Inflammatory/juvenile-like polyps in neurofibromatosis type 1 associated with epithelial dysplasia.

The term "juvenile-like (inflammatory/hyperplastic) mucosal polyps" (JLIHMP) has been recently introduced to describe a spectrum of polypoid lesions in patients with neurofibromatosis type 1 (NF-1). Due to the scarce number of reported cases and histopathological similarities with entities such as sporadic/syndromic juvenile polyps or inflammatory fibroid polyps, this entity remains a subject of debate. We describe herein a case of multiple JLIHMPs in a patient with NF-1, and we document the presence of low-grade dysplasia within one of these polyps.

[Fibrothecoma of the testis: A case report in an adult]. / Fibrothécome testiculaire : à propos d'un cas chez un adulte.

Fibrothecal tumors belong to sex cord/stromal tumors (SCSTS). They represent 1 to 4.7 % of the organics tumors of ovary (Chechia et al., 2008) but are extremely rare in the testis, with only a few cases described in the literature. We report a new case of a fibrothecoma in the testis in an adult. The extemporaneous diagnosis was made in the same time of the surgical intervention. The castration has been avoided.

Surgical pathology in cancer diagnosis: implications for quaternary prevention / Anatomia patológica no diagnóstico do câncer: implicações para a prevenção quaternária / Patología quirúrgica en el diagnóstico de cáncer: implicaciones para la prevención cuaternaria

Surgical pathology is the medical specialty in charge of cancer diagnosis. Although very important since oncology development, its link with overdiagnosis and overtreatment remains understudied. Despite big mediatisation, molecular biology has not brought much progress to tumour classifications. On the contrary, the silent apparition of immunohistochemistry at the end of the 1980's improved much of tumour classifications so significantly that it could cast doubts in some trials' results of that period. This article discusses how the booming and abuse of immunohistochemistry might have led to overdiagnosis. It also highlights that the ISO 15189 standardization, as well as the tumour classification complexity, might function to induce overtreatment. In summary, critical reading and understanding of pathology reports by general practitioners are essential. Therefore, family doctors should not hesitate to discuss the cancer diagnosis with the pathologist, and in some cases also question the oncologist decision. This approach can be considered a quaternary prevention action which can prevent overtreatment.

A anatomia patológica é a especialidade médica responsável pelo diagnóstico de câncer. Apesar de muito importante, a partir do desenvolvimento da oncologia, sua ligação com o sobrediagnóstico e sobretratamento permanece ainda pouco estudada. Apesar de grande midiatização, a biologia molecular não trouxe muito progresso para a classificação dos tumores. Ao contrário, a aparição silenciosa de imunohistoquímica, no final da década de 1980, foi o que melhorou significativamente as classificações tumorais, a ponto de ser possível lançar dúvidas sobre os resultados de alguns ensaios clínicos desse período. Este artigo discute como o auge e o abuso da imunohistoquímica pode ter levado ao sobrediagnóstico. Ele também destaca que a padronização ISO 15189, assim como a complexidade de classificação tumoral, podem também contribuir para a indução do sobretratamento. Em suma, a leitura crítica e a compreensão dos laudos de patologia por parte dos médicos de família são essenciais. Portanto, os médicos de família não deveriam hesitar em discutir o diagnóstico de câncer com o patologista e, em alguns casos, também questionar a decisão do oncologista. Essa abordagem pode ser considerada uma ação de prevenção quaternária que pode prevenir o sobretratamento.

La patología quirúrgica es la especialidad médica encargada del diagnóstico de cáncer. Aunque es muy importante, desde el desarrollo de la oncología, su vínculo con el sobrediagnóstico y sobretratamiento sigue pendiente de estudio. A pesar de gran mediatización, la biología molecular no ha traído mucho progreso para las clasificaciones tumorales. Por el contrario, la aparición silenciosa de la inmunohistoquímica, en el final de la década de 1980, mejoró mucho las clasificaciones tumorales, a punto de que sea posible plantear dudas sobre los resultados de algunos ensayos clínicos en ese período. Este artículo describe cómo el auge y el abuso de la inmunohistoquímica puede tener llevado al sobrediagnóstico. También destaca que la estandarización ISO 15189, así como la complejidad de la clasificación tumoral, pueden también contribuir para la inducción del sobretratamiento. En suma, la lectura crítica y la comprensión de los informes de patología por los médicos familiares son esenciales. Portanto, los médicos de familia no deberían vacilar en discutir el diagnóstico de cáncer con el patólogo y, en algunos casos, también cuestionar la decisión del oncólogo. Este enfoque puede ser considerado una acción de prevención cuaternaria que puede prevenir el sobretratamiento.

A functional sequence-specific interaction between influenza A virus genomic RNA segments.

Influenza A viruses cause annual influenza epidemics and occasional severe pandemics. Their genome is segmented into eight fragments, which offers evolutionary advantages but complicates genomic packaging. The existence of a selective packaging mechanism, in which one copy of each viral RNA is specifically packaged into each virion, is suspected, but its molecular details remain unknown. Here, we identified a direct intermolecular interaction between two viral genomic RNA segments of an avian influenza A virus using in vitro experiments. Using silent trans-complementary mutants, we then demonstrated that this interaction takes place in infected cells and is required for optimal viral replication. Disruption of this interaction did not affect the HA titer of the mutant viruses, suggesting that the same amount of viral particles was produced. However, it nonspecifically decreased the amount of viral RNA in the viral particles, resulting in an eightfold increase in empty viral particles. Competition experiments indicated that this interaction favored copackaging of the interacting viral RNA segments. The interaction we identified involves regions not previously designated as packaging signals and is not widely conserved among influenza A virus. Combined with previous studies, our experiments indicate that viral RNA segments can promote the selective packaging of the influenza A virus genome by forming a sequence-dependent supramolecular network of interactions. The lack of conservation of these interactions might limit genetic reassortment between divergent influenza A viruses.

Critical role of segment-specific packaging signals in genetic reassortment of influenza A viruses.

The fragmented nature of the influenza A genome allows the exchange of gene segments when two or more influenza viruses infect the same cell, but little is known about the rules underlying this process. Here, we studied genetic reassortment between the A/Moscow/10/99 (H3N2, MO) virus originally isolated from human and the avian A/Finch/England/2051/91 (H5N2, EN) virus and found that this process is strongly biased. Importantly, the avian HA segment never entered the MO genetic background alone but always was accompanied by the avian PA and M fragments. Introduction of the 5' and 3' packaging sequences of HA(MO) into an otherwise HA(EN) backbone allowed efficient incorporation of the chimerical viral RNA (vRNA) into the MO genetic background. Furthermore, forcing the incorporation of the avian M segment or introducing five silent mutations into the human M segment was sufficient to drive coincorporation of the avian HA segment into the MO genetic background. These silent mutations also strongly affected the genotype of reassortant viruses. Taken together, our results indicate that packaging signals are crucial for genetic reassortment and that suboptimal compatibility between the vRNA packaging signals, which are detected only when vRNAs compete for packaging, limit this process.

The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses.

Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus-host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

Importance of viral genomic composition in modulating glycoprotein content on the surface of influenza virus particles.

Despite progress in our knowledge of the internal organisation of influenza virus particles, little is known about the determinants of their morphology and, more particularly, of the actual abundance of structural proteins at the virion level. To address these issues, we used cryo-EM to focus on viral (and host) factors that might account for observed differences in virion morphology and characteristics such as size, shape and glycoprotein (GP) spike density. Twelve recombinant viruses were characterised in terms of their morphology, neuraminidase activity and virus growth. The genomic composition was shown to be important in determining the GP spike density. In particular, polymerase gene segments and especially PB1/PB2 were shown to have a prominent influence in addition to that for HA in determining GP spike density, a feature consistent with a functional link between these virus components important for virus fitness.

Acute hepatitis E: a cause of lymphocytic destructive cholangitis.

Lymphocytic destructive cholangitis is a histological pattern associating bile duct intraepithelial lymphocytic infiltration and bile duct epithelial damage. Lymphocytic destructive cholangitis is an important diagnostic feature of primary biliary cirrhosis, but it can also be seen in primary sclerosing cholangitis, autoimmune hepatitis, the so-called overlap syndrome, acute or chronic viral hepatitis C, drug-induced hepatitis, and acute rejection or graft-versus-host disease in liver or bone marrow transplantation. In the present paper we report a case of acute hepatitis with lymphocytic destructive cholangitis on liver biopsy. Clinical and biological examinations showed that the patient had hepatitis E with no other cause of liver disease. Therefore, hepatitis E should be considered as a diagnostic possibility when liver biopsy shows acute hepatitis and lymphocytic destructive cholangitis. The mechanism of bile duct damage in hepatitis E remains unknown.

Determination of DNA ploidy by fluorescence in situ hybridization (FISH) in hydatidiform moles: evaluation of FISH on isolated nuclei.

In the past 20 years, the diagnosis of hydatidiform moles has become more difficult because of the widespread use of early uterine evacuation. Differentiating hydropic degeneration, partial, and complete moles is important because of their different prognosis. However, clinical diagnosis is less obvious, and the pathologist has to separate the different entities on the basis of very subtle morphologic criteria. In difficult cases, ploidy may be determined by various methods, including fluorescence in situ hybridization (FISH) on routine histological sections from paraffin-embedded specimens. However, FISH analysis is often difficult because of the presence of numerous truncated nuclei. In this context, we have tested the advantages of FISH on isolated nuclei, a well-known variant of the technique that might be more sensitive. We reviewed 24 cases of products of abortion: hydropic degenerations, complete hydatidiform moles, partial moles, and nonmolar triploidies. After histological review, FISH on isolated nuclei proved conclusive in all cases. The results could be easily interpreted thanks to the reduced number of truncated nuclei. The percentage of cells with 2 signals was always >70% in the diploid cases and >60% in the triploid cases. In conclusion, this sensitive technique seems to be a valuable tool for the diagnosis of moles.