[Cholestasic toxic hepatitis due to clopidogrel in a patient with multiple conditions]. / Hepatitis tóxica colestástica por clopidogrel en un pacientepluripatológico.

Clopidogrel is a thienopyridine-class antiplatelet drug commonly used in ischemic heart disease,cerebrovascular disease and peripheral artery disease.Liver toxicity due to this drug is very infrequent.We found 16 cases in the literature, and in only two of them liver biopsy was carried out. We report the case of a 78 year old patient with multiple conditions affected by severe toxic cholestatic hepatitis due to clopidogrel and the results of the liver biopsy performed. Hepatitis was resolved after discontinuing the drug.Based on the characteristics of this case and other previously published cases, we review the characteristics of toxic hepatitis due to clopidogrel and its diagnosis and treatment.

EPB41L3, TSP-1 and RASSF2 as new clinically relevant prognostic biomarkers in diffuse gliomas.

Hypermethylation of tumor suppressor genes is one of the hallmarks in the progression of brain tumors. Our objectives were to analyze the presence of the hypermethylation of EPB41L3, RASSF2 and TSP-1 genes in 132 diffuse gliomas (astrocytic and oligodendroglial tumors) and in 10 cases of normal brain, and to establish their association with the patients' clinicopathological characteristics. Gene hypermethylation was analyzed by methylation-specific-PCR and confirmed by pyrosequencing (for EPB41L3 and TSP-1) and bisulfite-sequencing (for RASSF2). EPB41L3, RASSF2 and TSP-1 genes were hypermethylated only in tumors (29%, 10.6%, and 50%, respectively), confirming their cancer-specific role. Treatment of cells with the DNA-demethylating-agent 5-aza-2'-deoxycytidine restores their transcription, as confirmed by quantitative-reverse-transcription-PCR and immunofluorescence. Immunohistochemistry for EPB41L3, RASSF2 and TSP-1 was performed to analyze protein expression; p53, ki-67, and CD31 expression and 1p/19q co-deletion were considered to better characterize the tumors. EPB41L3 and TSP-1 hypermethylation was associated with worse (p = 0.047) and better (p = 0.037) prognosis, respectively. This observation was confirmed after adjusting the results for age and tumor grade, the role of TSP-1 being most pronounced in oligodendrogliomas (p = 0.001). We conclude that EPB41L3, RASSF2 and TSP-1 genes are involved in the pathogenesis of diffuse gliomas, and that EPB41L3 and TSP-1 hypermethylation are of prognostic significance.

Estudio del anticuerpo DOG1 en el diagnóstico de tumores del estroma gastrointestinal – GIST / The role of the DOG1 antibody in the diagnosis of gastrointestinal stromal tumours – GIST

Los tumores del estroma gastrointestinal (GIST)poseen mutaciones en los genes del receptor de la tirosínquinasa (RTKs) KIT y PDGFRA. La posibilidad debloquear esta actividad ha significado una nueva esperanzaterapéutica. El diagnóstico de GIST recae en laexpresión inmunohistoquímica del c-KIT, pero un 4-15%son c-KIT negativos (aún en presencia de mutación), ysin embargo estos pacientes podrían beneficiarse deltratamiento con inhibidores tirosín quinasa (TKIs).El DOG1 es un nuevo anticuerpo cuya sensibilidady especificidad parece ser superior o igual a la del c-KIT.El objetivo de este trabajo es evaluar la sensibilidad(Se) y especificidad (Sp) de DOG1 en GIST de tipo usual(c-KIT positivos), de tipo inusual (c-KIT negativos) yfrente a otros tumores fusocelulares mesenquimales, ycomparar la validez diagnóstica del DOG1 frente al c-KIT.Estudiamos 40 GIST, 39 c-KIT positivos y un c-KITnegativo. Se realizó un panel inmunohistoquímico conlos anticuerpos: c-KIT, CD34, actina músculo liso, DOG1y S100, en los GIST como en siete tumores fusocelulares.La Se y Sp de GIST para DOG1 fue del 100 y 97,5%para c-KIT. La inmunoreactividad para DOG1 en todoslos tumores fusocelulares fue negativa. La validez diagnósticade DOG1 y C-KIT fue similar a la hora de detectarGIST y no GIST.DOG1 es un marcador específico y sensible para eldiagnóstico y diagnóstico diferencial de GISTs (es capazde detectar algunos GIST sin mutación en RTK).El DOG1 debería de formar parte del panel inmunohistoquímicopara el diagnóstico de GIST(AU)

Gatrointestinal stromal tumours (GIST) harbouroncogenic mutations in tyrosin kynases receptors(RTKs) including KIT and PDGFRA. The inhibition ofthis activity has been regarded as the primary target forthe treatment of these patients. Diagnosis of GIST relieson c-KIT inmunoreactivity; however there is a 4-15% ofGISTs that are C-KIT negative which may lead to underdiagnosisof GISTs and possible withholding of therapy.The novel gene DOG1 has been found overexpressedin GISTs and has potential as a diagnostic markerfor GISTs showing even more sensitivity (Se) and specificity(Sp) than c-KIT for the diagnosis of these tumors.In this study we compared the (Se) and (Sp) of DOG1 intypical and atypical GISTs (c-KIT positive or negative)with c-KIT and other mesenchymal neoplasms in thedifferential diagnosis of GISTsWe examined 40 GIST (39 showed inmunoreactivityfor c-KIT and one was c-KIT negative) and anotherseven fusiform tumors. An inmunohistochemical panelwas performed with c-KIT, CD34, smooth muscle actin,DOG1 and S100 antibodies on both types of neoplasms.The overall Se and Sp of DOG1 and KIT in GISTswere nearly identical: 100 and 97,5%. Negativity forDOG1 was observed in all fusiform mesenchymal neoplasms.DOG1 is highly expressed in GIST and its expressionseems quite specific for these tumours when thedifferential diagnosis includes another mesenchymalneoplasms.DOG1 should be added to the diagnostic panel evaluatingGISTs(AU)

[Malignant transformation of a nevus of Ito: description of a rare case]. / Transformación maligna de un nevus de Ito: descripción de un caso extraordinario.

Dermal melanocytosis refers to congenital or acquired lesions characterized by the presence of dendritic cells derived from melanocytes that migrate from the neural crest to the epidermis. The nevus of Ito develops in the territory supplied by the acromioclavicular nerve. Malignant transformation in dermal melanocytosis is extremely rare, with only isolated case reports; only 2 cases of malignant transformation of a nevus of Ito have been reported. We report a very rare case that is the third to be described in the literature. The patient was a 24-year-old man who presented with a subcutaneous nodule that had developed in the anterolateral region of the thorax over the previous 8 months. The nodule was located beneath a faint blue-gray macule with poorly defined borders. Biopsy of the nodule revealed malignant melanoma; biopsies of the adjacent skin lesion showed a diffuse proliferation of scattered melanocytes in a collagen stroma in the reticular dermis. A diagnosis of malignant transformation of a nevus of Ito was made after other possibilities were ruled out.

Plasma proteins and immunoglobulins in penguins (Pygoscelis adeliae).

Total and fractionated proteins were evaluated in the serum of normal penguins. Four proteins with antibody activity, determined by passive haemagglutination, were isolated by Sephadex G-200 filtration and DEAE-cellulose chromatography, from the serum of penguins (Pygoscelis adeliae) inoculated with dinitrophenylated human gamma-globulin. Immunoelectrophoresis and immunodiffusion showed that all these proteins exhibited both their own and shared antigenic determinants. On account of their electrophoretic mobility, elution conditions and characteristics of the precipitation arcs, they have been tentatively denominated IgG2 (gamma2), IgG1 (gamma1), IgM (gammam) and IgX (probably IgA).