Histopathological and immunological characteristics of placentas infected with chikungunya virus.

Although vertical transmission of CHIKV has been reported, little is known about the role of placenta in the transmission of this virus and the effects of infection on the maternal-fetal interface. In this work we investigated five placentas from pregnant women who became infected during the gestational period. Four formalin-fixed paraffin-embedded samples of placenta (cases 1-4) were positive for CHIKV by RT-PCR. One (case 5) had no positive test of placenta, but had positive RT-PCR for CHIKV in the serum of the mother and the baby, confirming vertical transmission. The placentas were analyzed regarding histopathological and immunological aspects. The main histopathological changes were: deciduitis, villous edema, deposits, villous necrosis, dystrophic calcification, thrombosis and stem vessel obliteration. In infected placentas we noted increase of cells (CD8+ and CD163+) and pro- (IFN-γ and TNF-α) and anti-inflammatory (TGF-ß and IL-10) cytokines compared to control placentas. Moreover, CHIKV antigen was detected in decidual cell, trophoblastic cells, stroma villi, Hofbauer cells, and endothelial cells. In conclusion, CHIKV infection seems to disrupt placental homeostasis leading to histopathological alterations in addition to increase in cellularity and cytokines overproduction, evidencing an altered and harmful environment to the pregnant woman and fetus.

Cytokines and inflammatory mediators: Markers involved in interstitial damage to the pancreas in two dengue fever cases associated with acute pancreatitis.

Dengue viral (DENV) infections can lead to acute pancreatitis and associated tissue damage. This study examined the pancreas from two fatal cases of DENV for histopathological changes as well as for the detection of cytokines, and other inflammatory mediators. Tissue sections were prepared for examination by ultrastructural and histopathological techniques. Sections from the pancreas of non-infected individuals were prepared in parallel as a control. The presence of viral replication in macrophages was detected by co-staining for the proteins NS3 and CD68 by immunofluorescence. Immunohistochemistry was used to detect cells that expressed cytokines and inflammatory mediators to characterize the inflammatory response. Edema, acinar necrosis and fibrosis areas associated with a mononuclear infiltrate were found in infected tissues. The major site of virus replication appeared to be macrophages based on their exclusive presentation of the viral protein NS3. Pancreatic tissues from the infected individuals also displayed increased levels of high mobility group box-1, caspase-3, gelatinase B and tumor necrosis factor alpha compared to controls. The presence of virus replicating macrophages in the pancreas was associated with multiple changes in tissue structure that included elevated levels of cytokines and inflammatory markers that may differentiate acute pancreatitis due to DENV infections from other causes.

Fatal Dengue Cases Reveal Brain Injury and Viral Replication in Brain-Resident Cells Associated with the Local Production of Pro-Inflammatory Mediators.

Dengue is an arboviral disease caused by dengue virus (DENV), which is transmitted to humans by Aedes aegypti mosquitoes. Infection by DENV most commonly results in a mild flu-like illness; however, the disease has been increasingly associated with neurological symptomatology. This association draws attention to further investigations on the impact of DENV infection in the host's central nervous system. Here, we analyzed brain samples of three fatal dengue cases that occurred in 2002 during an outbreak in Rio de Janeiro, Brazil. Brain tissues of these cases were marked by histopathological alterations, such as degenerated neurons, demyelination, hemorrhage, edema, and increased numbers of astrocytes and microglial cells. Samples were also characterized by lymphocytic infiltrates mainly composed of CD8 T cells. DENV replication was evidenced in neurons, microglia and endothelial cells through immunohistochemistry and in situ hybridization techniques. Pro-inflammatory cytokines, such as TNF-α and IFN-γ were detected in microglia, while endothelial cells were marked by the expression of RANTES/CCL5. Cytoplasmic HMGB1 and the production of nitric oxide were also found in neurons and microglial cells. This work highlights the possible participation of several local pro-inflammatory mediators in the establishment of dengue neuropathogenesis.

Laryngeal paracoccidioidomycosis presenting as solitary true vocal fold disease.

Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis or P. lutzii. It is a neglected tropical infectious disease that poses a major public health burden in endemic areas of Latin America. Mucosae of the upper digestive and respiratory tracts are commonly involved and many patients have disease at multiple mucosal sites, with or without lung involvement. Mucosal PCM presenting as solitary true vocal fold disease is relatively rare. We present the case of a 67-year-old Brazilian forest guard who presented with a 6-month history of hoarseness and globus pharyngeus due to a solitary left true vocal fold infiltration and vegetation diagnosed as PCM. Silent pulmonary disease was also present. A laryngoscopy video is offered as supplemental material to this report. He completely remitted after surgical removal and amphotericin B deoxycholate treatment.

An unusual case of bacillary angiomatosis in the oral cavity of an AIDS patient who had no concomitant tegumentary lesions - case report and review.

Bacillary angiomatosis (BA) is an angioproliferative disease of immunocompromised patients that usually presents as vascular tumors in the skin and subcutaneous tissues. It is caused by chronic infections with either Bartonella henselae or B. quintana. Oral cavity BA is exceedingly rare and even rarer without simultaneous cutaneous disease. We report herein the case of a 51-year-old HIV-infected man who presented severe odynophagia and an eroded lesion on the hard palate that progressed to an oronasal fistula. No cutaneous lesions were recorded. Doxycycline led to complete resolution. To the best of our knowledge, only six previous cases of oral BA without tegumentary disease have been previously reported and none of them progressed to fistula.

First Report of AIDS-Related Burkitt's Lymphoma Presenting as Bilateral Orbital Masses.

Burkitt's lymphoma (BL) is an aggressive B-cell non-Hodgkin's lymphoma and one of the fastest growing tumors in humans. It is an acquired immunodeficiency syndrome- (AIDS-) defining disease and occurs with relatively preserved CD4 cell counts. It rarely affects the orbital region in the setting of AIDS. We report unusual presentation of a fatal case of AIDS-associated BL in a 42-year-old female patient with severe CD4 cell depletion who presented with dramatic fast growing (within days) bilateral orbital masses leading to striking facial deformities. To the best of our knowledge, this is the first report of bilateral orbital involvement in AIDS-associated BL.

Prognostic angiogenic markers (endoglin, VEGF, CD31) and tumor cell proliferation (Ki67) for gastrointestinal stromal tumors.

AIM: To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor (VEGF)], proliferative index (Ki67), and prognosis of patients with gastrointestinal stromal tumors (GIST). METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients' demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin (CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density (IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF, Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5% positive cells. The prognosis was classified as good (patient alive without recurrence) or poor (patient with recurrence/death). RESULTS: The distribution of tumor sites among the 54 analyzed samples was as follows: 27 (50%) in the stomach, 20 (37.1%) in the small intestine, 6 (11.1%) in the colon, and 1 (1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm (median: 8 cm); in 12 cases (22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases (77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis (P < 0.001). The cut-off values of CD105 (> 1.2%) and CD31 (> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis. Cases with a better prognosis showed significantly null/weak staining for VEGF (P < 0.001). Ki-67 expression of ≥ 5% was strongly correlated with a worse prognosis (P < 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis. CONCLUSION: The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.

GIST: avaliações morfológica e imuno-histoquímica do prognóstico / GIST: morphological and immunohistochemical prognostic evaluation

INTRODUÇÃO: os tumores estromais gastrointestinais possuem amplo espectro biológico, variando desde lesões de comportamento benigno até aquelas de caráter maligno, capazes de ampla disseminação e frequentes metástases viscerais. Atualmente, o prognóstico está baseado num escore, denominado grau de risco. Entretanto, este sistema apresenta falhas, com tumores classificados como de riscos intermediário e baixo associados ao desenvolvimento de metástases. Desta forma, são necessários estudos que visem ao aprimoramento desse sistema de classificação, destacando-se nesse campo, nos últimos anos, o índice de proliferação celular que tem mostrado valor prognóstico na predição da agressividade tumoral. OBJETIVOS: analisar critérios morfológicos (tamanho macroscópico, topografia do tumor, índice mitótico, necrose, subtipo histológico), verificar o grau de risco e pesquisar a aplicabilidade dos marcadores imuno-histoquímicos (actina músculo-específico, proteína S-100, Ki67 e p16ink4a) como fatores prognósticos do tumor estromal gastrointestinal (GIST). RESULTADOS: a análise univariada mostrou significância com tumores maiores que 5 cm, número de mitoses maior que 5/50 CGA, presença de necrose, de grau de risco alto e índice de proliferação celular (Ki67) maior que 5 por cento com relação à redução da sobrevida global dos pacientes (p = 0,017; 0,01; 0,001; 0,016; < 0,001 respectivamente). Os outros fatores analisados (subtipo histológico, imunofenótipo e p16ink4a) não mostraram significância. CONCLUSÃO: o grau de risco, o tamanho tumoral, o índice mitótico e a presença de necrose corroboram evidências prévias da sua utilização, como fatores morfológicos prognósticos e o emprego do índice de proliferação celular (Ki67) associado ao grau de risco para melhor esclarecimento do comportamento biológico dos GIST.

INTRODUCTION: Gastrointestinal stromal tumors (GIST) have a wide biological spectrum, ranging from benign to malignant lesions, which are prone to wide spread and frequent visceral metastasis. Currently, the prognosis is based on a score system known as risk level. However, this system has some drawbacks. For instance, tumors classified as low or intermediate risk may be associated with the development of metastasis. Therefore, studies are required to improve this classification system and incorporate recent developments such as cellular proliferation index, which has shown prognostic value in the prediction of tumor aggressiveness. OBJECTIVES: To analyze morphological criteria (macroscopic size, tumor topography, mitotic index, necrosis, histological subtype), observe risk and investigate the usefulness of immunohistochemical markers (muscle-specific actin, S-100 protein, Ki67 and p16ink4a) as prognostic markers of GIST. RESULTS: Univariate analysis showed that a reduced global survival was significantly associated with tumor size greater than 5cm, mitotic index greater than 5/50 CGA, presence of necrosis, a high risk level, and a cellular proliferation index (Ki67) higher than 5 percent on the reduction of overall survivel of patients (p = 0.017, 0.010, 0.001, 0.016 and 0.0005, respectively). Other factors such as histological subtype, immunophenotype and p16ink4a were not significant. CONCLUSION: According to our data, risk level, tumor size, mitotic index and the presence of necrosis stood as morphological predictors of reduced survival, which underpins previous evidence of their application. The cellular proliferation marker Ki67 associated with risk level also proved to be a useful predictor of tumor aggressiveness.