Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil.

OBJECTIVES: Screening for genes differentially expressed in placental tissues, aiming to identify transcriptional signatures that may be involved in ZIKV congenital pathogenesis. METHODS: Transcriptome data from placental tissues of pregnant women naturally infected with Zika virus during the third trimester were compared to those from women who tested negative for Zika infection. The findings were validated using both a cell culture model and an immunohistochemistry/morphological analysis of naturally infected placental tissues. RESULTS: Transcriptome analysis revealed that Zika virus infection induces downregulation of insulin-like growth factor II (IGF2) gene, an essential factor for fetal development. The Caco-2 cell culture model that constitutively expresses IGF2 was used for the transcriptome validation. Asiatic and African Zika virus strains infection caused downregulated IGF2 gene expression in Caco-2 cells, whereas other flaviviruses, such as dengue serotype 1, West Nile and wild-type yellow fever viruses, had no effect on this gene expression. Immunohistochemical assays on decidual tissues corroborated our transcriptome analysis, showing that IGF2 is reduced in the decidua of Zika virus-infected women. CONCLUSIONS: Our results draw attention to IGF2 modulation in uterine tissues, and this finding is expected to support future studies on strategies to ameliorate the harmful effects of Zika virus infection during pregnancy.

Zika Virus Infection at Different Pregnancy Stages: Anatomopathological Findings, Target Cells and Viral Persistence in Placental Tissues.

Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects are not completely elucidated. In this study, we analyzed placental samples obtained at the time of delivery from a group of 24 women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.

Giant nodular pseudoangiomatous stromal hyperplasia of the breast with fibroadenomatoid myxoid changes: a potential pitfall in the differential diagnosis of phyllodes tumor / Hiperplasia estromal pseudoangiomatosa mamária nodular gigante com padrão fibroadenomatoide mixoide: diagnóstico diferencial problemático com tumor phyllodes

ABSTRACT A 21-year old woman presented with a 17-cm left breast mass. Physical examination and ultrasound revealed the mass to be well-circumscribed, homogeneous and freely mobile, suggestive of giant fibroadenoma or phyllodes tumor. The mass was surgically excised and initially interpreted as benign phyllodes tumor. Subsequent slide review established the diagnosis of nodular pseudoangiomatous stromal hyperplasia (PASH) associated with fibroadenomatoid areas and myxoid stromal changes. This case illustrates the difficulty encountered in recognizing nodular PASH. A thorough discussion of the histopathologic differential diagnosis of nodular PASH is provided.

RESUMO Uma mulher de 21 anos desenvolveu uma massa mamária de grandes dimensões (17 cm). Exame físico e ultrassonografia revelaram um nódulo bem delineado, homogêneo e móvel, com características sugestivas de fibroadenoma gigante ou tumor phyllodes. O nódulo foi excisado e inicialmente interpretado como tumor phyllodes benigno. Subsequente revisão de lâminas estabeleceu o diagnóstico de hiperplasia estromal pseudoangiomatosa nodular associada a áreas de padrão fibroadenomatoide e focos de degeneração mixoide do estroma. Este caso ilustra a dificuldade encontrada no diagnóstico dessa entidade. Segue uma discussão detalhada do diagnóstico diferencial de hiperplasia estromal pseudoangiomatosa nodular.