RESUMO
Generalized lymphatic anomaly (GLA) and kaposiform lymphangiomatosis (KLA) are rare congenital disorders that arise through anomalous embryogenesis of the lymphatic system. A somatic activating NRAS p.Q61R variant has been recently detected in GLA and KLA tissues, suggesting that the NRAS p.Q61R variant plays an important role in the development of these diseases. To address this role, we studied the effect of the NRAS p.Q61R variant in lymphatic endothelial cells (LECs) on the structure of the lymphatics during embryonic and postnatal lymphangiogenesis applying inducible, LEC-specific NRAS p.Q61R variant in mice. Lox-stop-Lox NrasQ61R mice were crossed with Prox1-CreERT2 mice expressing tamoxifen-inducible Cre recombinase specifically in LECs. Whole-mount immunostaining of embryonic back skin using an antibody against the LEC surface marker VEGFR3 showed considerably greater lymphatic vessel width in LEC-specific NRAS p.Q61R mutant embryos than in littermate controls. These mutant embryos also showed a significant reduction in the number of lymphatic vessel branches. Furthermore, immunofluorescence staining of whole-mount embryonic back skin using an antibody against the LEC-specific nuclear marker Prox1 showed a large increase in the number of LECs in LEC-specific NRAS p.Q61R mutants. In contrast, postnatal induction of the NRAS p.Q61R variant in LECs did not cause abnormal lymphatic vessel morphogenesis. These results suggest that the NRAS p.Q61R variant in LECs plays a role in development of lymphatic anomalies. While this model does not directly reflect the human pathology of GLA and KLA, there are overlapping features, suggesting that further study of this model may help in studying GLA and KLA mechanisms.
Assuntos
Células Endoteliais , Linfangiogênese , Vasos Linfáticos , Animais , Camundongos , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Vasos Linfáticos/embriologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Linfangiogênese/genética , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Mutação , Morfogênese/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Humanos , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Embrião de Mamíferos/metabolismo , Proteínas de Homeodomínio , Proteínas Supressoras de TumorRESUMO
Multifocal lymphangioendotheliomatosis with thrombocytopenia is a rare disease characterized by progressive multiple vascular lesions and is accompanied by thrombocytopenia. The precise diagnosis of this disease is frequently difficult because of the heterogeneity of the clinical symptoms. We report a case of a male infant who presented with severe thrombocytopenia induced by local inflammation. In addition, enlargement of the extremities with soft tissue and bone involvement without gastrointestinal bleeding was observed. The thrombocytopenia resolved after a combination therapy of sirolimus and prednisolone. Our finding that plasma angiopoietin-2 concentrations reflected the disease status suggests its utility as a biomarker of Multifocal lymphangioendotheliomatosis with thrombocytopenia.
Assuntos
Transtornos da Coagulação Sanguínea , Trombocitopenia , Lactente , Humanos , Masculino , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Trombocitopenia/diagnóstico , Hemorragia Gastrointestinal/complicações , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Sirolimo/uso terapêutico , Prednisolona/uso terapêuticoRESUMO
Recent studies have shown that the PI3K signaling pathway plays an important role in the pathogenesis of slow-flow vascular malformations (SFVMs). Analysis of genetic mutations has advanced our understanding of the mechanisms involved in SFVM pathogenesis and may identify new therapeutic targets. We screened for somatic variants in a cohort of patients with SFVMs using targeted next-generation sequencing. Targeted next-generation sequencing of 29 candidate genes associated with vascular anomalies or with the PI3K signaling pathway was performed on affected tissues from patients with SFVMs. Fifty-nine patients with SFVMs (venous malformations n = 21, lymphatic malformations n = 27, lymphatic venous malformations n = 1, and Klippel-Trenaunay syndrome n = 10) were included in the study. TEK and PIK3CA were the most commonly mutated genes in the study. We detected eight TEK pathogenic variants in 10 samples (16.9%) and three PIK3CA pathogenic variants in 28 samples (47.5%). In total, 37 of 59 patients (62.7%) with SFVMs harbored pathogenic variants in these three genes involved in the PI3K signaling pathway. Inhibitors of this pathway may prove useful as molecular targeted therapies for SFVMs.
Assuntos
Fosfatidilinositol 3-Quinases , Malformações Vasculares , Humanos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Malformações Vasculares/genética , Malformações Vasculares/metabolismo , Malformações Vasculares/patologia , Sequenciamento de Nucleotídeos em Larga Escala , MutaçãoRESUMO
Poorly differentiated chordoma (PDC) is a rare, aggressive subtype of chordoma. A two-year-old girl presented with cervical pain, limb paralysis and respiratory failure. Magnetic resonance imaging and positron emission tomography-computed tomography revealed a tumor compressing the pons at the clivus and osteoblastic metastatic lesions of the left upper arm and right iliac bone. Her tumors shrank substantially after treatment with chemotherapy and proton beam therapy. Our initial diagnosis was an atypical teratoma/rhabdoid tumor, but final diagnosis of PDC was made on the basis of the immunohistochemical expression of brachyury. In addition, the detection of SMARCB1/INI1 mutation confirmed the diagnosis of PDC.
Assuntos
Cordoma , Neuroblastoma , Tumor Rabdoide , Teratoma , Feminino , Criança , Humanos , Pré-Escolar , Cordoma/genética , Cordoma/diagnóstico , Proteína SMARCB1/genética , Tumor Rabdoide/diagnóstico , Fossa Craniana Posterior/metabolismo , Biomarcadores TumoraisRESUMO
BACKGROUND: Infantile hemangioma (IH), formerly termed strawberry hemangioma, is a benign vascular tumor caused by capillary endothelial cell proliferation. The tumor regresses after 1 year of age, but sequelae occur in approximately half of the patients without systemic treatment. Propranolol (PPL) is currently the first-line therapeutic agent in Japan as well as in Western countries. It is not commonly known that PPL may induce severe hypoglycemia, in addition to cardiovascular and respiratory side effects. METHODS: We retrospectively analyzed patients with severe PPL-induced hypoglycemia in the 3 years since the launch of Hemangiol®, a PPL preparation specific for IH, in Japan in 2016. RESULTS: The incidence of severe hypoglycemia and of hypoglycemic convulsions following PPL treatment was estimated to be 0.54% and 0.35%, respectively. The incidence of hypoglycemic convulsions appeared to be higher in Japan than in Western countries. Severe hypoglycemia was common in infants aged >1 year, when PPL was used for ≥6 months. Severe hypoglycemia often develops from 05:00 a.m. to 09:00 a.m. and is frequently associated with prolonged periods of fasting, poor feeding, or poor physical conditions. CONCLUSION: To avoid the risk of hypoglycemia, the treatment should be initiated by 6 months of age during the proliferative phase at the latest, and should not be extended indiscriminately beyond 1 year of age. Guardians should be advised not to administer PPL on an empty stomach, in the presence of poor feeding, or who are in poor physical condition, not to prolong fasting after PPL administration, and to monitor the child's condition immediately after he or she wakes up.
Assuntos
Hemangioma Capilar , Hemangioma , Hipoglicemia , Neoplasias Cutâneas , Antagonistas Adrenérgicos beta/efeitos adversos , Criança , Feminino , Hemangioma/tratamento farmacológico , Hemangioma Capilar/tratamento farmacológico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Lactente , Propranolol/efeitos adversos , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do TratamentoRESUMO
The loss-of-function variants of the human asparagine synthetase (ASNS) gene cause asparagine synthetase deficiency (ASNSD). Diagnosis of ASNSD requires genetic tests because a specific biochemical diagnostic for ASNSD is not available. There are a few reports describing the functional evaluation of ASNS variants. Therefore, in vitro methods are needed to evaluate the detected variants in patients. In this report, five types of human ASNS proteins (wild-type and our reported four variants: p.Leu145Ser, p.Leu247Trp, p.Val489Asp, and p.Trp541Cysfs*5) were expressed in silkworm using a baculoviral expression system. An enzymatic activity assay of ASNS was performed, and the concentration of asparagine by ninhydrin and High Performance Liquid Chromatography methods using the purified recombinant proteins was measured. We established ASNS deficient HEK293 cells using the CRISPR/Cas9 method and evaluated the growth of cells without asparagine after transduction of ASNS variants with a lentiviral expression system. The four ASNS variants displayed significantly low enzymatic activity. The ASNS deficient HEK293 cells transduced with wild-type ASNS grew without asparagine, whereas cells transduced with the variants did not grow or showed significantly slower growth than cells transduced with wild-type ASNS. Herein, we established a method for evaluating the enzymatic activity of the recombinant human ASNS variants. The results of the cell-based assay corroborated the results of the enzymatic activity. These methods should enable the evaluation of the pathogenicity of ASNS variants.
Assuntos
Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-Amida/genética , Asparagina/metabolismo , Sistemas CRISPR-Cas , Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-Amida/deficiência , Variação Genética , Células HEK293 , HumanosRESUMO
BACKGROUND: Kaposiform lymphangiomatosis (KLA) is a recently characterized systemic lymphatic anomaly. Activation of RAS/MAPK and PI3K/AKT/mTOR pathways may affect KLA pathogenesis, but the cellular basis of KLA is unclear. Abnormal-spindle endothelial cells that express lymphatic endothelial cell (LEC) markers are characteristic of KLA histopathology. This study evaluated patient-derived KLA cells to establish their morphological and biological characteristics. PROCEDURE: We established cell lines from primary KLA tissues of two patients with KLA and examined their morphological and functional characteristics, messenger RNA and protein expression profiles, gene mutations, and responses to inhibitors of the RAS/MAPK and PI3K/AKT/mTOR pathways. RESULTS: Both KLA cell lines showed spindle-shaped morphology, stained positive for podoplanin (PDPN), and exhibited impaired tube-formation properties. They expressed LEC marker PDPN and mesenchymal stem cell markers (CD90, CD105) in the absence of endothelial cell markers (CD34, CD31, VWF), per real-time polymerase chain reaction. Both mTOR inhibitor rapamycin and MEK inhibitor trametinib inhibited growth of the two cell lines. A NRAS p.Q61R variant was found in one of two independent KLA tissue samples, but not in the KLA cells (per targeted next-generation sequencing); and KLA cells with this variant had elevated AKT phosphorylation levels. ERK phosphorylation levels were undetectable in both KLA cell lines. CONCLUSIONS: Inhibition of the RAS/MAPK and PI3K/AKT/mTOR pathways may represent potential therapeutic targets in KLA. These patient-derived KLA cell lines will be useful research tools to elucidate KLA etiology, and could pave the way for basic, translational, and preclinical studies of this disease.
Assuntos
Linfangioleiomiomatose , Linfangioma , Células Endoteliais , Humanos , Sistema de Sinalização das MAP Quinases , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Proteínas rasRESUMO
Gorham-Stout disease (GSD), a rare disorder of unknown etiology, is characterized by massive osteolysis that is associated with proliferation and dilation of lymphatic vessels. Variants in cancer-associated genes have been described in complex lymphatic anomalies. To explore the pathogenesis of GSD, we performed the amplicon-based deep sequencing on 50 cancer-related genes to assay affected tissues from the six patients with GSD. In one patient, a somatic activating KRAS c.182A > G variant (p.Q61R) was detected in 1% of the tissue sample. Conversely, the mutant allele was not detected in uninvolved normal skin and blood samples. Histopathology of the patient's tissue sample showed proliferation of abnormal lymphatic and blood vascular endothelial cells, osteoclasts, and activated macrophages. The activating KRAS variant is a known 'hotspot' variant, frequently identified in several types of human cancer. This is the first report of identifying a pathogenic variant in a patient with GSD. This finding may set the stage for elucidation of pathophysiology and the development of novel therapies for GSD.
Assuntos
Predisposição Genética para Doença , Proteínas de Neoplasias/genética , Osteólise Essencial/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adolescente , Adulto , Proliferação de Células/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Osteólise Essencial/patologia , Adulto JovemRESUMO
Pleuropulmonary blastoma (PPB) is a rare, progressive, and aggressive malignant intrathoracic tumor observed during childhood. Mutations in the DICER1 gene have been considered a major etiologic factor of PPB and cause a variety of tumor types in children and young adults. We present a 3-year-old boy with type II PPB. Multimodal treatment consisting of surgery and neoadjuvant chemotherapy was effective. DICER1 mutations were examined by Sanger sequencing, microarray comparative genomic hybridization, and microsatellite markers. The results revealed that a somatic biallelic DICER1 mutation with uniparental disomy was present in the tumor tissue.
Assuntos
RNA Helicases DEAD-box/genética , Homozigoto , Neoplasias Pulmonares/genética , Mutação , Proteínas de Neoplasias/genética , Blastoma Pulmonar/genética , Ribonuclease III/genética , Pré-Escolar , Humanos , Neoplasias Pulmonares/terapia , Masculino , Blastoma Pulmonar/terapiaRESUMO
The onset of malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH) may be associated with the secretion of proinflammatory cytokines from malignant cells. We here report a patient with recurrent neuroblastoma who developed hemophagocytic lymphohistiocytosis after surgery for brain metastases and relapsed after chemotherapy. The neuroblastoma cells in the recurrent tumor were positive for tumor necrosis factor-α and interleukin-6, whereas the primary site was negative. The secretion of proinflammatory cytokines from neuroblastoma cells may have been related to the pathogenesis of M-HLH in our patients. We should pay attention to possible development of M-HLH when treating advanced neuroblastoma.
Assuntos
Interleucina-6/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Proteínas de Neoplasias/sangue , Recidiva Local de Neoplasia/sangue , Neuroblastoma/sangue , Fator de Necrose Tumoral alfa/sangue , Pré-Escolar , Feminino , Humanos , Inflamação/sangue , Linfo-Histiocitose Hemofagocítica/etiologiaRESUMO
Emerging data have suggested that sirolimus may be a treatment option for complicated vascular anomalies (VAs). The present study aimed to investigate the immunologic effects of sirolimus treatment for 6 months in patients with VAs. Blood samples obtained from the patients enrolled in 2 multicenter studies to investigate the efficacy of sirolimus for VAs before and after sirolimus treatment for 6 months were used. Data for total white blood cell count, absolute lymphocyte count, serum immunoglobulins (Igs) levels (IgG, IgA, IgM), lymphocyte proliferation assays with mitogens including phytohemagglutinin and concanavalin A, and flow cytometric analysis of lymphocyte subsets were evaluated. A total of 18 patients with VAs receiving sirolimus treatment were included in the study. Comparisons of white blood cell, absolute lymphocyte count, IgG, IgA, IgM, and reaction rates of phytohemagglutinin and concanavalin A revealed no significant differences before and after treatment. No significant differences were observed in the absolute counts of lymphocyte subtypes before and after treatment, except for regulatory T-cell counts, which were significantly decreased after treatment. Severe infections were not observed during sirolimus treatment. The immunologic parameters assessed in the present study were hardly affected by sirolimus treatment for 6 months in patients with VAs.
Assuntos
Imunossupressores/uso terapêutico , Linfócitos/imunologia , Sirolimo/uso terapêutico , Linfócitos T Reguladores/imunologia , Malformações Vasculares/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Linfócitos/efeitos dos fármacos , Masculino , Prognóstico , Linfócitos T Reguladores/efeitos dos fármacos , Malformações Vasculares/imunologia , Malformações Vasculares/patologia , Adulto JovemRESUMO
The mammalian target of rapamycin (mTOR) inhibitor sirolimus is an effective treatment for difficult-to-treat lymphatic anomalies. However, little is known about the expression of mTOR pathway components in lymphatic anomalies. Here we investigated the expression pattern of mTOR pathway components and their phosphorylated forms (mTOR, p-mTOR, 4EBP1, p-4EBP1, S6K1 and p-S6K1) in normal lymphatic vessels and lymphatic anomalies using immunohistochemistry. We studied 18 patients of lymphatic anomalies, including lymphatic malformation (LM, n = 14), Kaposiform lymphangiomatosis (KLA, n = 2) and Kaposiform hemangioendothelioma (KHE, n = 2). Normal lymphatic vessels expressed 4EBP1, S6K1 and p-S6K1, but not p-4EBP1, mTOR or p-mTOR. The mTOR was detected in all lymphatic anomalies, whereas its activation form p-mTOR was detected in half cases of KLA and KHE but not in LM. All lymphatic anomalies expressed S6K1 and its activated form p-S6K1. The expression of 4EBP1 was also found in all lymphatic anomalies, but its activation was detected in approximately half of them. The activation of mTOR was seen in tumor (KLA and KHE) but not in malformation (LM), whereas the activation of S6K1 and 4EBP1 was seen in all and half of lymphatic anomalies, respectively.
Assuntos
Doenças Linfáticas/metabolismo , Sistema Linfático/anormalidades , Sistema Linfático/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/fisiologia , Adulto JovemRESUMO
The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.
Assuntos
Hemangioma/terapia , Malformações Vasculares/terapia , Malformações Arteriovenosas/terapia , Embolização Terapêutica/métodos , Medicina Baseada em Evidências , Humanos , Terapia a Laser/métodos , Escleroterapia/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Kaposiform lymphangiomatosis (KLA) has recently been distinguished as a novel subtype of generalized lymphatic anomaly (GLA), and is characterized by foci of spindle endothelial cells amid a background of malformed lymphatic channels. The etiology of these diseases remains unknown and diagnosis is confounded by their similar clinical findings. This study aimed to clarify differences in the clinical findings and plasma cytokine profiles of GLA and KLA patients. PROCEDURE: Clinical features data of GLA and KLA patients were obtained from a national survey. Differences in clinical findings, plasma levels of cytokines, and survival were analyzed. Plasma was obtained from healthy controls and GLA and KLA patients. Thirty-six angiogenic and lymphangiogenic factors were evaluated for cytokine concentration. RESULTS: Twenty-one patients with GLA and 11 with KLA were recruited. Mediastinal masses, hemorrhagic pericardial and pleural effusion, coagulation disorders, and thrombocytopenia were more frequent in KLA than in GLA. KLA had a significantly poorer outcome than GLA (P = 0.044). Soluble VEGFR3, angiopoietin 2, HGF, soluble HER2, tenascin C, and soluble HGFR levels were higher in KLA. Notably, soluble VEGFR3 and angiopoietin 2 levels were approximately 10-fold higher than those of other molecules measured. However, soluble VEGFR1 and soluble TIE2 were lower in KLA than in GLA and the controls. CONCLUSIONS: Patients with KLA have an unfavorable prognosis and serious symptoms (hemorrhagic pleural effusion and coagulation disorders). Our data indicate that eight angiogenic cytokines might be potential biomarkers of KLA.
Assuntos
Biomarcadores Tumorais/sangue , Citocinas/sangue , Linfangioleiomiomatose , Proteínas de Neoplasias/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Linfangioleiomiomatose/sangue , Linfangioleiomiomatose/classificação , Masculino , Estudos RetrospectivosRESUMO
PURPOSE: Airway obstruction caused by lymphatic malformation (LM) in the head and neck may require a tracheostomy. We present the results of our analysis of a nationwide survey on the indications for tracheostomy in children with head and neck LM. METHODS: We analyzed data in relation to tracheostomy based on a questionnaire about 518 children with head and neck LM without mediastinal involvement. RESULTS: Tracheostomy was performed for 43 of the 518 children. Most (32/43) of these children were younger than 1 year of age and the tracheostomy was almost always performed for airway obstruction (40/43). The lesion was in contact with the airway in 32 (72%) of these children, but in only 58 (12%) of the 473 children who were managed without tracheostomy. When the maximum circumferential area of contact was compared, only 20 (27%) of 74 patients with maximum contact of less than a half-circle required tracheostomy, whereas 11 of 13 with maximum contact of more than a half-circle required tracheostomy (P = 0.0001). Six patients without airway contact required tracheostomy because of acute swelling caused by hemorrhage, infection, or both. CONCLUSIONS: Children with head and neck LM required tracheostomy to relieve airway obstruction. Tracheostomy should be considered if the lesion is in contact with the airway and surrounds more than a half-circle, and when it causes acute swelling.
Assuntos
Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/cirurgia , Cabeça , Sistema Linfático/anormalidades , Pescoço , Inquéritos e Questionários , Traqueostomia/estatística & dados numéricos , Adolescente , Obstrução das Vias Respiratórias/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Sistema Linfático/patologia , MasculinoRESUMO
Complement system dysregulation, such as complement Factor H (CFH) autoantibodies and deletions in CFH-related (CFHR) genes 3 and 1, might cause transplant-associated thrombotic microangiopathy (TA-TMA). The use of eculizumab, a terminal complement inhibitor, could be a targeted therapy for TA-TMA. We report a 1-year-old girl who developed TA-TMA, just after autologous peripheral blood stem cell transplantation in neuroblastoma therapy. Eculizumab improved TA-TMA. Investigation for the complement alternative pathway showed a heterozygous CFHR3-CFHR1 gene deletion, which is involved in complement activation. The patient might develop TA-TMA as a result of complement regulatory gene mutation.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Proteínas Sanguíneas/genética , Proteínas Inativadoras do Complemento C3b/genética , Deleção de Genes , Neuroblastoma , Transplante de Células-Tronco/efeitos adversos , Microangiopatias Trombóticas , Autoenxertos , Feminino , Heterozigoto , Humanos , Lactente , Neuroblastoma/genética , Neuroblastoma/terapia , Microangiopatias Trombóticas/tratamento farmacológico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/genéticaRESUMO
Clear cell meningiomas (CCMs) are rare subtypes of meningiomas and usually treated by maximum safely achievable tumor resection. We here present three hereditary cases with CCMs which were confirmed by Sanger sequencing of lymphocyte DNA. Gross total resection was achieved in a 5-year-old son with a spinal CCM and a 34-year-old father with a CCM in the cerebellopontine angle (CPA). For a 14-year-old daughter with CCM in the CPA, total resection was not achieved due to its large size. Early detection by screening high-risk family with CCM is strongly recommended.
Assuntos
Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Adolescente , Adulto , Criança , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/genética , Meningioma/patologia , Meningioma/cirurgia , Mutação , LinhagemRESUMO
PURPOSE: Clinical guidelines on lymphatic malformation (LM) influencing the airway have been crafted in the Research Project for Intractable Diseases. We herein report an analysis of a nationwide survey of mediastinal LM and the therapeutic recommendations. METHODS: Eighty-seven registered cases with mediastinal involvement were analyzed with a review of the literature. RESULTS: Mediastinal LM was located more often in the upper and anterior mediastinum and was found without any accompanying symptoms in 56/87 cases. Tracheostomy was required in 23/87 cases, mostly < 2 years of age (87%). All patients who needed tracheostomy had a lesion in contact with the airway, while only 55% of those without tracheostomy had contact. Tracheostomy tended to be placed more when the longer segment of the airway was in contact with the LM. Multimodal treatments were performed in 29 patients, but the lesions remained in most cases, and chylothorax, hemorrhaging, nerve palsy, and infections were noted as complications. CONCLUSIONS: In patients with mediastinal LM, tracheostomy may be necessary, especially when the lesion is extensive and contacts the airway. Extirpation of the mediastinal LM may be the only therapeutic option, but in cases with few or no symptoms, non-surgical treatment should be considered in light of potential postoperative complications.