[Pleomorphic xanthoastrocytoma with intraventricular extension and anaplastic transformation in an adult patient: Case report]. / Xantoastrocitoma pleomórfico con extensión intraventricular y transformación anaplásica en paciente adulto: caso clínico.

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytic tumour that usually occurs in the superficial cerebral hemispheres of children and young adults. Although it has a relatively favourable prognosis, malignant progression of these tumours has been described. Therefore, we present an unusual case of a 54-year-old male with a right, multicystic, parietooccipital tumour extending through the ipsilateral ventricle. After surgical resection, histological examination revealed a lesion with pleomorphic cells, cytoplasmic lipidisation, intensely eosinophilic granular bodies, well-delimitated unique nuclei and focal, positive immunoreactivity for synaptophysin, glial fibrillary acidic protein (GFAP), S-100 protein, vimentin and CD56. Once other tumours, such as giant cell metastatic carcinoma or primary lesion like subependymal giant cell astrocytoma, were ruled out, a final diagnosis of XAP was established. After a follow-up period of 9 months, the patient suffered an extensive and local tumour relapse considered inoperable, with progressive neurological deterioration and radiological findings of malignant progression. The brain biopsy procedure revealed anaplastic changes, including necrosis foci, higher mitotic activity (5×10 high-power fields) and a 10% proliferation index measured by Ki67 labelling. The present case showed intraventricular extension and a more aggressive behaviour, both uncommon in these tumours (similar to anaplastic astrocytoma or glioblastoma multiforme), thus demanding an initial, optimal surgical treatment with close clinical and radiological follow-up, due to the high potential for malignant transformation of XAPs.

Three-dimensional vascular microenvironment landscape in human glioblastoma.

The cellular complexity of glioblastoma microenvironments is still poorly understood. In-depth, cell-resolution tissue analyses of human material are rare but highly necessary to understand the biology of this deadly tumor. Here we present a unique 3D visualization revealing the cellular composition of human GBM in detail and considering its critical association with the neo-vascular niche. Our images show a complex vascular map of human 3D biopsies with increased vascular heterogeneity and altered spatial relationship with astrocytes or glioma-cell counterparts. High-resolution analysis of the structural layers of the blood brain barrier showed a multilayered fenestration of endothelium and basement membrane. Careful examination of T cell position and migration relative to vascular walls revealed increased infiltration corresponding with tumor proliferation. In addition, the analysis of the myeloid landscape not only showed a volumetric increase in glioma-associated microglia and macrophages relative to GBM proliferation but also revealed distinct phenotypes in tumor nest and stroma. Images and data sets are available on demand as a resource for public access.

Infiltrating CTLs in human glioblastoma establish immunological synapses with tumorigenic cells.

The immunological synapse between T cells and tumor cells is believed to be important for effective tumor clearance. However, the immunological synapse has never been imaged or analyzed in detail in human tissue. In this work, intercellular interactions between T cells and tumor cells were analyzed in detail in human glioblastoma. After characterization of the population of infiltrating T cells by multiple immunofluorescence staining and stereological quantification, the microanatomy of T cell-tumor cell intercellular communication was analyzed in detail using confocal microscopy and three-dimensional rendering. Cytotoxic T lymphocytes that infiltrated human glioblastoma underwent rearrangement when in contact with tumor cells, to form a three-dimensional structure in the intercellular contact area; this was characterized by microclusters of the CD3/TCR complex, re-arrangement of the cytoskeleton, and granzyme B polarization. In addition, such T cell-targeted cells show fragmentation of the microtubular system and increased expression levels of cleaved caspase 3, which suggests that cytotoxic T lymphocytes likely provoke changes in tumor cells and subsequently induce cell death. These results show that the formation of the cytotoxic T lymphocyte immunological synapse occurs in human tissue and may be relevant for the effective immune-mediated clearance of tumorigenic cells, therefore opening up new avenues for glioblastoma immunotherapy.

Prevalence and distribution of human papillomavirus findings in swab specimens from gynaecology clinics of the east coast of Spain.

The objective of this study was to determine the prevalence of human papillomavirus (HPV) among females in the east coast of Spain. A total of 1956 women visiting gynaecology clinics for routine check-ups were included in the study. Swabs were analyzed for HPV DNA by consensus polymerase chain reaction followed by direct sequencing. The overall HPV prevalence was 12.99%. HPV vaccine types 6, 11, 16 and 18 were detected in 6.13% of female participants.

Distribution of human papillomavirus types in women from Valencia, Spain, with abnormal cytology.

OBJECTIVE: To determine human papillomavirus (HPV) types among cervical smears using polymerase chain reaction (PCR) and to contribute to the knowledge of human papillomavirus genotype distribution and prevalence of oncogenic types in cervical lesions in Spain. STUDY DESIGN: Consensus PCR and direct s quencing of PCR products (DNA HPV typing) were used in a retrospective study to determinate the type or types of HPVon 974 cytology smears of women with abnormal cytology results. RESULTS: Of 974 smears, 79.8% were high-risk (H-R) HPVs, 19.7% low-risk (L-R) HPVs, 4.6% indeterminate-risk (I-R) HPVs, considering both single and multiple infections. Multiple infections were detected in 4.7% of the cytologies. We detected 40 different HPV types: 17 H-R (HPV26 not detected), 10 L-R (HPVs 40 and HPV 61 not detected) and 13 I-R. The highest percentage of H-R HPV was found in those women with a cytologic high grade squamous intraepithelial lesion (HSIL) (87.4%). HPV 16 was the most frequent genotype. CONCLUSION: There was a significantly her prevalence rate of H-R HPV in HSIL than in low grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASC-US) (p < 0.01). HPV 16 (39.5%) was the most frequent genotype, with a significantly higher prevalence rate of this type in HSIL than in LSIL and ASC-US (p < 0.05 and p < 0.001, respectively). The study of the distribution of HPV and the presence of oncogenic HPV types in our population is important to assess the cost effectiveness of the current vaccines.

Phagocytic glioblastoma-associated microglia and macrophages populate invading pseudopalisades.

Hypoxic pseudopalisades are a pathological hallmark of human glioblastoma, which is linked to tumour malignancy and aggressiveness. Yet, their function and role in the tumour development have scarcely been explored. It is thought that pseudopalisades are formed by malignant cells escaping from the hypoxic environment, although evidence of the immune component of pseudopalisades has been elusive. In the present work, we analyse the immunological constituent of hypoxic pseudopalisades using high-resolution three-dimensional confocal imaging in tissue blocks from excised tumours of glioblastoma patients and mimic the hypoxic gradient in microfluidic platforms in vitro to understand the cellular motility. We visualize that glioblastoma-associated microglia and macrophages abundantly populate pseudopalisades, displaying an elongated kinetic morphology across the pseudopalisades, and are oriented towards the necrotic focus. In vitro experiments demonstrate that under hypoxic gradient, microglia show a particular motile behaviour characterized by the increase of cellular persistence in contrast with glioma cells. Importantly, we show that glioblastoma-associated microglia and macrophages utilize fibres of glioma cells as a haptotactic cue to navigate along the anisotropic structure of the pseudopalisades and display a high phagocytic activity at the necrotic border of the pseudopalisades. In this study, we demonstrate that glioblastoma-associated microglia and macrophages are the main immune cells of pseudopalisades in glioblastoma, travelling to necrotic areas to clear the resulting components of the prothrombotic milieu, suggesting that the scavenging features of glioblastoma-associated microglia and macrophages at the pseudopalisades serve as an essential counterpart for glioma cell invasion.

[Chondromyxoid fibroma of the left maxillary and ethmoid sinuses]. / Fibroma condromixoide de seno maxilar y etmoides izquierdos.

Chondromyxoid fibroma is an infrequent bone tumour in the craniofacial bones and exceptional in the paranasal sinuses. This unusual location, its non-specific clinical manifestation and aggressive behaviour with local destruction and a high recurrence rate can complicate precise diagnosis and treatment.

Malignant fibrohistiocytoma of the parotid region. Report of a case.

Most salivary gland tumors are benign, malignant lesions accounting for 15-30% of the total. The most frequent site of salivary gland neoplasms is the parotid gland (80% of all cases). We present a case of malignant fibrohistiocytoma with atypical features due to its location (in the parotid region), size and rapid growth. Generally, this type of tumor arises in the lower limbs and in the abdomen. When located in the parotid gland, these lesions appear as a firm, slow growing and painless mass. Due to the low frequency of such lesions and their clinical behavior, the imaging study and fine-needle aspiration biopsy findings tend to diagnose them as pleomorphic adenoma. The definitive diagnosis requires microscopic study of the resection piece using immunohistochemical techniques. The treatment of choice is surgery, occasionally associated to radiotherapy. The success of treatment is dependent upon complete resection of the tumor - long term follow-up being necessary due to the risk of recurrence or distant metastasis.

Imbalance of immunological synapse-kinapse states reflects tumor escape to immunity in glioblastoma.

Since the proper activation of T cells requires the physical interaction with target cells through the formation of immunological synapses (IS), an alteration at this level could be a reason why tumors escape the immune response. As part of their life cycle, it is thought that T cells alternate between a static phase, the IS, and a dynamic phase, the immunological kinapse (IK), depending on high or low antigen sensing. Our investigation performed in tissue samples of human glioma shows that T cells are able to establish synapsing interactions not only with glioma tumorigenic cells, but also with stromal myeloid cells. Particularly, the IS displaying a T cell receptor-rich (TCR-rich) central supramolecular activation cluster (cSMAC) is preferentially established with stromal cells, as opposed to malignant cells. Conversely, T cells in the malignant areas showed distinct morphometric parameters compared with nonneoplastic tissue - the former characterized by an elongated shape, well-suited to kinaptic dynamics. Importantly, high-resolution 3-dimensional analyses demonstrated the existence of bona-fide IK preferentially arranged in malignant areas of the tumor. This imbalance of IS/IK states between these 2 microenvironments reveals the low antigenic sensing of T cells when patrolling tumorigenic cells and reflects the immunoevasive environment of the tumor.

Lymphoepithelioma-like carcinoma of the uterine cervix.

CONTEXT: It has been proposed that Epstein-Barr virus (EBV) plays a role in the etiology of lymphoepithelioma-like carcinoma (LELC) in diverse anatomic locations. In contrast to Asian women, Western women have a low prevalence of LELC of the uterine cervix, and EBV genomes have not been identified. OBJECTIVE: To assess the presence of EBV in LELC of the uterine cervix in 4 white Western women. DESIGN: We collected 4 cases of LELC of the uterine cervix between 1990 and 2000. We performed histologic and immunohistochemical analyses of formalin-fixed, paraffin-embedded tumor samples. We amplified tumor DNA with polymerase chain reaction to detect EBV, human papillomavirus, and simian virus 40 DNAs. RESULTS: Immunohistochemically, tumor cells were positive for cytokeratins and showed strong expression of p53 and MIB-1. Staining for the oncoprotein c-Erb-B2 was focally positive, and staining for Bcl-2 and progesterone receptors was negative. Only one case showed focal nuclear staining for estrogen receptors. All cases had a dense infiltrate of mature lymphocytes expressing T-cell antigens CD45RO, CD3, and CD8. Polymerase chain reaction analysis did not detect EBV, human papillomavirus, or simian virus 40 DNA sequences in any of the 4 cases. One case had positive serologic results for anti-EBV antibodies, indicating a mild or chronic infection. CONCLUSIONS: LELC of the uterine cervix shows the immunohistochemical profile of an aggressive tumor in spite of its good prognosis, in which CD8 cytotoxic suppressor lymphocytes could play an important role. Based on our results, the role of EBV, human papillomavirus, or simian virus 40 in the pathogenesis of LELC of the uterine cervix in Western women remains unclear.