Thrombus Histology as It Relates to Mechanical Thrombectomy: A Meta-Analysis and Systematic Review.

BACKGROUND: Appropriate thrombus-device interaction is critical for recanalization. Histology can serve as a proxy for mechanical properties, and thus inform technique selection. OBJECTIVE: To investigate the value of histologic characterization, we conducted a systematic review and meta-analysis on the relationship between thrombus histology and recanalization, technique, etiology, procedural efficiency, and imaging findings. METHODS: In this meta-analysis, we identified studies published between March 2010 and March 2020 reporting findings related to the histologic composition of thrombi in large vessel occlusion stroke. Studies with at least 10 patients who underwent mechanical thrombectomy using stent retriever or aspiration were considered. Only studies in which retrieved thrombi were histologically processed were included. Patient-level data were requested when data could not be directly extracted. The primary outcome assessed was the relationship between thrombus histology and angiographic outcome. RESULTS: A total of 22 studies encompassing 1623 patients met inclusion criteria. Clots associated with good angiographic outcome had higher red blood cell (RBC) content (mean difference [MD] 9.60%, 95% CI 3.85-15.34, P = .008). Thrombi retrieved by aspiration had less fibrin (MD -11.39, 95% CI -22.50 to -0.27, P = .046) than stent-retrieved thrombi. Fibrin/platelet-rich clots were associated with longer procedure times (MD 13.20, 95% CI 1.30-25.10, P = .037). Hyperdense artery sign was associated with higher RBC content (MD 14.17%, 95% CI 3.07-25.27, P = .027). No relationship was found between composition and etiology. CONCLUSION: RBC-rich thrombi were associated with better recanalization outcomes and shorter procedure times, suggesting that preinterventional compositional characterization may yield important prognostic and therapeutic guidance.

Fibrin-Platelet Clots in Acute Ischemic Stroke. Predictors and Clinical Significance in a Mechanical Thrombectomy Series.

Introduction: The histological composition of the clot influences its mechanical properties, affects the efficacy of endovascular treatment (EVT), and could determine the clinical outcome of patients with acute ischemic stroke (AIS). Insights into clot composition may guide therapeutic decision-making prior to EVT and facilitate revascularization therapies. Material and Methods: Consecutive patients with AIS recorded in a prospective single-center reperfusion registry from December 2015 to December 2019 and treated with EVT were included. Baseline, laboratory [including post-procedural C-reactive protein (CRP)], radiological, and angiographic variables were analyzed. We aimed to study the relationship between histological composition of the clot with basal neuroimaging, laboratory markers, and recanalization technique. The secondary outcome was to analyze the correlation between clot composition and functional outcome at 3 months assessed by the modified Rankin scale (mRS). Results: From the study period, 360 AIS patients treated with EVT were included, of whom 189 (53%) fulfilled the inclusion criteria. One hundred (53%) cases of fibrin-predominant clot (FPC) were recorded. Full recanalization in FPC cases was achieved with higher probability when stent retrievers (SR) were selected as the first-line device (68.2%, p = 0.039). Patients with FPC had higher levels of CRP (p = 0.02), lower frequency of the hyperdense middle cerebral artery (HMCA) in baseline imaging (p = 0.039), and higher rates of mortality (p = 0.012). The multivariate analysis showed that the absence of HMCA (OR = 0.420; 95% CI 0.197-0.898; p = 0.025) and higher levels of CRP (OR = 1.01; 95% CI 1.003-1.019; p = 0.008) were predictors of FPC. Leukocytes and platelet counts were not associated with clot histology. Conclusions: The absence of HMCA and higher levels of CRP were markers of FPC. In patients with FPC, complete recanalization was most likely to be achieved when a SR was selected as first line of treatment. Mortality was higher in patients within this histologic group.

Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells.

Chemotherapy for high-grade astrocytic tumors is mainly based on the use of temozolomide (TMZ), whose efficacy is limited by resistance mechanisms. Despite many investigations pointing to O6-methylguanine-DNA-methyltransferase (MGMT) as being responsible for tumor chemo-resistance, its expression does not predict an accurate response in most gliomas, suggesting that MGMT is not the only determinant of response to treatment. In this sense, several reports indicate that N-methylpurine-DNA-glycosylase (MPG) may be involved in that resistance. With that in mind, we evaluated for the first time the degree of resistance to TMZ treatment in 18 patient-derived glioma cells and its association with MGMT and MPG mRNA levels. Viability cell assays showed that TMZ treatment hardly caused growth inhibition in the patient-derived cells, even in high concentrations, indicating that all primary cultures were chemo-resistant. mRNA expression analyses showed that the TMZ-resistant phenotype displayed by cells is associated with an elevated expression of MPG to a greater extent than it is with transcript levels of MGMT. Our findings suggest that not only is MGMT implicated in resistance to TMZ but MPG, the first enzyme in base excision repair processing, is also involved, supporting its potential role as a target in anti-resistance chemotherapy for astrocytoma and glioblastoma.

Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of individuals worldwide. Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection. Patients were confirmed by microbiological/serological testing, or on chest CT semiology. Available data on co-morbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed. A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes. A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis. In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease. Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%). Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi). Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type. Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004). Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%). In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas. Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis. The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043). Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality. We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

Transformación maligna de un tumor odontogénico queratósico con gran componente inflamatorio. Presentación de un caso y revisión de la literatura / Primary intraosseous squamous cell carcinoma derived from a keratocystic odontogenic tumor with a large inflammatory component. Case report and a review of the literature

El desarrollo de un carcinoma de células escamosas a partir del revestimiento epitelial de un tumor odontogénico queratósico (TOQ) corresponde a una neoplasia maligna infrecuente exclusiva de los huesos maxilares, denominada también cómo carcinoma de células escamosas intraóseo primario (CCEIP). Afecta principalmente a personas de mediana edad, especialmente a hombres (2:1) y se localiza usualmente en la zona posterior de la mandíbula. Aunque la patogénesis del CCEIP es desconocida y no se le puede atribuir asociación con factores predisponentes para el desarrollo de carcinoma de células escamosas de la mucosa oral, actualmente se refuerza la idea del componente inflamatorio como predisponente de malignización. Se presenta un caso clinicopatológico de un varón de 61 años de edad con diagnóstico de CCEIP derivado de un TOQ con un gran componente inflamatorio asociado (AU)

The development of a squamous cell carcinoma from the epithelial lining of a keratotic odontogenic tumor (KOT) corresponds to a rare malignant neoplasm exclusive to the jawbone, also referred to as primary intraosseous squamous cell carcinoma (PIOC). It mainly affects middle-aged people, especially men (2: 1) and is usually located in the rear area of the jaw. The pathogenesis of PIOC is unknown and no predisposing factor for the development of squamous cell carcinoma of the oral mucosa has been identified. However, many authors support the hypothesis that a component of a chronic inflammatory process could prove to be the underlying factor of malignant change. We present a case of a 61-year-old male diagnosed with PIOC derived from a KOT associated with an extensive inflammatory process (AU)

Histopathological and Bacteriological Analysis of Thrombus Material Extracted During Mechanical Thrombectomy in Acute Stroke Patients.

PURPOSE: Management of stroke secondary to septic emboli (SE) remains challenging, due to both the lack of specific recommendations and the gravity of the underlying pathology.The aim of this study is to describe the presence of SE in a series of mechanical thrombectomies (MT), analyzing technical complexity and outcomes with respect to the patients by means of histological analysis and microbiological study of the clot. METHODS: All the retrieved clots were studied under an established protocol, including histopathological and bacteriological study with hematoxylin-eosin, Gram and Gomori trichrome staining.Technical complexity in SE with respect to the series was evaluated by analyzing time of the procedures, number of passes and use of intracranial definitive stents. RESULTS: Over a 24-month period, bacteria were detected in the retrieved clot of four out of 65 patients (incidence 6.2%). Two cases were eventually diagnosed with infective endocarditis, while the remaining two were diagnosed with urinary tract infection and respiratory septicemia, respectively. Three of the four patients (75%) required an intracranial definitive stent in order to achieve successful recanalization.These procedures were significantly longer (137.7 vs. 59.8 min, p < 0.001), needed a higher number of passes (5.8 vs. 2.2, p < 0.001), and delivery of an intracranial stent more frequently (75% vs. 1.6%, p = 0.008), with respect to the rest of the series. CONCLUSIONS: In our series, systematic histopathological and bacteriological study of the MT samples allowed a higher proportion of SE diagnosis in comparison with previous reports.

Correlación cito-histológica del tumor papilar de la glándula pineal. Presentación de un caso / Papillary pineal tumor: cyto-histological correlation. Case report

En la última revisión de la Organización Mundial de la Salud (OMS) en relación a los tumores del sistema nervioso central (SNC), se describieron nuevas entidades, como el Tumor Papilar de la Glándula Pineal. Esta lesión de rara aparición, se ha identificado en adultos jóvenes. El diagnóstico de estos tumores es complejo ya que depende de su ubicación, edad de aparición y el aspecto histológico; éste último tiene similitudes con otras lesiones como el ependimoma papilar o el papiloma/carcinoma de plexos coroides. Citológicamente presentan características claras que pueden ayudar al diagnóstico a través de la impronta en el estudio intraoperatorio; reconocer ciertos criterios con éste importante y sencillo método diagnóstico ha sido la motivación principal para el estudio de entidades poco frecuentes del SNC, además de corroborar el necesario trabajo de un equipo multidisciplinar.

In the latest revision of the central nervous system tumors (CNS) of the World Health Organization (WHO), new entities has been described, as papillary tumor of the pineal region. This rare lesion has been identified in young adults. The diagnosis of these tumors is complex, depends on the location, age of onset and histological appearance. Histological characteristics have similarities with other lesions such as papillary ependymoma, papiloma / choroid plexus carcinoma. Cytologically have clear characteristics that can aid in the diagnosis through the smears on the intraoperative study. Certain criteria for recognize this important and simple diagnostic method has been the main motivation for the study of CNS rare entities, as our case, in addition to corroborating the necessary work of a multidisciplinary team.

Xantoastrocitoma pleomórfico con extensión intraventricular y transformación anaplásica en paciente adulto: caso clínico / No disponible

El xantoastrocitoma pleomórfico (XAP) es un tumor astrocitario raro, de localización más frecuente superficial en hemisferios cerebrales de niños y adultos jóvenes. Se trata de un tumor de bajo grado que tiene un pronóstico relativamente favorable; sin embargo, se han descrito pacientes con progresión maligna. Presentamos así un caso inusual de un varón de 54 años con una tumoración multiquística parietooccipital derecha con extensión intraventricular. Tras la exéresis quirúrgica el estudio histológico mostró una lesión con células pleomórficas, cúmulos de lípidos en su citoplasma, cuerpos granulares intensamente eosinófilos, núcleos únicos bien delimitados y positividad inmunohistoquímica frente a sinaptofisina, proteína gliofibrilar ácida (GFAP), proteína S-100, vimentina y CD56 de forma focal. Tras descartar otras entidades, como metástasis por carcinoma de células grandes y una lesión primaria tipo astrocitoma subependimario de células grandes, se diagosticó de XAP. A los 9 meses de seguimiento el paciente presentó una extensa recidiva tumoral local considerada irresecable, con deterioro neurológico progresivo y signos radiológicos de progresión maligna, confirmados histológicamente mediante la realización de una biopsia cerebral que demostró cambios respecto a la lesión inicial que incluían focos de necrosis, mayor actividad mitótica (5×10 campos de gran aumento) e índice de proliferación celular medido con la tinción nuclear de Ki67 del 10%. El presente caso ilustra la extensión intraventricular, así como un comportamiento agresivo no característico de estas lesiones (similar a un astrocitoma anaplásico o glioblastoma primario), exigiendo un tratamiento quirúrgico óptimo inicial con seguimiento estrecho clínico-radiológico, considerando el potencial de transformación maligna del XAP (AU)

[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.

Poliquistosis renal infantil autosómica recesiva con disgenesia biliar. A propósito de un caso / Autosomal recessive polycystic kidney disease. A case report

IntroducciónLa poliquistosis renal autosómica recesiva (PQRAR) es una enfermedad producida por mutaciones del gen PKDH1 que codifica una proteína llamada fibroquisina en el cromosoma 6p13.3. Se caracteriza por la asociación constante de túbulos colectores renales dilatados que forman quistes y por una fibrosis hepática congénita secundaria a una disgenesia biliar.Caso clínicoPresentamos un caso de estudio de autopsia de un recién nacido hembra pretérmino de 35 semanas de edad gestacional, de 2 horas de vida con oligoamnios severo de un embarazo no controlado. En el primer trimestre de embarazo se constató nefromegalia en una ecografía. Los hallazgos macroscópicos más significativos fueron riñones de aspecto esponjoso compuestos con múltiples pequeños quistes y una fibrosis hepática focal. Tras el estudio microscópico se llegó al diagnóstico de enfermedad poliquística renal infantil autosómica recesiva con disgenesia biliar.DiscusiónLa PQRAR plantea el diagnóstico diferencial histológico con: la displasia quística fibrosa y la enfermedad poliquística renal autosómica dominante. Es la alteración en el locus gen denominado PKDH1 del ADN, independientemente de la severidad de la afectación la que confirma el diagnóstico(AU)

IntroductionAutosomal recessive polycystic kidney disease (ARPKD) is a genetic disorder caused by a mutation in the PKD1 gene, which codes for protein polycystin 1, mapped on chromosome 6p13.3. ARPKD is characterised by the formation of cysts from coalescing dilated renal collecting ducts coexisting with congenital hepatic fibrosis secondary to biliar dysgenesis.Case reportWe report the autopsy findings in a 2h old, term female infant with severe oligohydramnios. The pregnancy had not been monitored, although a previous ultrasonography revealed foetal kidney enlargement. The most significant macroscopic findings were sponge kidneys composed of multiple small cysts and focal hepatic fibrosis. Microscopically a diagnosis of autosomal recessive polycystic kidney disease with biliary dysgenesis was made.DiscussionThe clinical and pathological findings are correlated and the most important necropsy findings are described. The relevant literature is reviewed and recent advances in the pathology, genetics, diagnosis, ultrasonography, prevention and treatment of ARPKD are discussed(AU)

Marcadores vasculares en molas hidratiformes completas y parciales / vascular markers in molas complete and partial hidratiformes

Las molas hidatiformes completas se consideraron clásicamente avasculares. Estudios recientes demuestran lo contrario. Usando el anticuerpo monoclonal CD34 se pueden inmunomarcar células endoteliales de vasos sanguíneos. Se realizaron estudios histopatológicos e inmunohistoquímicos en molas completas y parciales para determinar la presencia de vasos sanguíneos y comparar los hallazgos. Se identificaron 50 bloques de parafina cuyas secciones de 3 micras se colorearon con hematoxilina-eosina; clasificándose de acuerdo a los criterios de la Sociedad Internacional de Patología Ginecológica. Utilizamos la técnica del polímero marcado con peroxidasa conjugado al anticuerpo secundario y el cromógeno diaminobenzidina para demostrar la reactividad al anticuerpo CD34. Inicialmente se clasificaron en 23 molas completas (46 por ciento), 25 parciales (50 por ciento), y 2 (4 por ciento) huevos muertos retenidos. Se clasificaron obteniendo concordancia de 84 por ciento. La reacción fue positiva para CD34 91, 67 por ciento. Estos hallazgos demuestran que las vellosidades coriales de las molas completas y parciales tienen vasos sanguíneos.

Histopathologic and immunohistochemical evaluation of blood vessels in complete and partial hydatidiform mole.

OBJECTIVE: To assess 46 cases diagnosed as complete and partial hydatidiform mole in regard to their histopathologic aspects according to current World Health Organization (WHO) criteria and to determine whether their immunohistochemical features are related to the presence of blood vessels. STUDY DESIGN: An observational, descriptive study was done on the histopathologic and immunohistochemical findings of 46 molar pregnancy cases seen at the Gynecological Pathology Department, Anatomopathological Institute, Central University of Venezuela, during 1990-2003. Data were obtained primarily from the tumor registry. These cases were histopathologically and immunohistochemically evaluated with CD34 antibody to detect endothelial cells. RESULTS: Baseline histopathologic diagnoses were partial moles in 25 cases (54%) and complete moles in 21 (46%). Based on the current criteria we demonstrated 25 cases of partial moles, 20 of complete moles and 1 anembryonic pregnancy case. Diagnostic differences in 4 cases from complete to partial mole, 3 cases from partial to complete mole and 1 case from partial mole to anembryonic pregnancy were determined. Blood vessels were identified in 93.8% of complete moles, in which cisterns were predominantly extensive. CONCLUSION: Using CD34 immunostain, blood vessels were found in complete and partial hydatidiform moles, without significant differences between them.