Differential activation of MAPK and PI3K/AKT/mTOR pathways and IGF1R expression in gastrointestinal stromal tumors.

AIM: To characterize the differentially-activated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) pathways in mutant (m) and wild-type (wt) GISTs and to investigate the role of insulin-like growth factor 1 receptor (IGF1R) expression. MATERIALS AND METHODS: Ninety-nine paraffin-embedded gastrointestinal stromal tumors (GISTs) were selected. CD117, IGF1R, phospho-ERK1/2, phospho-Akt, p70S6, eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and pS6 expression were investigated using immunohistochemical methods. KIT exons 9, 11, 13 and 17 and platelet derived growth factor receptor alpha (PDGFRA) exons 12 and 18 were amplified by PCR and sequenced. RESULTS: Significant differences were found in the expression of phospho-ERK1/2 between mGISTs and wtGISTs. Complex evaluation of all PI3K/Akt/mTOR pathway markers revealed greater activation in mGISTs, particularly in PDGFRA-mutated GISTs. No significant correlation was observed between IGF1R expression and either mutational status or pathway activation. CONCLUSION: There appears to be no MAPK pathway activation in wtGISTs. Tumors harboring PDGFRA mutations tended to use the PI3K/Akt/mTOR signaling pathway. Most adult GISTs, irrespective of mutational status, displayed no IGFR1 expression; tumors positive for IGFR1 showed no preferential activation of the MAPK or AKT pathways.

Tumores del estroma gastrointestinal múltiples no metastásicos. Aspectos diferenciales / Multiple non-metastatic gastrointestinal stromal tumors. Differential features

Introducción: los tumores del estroma gastrointestinal (GIST)son neoplasias mesenquimales del tubo digestivo que generalmenteexpresan el receptor KIT (CD117) y muestran mutaciones enlos genes KIT o PDGFRA. Aunque la forma de presentación clínicahabitual es como una neoplasia mural solitaria, excepcionalmentepueden presentarse formas múltiples en el mismo o diferenteórgano.Objetivo: revisar las características morfológicas, inmunohistoquímicasy moleculares de las formas de GIST múltiples no metastásicos.Fuentes: revisión de la literatura en Medline y la propia experiencia.Conclusiones: los GIST múltiples pueden presentarse en trescontextos diferentes: lesiones espontáneas (del adulto o de la edadinfantil); síndrome familiar propio (transmitido con herencia autosómicadominante); y lesiones asociadas a síndromes específicos(tríada de Carney, síndrome de Carney-Stratakis, y neurofibromatosistipo I). Fuera de estos ámbitos, se interpreta que todo GISTmúltiple es el resultado de siembras tumorales metastásicas y, portanto, corresponde a enfermedad avanzada. Estas variantes debenser conocidas por el clínico dado las connotaciones pronósticas yterapéuticas que ello conlleva(AU)

Introduction: gastrointestinal stromal tumors (GISTs) are specific,generally KIT (CD117)-positive, mesenchymal tumors of thedigestive tract displaying KIT or PDGFRA gene mutations. Clinically,they tend to present as solitary tumors of the intestinal wall;more rarely, multiple tumors may occur in one or more organs.Objective: to review the morphological, immunohistochemicaland molecular features of multiple, non-metastatic forms ofGIST.Sources: review of the literature on Medline, and authors’own experience.Conclusions: multiples GISTs may occur in three differentcontexts: as spontaneous lesions (in both adults and children); dueto familial GIST syndrome (autosomal dominant inheritance); orin association with specific syndromes (e.g. Carney’s triad, Carney-Stratakis syndrome, type I neurofibromatosis). Outside thesecontexts, the existence of multiple GISTs is deemed to be the resultof tumor metastasis, and therefore indicative of advanced-stagedisease. Clinicians need to be aware of these variants, whoseprognosis and treatment differ(AU)

Multiple non-metastatic gastrointestinal stromal tumors. Differential features.

INTRODUCTION: gastrointestinal stromal tumors (GISTs) are specific, generally KIT (CD117)-positive, mesenchymal tumors of the digestive tract displaying KIT or PDGFRA gene mutations. Clinically, they tend to present as solitary tumors of the intestinal wall; more rarely, multiple tumors may occur in one or more organs. OBJECTIVE: to review the morphological, immunohistochemical and molecular features of multiple, non-metastatic forms of GIST. SOURCES: review of the literature on Medline, and authors own experience. CONCLUSIONS: multiples GISTs may occur in three different contexts: as spontaneous lesions (in both adults and children); due to familial GIST syndrome (autosomal dominant inheritance); or in association with specific syndromes (e.g. Carney s triad, Carney-Stratakis syndrome, type I neurofibromatosis). Outside these contexts, the existence of multiple GISTs is deemed to be the result of tumor metastasis, and therefore indicative of advanced-stage disease. Clinicians need to be aware of these variants, whose prognosis and treatment differ.

Sarcoma de Kaposi gástrico y Mycobacterium genavense / No disponible

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Carcinoma ureteral. El convidado de piedra de la patología urológica / Ureteral carcinoma. The mute in urological pathology

OBJETIVO: Si bien la citología de orina juega un importante papel en el diagnóstico de neoplasias de vías urinarias bajas, deberá ser auxiliada por otras pruebas diagnósticas en el diagnóstico de las neoplasias del tracto superior. MÉTODOS: Presentamos un caso de carcinoma urotelial de uréter sincrónico con neoplasia papilar y carcinoma in situ vesicales. RESULTADOS: La positividad persistente de estudios citológicos de orina en pacientes tratados de lesiones en vías inferiores sin evidencias de imagen de lesión a este nivel debe despertar la sospecha de lesiones de vías superiores. CONCLUSIONES: El carcinoma de uréter es una neoplasia agresiva que puede beneficiarse de un diagnóstico no tardío, acción que a su vez repercutirá en la funcionalidad del riñón homolateral (AU)

OBJECTIVE: Although urine cytology plays an important role in the diagnosis of lower urinary tract neoplasias, it should be complemented with other diagnostic tests for the diagnosis of upper urinary tract tumors. METHODS: We present one case of synchronic transitional cell carcinoma of the ureter and bladder papilary neoplasia and carcinoma in situ. RESULTS: The persistent positivity of urine cytology in patients treated for lower urinary tract lesions without evidence of lesion in that level should raise the suspicion of upper urinary tract lesions. CONCLUSIONS: Ureteral carcinoma is an aggressive neoplasia and early diagnosis may be beneficial and also have repercussions in the ipsilateral kidney function (AU)

Pseudotumor de Masson lingual: un posible falso positivo / Masson’s pseudotumor of the tongue: a possible false positive

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[Clinical features of familial Creutzfeldt-Jakob disease and the E200K mutation in Spain]. / Características clínicas de la enfermedad de Creutzfeldt-Jakob familiar y mutación E200K en España.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is an infrequent pathology affecting the central nervous system (about 1/1,000000) that has a subacute progression and, for the time being, a fatal prognosis. The familial forms account for between 5-10% of cases and one of the most frequent is that produced by the E200K mutation of prion protein gene (PRNP), which has not been reported in Spanish families although Spain is considered to be part of the expansion circuit of the mutation. CASE REPORTS: We report on a Spanish family with three cases of CJD. The disease affected three females (our patient and two paternal aunts), who started with dementia, myoclonias, gait disorders and cortical blindness at the ages of 61, 53 and 55 years. Progress in all three cases was torpid and the symptoms advanced in a short time. Results of the complementary tests that were carried out were normal, except for the electroencephalogram, which was compatible with CJD in all three cases, and the imaging tests, which revealed cortical-subcortical atrophy. A confirmatory diagnosis was reached from a biopsy, the clinical picture and the family history in the cases of the paternal aunts and from a genetic study of our patient, which confirmed the E200K mutation. CONCLUSIONS: This family confirms the presence of familial forms of CJD in Spain, more specifically the E200K mutation, and highlights the role of Spain in the possible transmission of this mutation.

Características clínicas de la enfermedad de Creutzfeldt-Jakob familiar y mutación E200K en España / Clinical features of familial Creutzfeldt-Jakob disease and the E200K mutation in Spain

Introducción. La enfermedad de Creutzfeldt-Jakob (ECJ) es una patología infrecuente del sistema nervioso central (alrededor de 1/1.000.000) que presenta una evolución subaguda y, por ahora, un pronóstico fatal. Las formas familiares suponen entre el 5-10% de los casos, y una de las más frecuentes es la producida por la mutación E200K del gen de la proteína priónica (PRNP), de la que no se han publicado casos en familias españolas, a pesar de que España se considera integrada en el circuito de expansión de la mutación. Casos clínicos. Presentamos una familia española con tres casos de ECJ. Las enfermas eran tres mujeres (nuestra paciente y dos tías paternas) que comenzaron a edades de 61, 53 y 55 años con demencia, mioclonías, alteraciones de la marcha y ceguera cortical. La evolución en todas ellas fue tórpida, con una progresión de los síntomas en poco tiempo. Las pruebas complementarias realizadas estaban dentro de la normalidad, salvo el electroencefalograma, que en los tres casos fue compatible con la ECJ, y las pruebas de imagen, que mostraban una atrofia corticosubcortical. El diagnóstico de confirmación se hizo por biopsia, clínica y antecedentes familiares en los casos de las tías paternas y por estudio genético en nuestra paciente, que confirmó la mutación E200K. Conclusiones. Esta familia confirma la presencia de formas familiares de la ECJ en España, en concreto de la mutación E200K, y refuerza el papel de España en la posible transmisión de esta mutación

INTRODUCTION. Creutzfeldt-Jakob disease (CJD) is an infrequent pathology affecting the central nervous system (about 1/1 000 000) that has a subacute progression and, for the time being, a fatal prognosis. The familial forms account for between 5-10% of cases and one of the most frequent is that produced by the E200K mutation of prion protein gene (PRNP), which has not been reported in Spanish families although Spain is considered to be part of the expansion circuit of the mutation. CASE REPORTS. We report on a Spanish family with three cases of CJD. The disease affected three females (our patient and two paternal aunts), who started with dementia, myoclonias, gait disorders and cortical blindness at the ages of 61, 53 and 55 years. Progress in all three cases was torpid and the symptoms advanced in a short time. Results of the complementary tests that were carried out were normal, except for the electroencephalogram, which was compatible with CJD in all three cases, and the imaging tests, which revealed cortical-subcortical atrophy. A confirmatory diagnosis was reached from a biopsy, the clinical picture and the family history in the cases of the paternal aunts and from a genetic study of our patient, which confirmed the E200K mutation. CONCLUSIONS. This family confirms the presence of familial forms of CJD in Spain, more specifically the E200K mutation, and highlights the role of Spain in the possible transmission of this mutation

[Ureteral carcinoma. The mute in urological pathology]. / Carcinoma ureteral. El convidado de piedra de la patología urológica.

OBJECTIVE: Although urine cytology plays an important role in the diagnosis of lower urinary tract neoplasias, it should be complemented with other diagnostic tests for the diagnosis of upper urinary tract tumors. METHODS: We present one case of synchronic transitional cell carcinoma of the ureter and bladder papilary neoplasia and carcinoma in situ. RESULTS: The persistent positivity of urine cytology in patients treated for lower urinary tract lesions without evidence of lesion in that level should raise the suspicion of upper urinary tract lesions. CONCLUSIONS: Ureteral carcinoma is an aggressive neoplasia and early diagnosis may be beneficial and also have repercussions in the ipsilateral kidney function.

Nota sobre la interpretación de diagnósticos de PAAF de mama / No disponible

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Adenoma pleomorfo intraoral / Intraoral Pleomorphic Adenoma

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