumors of the olfactory groove showed more PBE than sphenoid wing and parassagittal tumors. Transitional subtype showed more PBE than fibroblastic and meningothelial subtypes.

A presença de edema cerebral peritumoral (ECP) em meningiomas tem sido associada a diversos fatores nos últimos anos, embora o seu mecanismo fisiopatológico ainda não tenha sido inteiramente elucidado. O objetivo desse estudo foi analisar a correlação entre a presença/grau de ECP e fatores como sexo, idade, volume e subtipo histológico do tumor. Foram analisadas imagens de RM de 74 pacientes operados no Hospital Beneficência Portuguesa de Porto Alegre quanto à presença/grau de ECP e os dados correlacionados estatisticamente com os parâmetros do paciente. ECP estava presente em 70,1 por cento dos pacientes. Tumores com maior volume apresentaram mais ECP. Tumores da goteira olfatória apresentaram mais ECP que os da asa do esfenóide e que os parassagitais. Meningiomas transicionais apresentaram mais ECP que os fibroblásticos e que os meningoteliais.

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.

Effect of N-acetylcysteine on vasospasm in subarachnoid hemorrhage.

Vasospasm remains an extremely serious complication that affects patients presenting with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms. The current therapeutic armamentarium is still insufficient in many cases, and the search for new therapies is necessary. In this study, we evaluated the effect of N-acetylcysteine (NAC) on cerebral arterial vasospasm using an experimental model. Twenty-four wistar rats were divided into 4 groups: [1] Control, [2] SAH, [3] SAH+NAC and [4] SAH+Placebo. The experimental model employed double subarachnoid injections of autologous blood. The proposed dose of NAC was 250 mg/kg intraperitoneally per day. We analyzed the inner area of the basilar artery to assess the action of NAC. The experimental model proved to be very adequate, with a mortality rate of 4%. The inner area of the basilar artery in the SAH group showed significant difference to the control group (p=0.009). The use of NAC significantly reduced vasospasm as compared to the untreated group (p=0.048) and established no significant difference to the control group (p=0.098). There was no significant improvement with the administration of placebo (p=0.97). The model of the dual hemorrhage proved to be very useful for vasospasm simulation, with overall low mortality. The administration of NAC significantly reduced vasospasm resulting from SAH, and may represent a new therapeutic alternative.

The prognostic value of angiogenesis by Chalkley counting in gallbladder carcinoma.

BACKGROUND/AIMS: Tumor angiogenesis has been proposed as essential to tumor growth, proliferation and metastases however, for gallbladder neoplasia, these data remain obscure. Therefore, it was performed this study with the objective of evaluating the prognostic value of angiogenesis in gallbladder cancer. METHODOLOGY: Thirty cases of gallbladder carcinoma were studied by immunohistochemical technique with antibody anti-CD105 for the identification of neoformed intratumoral vessels. The intratumoral micro vessel density was evaluated by Chalkley counting method, and researched the association of this index with the survival rate and the prognostic factors. RESULTS: It was obtained, starting from the analysis of these data, a cut off in the index of the tumor vascular density at 8.5. It was observed an association between high intratumoral micro vessel density (index above or equal to 8.5) and survival rate lower to 6 months in 84.6% of cases. CONCLUSION: The present study confirms the hypothesis that a high vascular density, appraised through the Chalkley counting method, is associated to a worse prognosis in patients of gallbladder carcinoma.

[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.

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).

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).

Immunohistochemical evaluation of the microvascular density through the expression of TGF-beta (CD 105/endoglin) and CD 34 receptors and expression of the vascular endothelial growth factor (VEGF) in oligodendrogliomas.

Angiogenesis has been proposed as essential for the growth of solid tumors. The determinants of this process, the growth factors and the vascular endothelial receptors have brought a potential in the tumor prognostic determination as well as perspectives of "targets" for antiangiogenic therapy. In oligodendrogliomas (OL), angiogenesis is little known and/or has generated conflicting results. In order to clarify angiogenesis in OL, we have evaluated the immunohistochemical expression of vascular endothelial growth factor (VEGF) and the microvascular density (MVD) through the expression of TGF-beta (CD105/endoglin) (MVD-CD105) and CD34 (MVD-CD34) receptors using the Chalkley point method in 30 OL. No significant immune reaction was found for the VEGF. There was expression in <10% of tumor cells and/or staining of weak intensity in 15 (50.0%), >10% of cells and moderate intensity staining in 1 (3.33%), and negative expression in 14 (46.67%). If present, the expression was restricted to tumor and endothelial cells. Our findings suggest that VEGF has little influence on OL angiogenesis. All specimens showed CD105 and CD34 expression in the intratumor vascular endothelium, suggesting involvement of CD105 in OL angiogenesis. The mean +/- SD MVD-CD105 and MVD-CD34 were 10.83 +/- 2.24 and 11.00 +/- 2.76 in OL (P = 0.086; r = 0.319); 10.00 +/- 2.00 and 10.40 +/- 3.02 in OL grade II (n = 15) (P = 0.547; r = 0.105), and 11.67 +/- 2.22 and 11.53 +/- 2.45 in OL grade III (n = 15) (P = 0.817; r = 0.551), respectively. The absence of correlation between DMV-CD105, DMV-CD34 and tumor grades suggests that anti-CD105 and anti-CD34 antibodies have different vascular specificities. MVD-CD105 was greater in OL grade III than in OL grade II (P = 0.0032), indicating an increase in the vascular neoformation, something which must be evaluated as a possible prognostic factor in OL. Both TGF-beta and CD105 bring perspectives as "targets" for antiangiogenic treatments in OL.

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.

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.

[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.

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.

Expressão imuno-histoquímica e valor prognóstico da proteína p53 no carcinoma de vesícula biliar: estudo de 60 casos / Immunohistochemical expression and prognostic value of the p53 protein in gallbladder carcinoma: a 60-case study

BASE TEORICA/OBJETIVO: Poucos estudos, com pequenas amostras e resultados divergentes, têm sido realizados para avaliar a expressão da proteína p53 no carcinoma de vesícula biliar e sua relação com diferentes parâmetros clinicopatológicos. Baseados nesses fatos realizamos um estudo com objetivo de avaliar a expressão do p53 nessa afeccção e sua associação a fatores prognósticos. MATERIAL E MÉTODO: Amostras de 60 casos de carcinoma de vesícula biliar foram avaliadas por técnica imuno-histoquímica quanto à expressão da proteína p53 e analisadas em relação ao prognóstico, avaliado através do sistema de estádio TNM e Nevin, sobrevida e outros parâmetros clinicopatológicos. RESULTADOS: A expressão p53 foi positiva em 58,3 por cento dos tumores malignos de vesícula biliar. Não foi observada associação estatisticamente significante entre a expressão dessa proteína e fatores prognósticos, tipo ou grau histológico, presença de cálculos ou sobrevida. CONCLUSAO: A mutação do gene p53 está, muito provavelmente, envolvida na patogênese do carcinoma de vesícula biliar. Entretanto não parece haver, de acordo com nossos dados, associação entre a expressão da proteína p53 e o prognóstico ou a sobrevida dos pacientes portadores dessa afecção.

The value of p53 protein expression in gallbladder carcinoma: analysis of 60 cases.

BACKGROUND/AIMS: Few studies, with small samples and diverging results, have been performed to evaluate the p53 protein expression in gallbladder carcinoma and its relationship to different clinicopathological parameters. Based on these facts, we performed a study for the purpose of assessing p53 expression in this disease and its association to prognostic factors. METHODOLOGY: Samples of 141 gallbladders, with 60 cases of carcinoma, 62 cholelithiasis and 19 without gallstones were assessed using an immunohistochemical technique for the expression of p53 protein, and analyzed for prognosis, survival and other clinicopathological parameters. RESULTS: p53 expression was positive in 58.3% of carcinomas of the gallbladder, 9.7% of the chronic cholecystitis and 10.5% of the gallbladders not associated to stones. In cases of carcinoma of the gallbladder there was no statistically significant association between the expression of this protein, the prognostic factors, histological type or grade, presence of gallstones and survival. CONCLUSIONS: The mutation of gene p53 is involved in the pathogenesis of carcinoma of the gallbladder, and the intense chronic inflammatory process associated or not with cholelithiasis, appears to be one of the factors involved in the genesis of this process. Our data do not show an association between p53 protein expression and patient's survival prognosis.