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Mod Pathol ; 32(12): 1795-1805, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300804


Histologically, drug-induced liver injury could be classified into acute hepatitis, chronic hepatitis, acute cholestasis, chronic cholestasis, and cholestatic hepatitis. The correlation between these histologic patterns and long-term clinical outcomes has not been well established. Therefore, we conducted a retrospective cohort study to investigate the association of histologic patterns and long-term clinical outcomes defined as biochemical normalization, persistent abnormal liver biochemistry or death at designated time points. In this study, biochemical classification was determined by R-values; histologic injury pattern was determined by morphological features. Predictive ability of clinical outcomes by these two classifications was assessed using Receiver Operating Characteristic Curves. Logistic regression was performed to identify histologic factors associated with outcomes. Totally, 88 patients with drug-induced liver injury were included for final analysis. Biochemical and histologic classification were consistent in 50 (57%) cases. 53 (60%) cases showed biochemical normalization within 6 months, and a further 11 (13%), 16 (18%), and 6 (7%) cases within 1, 2, and 3 years, respectively. Compared with biochemical classification, histologic injury pattern had better predictive ability for abnormal biochemistry at 6 months (Areas under Receiver Operating Characteristic Curves 0.92 versus 0.60, P < 0.001) and 1 year (Areas under Receiver Operating Characteristic Curves 0.94 versus 0.69, P < 0.001). Interlobular bile duct loss in >25% portal areas was independently associated with abnormal biochemistry at 6 months, 1 year, and 2 years. In conclusion, histologic injury pattern is better correlated with clinical outcome at 6 months and 1 year than biochemical classification. Moderate bile duct loss is an important histologic feature associated with persistent biochemical abnormality at 6 months, 1 year, and 2 years.

Virchows Arch ; 474(5): 619-623, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30666415


We report the first patient (a 13-year-old girl) with a sinonasal low-grade non-intestinal-type adenocarcinoma showing aberrant CDX2 expression both within morular areas and in the tubular component and demonstrate for the first time a SYN2-PPARG gene fusion in this tumor type. The tumor arose from the nasal septum and had not spread beyond the nasal cavity.

Fator de Transcrição CDX2/metabolismo , Cavidade Nasal/patologia , PPAR gama/metabolismo , Neoplasias dos Seios Paranasais/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adolescente , Biomarcadores Tumorais/metabolismo , Fator de Transcrição CDX2/genética , Feminino , Fusão Gênica/fisiologia , Proteínas de Homeodomínio/metabolismo , Humanos , Imuno-Histoquímica , Neoplasias dos Seios Paranasais/diagnóstico
Medicine (Baltimore) ; 97(31): e11291, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075496


RATIONALE: Spontaneous regression of non-small cell lung cancer is exceptionally rare. PATIENT CONCERNS: Treatment-related toxicity. DIAGNOSES: We report a case of a patient diagnosed with locally advanced non-small cell lung cancer. INTERVENTIONS: The patient declined potentially curative treatment, and did not receive any anti-cancer treatment. OUTCOMES: He has survived more than two years since his initial diagnosis, maintaining his good performance status. Serial imaging with computed tomography scans showed tumour regression and near-complete resolution of his disease. LESSONS: Spontaneous regression of non-small cell lung cancer, by virtue of its scarcity, has not been well-studied and is poorly understood. Further studies are required, in order to clarify the mechanisms by which spontaneous regression occurs, and possibly identify new targets for cancer treatment.

Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/terapia , Dieta , Exercício , Comportamentos Relacionados com a Saúde , Humanos , Neoplasias Pulmonares/terapia , Masculino , Remissão Espontânea , Tomografia Computadorizada por Raios X
Int J Mol Sci ; 19(7)2018 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-29966370


Extranodal NK/T-cell lymphoma, nasal type (ENKTL), is an aggressive malignancy with a poor prognosis. While the introduction of L-asparaginase in the treatment of this disease has significantly improved the prognosis, the outcome of patients relapsing after asparaginase-based chemotherapy, which occurs in up to 50% of patients with disseminated disease, remains dismal. There is hence an urgent need for effective targeted therapy especially in the relapsed/refractory setting. Gene expression profiling studies have provided new perspectives on the molecular biology, ontogeny and classification of ENKTL and further identified dysregulated signaling pathways such as Janus associated kinase (/Signal Transducer and activation of transcription (JAK/STAT), Platelet derived growth factor (PDGF), Aurora Kinase and NF-κB, which are under evaluation as therapeutic targets. Copy number analyses have highlighted potential tumor suppressor genes such as PR Domain Zinc Finger Protein 1 (PRDM1) and protein tyrosine phosphatase kappa (PTPRK) while next generation sequencing studies have identified recurrently mutated genes in pro-survival and anti-apoptotic pathways. The discovery of epigenetic dysregulation and aberrant microRNA activity has broadened our understanding of the biology of ENKTL. Importantly, immunotherapy via Programmed Cell Death -1 (PD-1) and Programmed Cell Death Ligand1 (PD-L1) checkpoint signaling inhibition is emerging as an attractive therapeutic strategy in ENKTL. Herein, we present an overview of the molecular biology and genomic landscape of ENKTL with a focus on the most promising translational opportunities.

Genômica/métodos , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/metabolismo , Animais , Variações do Número de Cópias de DNA/genética , Epigenômica/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Tirosina Fosfatases/metabolismo
Ann Hepatobiliary Pancreat Surg ; 21(3): 157-162, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28990003


Peliosis Hepatis (PH) is a rare vascular disorder of the liver, characterized by the presence of cystic blood-filled cavities distributed throughout the hepatic parenchyma. The pathogenesis of PH remains controversial. The preoperative diagnosis of PH is difficult, due to the non-specific imaging characteristics of PH and almost all cases are diagnosed on histology post resection. This study presents a case of PH masquerading as hepatocellular carcinoma (HCC). The patient is a 45-year old Chinese lady, who presented with transaminitis. She was found to be hepatitis B virus core total antibody-positive with an alpha-fetoprotein (AFP) of 29.4 ng/ml. Triphasic liver computed tomography showed several arterial hypervascular lesions and hypoenhancing lesions on the venous phase, particularly in the segments 6/7. Subsequently, a magnetic resonance imaging scan showed multiple lesions in the right hemiliver with an indeterminate enhancement patterns. Subsequently, she decided to undergo a resection procedure. Histopathology revealed findings consistent with PH with some unusual features. This case demonstrates a clinical conundrum, in which PH presented with a raised AFP, in a patient with risk factors for the development of HCC. The clinical suspicion of PH should be high in patients, who present with multiple hepatic lesions with variable enhancement patterns.

Dermatol Online J ; 21(1)2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25612121


We describe a rare case of a patient with pancreatic adenocarcinoma who presented initially with a rash on her lower legs. Skin biopsy showed lobular panniculitis and characteristic "ghost" adipocytes consistent with pancreatitic panniculitis. This clinical case is an interesting example where a seemingly innocuous skin condition heralds an underlying malignant disease process.

Adenocarcinoma/complicações , Neoplasias Pancreáticas/complicações , Paniculite/etiologia , Paniculite/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adipócitos/patologia , Necrose Gordurosa/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Pele/patologia