Epilepsies Associated With Hippocampal Sclerosis.

Hippocampal sclerosis (HS) is considered the most frequent neuropathological finding in patients with mesial temporal lobe epilepsy (MTLE). Hippocampal specimens of pharmacoresistant MTLE patients that underwent epilepsy surgery for seizure control reveal the characteristic pattern of segmental neuronal cell loss and concomitant astrogliosis. However, classification issues of hippocampal lesion patterns have been a matter of intense debate. International consensus classification has only recently provided significant progress for comparisons of neurosurgical and clinic-pathological series between different centers. The respective four-tiered classification system of the International League Against Epilepsy subdivides HS into three types and includes a term of gliosis only, no-HS. Future studies will be necessary to investigate whether each of these subtypes of HS may be related to different etiological factors or with postoperative memory and seizure outcome. Molecular studies have provided potential deeper insights into the pathogenesis of HS and MTLE on the basis of epilepsy-surgical hippocampal specimens and corresponding animal models. These include channelopathies, activation of NMDA receptors, and other conditions related to Ca(2+) influx into neurons, the imbalance of Ca(2+)-binding proteins, acquired channelopathies that increase neuronal excitability, paraneoplastic and non-paraneoplastic inflammatory events, and epigenetic regulation promoting or facilitating hippocampal epileptogenesis. Genetic predisposition for HS is clearly suggested by the high incidence of family history in patients with HS, and by familial MTLE with HS. So far, it is clear that HS is multifactorial and there is no individual pathogenic factor either necessary or sufficient to generate this intriguing histopathological condition. The obvious variety of pathogenetic combinations underlying HS may explain the multitude of clinical presentations, different responses to clinical and surgical treatment. We believe that the stratification of neuropathological patterns can help to characterize specific clinic-pathological entities and predict the postsurgical seizure control in an improved fashion.

Cytotoxic Granules In Distinct Subsets Of Cutaneous Lupus Erythematosus.

In cutaneous lupus erythematosus (CLE), the pathogenetic role of cytotoxic granules has been demonstrated in the subacute and discoid subtypes, which show interface dermatitis, but little is known about tumid (T)CLE, which does not show this interface dermatitis, and evolves with minimal epidermal changes. We studied cytotoxic T lymphocytes and cytotoxic granules in discoid (n = 21), subacute (n = 17), and tumid (n = 21) CLE samples. Skin sections were immunohistochemically stained for CD8, CD56, perforin, granzyme A, granzyme B, and granulysin. Inflammatory cells containing the four subtypes of cytotoxic granules were found in all the three CLE forms; however, only the TCLE group showed a positive correlation between the density of CD8+ cells and each subtype of cytotoxic granule-positive cells. In addition, only the TCLE group showed synergy between the densities of cells containing cytotoxic granule subtypes. Cytotoxic granules are important in the pathomechanism of TCLE. They may perform functions other than apoptosis, including maintenance of inflammation and dermal mucinous deposits in TCLE.

Tubular Variant Of Basal Cell Adenoma Shares Immunophenotypical Features With Normal Intercalated Ducts And Is Closely Related To Intercalated Duct Lesions Of Salivary Gland.

The morphological criteria for identification of intercalated duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs. The aim of this study was to analyse the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular and non-tubular subtypes, to determine whether or not IDL and tubular BCA represent distinct entities. Eight IDLs, nine tubular BCAs and 19 non-tubular BCAs were studied. All tubular BCAs contained IDL-like areas, which represented 20-70% of the tumour. In non-tubular BCA, IDL-like areas were occasional and small (<5%). One patient presented IDLs, tubular BCAs and IDL/tubular BCA combined lesions. Luminal ductal cells of IDLs and tubular BCAs exhibited positivity for CK7, lysozyme, S100 and DOG1. In the non-tubular BCA group, few luminal cells exhibited such an immunoprofile; they were mainly CK14-positive. Basal/myoepithelial cells of IDLs, tubular BCAs and non-tubular BCAs were positive for CK14, calponin, α-SMA and p63; they were more numerous in BCA lesions. IDL, tubular BCA and non-tubular BCA form a continuum of lesions in which IDLs are related closely to tubular BCA. In both, the immunoprofile of luminal and myoepithelial cells recapitulates the normal intercalated duct. The difference between the adenoma-like subset of IDLs and tubular BCA rests mainly on the larger numbers of myoepithelial cells in the latter. Our findings indicate that at least some BCAs can arise via IDLs.

[the New Classification Of Breast Cancers: Finding The Luminal A].

To compare the distributions of patients with clinical-pathological subtypes of luminal B-like breast cancer according to the 2011 and 2013 St. Gallen International Breast Cancer Conference Expert Panel. We studied 142 women with breast cancer who were positive to estrogen receptor and had been treated in São Paulo state, southeast Brazil. The expression of the following receptors was assessed by immunohistochemistry: estrogen, progesterone (PR) and Ki-67. The expression of HER-2 was measured by fluorescent in situ hybridization analysis in tissue microarray. There were 29 cases of luminal A breast cancers according to the 2011 St. Gallen International Breast Cancer Conference Expert Panel that were classified as luminal B-like in the 2013 version. Among the 65 luminal B-like breast cancer cases, 29 (45%) were previous luminal A tumors, 15 cases (20%) had a Ki-67 >14% and were at least 20% PR positive and 21 cases (35%) had Ki-67 >14% and more than 20% were PR positive. The 2013 St. Gallen consensus updated the definition of intrinsic molecular subtypes and increased the number of patients classified as having luminal B-like breast cancer in our series, for whom the use of cytotoxic drugs will probably be proposed with additional treatment cost.

Genetic Diversity Of Giardia Duodenalis: Multilocus Genotyping Reveals Zoonotic Potential Between Clinical And Environmental Sources In A Metropolitan Region Of Brazil.

Giardia duodenalis is a flagellate protozoan that parasitizes humans and several other mammals. Protozoan contamination has been regularly documented at important environmental sites, although most of these studies were performed at the species level. There is a lack of studies that correlate environmental contamination and clinical infections in the same region. The aim of this study is to evaluate the genetic diversity of a set of clinical and environmental samples and to use the obtained data to characterize the genetic profile of the distribution of G. duodenalis and the potential for zoonotic transmission in a metropolitan region of Brazil. The genetic assemblages and subtypes of G. duodenalis isolates obtained from hospitals, a veterinary clinic, a day-care center and important environmental sites were determined via multilocus sequence-based genotyping using three unlinked gene loci. Cysts of Giardia were detected at all of the environmental sites. Mixed assemblages were detected in 25% of the total samples, and an elevated number of haplotypes was identified. The main haplotypes were shared among the groups, and new subtypes were identified at all loci. Ten multilocus genotypes were identified: 7 for assemblage A and 3 for assemblage B. There is persistent G. duodenalis contamination at important environmental sites in the city. The identified mixed assemblages likely represent mixed infections, suggesting high endemicity of Giardia in these hosts. Most Giardia isolates obtained in this study displayed zoonotic potential. The high degree of genetic diversity in the isolates obtained from both clinical and environmental samples suggests that multiple sources of infection are likely responsible for the detected contamination events. The finding that many multilocus genotypes (MLGs) and haplotypes are shared by different groups suggests that these sources of infection may be related and indicates that there is a notable risk of human infection caused by Giardia in this region.