RESUMEN
Targetable NTRK gene fusions can be detected across tumor types using methodologies such as pan-TRK IHC, DNA or RNA NGS testing, or FISH. Challenges for implementation of clinical testing for NTRK fusions may arise due to the range in NTRK fusion prevalence across tumors, endogenous levels of TRK expression in tissues, and the large number of potential fusion partners. In this study, we examined our experience evaluating driver mutation negative lung, urothelial or cholangiocarcinoma cases, in addition to cases with positive, equivocal, or weak staining by pan-TRK IHC for NTRK fusions. 63/127 (49.6%) of these cases were positive for pan-TRK IHC, of which 71.4% showed weak or focal staining, potentially due to physiologic or non-specific TRK expression. Of these 127 cases, 4 harbored a NTRK fusion (1 fusion was seen in two separate samples from the same patient) as confirmed by RNA fusion panel testing. Pan-TRK IHC was positive in 1 case with TPM3-NTRK1 fusion, equivocal in 1 case with GOLGA4-NTRK3 fusion, and negative in 2 samples with ADAM19-NTRK3 fusion. Our findings show that we were able to successfully identify NTRK fusions that resulted in targeted therapy. However, our results suggest limited sensitivity of pan-TRK IHC for NTRK3 fusions, and that the reduced specificity for pan-TRK IHC in tumors with physiologic or non-specific TRK expression, results in false positive samples that require confirmatory testing by RNA based NGS.
Asunto(s)
Neoplasias , Receptor trkC , Biomarcadores de Tumor/genética , Fusión Génica , Reordenamiento Génico , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Neoplasias/genética , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , ARN , Receptor trkA/genética , Receptor trkC/genéticaRESUMEN
To develop a method for noninvasive evaluation of liver fibrosis, we investigated the differential sensitivities of quantitative susceptibility mapping (QSM) and R2 * mapping using corrections for the effects of liver iron. Liver fibrosis is characterized by excessive accumulation of collagen and other extracellular matrix proteins. While collagen increases R2 * relaxation, measures of R2 * for fibrosis are confounded by liver iron, which may be present in the liver over a wide range of concentrations. The diamagnetic collagen contribution to susceptibility values measured by QSM is much less than the contribution of highly paramagnetic iron. In 19 ex vivo liver explants with and without fibrosis, QSM (χ), R2 * and proton density fat fraction (PDFF) maps were constructed from multiecho gradient-recalled echo (mGRE) sequence acquisition at 3 T. Median parameter values were recorded and differences between the MRI parameters in nonfibrotic vs. advanced fibrotic/cirrhotic samples were evaluated using Mann-Whitney U tests and receiver operating characteristic analyses. Logistic regression with stepwise feature selection was employed to evaluate the utility of combined MRI measurements for detection of fibrosis. Median R2 * increased in fibrotic vs. nonfibrotic liver samples (P = .041), while differences in χ and PDFF were nonsignificant (P = .545 and P = .395, respectively). Logistic regression identified the combination of χ and R2 * significant for fibrosis detection (logit [prediction] = -8.45 + 0.23 R2 * - 28.8 χ). For this classifier, a highly significant difference between nonfibrotic vs. advanced fibrotic/cirrhotic samples was observed (P = .002). The model exhibited an AUC of 0.909 (P = .003) for detection of advanced fibrosis/cirrhosis, which was substantially higher compared with AUCs of the individual parameters (AUC 0.591-0.784). An integrated QSM and R2 * analysis of mGRE 3 T imaging data is promising for noninvasive diagnostic assessment of liver fibrosis.
Asunto(s)
Cirrosis Hepática/diagnóstico por imagen , Imagen por Resonancia Magnética , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Factibilidad , Femenino , Humanos , Lactante , Recién Nacido , Cirrosis Hepática/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Protones , Curva ROC , Adulto JovenRESUMEN
AIMS: In situ hybridisation (ISH) for albumin mRNA is a sensitive marker of primary liver tumours in adults. However, paediatric tumours, such as hepatoblastoma (HB) and fibrolamellar hepatocellular carcinoma (FLC), have not been tested thoroughly and may require ancillary tests to diagnose with confidence. We aim to determine if albumin ISH is useful in the pathological evaluation of these malignancies and to compare it to commonly used immunohistochemical markers HepPar 1 (HEPA) and arginase-1 (ARG). METHODS: Tissue microarrays of 26 HB and 10 FLC were constructed. Controls included 4 embryonal undifferentiated sarcomas of the liver, 51 neuroblastomas and 64 Wilms tumours. We evaluated a commercially available RNA ISH to detect albumin mRNA. Immunohistochemistry for HEPA and ARG was performed in the usual fashion. RESULTS: Twenty-six of 26 HB showed positive staining by albumin ISH including 14 fetal, 8 embryonal and 4 mixed variants. All 10 FLC were diffusely positive. The sensitivity and specificity of albumin ISH were 100% for HB and FLC. ARG had 100% sensitivity and specificity for HB (26 of 26 cases) and FLC (9 of 9). HEPA stained 22 of 26 HB (85% sensitivity, 99.2% specificity) and 7 of 9 FLC (78% sensitivity, 99.1% specificity). CONCLUSION: Albumin RNA ISH is a useful test to determine hepatocytic origin in HB and FLC. ARG was equally sensitive and easy to interpret, while HEPA was inferior to both in HB and FLC.
Asunto(s)
Albúminas/análisis , Biomarcadores de Tumor/análisis , Hibridación in Situ/métodos , Neoplasias Hepáticas/diagnóstico , ARN Mensajero/análisis , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Lactante , Masculino , Sensibilidad y EspecificidadRESUMEN
HHLA2 is a newly identified member of the B7 immune checkpoint family, but its function and crosstalk with immune cells is not fully understood. To gain insights into the HHLA2 expression profile and to determine the clinical significance and function of HHLA2 in pancreatic cancer, we performed immunohistochemistry (IHC) analyses on tissue microarrays (TMAs) of pancreatic ductal adenocarcinoma (PDAC, nâ¯=â¯92) with matched peritumoral tissues as well as in cohorts of precancerous lesions: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). We found that HHLA2 was rarely detected in normal acinar, islet, and ductal cells but widely expressed from early pancreatic precancerous lesions to invasive PDAC. The overall HHLA2 positivity was 95% (19/20) in low grade PanIN and 70.73% (29/41) in IPMN. HHLA2 expression was detected in 77.17% (71/92) of the PDAC cases and was significantly associated with better prognosis in this cohort. Our findings suggest that HHLA2 may behave as a costimulatory ligand in pancreatic cancer, which differs from other B7 family members that are largely characterized as checkpoint inhibitors. Further investigation of the HHLA2 signaling pathway and its receptors is warranted by our data and may lead to novel therapeutic interventions.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma in Situ/inmunología , Carcinoma Ductal Pancreático/inmunología , Inmunoglobulinas/análisis , Neoplasias Intraductales Pancreáticas/inmunología , Neoplasias Pancreáticas/inmunología , Carcinoma in Situ/mortalidad , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pancreatectomía , Neoplasias Intraductales Pancreáticas/mortalidad , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Intraductales Pancreáticas/cirugía , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Factores de Tiempo , Análisis de Matrices Tisulares , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
Tissue diagnosis is the gold standard for mass lesions of the liver, but needle core biopsies may sometimes prove challenging. Presented here is a review of a panel of immunohistochemical stains, including hepatocyte in paraffin 1, arginase-1, polyclonal carcinoembryonic antigen, CD10, bile salt export pump, glypican-3, as well as in situ hybridization for albumin RNA, to establish hepatocellular origin in cases in which hepatocellular carcinoma is suspected but the sample is limited or the morphology is challenging, as it may be with cases of scirrhous, fibrolamellar carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Albúminas/genética , Neoplasias de los Conductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Diagnóstico Diferencial , Humanos , Hibridación in Situ/métodosRESUMEN
Liver injury due to acute and chronic heart failure has long been recognized. This article discusses the concepts of acute cardiogenic liver injury (ACLI) and cardiac or congestive hepatopathy (CH) along with their clinical manifestations and sequelae. Histologically, ACLI manifests as centrilobular hepatocellular necrosis, whereas CH is associated with centrilobular hepatocyte atrophy, dilated sinusoids, and perisinusoidal fibrosis, progressing to bridging fibrosis and ultimately cirrhosis. ACLI is associated with marked increases in aminotransferase levels, whereas CH is associated with a cholestatic pattern of laboratory tests. Certain cardiac medications have also been implicated as a cause of liver fibrosis.
Asunto(s)
Cardiopatías Congénitas/complicaciones , Insuficiencia Cardíaca/complicaciones , Hepatopatías/patología , Hígado/patología , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Aspartato Aminotransferasas/sangre , Fibrosis , Procedimiento de Fontan , Cardiopatías Congénitas/cirugía , Humanos , L-Lactato Deshidrogenasa/sangre , Hepatopatías/sangre , Hepatopatías/etiología , gamma-Glutamiltransferasa/sangreRESUMEN
Choriocarcinoma is an aggressive malignant trophoblastic tumor that mostly occurs during reproductive years. Cytological features of choriocarcinoma in gynecologic Pap smears have not been described. Herein, we report a case of choriocarcinoma in a Pap smear of a patient who had a history of choriocarcinoma with metastatic disease.
Asunto(s)
Coriocarcinoma/diagnóstico , Neoplasias del Ojo/diagnóstico , Enfermedad Trofoblástica Gestacional/diagnóstico , Neoplasias Pulmonares/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Coriocarcinoma/tratamiento farmacológico , Coriocarcinoma/patología , Coriocarcinoma/cirugía , Neoplasias del Ojo/tratamiento farmacológico , Neoplasias del Ojo/secundario , Neoplasias del Ojo/cirugía , Femenino , Enfermedad Trofoblástica Gestacional/tratamiento farmacológico , Enfermedad Trofoblástica Gestacional/patología , Enfermedad Trofoblástica Gestacional/cirugía , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Prueba de Papanicolaou , Embarazo , Frotis VaginalRESUMEN
Immunohistochemistry often plays an important role in the evaluation of liver tumors. Recent advances have established a classification system for hepatocellular adenomas (HCAs) based on morphology, molecular alterations, and immunohistochemistry. Specifically, loss of liver fatty acid binding protein is seen in HNF1α-inactivated HCA, staining with serum amyloid A is seen in inflammatory HCA, and diffuse staining with glutamine synthetase (GS) is seen in ß-catenin activated HCA. A panel of immunohistochemical stains including glypican-3 (GPC-3), heat shock protein 70, and GS are useful in distinguishing HCC from non-malignant dysplastic nodules. Immunohistochemistry is also useful to determine whether a liver tumor is of primary hepatocellular or metastatic origin. Recently described markers useful for this purpose include arginase-1, GPC-3, and bile salt export pump. These newer markers may offer superior utility when compared to traditional markers of hepatocellular differentiation such as alpha-fetoprotein, hepatocyte paraffin-1, polyclonal carcinoembryonic antigen, and CD10. This paper will review recent advances in the immunohistochemical evaluation of liver tumors.