RESUMEN
Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1 (ROS1) gene rearrangements show dramatic response to the tyrosine kinase inhibitor (TKI) crizotinib. Current best practice guidelines recommend that all advanced stage non-squamous NSCLC patients be also tested for ROS1 gene rearrangements. Several studies have suggested that ROS1 immunohistochemistry (IHC) using the D4D6 antibody may be used to screen for ROS1 fusion positive lung cancers, with assays showing high sensitivity but moderate to high specificity. A break apart fluorescence in situ hybridization (FISH) test is then used to confirm the presence of ROS1 gene rearrangement. The goal of Canadian ROS1 (CROS) study was to harmonize ROS1 laboratory developed testing (LDT) by using IHC and FISH assays to detect ROS1 rearranged lung cancers across Canadian pathology laboratories. Cell lines expressing different levels of ROS1 (high, low, none) were used to calibrate IHC protocols after which participating laboratories ran the calibrated protocols on a reference set of 24 NSCLC cases (9 ROS1 rearranged tumors and 15 ROS1 non-rearranged tumors as determined by FISH). Results were compared using a centralized readout. The stained slides were evaluated for the cellular localization of staining, intensity of staining, the presence of staining in non-tumor cells, the presence of non-specific staining (e.g. necrosis, extracellular mater, other) and the percent positive cells. H-score was also determined for each tumor. Analytical sensitivity and specificity harmonization was achieved by using low limit of detection (LOD) as either any positivity in the U118 cell line or H-score of 200 with the HCC78 cell line. An overall diagnostic sensitivity and specificity of up to 100% and 99% respectively was achieved for ROS1 IHC testing (relative to FISH) using an adjusted H-score readout on the reference cases. This study confirms that LDT ROS1 IHC assays can be highly sensitive and specific for detection of ROS1 rearrangements in NSCLC. As NSCLC can demonstrate ROS1 IHC positivity in FISH-negative cases, the degree of the specificity of the IHC assay, especially in highly sensitive protocols, is mostly dependent on the readout cut-off threshold. As ROS1 IHC is a screening assay for a rare rearrangements in NSCLC, we recommend adjustment of the readout threshold in order to balance specificity, rather than decreasing the overall analytical and diagnostic sensitivity of the protocols.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Canadá , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas/genética , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/genética , Proto-Oncogenes , Especies Reactivas de OxígenoRESUMEN
The IL-17 receptor (IL-17R) has a perplexing role in cancer, which may be explained by its yin-yang signaling pathways. Recently, the critical role of IL-17R in maintaining basal levels of A20-a key negative regulator of NF-κB and JNK-c-Jun pathways has been demonstrated in cancer cell lines. Cross-cancer analyses of somatic copy number alterations in IL-17RA, IL-17RC and A20 genes reveal that IL-17RA-deletion is common in colorectal cancer (CRC) patients, representing 24, 26, 37 and 49% of stage I, II, III and IV of patients, respectively, and mutually exclusive with patients displaying microsatellite instability. Importantly, patients with IL-17R-deletion or concurrent deletions of A20 show significantly reduced overall survival. Analysis of multiple published microarray studies confirms that IL-17RA expression is significantly reduced in CRC samples compared to normal counterparts, and its level is closely associated with A20 expression. Analyses of RNAseq data indicate that tumors with IL-17R-deletion express strong molecular markers of tumor invasion, growth and metastasis. Notably, approximately 20 genes responsible for protein synthesis and mitochondrial metabolism are inversely correlated with both IL-17RA and A20. Immunohistochemistry staining in human colorectal tissue arrays further reveals that high-grade tumors have significantly reduced IL-17RA staining compared to low-grade tumors. Thus, collective evidence strongly supports a previously unrecognized CRC-promoting mechanism triggered by IL-17RA-deletion and highlights its utility as a prognostic marker in CRC.
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Neoplasias Colorrectales/patología , Regulación hacia Abajo , Eliminación de Gen , Receptores de Interleucina-17/genética , Receptores de Interleucina-17/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Inestabilidad de Microsatélites , Clasificación del Tumor , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Análisis de Supervivencia , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Solid-pseudopapillary neoplasms (SPNs) of the exocrine pancreas are rare, accounting for only 2% of pancreatic tumours. These tumours predominantly affect women during the second and third decades of life. They frequently present with vague symptoms and can pose a diagnostic challenge. Surgical resection remains the treatment of choice that can cure up to 95% of patients when negative resection margins are obtained. SPNs diagnosed during pregnancy are exceptional and with profound implications on the mother and fetus. The authors present a case of an asymptomatic SPN in a 24-year-old woman diagnosed at 14 weeks of gestation on a routine prenatal ultrasound. Distal pancreatectomy, splenectomy and cholecystectomy were successfully performed at 18 weeks of gestation. A healthy full-term male child was born 5 months following surgery without complications.
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Carcinoma Papilar/cirugía , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Complicaciones Neoplásicas del Embarazo/cirugía , Diagnóstico Prenatal/métodos , Carcinoma Papilar/diagnóstico , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Masculino , Neoplasias Pancreáticas/diagnóstico , Embarazo , Complicaciones Neoplásicas del Embarazo/diagnóstico , Resultado del Embarazo , Esplenectomía , Adulto JovenRESUMEN
Malignant serous cystic neoplasms (SCN) of the pancreas are exceptionally rare, and only a few cases have been reported. As a result, SCN have been unanimously classified as benign tumours. Contrary to this conviction, in 1989, George et al published the very first case of a patient found to have a malignant pancreatic SCN. Up to the time of the submission of this paper, 27 cases of serous cystoadenocarcinomas have been published. In all the previously published cases of malignant SCN, the correct diagnosis was made postoperatively or at the time of autopsy. The authors present a case of a 68-year-old patient who was incidentally found to have a large liver mass on transthoracic echocardiogram ordered for suspected coronary artery insufficiency. Subsequent investigations revealed an additional large mass in the pancreas and percutaneous biopsies of both lesions revealed histological features consistent with malignant SCN metastasised to the left hepatic lobe.
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Cistadenocarcinoma Seroso/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Anciano , Enfermedades Asintomáticas , Biopsia con Aguja , Cistadenocarcinoma Seroso/diagnóstico por imagen , Cistadenocarcinoma Seroso/patología , Diagnóstico Diferencial , Humanos , Hallazgos Incidentales , Masculino , Páncreas/diagnóstico por imagen , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Radiografía , UltrasonografíaRESUMEN
PURPOSE: Our recent studies of renal histology in congenital ureteropelvic obstruction cases prompted us to review the literature in this regard, focusing on issues of development, normal variation, clinicopathological correlations and pathogenesis. MATERIALS AND METHODS: The period from 1971 to 2006 was analyzed, including all relevant articles, which were critically reviewed. RESULTS: There have been many studies encompassing the entity of ureteropelvic junction obstruction that include clinical findings, radiographic imaging, pathological examination of ureteropelvic junction obstruction per se and renal biopsies during pyeloplasty procedures. We synthesized this information in a cohesive review with a proposed classification. CONCLUSIONS: Congenital ureteropelvic junction obstruction is a spectrum that ranges from the radiological demonstration of apparent physiological ureteropelvic junction obstruction to a disordered ureteropelvic junction, characterized by smooth muscle hypertrophy and fibrosis associated with renal parenchymal changes that may necessitate pyeloplasty or nephrectomy. However, renal biopsies in patients in whom pyeloplasty is done show in most of them relatively well maintained parenchyma, in which overt changes are mainly glomerular. More subtle alterations have been described that relate to shifts in proximal-to-distal tubular ratios. Extreme thinning of the renal parenchyma can occur with only limited tubulointerstitial injury. Recently ureteropelvic junction obstruction was described in a series of genetically altered animals and placed in a more global context, ie CAKUT (congenital abnormalities of the kidney and urinary tract).
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Enfermedades Renales/clasificación , Riñón/patología , Obstrucción Ureteral/cirugía , Humanos , Riñón/cirugía , Pelvis Renal , Nefrectomía , Uréter , Obstrucción Ureteral/clasificación , Obstrucción Ureteral/congénito , Obstrucción Ureteral/fisiopatologíaRESUMEN
Clinicopathologic trends of recurrent hepatitis C after liver transplantation (LT) in hepatitis C (HCV) patients seem to have changed in recent years. Our aims were to define the current post-LT patterns of HCV recurrence and identify features of diagnostic and/or prognostic significance. Detailed analysis was performed on 92 HCV patients who underwent LT from June 1999 to December 2003 and survived early post-LT period. The study patients were grouped, as follows: no histologic recurrence (n = 31), "typical" recurrent HCV (n = 52), and post-LT autoimmune-like hepatitis ("AIH-like") (n = 9). The typical and AIH-like groups had mostly common features with post-LT progressive fibrosis (stage > or =2) more frequent in the latter. Based on post-LT progressive fibrosis (stage > or =2), the 2 post-LT hepatitis categories were regrouped as progressive (n = 24) and nonprogressive (n = 37). High viral counts, HCV genotype 1, and native liver inflammation grade 2 or higher with plasmacytic periseptitis were more frequent in progressive cases than nonprogressive or nonrecurrent cases. Sex mismatch of male recipient and female donor was more common in nonrecurrent group. Overall, death rate was comparable in all groups; however, post-LT HCV-related deaths were more common in progressive cases. In conclusion (1) two thirds (66.2%) of HCV patients developed histologic hepatitis after LT with either typical or AIH-like features; (2) progressive fibrosis was seen in 39.3% of patients with post-LT hepatitis and 26% of the entire study group and was more frequent in AIH-like cases; (3) inflammation grade 2 or higher with plasmacytic periseptitis in native livers may be a predictor of post-LT progressive fibrosis; and (4) male recipient/female donor combination was more common in nonrecurrent cases.
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Hepatitis C/cirugía , Trasplante de Hígado , Adulto , Antivirales/uso terapéutico , Estudios de Cohortes , Femenino , Hepatitis C/patología , Hepatitis Autoinmune/patología , Humanos , Inmunosupresores/uso terapéutico , Hígado/patología , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
In industrialized countries, over-the-counter dietary supplements have become popular in preventing and treating an expanding list of medical conditions. Although most commercially available supplements have not been rigorously tested for safety and efficacy, they have found an enlarging market because they are considered natural. Oral supplements containing green tea extract have been marketed as effective for weight loss and to prevent and cure some solid tumors. Although there is little scientific evidence of the effectiveness of green tea extracts to improve the quality of health of regular consumers, there is an increasing body of medical literature supporting the hypothesis that they can cause serious side effects. Our experience adds to previous reports of acute liver toxicity observed in individuals consuming supplements containing green tea extract. We highlight the importance of obtaining a detailed history of dietary supplement consumption when evaluating a patient presenting with acute liver dysfunction.