Estudo morfológico e imunoistoquímico das anomalias vasculares da infância / Morphological and immunohistochemical study of vascular anomalies of infancy and childhood

RESUMO

Os hemangiomas e linfangiomas são anomalias vasculares (AV) com grande diversidade clínica, algumas lesões são transitórias, outras permanentes. Na classificação clínica, as AV transitórias são os hemangiomas fragiformes e tuberosos, e as permanentes são os hemangiomas planos, cavernosos e os linfangiomas. A classificação biológica divide as anomalias vasculares em dois grupos os hemangiomas proliferativos (HP) e as más-formações vasculares (MF). O padrão morfológico nem sempre identifica o tipo de AV e, recentemente, o marcador GLUT1 (erythrocyte-type glucose transporter protein) foi relatatado como positivo em todas as fases de evolução dos HP e negativo nas MF... Os HP respondem ao tratamento sistêmico (corticóide e/ou interferon alfa), recomendado para as casos complicados, cujas características comprometem funções e ameaçam a vida. A resposta ao tratamento não é mensurada com parâmetros clínicos, dificultando a análise de protocolos terapêuticos e a comparação de resultados. O presente trabalho estudou retrospectivamente as características morfológicas e imunoistoquímicas de 262 casos operados no Hospital do Câncer, no período de 1988 a 2004, com diagnósticos de HP (126) e MF (136), revisando a morfologia e usando marcadores imunoistoquímicos. Os HP foram positivos para GLUT1 em 80,5%, enquanto as MF foram negativas em 99,3% (p<0,001)... A apoptose foi analisada em 36 casos de HP, pela técnica de TUNEL. A porcentagem média de células em apoptose foi de 21,5% para os 22 pacientes não tratados e 57,7% para os 14 tratados com corticóide e/ou interferon alfa, p(Mann-Whitney)=0,004, concluindo que o tratamento sistêmico deve induzir a regressão precoce dos hemangioma proliferativos...

ABSTRACT

Hemangiomas and lymphangiomas are vascular anomalies (VA) that present with a large clinicai diversity. Some of them are transitory, whereas others are permanent. Clinically, transitory VA are classified as fragiform and tuberous hemangiomas, and permanent VA are flat and cavernous hemangiomas and lymphangiomas. According to their biological classification, VA are divided into two groups proliferative hemangiomas (PH) as transitory lesions and vascular malformation (VM) as permanent lesions. Morphologically, it is not always possible to identify the type of VA. Recently, the GLUT1 (erythrocyte-type glucose transporter protein) marker has been found positive in the majority of lesion phases in PH and negative in VM. Treatment of AV depends on several factors but the diagnosis of the type of lesion is determinant to decide on the best therapeutic modality. PH are sensitive to systemic treatment (steroids and/ or alpha interferon), which is recommended for complicated cases that present with characteristics that impair body functions and threaten patients' life. Systemic treatment response cannot be clinically measured, which makes it difficult analyze protocols and compare results. We retrospectively analyzed morphological and immunohistochemical characteristics of 262 patients diagnosed with PH (n = 126) and VM (n = 136) who underwent surgery at Centro de Tratamento e Pesquisa Hospital do Câncer A. C. Camargo, São Paulo, Brazil, from 1988 to 2004. There was correlation between GLUt1 and Ki-67 markers (p < 0.001). PH were positive for GLUT1 in 80.6°/o, whereas VM were negative in 99.3°/o (p < 0.001). Divergence was found among clinicai diagnosis, morphology, and GLUT1 response, which was crucial in order to define diagnosis. PH presented with 3.6o/o of mean positivity rate for Ki-67 (proliferation marker) and 1.94o/o for VM (p < 0.001). In 118 cases of PH we could analyze the immunoreactivity for angiogenesis and apoptosis markers. VEGF (vascular endothelial growth Jacto r) and NOS3 ( endothelial nitric oxide synthase) angiogenic markers, as well as apoptosis inhibitor Bcl-X and pro-apoptosis Bax, Bak, FAS, FAS-L were positive in almost ali cases, whereas proapoptosis p53 and caspase-3 were partially positive (39o/o and 17o/o, respectively). There was no positivity for apoptosis inhibitor apBcl-2. There was no correlation between immunoreactivity to such markers and previous systemic treatment. Apoptosis was analyzed in 36 cases of PH using the TUNEL technique. Mean percentage of cells in apoptosis was 21.5o/o for 22 non-treated cases and 57.7°/o for 14 others previously treated with steroids and/ or alpha interferon, p(Mann-Whitney) = 0.004. GLUT1 marker was found reliable to diagnose proliferative hemangiomas. Proapoptosis molecules were confirmed to have participation in the pathogenesis of such lesions. We conclude that treatment may induce early regression of the PH (AU)