RESUMO
OBJECTIVE: To describe the clinical, radiologic, and histopathologic features of "congenital disseminated pyogenic granuloma" involving various organs with high morbidity related to cerebral hemorrhagic involvement. STUDY DESIGN: We searched the database of the Vascular Anomalies Center at Boston Children's Hospital from 1999 to 2019 for patients diagnosed as having multiple vascular lesions, visceral vascular tumors, congenital hemangiomatosis, multiple pyogenic granulomas, or multiple vascular lesions without a definite diagnosis. A retrospective review of the medical records, photographs, histopathologic, and imaging studies was performed. Only patients with imaging studies and histopathologic diagnosis of pyogenic granuloma were included. RESULTS: Eight children (5 male, 3 female) had congenital multifocal cutaneous vascular tumors. Lesions also were found in the brain (n = 7), liver (n = 4), spleen (n = 3), muscles (n = 4), bone (n = 3), retroperitoneum (n = 3), and intestine/mesentery (n = 2). Less commonly affected were the spinal cord, lungs, kidneys, pancreas, and adrenal gland (n = 1 each). The mean follow-up period was 21.8 months. The cerebral and visceral lesions were hemorrhagic with severe neurologic sequelae. The histopathologic diagnosis was pyogenic granuloma with prominent areas of hemorrhage and necrosis. The endothelial cells had enlarged nuclei, pale cytoplasm and were immunopositive for CD31 and negative for D2-40 and glucose transporter 1. CONCLUSIONS: Congenital disseminated pyogenic granuloma is a distinct multisystemic aggressive disorder that primarily affects the skin, brain, visceral organs, and musculoskeletal system. Differentiation of this entity from other multiple cutaneous vascular lesions is critical because of possible cerebral hemorrhagic involvement.
Assuntos
Granuloma Piogênico/congênito , Granuloma Piogênico/diagnóstico , Dermatopatias/congênito , Dermatopatias/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To define the types of hepatic hemangiomas using the updated International Society for the Study of Vascular Anomalies classification and to create a set of guidelines for their diagnostic evaluation and monitoring. STUDY DESIGN: We used a rigorous, transparent consensus protocol defined by an approved methodology, with input from multiple pediatric experts in vascular anomalies from hematology-oncology, surgery, pathology, radiology, and gastroenterology. RESULTS: In the first section, we define the subtypes of hepatic hemangiomas based on the clinical course, histology, and radiologic characteristics. We recommend against using the term "hemangioma" for any vascular malformations affecting the liver or any hypervascular tumors that are not characterized by the approved definitions. We recommend against using the term "hemangioendothelioma" for infantile or congenital hemangioma. The following 2 sections dedicated to infantile hepatic hemangioma and to congenital hepatic hemangioma individually describe these subtypes in further detail, including complications to be considered during monitoring and respectively recommended screening evaluations. CONCLUSIONS: Although institutional variations may exist for specific clinical details, a clear understanding of the diagnosis of hepatic hemangiomas affecting children and the possible complications that require screening during the monitoring period should be standard. As children with hepatic hemangiomas are managed by different medical and surgical specialties, we offer an expert opinion multidisciplinary consensus based on current literature and on data extracted from the liver hemangioma registry.
Assuntos
Hemangioma/classificação , Hemangioma/diagnóstico , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/diagnóstico , Pré-Escolar , Feminino , Hemangioendotelioma , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Programas de Rastreamento , Oncologia , Pediatria/normas , Guias de Prática Clínica como Assunto , Sistema de Registros , Ultrassonografia Doppler , Estados Unidos , Malformações Vasculares/classificação , Malformações Vasculares/diagnósticoRESUMO
OBJECTIVES: To test the hypothesis that somatic phosphatidylinositol-4,5-bisphospate 3-kinase, catalytic subunit alpha (PIK3CA) mutations would be found in patients with more common disorders including isolated lymphatic malformation (LM) and Klippel-Trenaunay syndrome (KTS). STUDY DESIGN: We used next generation sequencing, droplet digital polymerase chain reaction, and single molecule molecular inversion probes to search for somatic PIK3CA mutations in affected tissue from patients seen at Boston Children's Hospital who had an isolated LM (n = 17), KTS (n = 21), fibro-adipose vascular anomaly (n = 8), or congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (n = 33), the disorder for which we first identified somatic PIK3CA mutations. We also screened 5 of the more common PIK3CA mutations in a second cohort of patients with LM (n = 31) from Seattle Children's Hospital. RESULTS: Most individuals from Boston Children's Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), fibro-adipose vascular anomaly (5/8), and congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (31/33) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for â¼ 80% of cases. Seventy-four percent of patients with LM from Seattle Children's Hospital also were somatic mosaic for 1 of 5 specific PIK3CA mutations. Many affected tissue specimens from both cohorts contained fewer than 10% mutant cells. CONCLUSIONS: Somatic PIK3CA mutations are the most common cause of isolated LMs and disorders in which LM is a component feature. Five PIK3CA mutations account for most cases. The search for causal mutations requires sampling of affected tissues and techniques that are capable of detecting low-level somatic mosaicism because the abundance of mutant cells in a malformed tissue can be low.
Assuntos
Anormalidades Múltiplas , DNA/genética , Síndrome de Klippel-Trenaunay-Weber/genética , Anormalidades Linfáticas/genética , Mutação , Fosfatidilinositol 3-Quinases/genética , Malformações Vasculares/genética , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Síndrome de Klippel-Trenaunay-Weber/diagnóstico , Síndrome de Klippel-Trenaunay-Weber/metabolismo , Anormalidades Linfáticas/diagnóstico , Anormalidades Linfáticas/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Reação em Cadeia da Polimerase , Malformações Vasculares/diagnóstico , Malformações Vasculares/metabolismoRESUMO
OBJECTIVE: To describe the clinical and imaging characteristics of a new lymphatic disorder with a unique histological pattern and poor prognosis. STUDY DESIGN: An observational, retrospective study identified and characterized 20 patients with distinct lymphatic histopathology referred to the Vascular Anomalies Center at Boston Children's Hospital between 1995 and 2011. RESULTS: The median age at onset was 6.5 years (range, birth to 44 years). Clinical and radiologic findings suggested a generalized process. The most common presentations were respiratory symptoms (50%), hemostatic abnormalities (50%), and an enlarging, palpable mass (35%). All patients had mediastinal involvement; 19 patients developed pericardial (70%) and/or pleural effusions (85%). Extrathoracic disease manifested in bone and spleen and less frequently in abdominal viscera, peritoneum, integument, and extremities. Despite aggressive procedural and medical therapies, the 5-year survival was 51% and the overall survival was 34%. Mean interval between diagnosis and death was 2.75 years (range, 1-6.5 years). CONCLUSIONS: We describe a clinicopathologically distinct lymphatic anomaly. We propose the term kaposiform lymphangiomatosis (KLA) because of characteristic clusters or sheets of spindled lymphatic endothelial cells accompanying malformed lymphatic channels. The intrathoracic component is most commonly implicated in morbidity and mortality; however, extrathoracic disease is frequent, indicating that KLA is not restricted to pulmonary lymphatics. The mortality rate of KLA is high despite aggressive multimodal therapy.
Assuntos
Hemangioendotelioma/diagnóstico , Síndrome de Kasabach-Merritt/diagnóstico , Linfonodos/patologia , Estadiamento de Neoplasias , Sarcoma de Kaposi/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Diagnóstico Diferencial , Células Endoteliais/patologia , Feminino , Hemangioendotelioma/mortalidade , Hemangioendotelioma/terapia , Humanos , Lactente , Recém-Nascido , Síndrome de Kasabach-Merritt/mortalidade , Síndrome de Kasabach-Merritt/terapia , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Estudos Retrospectivos , Sarcoma de Kaposi/mortalidade , Sarcoma de Kaposi/terapia , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To examine the presentation characteristics of patients with Kaposiform hemangioendothelioma (KHE) to describe the spectrum of disease and risk factors for Kasabach-Merritt phenomenon (KMP). STUDY DESIGN: A retrospective review of 163 patients referred to the Vascular Anomalies Center at Children's Hospital Boston for KHE between 1991 and 2009 identified 107 patients with sufficient data for inclusion. RESULTS: The prevalence of KHE in Massachusetts is â¼0.91 case per 100000 children. KHE manifested in infancy in 93% of cases, with 60% as neonates. Common presenting features included enlarging cutaneous lesion (75%), thrombocytopenia (56%), and musculoskeletal pain or decreased function (23%). Cutaneous KHE favored the extremities, especially overlying joints. In our cohort, 71% developed KMP (11% after initial presentation), and 11% of patients lacked cutaneous findings. Retroperitoneal and intrathoracic lesions, though less common, were complicated by KMP in 85% and 100% of cases, respectively. Compared with superficial lesions, KHE infiltrating into muscle or deeper was 6.3-fold more likely to manifest KMP and 18-fold higher if retroperitoneal or intrathoracic. KHE limited to bone or presenting after infancy did not manifest KMP. CONCLUSION: An enlarging cutaneous lesion is the most common presenting feature of KHE in infancy. Older patients with KHE or those lacking cutaneous manifestations present with musculoskeletal complaints or atypical symptoms. The risk of KMP increases dramatically when tumor infiltrates muscle or when KHE arises in the retroperitoneum or mediastinum.