RESUMO
Histological assessment of endoscopic biopsies in inflammatory bowel disease [IBD] plays an important role in clinical management, investigative studies, and clinical trials. Scoring schemes consisting of multiple histological items and offering considerable precision are widely available. However, definitions of histological abnormalities are often inconsistent. Furthermore, interobserver variability for their recognition and assessment may be high. The European Crohn's and Colitis Organisation [ECCO] formed an expert panel to explore definitions of histological abnormalities in IBD, with the aim of improving the quality of diagnosis and facilitating development of scoring schemes. The process confirmed that the current definitions often have no evidence base and vary between sources. Using available evidence and expert knowledge, the panel produced a series of ECCO consensus position statements on histological features in IBD.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/tratamento farmacológico , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/patologia , Doença de Crohn/tratamento farmacológicoRESUMO
Drug-induced mucosal injury (DIMI) in the gastrointestinal tract is important to recognise, partly because cessation of the culprit agent alone may result in resolution of symptoms. An ever-growing list of medications, including newer immunotherapeutic agents and targeted therapies, can cause gastrointestinal inflammation of varying severity. However, the diagnosis of DIMI is challenging, as a single drug can induce a variety of histopathological patterns of injury including acute colitis, chronic colitis, microscopic colitis, apoptotic colopathy, and ischaemic-type colitis. An additional consideration is the potential clinical, endoscopic and histological overlap of DIMI with gastrointestinal mucosal injury secondary to other entities such as inflammatory bowel disease (IBD). We discuss DIMI of the gastrointestinal tract with an emphasis on histological patterns that mimic IBD, histological features which may distinguish the two entities, and the diagnostic role and limitations of the pathologist.
Assuntos
Colite Ulcerativa , Colite , Doença de Crohn , Doenças Inflamatórias Intestinais , Doença Crônica , Colite/complicações , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológicoAssuntos
Neoplasias Cardíacas , Sarcoma Mieloide , Taquicardia Sinusal , Adolescente , Feminino , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/tratamento farmacológico , Neoplasias Cardíacas/metabolismo , Neoplasias Cardíacas/patologia , Humanos , Sarcoma Mieloide/diagnóstico por imagem , Sarcoma Mieloide/tratamento farmacológico , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/patologia , Taquicardia Sinusal/diagnóstico por imagem , Taquicardia Sinusal/tratamento farmacológico , Taquicardia Sinusal/metabolismo , Taquicardia Sinusal/patologiaAssuntos
Neoplasias Hematológicas , Células-Tronco Hematopoéticas , Transtornos Mieloproliferativos , Células-Tronco Neurais , Nicho de Células-Tronco , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Humanos , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/terapia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologiaRESUMO
PURPOSE: Monosomy 3 (M3) or the presence of a specific RNA expression profile, known as class 2, is strongly associated with death from uveal melanoma (UM). Given the important role of epigenetic processes in cancer development and progression, we compared the transcriptional profiles of a selection of epigenetic regulators between primary UM with a good and a bad prognosis. METHODS: Transcriptional levels of 59 epigenetic regulator genes were measured by quantitative PCR (qPCR) in 20 UM, 12 with monosomy of chromosome 3 (M3) and 8 with disomy of chromosome 3 (D3). Validation was performed in an independent cohort. Expression levels were compared to clinicopathological characteristics, including class type. Bisulfite sequencing was used to evaluate the role of DNA methylation in gene silencing. RESULTS: In the first set of tumors, general downregulation of transcription of the genes encoding epigenetic regulatory enzymes was seen in association with M3. The 10 genes with the highest differential expression between M3 and D3 were selected and were analyzed in a second set of tumors. In the validation set, significantly lower levels of KAT2B (P = 0.008), HDAC11 (P = 0.009), KMT1C (P = 0.05), KDM4B (P = 0.003), KDM6B (P = 0.04), and BMI-1 (P = 0.001) transcripts were found in tumors with M3/class 2. Methylation of C-phosphate-G (CpG) residues was not observed on the putative regulatory regions of KAT2B, KDM4B, or KDM6B. CONCLUSIONS: Expression levels of a number of histone-modifying genes and polycomb family members are significantly lower in uveal melanoma with monosomy 3/class 2, supporting a general dysregulation of epigenetic modifiers in UM with a bad prognosis.