RESUMO
The term PROS (PIK3CA-Related Overgrowth Spectrum) indicates a wide spectrum of overgrowth disorders related to somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) pathway. We present three cases with PIK3CA mutation and clinical characteristics encompassing MCAP (megalencephaly-capillary malformation) condition but lacking all criteria to a certain diagnosis, most of all showing prevalent and peculiar involvement of cerebellar structures at MRI (magnetic resonance imaging) mainly consisting in cortical rim thickening and abnormal orientation of folia axis. These cases expand the spectrum of intracranial MRI features in PIK3CA disorders.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Megalencefalia/genética , Mutação/genética , Malformações do Sistema Nervoso/genética , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , FenótipoRESUMO
AIMS: Vascular malformations (vMs) encompass a wide range of diseases often associated with somatic or, more rarely, germinal genetic mutations. A mutation in the PIK3Ca/mTOR pathway is more often involved in various vMs. CD10 and CD34 are cellular markers that may play a role in mesenchymal differentiation and proliferation. The aim of our study was to find a possible link between the immunohistochemical expression of CD10 and CD34 in vMs and their relationship with mutations in the PIK3CA/mTOR signaling pathway. METHODS AND RESULTS: Our study on 58 samples of vMs showed that in endothelial cells, CD10 was significantly expressed in PIK3CA-mutated samples compared with samples without any mutation (p < 0.05), especially and even more consistently when compared with samples with mutation in other pathways (p < 0.0001). Conversely, in the same PIK3CA-mutated samples, CD34 expression in endothelial cells was significantly reduced compared with samples either without any mutation or mutations in other pathways (p < 0.05 and p < 0.0005). Compared with samples with mutations in other pathways, a significant overexpression of endothelial CD10 was also found in samples with TEK/TIE2 mutation, a gene linked to the PIK3CA/mTOR pathway (p < 0.01). However, CD34 expression was not altered. In samples with PIK3CA mutation, the CD10 expression was significantly increased in the stroma compared with samples with TEK/TIE2 gene or other gene mutations (p < 0.05). CONCLUSION: Therefore, the CD10 and CD34 immunohistochemical profile could suggest/support the presence of mutations in the PIK3CA/mTOR pathway in samples of vMs.
Assuntos
Antígenos CD34/análise , Classe I de Fosfatidilinositol 3-Quinases/genética , Células Endoteliais/química , Mutação , Neprilisina/análise , Receptor TIE-2/genética , Malformações Vasculares/genética , Malformações Vasculares/metabolismo , Adolescente , Adulto , Biomarcadores/análise , Criança , Pré-Escolar , Análise Mutacional de DNA , Células Endoteliais/patologia , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Lactente , Masculino , Fenótipo , Malformações Vasculares/patologia , Adulto JovemRESUMO
BACKGROUND/PURPOSE: Surgical excision of critical infantile haemangiomas (HMs) is usually delayed until intralesional blood flow spontaneously decreases, but fibrofatty tissue and exuberant skin invariably remain even after total involution. The aim of this study was to describe 2 surgical techniques used for early excision in 50 selected cases of HM defined critical in site or size. METHODS: Among a total of 952 patients affected by HM observed from 1999 to 2005, 50 children (5.2%) were submitted to early surgical removal of the tumour (age range, 6-24 months). In group 1, a technique of lenticular incision and linear closure was used in 34 patients using an original clamp for haemostasis during excision. In group 2, a modified round-block excision and purse-string closure technique was performed in 16 patients. RESULTS: Only 2 patients required transfusion to replace intraoperative blood losses. Infection, delayed wound healing, and cheloids occurred in 3 patients in group 2. Satisfactory cosmetic results have been observed in most cases in both groups at a follow-up ranging from 6 months to 6 years. CONCLUSIONS: The range of indications for early surgical removal of critical HM might be enlarged to achieve earlier the better cosmetic results. A few surgical tricks can minimize intraoperative bleeding and optimise the surgical scar.