RESUMEN

Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary glands neoplasms with an indolent clinical course, slow-growing but locally aggressive and quite often with delayed recurrence and distant metastasis. In order to elucidate this tumoral behavior, we conducted an immunohistochemical study investigating the alterations of epithelial phenotype with anti-cytokeratin (CK) AE1∕AE3 and anti-E-cadherin antibodies, and the acquisition of mesenchymal phenotype with vimentin, fibronectin, N-cadherin and P-cadherin in salivary ACCs. Thus, we recorded a reduction of CK AE1∕AE3, E-cadherin, P-cadherin and fibronectin reactivity in the solid variant and especially in the cells from the periphery of invasive neoplastic proliferations, regardless histological type. These phenotypical alterations suggest the involvement of the epithelial-mesenchymal transition (EMT) process in the progression of salivary ACCs.

Asunto(s)

RESUMEN

Adenoid cystic carcinoma is a rare tumor, accounting for about 7.5% of all salivary gland neoplasms. More frequent developing in minor salivary gland, this is a slow-growing tumor with a long-lasting natural evolution, quite aggressive locally, but which has a tendency toward local recurrence and even for distant metastasis. We conducted a retrospective study limited to a period of 10 years in a single medical institution to investigate the morphoclinical profile of this tumor. Thus, we have established that about 60% of the tumors developed in men, with near 40% of the cases in patients in the sixth decade and, most common, the pathology affected the parotid and minor salivary glands from the hard palate mucosa. Histopathologically, prevailed the solid variant, with 72% cases presenting perineural invasion, and 41% cases showing positive surgical resection margins. Most cases had a long-standing asymptomatic evolution, so that at the time of diagnosis, more than two thirds of the patients were at least in stage II-pTNM, and in one-fifth of the cases histopathology showed lymph nodes disseminations.

RESUMEN

The literature date estimated that about 5% of all oral cavity cancers are hard palate cancers while soft palate cancers account for about 5-12% of oropharyngeal cancers. Although rare, usually these tumors had a more aggressively behavior than other oral cancer sites. That is why our study aimed to investigate comparatively the epidemiological, clinical and histopathological peculiarities of the two palatal sites of oral squamous cell carcinomas. We conducted a retrospective study limited to a period of 10 years in a single medical institution to investigate the morphoclinical profile of such tumors. We found that patients with hard palate SCCs had an average age slightly larger compared to those who developed soft palate tumors. Also, those with hard palate tumors are mostly diagnosed in less advanced stages compared to those at the level of the soft palate, and implicitly the former had a longer survival time. Histopathologically the most encountered hard palate SCC were the conventional well-differentiated tumor, and from the peculiar SCC variant the papillary and verrucous forms while for the soft palate SCC prevailed the moderate and poor differentiated conventional SCC and from the peculiar SCC variant the basaloid and acantholytic forms. In conclusion hard palate tumors differ in many aspects from those of the soft palate, and thus specification of the origin tumor site become important for the assessment of prognosis, treatment and survival outcome of such patients.

RESUMEN

Adenoid cystic carcinoma (ACC) is the second most common malignant salivary glands neoplasms with a controversial biological behavior. Even though these tumors grow slowly, they have increased potential for recurrence and distant metastasis. In order to elucidate this behavior, our study aimed to investigate the immunoexpression in such tumors of the most important transcriptional factors [Twist, Snail, Slug, and zinc finger E-box binding homeobox 1 (ZEB1)] involved in the epithelial-mesenchymal transition process. The highest level of expression was recorded for Twist, present in all the investigated cases, followed by the Slug and Snail, while no tumor parenchyma reactivity was noticed for the ZEB1 factor. There were tumor reactivity differences regarding topography, histopathological variant, and nerve and lymph node invasion status. Thus, tumors developed from the intraoral minor salivary glands, with solid pattern, perineural invasion, locally aggressive and with lymph node metastasis were the most reactive. Therefore, these transcription factors could be useful as prognostic biomarkers and efficient therapeutic targets in such salivary malignancies.

Asunto(s)

RESUMEN

Atypical meningiomas with a mixed glial-epithelial phenotype are rare reports, and here we described an aggressive case on which double immunofluorescence ascertained the co-expression of epithelial membrane antigen (EMA) with glial fibrillary acidic protein (GFAP) in the same tumor cells. A 62-year-old female presented with acute intracranial hypertension symptoms occurred over the last 24 hours, muscle weakness on the right side, cerebellar dysarthria, and wide base gate. Magnetic resonance imaging (MRI) examination showed a right cerebellar hemisphere non-homogenous tumor, with intense gadophylia, diffuse contours, and necrotic inner areas. There were also scar-like areas at the level of the left cerebellar hemisphere, and the patient recalled a previous surgical intervention at the age of 6 years old without further diagnostic data. The patient suffered an ischemic event in the brain stem and died shortly after the surgical removal of the tumor. Histopathology revealed an epithelial-like tumor with moderately pleomorphic and elongated cells arranged in fascicles, rare necrotic areas, and a few proliferating multilayered vessels structures. Immunohistochemistry (IHC) revealed variable EMA positivity, intense vimentin staining, rare GFAP-positive intra-tumor areas, a moderate expression for cytokeratin 8/18, reduced labeling for an anti-progesterone receptor (PrgR) antibody, cluster of differentiation (CD) 10 negativity, and a high Ki-67 proliferating index of around 40%. The case was deemed as an atypical meningioma, and interestingly, a double IHC for GFAP∕EMA revealed a strong colocalization of the two markers in the tumor mass. Although extremely rare, the reports of meningiomas expressing a mixed epithelial∕glial profile might be connected with their aggressive evolution. Double IHC might help in predicting the evolution of these cases and determine which patients should benefit from closer surveillance.

Asunto(s)

RESUMEN

Despite the clinical significance of post-stroke angiogenesis, a detailed phenotypic analysis of pre-stroke vascular remodeling and post-stroke angiogenesis had not yet been done in a model of focal ischemia. In this study, using BrdU-labeling of proliferating cells and immunofluorescence of pre- and post-stroke rats, we found that, (i) BrdU administered before stroke was incorporated preferentially into the nuclei of endothelial cells lining the lumen of existing blood vessels and newly born neurons in the dentate gyrus but not in the subventricular zone or proliferating microglia, (ii) BrdU injection prior to stroke led to the patchy distribution of the newly incorporated endothelial cells into existing blood vessels of the adult rat brain, (iii) BrdU injection prior to stroke specifically labeled neuronal precursors cells in a region of soft tissue beyond the inhibitory scar, which seems to be permissive to regenerative events, (iv) BrdU injection after stroke led to labeling of endothelial cells crossing or detaching from the disintegrating blood vessels and their incorporation into new blood vessels in the stroke region, scar tissue and the region beyond, (v) BrdU injection after stroke led to specific incorporation of BrdU-positive nuclei into the "pinwheel" architecture of the ventricular epithelium, (vi) blood vessels in remote areas relative to the infarct core and in the contralateral non-lesioned cortex, showed co-labeled BrdU/RECA+ endothelial cells shortly after the BrdU injection, which strongly suggests a bone marrow origin of the endothelial cells. In the damaged cortex, a BrdU/prolyl 4-hydroxylase beta double labeling in the close proximity to collagen IV-labeled basement membrane, suggests that, in addition to bone marrow derived endothelial cells, the disintegrating vascular wall itself could also be a source of proliferating endothelial cells, (vii) By day 28 after stroke, new blood vessels were observed in the perilesional area and the scar tissue region, which is generally considered to be resistant to regenerative events. Finally, (viii) vigorous angiogenesis was also detected in a region of soft tissue, also called "islet of regeneration," located next to the inhibitory scar. Conclusion: BrdU administered prior to, and after stroke, allows to investigate brain vasculature remodeling in the adult brain.

RESUMEN

The aging process, comorbidities, and age-associated diseases are closely dependent on each other. Cerebral ischemia impacts a wide range of systems in an age-dependent manner. However, the aging process has many facets which are influenced by the genetic background and epigenetic or environmental factors, which can explain why some people age differently than others. Therefore, there is an urgent need to identify age-related changes in body functions or structures that increase the risk for stroke and which are associated with a poor outcome. Multimodal imaging, electrophysiology, cell biology, proteomics, and transcriptomics, offer a useful approach to link structural and functional changes in the aging brain, with or without comorbidities, to post-stroke rehabilitation. This can help us to improve our knowledge about senescence firstly, and in this context, aids in elucidating the pathophysiology of age-related diseases that allows us to develop therapeutic strategies or prevent diseases. These processes, including potential therapeutical interventions, need to be studied first in relevant preclinical models using aged animals, with and without comorbidities. Therefore, preclinical research on ischemic stroke should consider age as the most important risk factor for cerebral ischemia. Furthermore, the identification of effective therapeutic strategies, corroborated with successful translational studies, will have a dramatic impact on the lives of millions of people with cerebrovascular diseases.

Asunto(s)

RESUMEN

Meningitis and encephalitis are inflammatory diseases in which acute and chronic inflammatory cells infiltrate leptomeninges, especially the arachnoid, and migrate through the subarachnoid space and by diapedesis, in order to extend around blood vessels and into the brain parenchyma. To what extent migrated/resident inflammatory cells participate to these interactions, or what are exactly the initial steps by which these cells reach the brain interstitium, it is not yet completely known. Recent years have brought new insights into the description of water flow circuits in the brain, suggesting that the cerebrospinal fluid enters the brain within the perivascular spaces of arteries, while interstitial fluid drains along perivascular venous sector. Moreover, it has been showed that vascular basement membranes have a complex multi-layered architecture that originates with epithelial, endothelial, smooth muscle cells and glial cells, and that the virtual space between these layers might be in fact an essential component of these perivascular spaces. Starting from a patient that presented with active pulmonary tuberculosis and with consecutive purulent-hemorrhagic meningitis and encephalitis, we have characterized here the compartments in which immune cells can be found in the brain tissue. Besides the classical histopathological description, what was of interest here, was that we identified for the first time mononucleated inflammatory cells that seemed to be present in pockets of the vascular basement membranes, small spaces devoid of red blood cells. Although this is mere a morphological observation, future high-resolution studies should clarify it this is a possible route for the immune cells entering the brain.

Asunto(s)

RESUMEN

E-cadherin, ß-catenin and Snail are important molecules involved in cellular adhesion and epithelial-mesenchymal transition. Loss of E-cadherin expression, nuclear relocation of ß-catenin and high expression of Snail are connected to tumor progression, rapid cell growth and metastasis. The aim of our study was to analyze the immunohistochemical expression of ß-catenin, E-cadherin and Snail, depending on clinico-morphological aspects of the laryngeal squamous cell carcinomas. Our results revealed variable E-cadherin, ß-catenin and Snail expression, depending on differentiation degree and tumor stage. These markers can be helpful in identifying the aggressive laryngeal squamous carcinomas.

Asunto(s)

RESUMEN

p53 is a marker described in the premalignant lesions with a high risk of malignant transformation for laryngeal cancer. It is a tumor suppressor gene that during the cancer gains also oncogenic activity. We aimed to study the p53 immunoexpression in 38 cases of laryngeal squamous cell carcinomas and the relation with the clinicopathological aspects. We obtained variable p53 expression regarding the differentiation degree and tumor stage. The higher p53 immunotaining values were observed in high grade and advanced stages lesions. P53 may be useful in identifying aggresive laryngeal squamous carcinomas, a useful aspect for better stratification of patients for therapy.

RESUMEN

Epidermal growth factor receptor (EGFR) is a tyrosine kinase molecule associated to the initial stages of neoplastic transformation. High expression of EGFR is connected to aggressive tumor behavior and high risk of metastasis and treatment failure. The aim of our study was to analyze the immunohistochemical expression of EGFR in 38 cases of laryngeal squamous cell carcinomas depending on clinicopathological parameters related to prognosis. The EGFR immunoreactions have statistical significant higher values in high grade carcinomas. Although the EGFR values were superior in advanced stages lesions, the aspect was not significant EGFR may be useful in identifying the aggressive laryngeal squamous carcinomas.

RESUMEN

Basal cell carcinoma is the most common malignant tumor of the skin, and it develops most frequently on the head and neck regions. Although most of these tumors are slow growing and with a limited evolution, the existence of some aggressive variants accompanied by a complete neglect from the patient may occasionally lead to invasion of the face and organs of the head and neck. Even though, intracranial invasion of basal cell carcinoma of the scalp is a rare presentation. We describe here the case of a woman who developed an aggressive and neglected morpheiform basal cell carcinoma (ulcus terebrans), which showed a complete invasion through the skull, but with an apparent self-limitation to the pia mater.

Asunto(s)

RESUMEN

Matrix metalloproteinases (MMPs) are well-recognized denominators for extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic strokes. Recent data on non-nervous system tissue showed intracellular and even intranuclear localizations for different MMPs, and together with this, a plethora of new functions have been proposed for these intracellular active enzymes, but are mostly related to apoptosis induction and malign transformation. In neurons and glial cells, on human tissue, animal models and cell cultures, different active MMPs have been also proven to be located in the intra-cytoplasmic or intra-nuclear compartments, with no clear-cut function. In the present study we show for the first time on human tissue the nuclear expression of MMP-9, mainly in neurons and to a lesser extent in astrocytes. We have studied ischemic and hemorrhagic stroke patients, as well as aged control patients. Age and ischemic suffering seemed to be the best predictors for an elevated MMP-9 nuclear expression, and there was no evidence of a clear-cut extracellular proteolytic activity for this compartment, as revealed by intact vascular basement membranes and assessment of vascular densities. More, the majority of the cells expressing MMP-9 in the nuclear compartment also co-expressed activated-caspase 3, indicating a possible link between nuclear MMP-9 localization and apoptosis in neuronal and glial cells following an ischemic or hemorrhagic event. These results, besides showing for the first time the nuclear localization of MMP-9 on a large series of human stroke and aged brain tissues, raise new questions regarding the unknown spectrum of the functions MMPs in human CNS pathology.

Asunto(s)

RESUMEN

Vascular endothelial growth factor (VEGF) is considered one of the main molecules involved in tumor angiogenesis and is largely expressed in oral squamous cell carcinoma (OSCC). His signal is transmitted intracellulary by binding with class III tyrosine kinase receptors, known as VEGF receptor family (VEGFRs). Therefore, we designed this study for quantification of VEGFR1 and VEGFR2 immunohistochemical expression in the tumor cells of OSCC, and compare this expression with clinicopathologic parameters. For this purpose, 46 formalin-fixed, paraffin-embedded tissue blocks of OSCC were processed by immunohistochemistry. The immunohistochemical signal was assessed by estimating the area of the objects and the medium pixel intensity per object, as the integrated optical density (IOD). In our study, VEGFR1 staining intensity was significantly higher for tongue localization, while VEGFR2 was higher for the lip. Both markers were higher expressed in the center of the tumor compared to the tumor front. Moderate differentiated tumors exert higher expression levels for VEGFR1 but lower for VEGFR2. pT1 tumors had higher VEGFR1 levels, and when lymph node involvement was present, this was accompanied by elevated expression levels for VEGFR2 and lower levels for VEGFR1. These results point to an inverse profile of these receptors in OSCC, suggesting their involvement in a sequential manner in VEGF signaling regulation. In conclusion, our study revealed that VEGFR1 and VEGFR2 correlate with tumor localization, tumoral area (front vs. center of the tumor), histological differentiation degree, and lymph node involvement, while only VEGFR1 correlated with pT stage.

Asunto(s)

RESUMEN

Ischemic stroke is the third most common cause of death in humans, requiring further studies to elucidate its pathophysiological background. One potential mechanism to increase oxygen delivery to the affected tissue is induction of angiogenesis. The most potent proangiogenic factor is VEGF. For this reason, our study investigated immunohistochemically VEGF reactivity in different cellular brain compartments from 15 ischemic stroke patients, as well as from 2 age control cases. By enzymatic immunohistochemistry, we investigate VEGF expression in different brain cell compartments and then we quantified its signal intensity by assessing integrated optical densities (IOD). To establish the exact cellular brain topography of VEGF immunoreactivity we performed double fluorescent immunohistochemistry series (VEGF÷NeuN, GFAP, CD68, CD105). In control samples, VEGF reactivity was observed especially in neurons from the Brodmann cortical layers IV to VI and in protoplasmic astrocytes from the deeper layers of gray matter and in endothelial cells from normal blood vessels because of systemic hypoxia generated after death. In acute ischemic stroke samples, this reactivity was noticed in all brain cellular compartments but with different intensities. The most reactive compartment was the neurons, the intensity of VEGF reaction decreasing with the lesional age from the core infarct toward intact adjacent brain cortex. With a lower intensity, VEGF reaction was noticed in astrocytes compartments, especially in gemistocytic astrocytes adjacent to the liquefaction zone. We also noticed a weak reaction in activated non-phagocytic microglia from the periphery of liquefaction zones, and high VEGF-CD105 colocalization values at the level of microvessels that surround the infarcted brain area. In conclusion, this reactivity could suggest that VEGF might exhibit neuronal and glial protective effects and also a neoangiogenic property in acute ischemic stroke, facts that may have significant therapeutically impact on these patients.

Asunto(s)

RESUMEN

BACKGROUND: We report a case of a 78-year-old woman with a large cerebral infarction probably due to athermanous embolism following atrial fibrillation. CASE DESCRIPTION: The patient, known with atrial fibrillation, high blood pressure and heart failure, complained of headache and motor impairment on the left side of the body. CT imaging revealed a subacute ischemic lesion in the right fronto-occipital lobes, and an old ischemic lesion in the right fronto-parietal lobes. Anticoagulant treatment was conducted with careful monitoring of the coagulability status. After almost three weeks, suddenly the patient became comatose and died shortly after. Macroscopic and microscopic examination confirmed the cortico-subcortical ischemic lesions, but also identified a fresh hemorrhagic site in pons, distant from the initial lesion sites. An immunohistochemical study identified blood vessels in the ischemic sites completely isolated from any glial support. CONCLUSIONS: This is a rare case of a large cerebral infarction with a pontine hemorrhagic event.

Asunto(s)

RESUMEN

We study here the histopathological changes in twenty-two cases of acute ischemic stroke. The average age of the patients was 62-year-old, and the interval from the onset of the disease to the death varied from 6 hours to 15 years. The brain lesions after acute stroke were observed in all regions. Their evolution allowed us to classify them in fourth stages. Phase one changes (1-2 days after onset) (n=2 patients) included red hypoxic and "ghost" neurons and other acute neuronal injury and spongiosis. The second phase (n=14 patients) was subdivided into: (a) a phase of acute inflammation (3-37 days after onset) (n=5 patients), where we observed especially features of acute inflammation together with coagulative necrosis, and (b) phase of chronic inflammation (10 days-53 years after the onset) (n=9 patients), in which prevail mononuclear and macrophage infiltrate, astrogliosis, spongiosis and neo-vascularization. In the third phase (26 days-23 years after the onset), we included six cases characterized by the absence of an inflammatory reaction, presence of cavitation, astrogliosis and macrophages. Our study describes the heterogeneity of brain injury after acute ischemic stroke with the participation of all brain components, and the chronology in which these lesions develop and evolve.

Asunto(s)

RESUMEN

The varied morphological forms in which astrocytes occur in brain of ischemic/hemorrhagic stroke and Alzheimer's disease (AD) patients are complex and the mechanisms that drive their formation are not yet properly understood. Subjective differences can be described between these pathologies in what it concerns astrocyte implication, but these have not been yet subjected to a morphometrical quantification. Here we apply a fractal dimension (FD) analysis algorithm to differentiate both between fibrous, protoplasmatic and activated astroglia; but also between the three pathological conditions studied. Analyzing more than 1000 astroglia, we show here first that FD can clearly differentiate between the three morphological subtypes. Second, we describe resemblances of the FD values for ischemic and hemorrhagic lesions, and significant differences when these are compared to AD patients. These results are further discussed and integrated in what it regards the preferential regions proved to be affected in these conditions, and which parallels our results. This work illustrates that fractal dimension analysis of astroglia is a useful method for quantitatively describing gliosis in different pathologies, and that it may offer more insight into the pathogenesis of brain diseases.

Asunto(s)