RESUMEN
AIMS: Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before the age of 6 years, encompassing both 'pure' IBD, such as ulcerative colitis (UC) and Crohn's disease (CD) and monogenic diseases (MDs), the latter often involving genes associated with primary immunodeficiencies. Moreover, histological features in gastrointestinal (GI) biopsies in MD can also have IBD-like morphology, making differential diagnosis difficult. Correct diagnosis is fundamental, as MDs show a more severe clinical course and their inadequate/untimely recognition leads to inappropriate therapy. METHODS AND RESULTS: Biopsy samples from the lower and upper GI tract of 93 clinically diagnosed VEO-IBD children were retrospectively selected in a multicentre cohort and histologically re-evaluated by 10 pathologists blinded to clinical information. Each case was classified according to morphological patterns, including UC-like; CD-like; enterocolitis-like; apoptotic; eosinophil-rich; and IBD-unclassified (IBD-U). Nine (69%) MD children showed IBD-like morphology; only the IBD-U pattern correlated with MD diagnosis (P = 0.02) (available in 64 cases: 51 non-MD, true early-onset IBD/other; 13 MD cases). MD patients showed earlier GI symptom onset (18.7 versus 26.9 months) and were sent to endoscopy earlier (22 versus 37 months), these differences were statistically significant (P < 0.05). Upper GI histology was informative in 37 biopsies. CONCLUSIONS: The diagnosis of the underlying cause of VEO-IBD requires a multidisciplinary setting, and pathology, while being one of the fundamental puzzle pieces, is often difficult to interpret. A pattern-based histological approach is therefore suggested, thus aiding the pathologist in VEO-IBD reporting and multidisciplinary discussion.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Tracto Gastrointestinal Superior , Niño , Humanos , Estudios Retrospectivos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/patología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/patología , Endoscopía Gastrointestinal , Tracto Gastrointestinal Superior/patología , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/patologíaAsunto(s)
Ictiosis/complicaciones , Proteínas de Filamentos Intermediarios/genética , Fallo Hepático/complicaciones , Enfermedades Mitocondriales/diagnóstico , Proteínas Mitocondriales/genética , ARNt Metiltransferasas/genética , ADN Mitocondrial/genética , Proteínas Filagrina , Humanos , Ictiosis/genética , Lactante , Fallo Hepático/genética , Masculino , Enfermedades Mitocondriales/genética , Mutación , Secuenciación del Exoma/métodosRESUMEN
INTRODUCTION: Oncological aggressiveness and the ability to present distant localizations are known in high-grade gliomas (HGGs), but the knowledge about the possible aggressiveness of LGGs is scarce, especially concerning possible spinal localization. EVIDENCE ACQUISITION: A systematic search of low-grade gliomas (LGGs) with spinal localization on the three primary online databases (PubMed/MEDLINE, Embase, and Cochrane) was conducted. We included adult patients with histological diagnosis of intracranial LGG and specified WHO grade showing a remote spinal localization during follow-up. Additionally, we present a case of a left temporal LGG presenting a spinal localization fourteen years after the first appearance. We compared the survival rates of LGGs in our series with those of LGGs without spinal localizations. EVIDENCE SYNTHESIS: Seven articles dealing with the subject and eight patients were considered (including our case), with a mean age at diagnosis of 42.25 years (range 26-69 years). The mean latency between a diagnosis of intracranial LGGs and a spinal localization occurrence was 7.37 years (range 2-14 years), and an increased WHO grade of the spinal localization compared to the brain LGG was observed in all patients. There was no sign of intracranial progression at the time of spinal glioma diagnosis in four cases, including ours. Survival at ten years was 28% against a 10-year survival rate of 65-71% for LGGs without distant localization, as reported in the literature. CONCLUSIONS: Spinal metastasis of intracranial LGGs is an adverse prognostic factor. Surgical violation of ventricles can play a role in the pathophysiology of CSF spread of tumor cells in LGGs.
Asunto(s)
Neoplasias Encefálicas , Glioma , Adulto , Anciano , Encéfalo/patología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Glioma/patología , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Tasa de SupervivenciaRESUMEN
Recurrent glycine-to-arginine/valine alterations at codon 34 (G34R/V) within H3F3A gene characterize a subset of hemispheric high-grade gliomas (HGG) affecting children and young adults. These tumors, defined as G34R/V-mutant gliomas, are histologically heterogenous, with microscopic features of either HGG or embryonal tumors (primitve neuroectodermal tumor-like features). To assess the value of immunohistochemistry (IHC) to detect G34R/V-mutated cases, we tested anti-histone G34V (clone 329E5) and anti-histone G34R (clone RM240) antibodies in a series of 28 formalin-fixed and paraffin-embedded samples. A total of 28 cases of hemispheric, IDH-wt HGG mainly affecting children and young adults were evaluated by IHC and by sequencing. The median age of patients at diagnosis was 17 years (0.1 to 26 y). By IHC, 10 of the 28 cases showed nuclear positivity for G34R and 3 of the 28 cases for G34V. Molecular analysis of G34R/V-mutation status was successful in 24 of the 28 cases. Mutation at glycine 34 of the H3F3A gene was identified in 9 of the 24 tumors (37%) by direct sequencing, revealing 7 of 9 positive case by sequencing and 2 of 9 false negative cases by IHC. Two of 15 negative case by sequencing demonstrated a false positivity by IHC. In total, in 4 (16.6%) of 24 cases, IHC and mutational results were discordant: 2 tumors were negative by IHC (false negative) but harbored G34R mutation by sequencing, and 2 cases were positive by IHC (false positive by IHC) but wild type by sequencing. Moreover, most mutated cases showed loss of ATRX expression and/or p53 expression. The positivity by IHC with specific antibody tested is not highly predictive for presence of G34R/V mutation, but confirmation by sequencing is mandatory; G34R/V mutations should be suspected in all hemispheric tumor IDH1/2 wild type, showing loss of OLIG2 and ATRX and/or p53 expression.
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Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Glioma/genética , Histonas/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Lactante , Masculino , Mutación , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Subependymal giant-cell astrocytoma (SEGA) is a rare intra-ventricular low-grade tumor which frequently occurs as a manifestation of tuberous sclerosis complex. The histogenesis of SEGA is controversial and its astrocytic nature has been doubted. First studies suggested the astrocytic nature of SEGA while several recent reports demonstrate its glio-neuronal nature. In spite of this, in the recently revised WHO classification of the CNS tumors, SEGA has been still included in the group of astrocytomas. We studied nine tuberous sclerosis complex-associated SEGAs. Patients were 1-18 years old. Eight patients (89%) had a solitary lesion located in the lateral ventricle close to of the head of the caudate nucleus, the remaining patient (11%) had two tumors, one located close to the head of the left caudate nucleus and the other in the central part of the right lateral ventricle. Histologically, tumors were composed of three types of cells: spindle, gemistocytic and ganglion-like. Four tumors (44%) had a prominent vascularization and three (33%) showed an angiocentric pattern. Calcifications were observed in six cases (66%). By immunohistochemistry, the majority of the tumors were GFAP- (9; 100%), neurofilament- (8, 89%), neuron-specific enolase- (9, 100%), and synaptophysin- (8; 89%) positive. Ultrastructural studies were performed on four cases. In all four there were glial cell processes filled with intermediate filaments. In one case dense core putative neurosecretory granules were appreciable. Our results emphasize the glio-neuronal nature of SEGA. We suggest moving it into the group of mixed glio-neuronal tumors under the denomination of subependymal giant cell tumor.
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Astrocitoma/patología , Neoplasias Primarias Múltiples/patología , Adolescente , Astrocitoma/química , Astrocitoma/clasificación , Astrocitoma/ultraestructura , Neoplasias Encefálicas/química , Neoplasias Encefálicas/clasificación , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/ultraestructura , Neoplasias del Ventrículo Cerebral/química , Neoplasias del Ventrículo Cerebral/clasificación , Neoplasias del Ventrículo Cerebral/patología , Neoplasias del Ventrículo Cerebral/ultraestructura , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Lactante , Filamentos Intermedios/ultraestructura , Masculino , Neoplasias Primarias Múltiples/química , Neoplasias Primarias Múltiples/ultraestructura , Proteínas del Tejido Nervioso/análisis , Proteínas de Neurofilamentos/análisis , Neuroglía/patología , Neuroglía/ultraestructura , Fosfopiruvato Hidratasa/análisis , Sinaptofisina/análisisRESUMEN
OBJECTIVES: The aim of the study was to investigate the distribution of the sialoderivatives of the glycoconjugates in the oviduct of normally menstruating and postmenopausal women. METHODS: Biopsies of ampullary and isthmic portions of the oviduct were obtained from fertile women, in proliferative and secretive phases, and from postmenopausal subjects. The study was carried out using digoxigenin-labelled lectins (MAA, SNA and PNA) in addition to the use of enzymatic and chemical treatments to characterize the different glycosidic linkages of the sialoderivatives and to obtain information on their structure. RESULTS: No appreciable difference in sialoderivatives distribution was observed among the oviducts, particularly at the epithelium luminal surface, of the fertile women in the two menstrual cycle phases or among those of the fertile and some postmenopausal women, independently from age. Moreover, no appreciable difference of distribution was observed between the ampullary and the isthmic portions in both the study groups. CONCLUSIONS: In the fertile women sialoderivatives present at the luminal surface of the epithelial cells could play a role in sperm capacitation and mobility, and facilitate the transit of the egg and of the early embryo along the oviducts. The similar distribution of sialoderivatives in the oviduct epithelium of some postmenopausal women of different age, compared to the fertile ones, suggests a maintaining of some functions of the organ, independently from the age of the woman. This could be due, in some cases, to the influence of remaining still sufficient sex hormonal levels.
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Endometrio/metabolismo , Trompas Uterinas/metabolismo , Glicoconjugados/metabolismo , Ácidos Siálicos/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Epitelio/metabolismo , Femenino , Fertilidad , Humanos , Persona de Mediana Edad , PosmenopausiaRESUMEN
Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated the accuracy of liquid-based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety-one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures.
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Adenocarcinoma/patología , Técnicas Citológicas , Hiperplasia Endometrial/patología , Neoplasias Endometriales/patología , Endometrio/patología , Adenocarcinoma/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Hiperplasia Endometrial/diagnóstico por imagen , Neoplasias Endometriales/diagnóstico por imagen , Endometrio/diagnóstico por imagen , Endosonografía , Femenino , Humanos , Persona de Mediana Edad , Sensibilidad y Especificidad , Enfermedades Uterinas/diagnóstico por imagen , Enfermedades Uterinas/patologíaRESUMEN
Malignant meningioma has a bad prognosis. Surgery and radiotherapy are the most effective therapeutic options, without an established role for chemotherapy. We report a case of 2-year-old male child with diagnosis of postoperative relapse of a malignant meningioma. Considering the rapid progression, the young age and the lack of effective therapeutic alternatives, the patient underwent multidisciplinary anticancer treatment with a protocol made for soft tissue sarcomas (EpSSG NRSSTS 2005 protocol), with positive outcome. This case represents a successful management of an anaplastic meningioma with a multimodal treatment, including chemotherapy, in a pediatric patient.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/uso terapéutico , Ifosfamida/uso terapéutico , Neoplasias Meníngeas/tratamiento farmacológico , Meningioma/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Preescolar , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/diagnóstico por imagen , Meningioma/diagnóstico por imagen , Sarcoma/tratamiento farmacológicoAsunto(s)
Enfermedades Cutáneas Vesiculoampollosas/patología , Niño , Errores Diagnósticos , Femenino , Humanos , RecurrenciaRESUMEN
One of the most common regions involved in the meningiomas tumorigenesis is chromosome 22q where the NF2 gene resides. The deficiency or loss of the NF2 gene product, merlin/schwannomin, plays a role in tumor development and metastatization. Conflicting results have been reported on the prognostic value of merlin in meningiomas. Several studies have indicated NF2 gene inactivation as an early tumorigenic event unrelated to the histological grade or clinical behavior. On the contrary, the NF2 gene alteration rate differs between the different histotypes. A pathogenesis independent from the NF2 gene has been suggested in meningothelial meningiomas. In the present work, we studied the NF2 gene expression through real time-PCR (RT-PCR) in 30 meningiomas. The average of the NF2 gene expression of all meningiomas was considered as reference value. The average of expression of WHO grade I and II meningiomas was higher than the average of all meningiomas, whereas that of WHO grade III meningiomas was lower. When we compared the NF2 gene expression in the different meningioma grades we did not note a significant difference (P = 0.698) despite the tendency to decrease from grade I to grade III. The average expression of meningothelial meningiomas was higher than the reference value, and that of non-meningothelial meningiomas was lower. The difference in NF2 gene expression between meningothelial and non-meningothelial meningiomas was statistically significant (P = 0.013). Our data supports the finding that alterations in NF2 gene alteration are histotype related but not grade related.