Meduloblastoma: de la clasificación histológica a la molecular / Medulloblastoma: from histological to molecular classification / Meduloblastoma: da classificação histológica à molecular

El meduloblastoma es un tumor frecuente en la población pediátrica, pero es raro en pacientes adultos. Es la segunda causa de muerte por cáncer en menores de 15 años. El hallazgo de una lesión tumoral cerebelosa mediana o paramediana que capta el medio de contraste y que a menudo comprime el cuarto ventrículo sugiere la presencia de este tumor. A través del uso de estudios de expresión génica y marcadores moleculares se ha generado una nueva aproximación a la clasificación del meduloblastoma. Así, se ha venido a entender el concepto de meduloblastoma no como una patología sino como un grupo de patologías distintas clínica y molecularmente. La resonancia magnética nuclear espinal y la punción lumbar deben ser realizadas en todos los pacientes como parte de la evaluación de la extensión de la enfermedad, debido a que las leptomeninges espinales son un sitio frecuente de diseminación. El tratamiento implica idealmente la interacción de un grupo interdisciplinario que pueda ofrecer al paciente: cirugía, radioterapia y quimioterapia. El pronóstico depende de variables como edad (menor de tres años), diseminación de la enfermedad, residuo tumoral posquirúrgico, variante histológica de células grandes/anaplásico, y pertenecer al grupo 3 (grupo de amplificacón del MYC).

Medulloblastoma is a common tumor in children, but is rare in adults. It is the second most common cause of cancer-related death in patients under 15 years. The presence of a median or paramedian enhancing cerebellar mass, often compressing the fourth ventricle may indicate the presence of this tumor. Genetic and molecular markers offer a new approach to the understanding and classification of medulloblastomas. Hence, we have come to understand medulloblastoma not as a sole disease but rather, as a group of clinically and molecularly distinct pathologies. Magnetic resonance imaging of the spine and lumbar puncture must be performed in all patients as part of the assessment of the extent of disease, since spinal leptomeninges are common sites for metastatic dissemination. Ideally, its treatmeant involves an interdisciplinary group that provides surgery, radiotherapy, and chemotherapy. Prognosis depends upon variables such as age (under three years), metastatic dissemination, residual tumor after surgery, large cell/anaplastic histological variant, and group 3 tumor (MYC amplification group).

O meduloblastoma é um tumor frequente na população pediátrica, mas é raro em pacientes adultos. É a segunda causa de morte por câncer em menores de 15 anos. A descoberta de uma lesão tumoral no cerebelo média ou paramedia que capta o médio de contraste e que com frequência comprime o quarto ventrículo sugere a presença deste tumor. Através do uso de estudos de expressão gênica e marcadores moleculares se há gerado uma nova aproximação à classificação do meduloblastoma. Assim, se veio entender o conceito de meduloblastoma não como uma patologia se não como um grupo de patologias diferente clínica e molecularmente. A ressonância magnética nuclear espinal e a punção lombar devem ser realizadas em todos os pacientes como parte da avaliação da extensão da doença, devido a que as leptomeninges espinais são um lugar frequente de disseminação. O tratamento implica idealmente a interação de um grupo interdisciplinar que possa oferecer ao paciente: cirurgia, radioterapia e quimioterapia. O prognóstico depende de variáveis como idade (menor de três anos), disseminação da doença, resíduo tumoral pós-cirúrgico, variante histológica de células grandes/anaplásico, e pertencer ao grupo 3 (grupo de amplificação do MYC).

Patients with a new variant of endemic pemphigus foliaceus have autoantibodies against arrector pili muscle, colocalizing with MYZAP, p0071, desmoplakins 1 and 2 and ARVCF.

BACKGROUND: We identified a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America, which we term El Bagre-EPF, and observed reactivity to arrector pili muscle (APM), thus we tested for autoimmunity to APM. METHODS: We took skin biopsies from 30 patients with El Bagre-EPF and 30 healthy controls (HCs) matched by age, sex and occupation, who were all from the endemic area, and tested these using direct immunofluorescence (DIF), confocal microscopy, immunohistochemistry and immunoblotting (IB). RESULTS: Of the 30 patients with El Bagre-EPF, 27 had autoantibodies to APM that colocalized with commercial antibodies to myocardium-enriched zonula occludens-1-associated protein (MYZAP), desmoplakin (DP)1 and DP2, plakophilin 4, and Armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) (P < 0.001, Fisher exact test). The positive staining also colocalized with Junctional Adhesion Molecule 1 (JAM-A), a control antibody for gap cell junctions. No HC samples were positive. In 27 of the 30 patients, serum that was APM-positive also displayed IB colocalization of their autoantibody molecular weights with the Progen antibodies (P < 0.001, Fisher exact test). CONCLUSIONS: Patients affected by El Bagre-EPF have autoantibodies to APM, colocalizing with the antibodies MYZAP, ARVCF, p0071, DP1 and DP2, suggesting that these molecules are El Bagre-EPF antigens. Further, all of these antigens represent components of cell junctions, indicating that the immune response is directed, at least partially, against cell junctions. The immune response in patients affected by El Bagre-EPF is polyclonal, and it includes B and T lymphocytes, mast cells, IgG, IgA, IgM, IgD, IgE, fibrinogen, albumin, complement/C1q, C3c and C4.