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Recently, a low-level somatic mutation in the NRAS gene (c.182 A > G, Q61R) was identified in various specimens from patients with kaposiform lymphangiomatosis. However, it is unknown how these low-frequency mutated cells can affect the characterization and surrounding environment of their lesions. To understand the pathogenesis and association of these gene abnormalities, we established NRASQ61R mutated lymphatic endothelial cells transfected with lentivirus vector and undertook morphological and functional characterization, protein expression profiling, and metabolome analysis. NRASQ61R human dermal lymphatic endothelial cells showed poor tube formation, a low proliferation rate, and high migration ability, with an increase in the ratio of mutated cells. An analysis of signaling pathways showed inactivation of the PIK3/AKT/mTOR pathway and hyperactivation of the RAS/MAPK/ERK pathway, which was improved by MAPK kinase (MEK) inhibitor treatment. This study shows the theoretical circumstances induced in vitro by NRASQ61R-mutated cells in the affected lesions of kaposiform lymphangiomatosis patients.
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Células Endoteliales , GTP Fosfohidrolasas , Proteínas de la Membrana , Mutación , Humanos , Células Endoteliales/metabolismo , Células Endoteliales/patología , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proliferación Celular/genética , Transducción de Señal/genética , Movimiento Celular/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genéticaRESUMEN
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.
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Células Endoteliales , Linfangiogénesis , Vasos Linfáticos , Animales , Ratones , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patología , Vasos Linfáticos/embriología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Linfangiogénesis/genética , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Mutación , Morfogénesis/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Humanos , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/genética , Embrión de Mamíferos/metabolismo , Proteínas de Homeodominio , Proteínas Supresoras de TumorRESUMEN
INTRODUCTION AND IMPORTANCE: The Kasabach-Merritt Phenomenon (KMP), characterized by thrombocytopenia and consumptive coagulopathy due to endothelial cell growth in the infantile vascular tumor kaposiform hemangioendothelioma, presents a therapeutic challenge. This case highlights the novel use of sirolimus in a neonate, an approach less explored in this age group. CASE PRESENTATION: A female neonate presented with a right anterior chest mass, progressing to respiratory distress and congestive heart failure. Diagnosed with KMP, she exhibited low platelet count and coagulation abnormalities. Treatment with sirolimus (0.06 mg/day) led to mass reduction, improved bleeding, and a stable tumor after 12 months, without side effects. This case contrasts with existing literature advocating for combination therapy or higher sirolimus concentrations for effective treatment. Yet, our patient achieved favorable outcomes with low-dose monotherapy, suggesting a potentially safer approach in neonates with immature hepatic and renal metabolism. CLINICAL DISCUSSION: This case demonstrates the efficacy of low-dose sirolimus monotherapy in treating KMP in a neonate, challenging current preferences for combination therapies or higher doses. It emphasizes the need for further research into age-specific treatment protocols in KMP, considering the unique metabolic profiles of neonates and infants. CONCLUSION: Sirolimus has demonstrated potential in treating KMP in pediatric patients. While initial results are promising, determining optimal dosages and trough concentrations, especially in neonates and infants, remains essential.
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Introduction: Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham-Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs. Methods: This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5-15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration. Results: Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham-Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4-83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable. Conclusion: Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.
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Venous malformations (VMs) are the most common vascular malformations. TEK and PIK3CA are the causal genes of VMs, and may be involved in the PI3K/AKT pathway. However, the downstream mechanisms underlying the TEK or PIK3CA mutations in VMs are not completely understood. This study aimed to identify a possible association between genetic mutations and clinicopathological features. A retrospective clinical, pathological, and genetic study of 114 patients with VMs was performed. TEK, PIK3CA, and combined TEK/PIK3CA mutations were identified in 49 (43%), 13 (11.4%), and 2 (1.75%) patients, respectively. TEK-mutant VMs more commonly occurred in younger patients than TEK and PIK3CA mutation-negative VMs (other-mutant VMs), and showed more frequent skin involvement and no lymphocytic aggregates. No significant differences were observed in sex, location of occurrence, malformed vessel size, vessel density, or thickness of the vascular smooth muscle among the VM genotypes. Immunohistochemical analysis revealed that the expression levels of phosphorylated AKT (p-AKT) were higher in the TEK-mutant VMs than those in PIK3CA-mutant and other-mutant VMs. The expression levels of p-mTOR and its downstream effectors were higher in all the VM genotypes than those in normal vessels. Spatial transcriptomics revealed that the genes involved in "blood vessel development", "positive regulation of cell migration", and "extracellular matrix organization" were up-regulated in a TEK-mutant VM. Significant genotype-phenotype correlations in clinical and pathological features were observed among the VM genotypes, indicating gene-specific effects. Detailed analysis of gene-specific effects in VMs may offer insights into the underlying molecular pathways and implications for targeted therapies.
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Proteínas Proto-Oncogénicas c-akt , Malformaciones Vasculares , Humanos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estudios Retrospectivos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Malformaciones Vasculares/genética , Malformaciones Vasculares/patología , Mutación , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , GenómicaRESUMEN
Haematopoietic stem-cell transplantation (HSCT)-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with high mortality. Accumulating evidence suggests that complement dysregulation is potentially involved in the development of HSCT-TMA. We retrospectively analysed the clinical characteristics and outcomes of thirteen paediatric patients who were diagnosed with atypical haemolytic uremic syndrome and treated with eculizumab to manage HSCT-TMA during post-marketing surveillance in Japan. The median time from HSCT to TMA was 31 days (Interquartile range, IQR;21-58) and the median doses of eculizumab was three (IQR;2-5). Seven patients (54%) were alive at the last follow-up while six died due to complications related to HSCT. Six of seven survivors initiated eculizumab after insufficient response to plasma therapy. Following eculizumab treatment, median platelet counts and LDH levels in all survivors significantly improved and renal function improved in 4/7 patients. All survivors possessed potential risk factors of complement overactivation. During the follow-up period after eculizumab discontinuation (median;111.5 days, IQR;95-555), no TMA recurrence was observed. In this analysis, eculizumab showed benefit in over half of this paediatric patient population. Ongoing clinical studies are expected to optimize the treatment regimen of terminal complement pathway inhibitor, and it may become a therapeutic option for paediatric HSCT-TMA in the future.
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Anticuerpos Monoclonales Humanizados , Trasplante de Células Madre Hematopoyéticas , Microangiopatías Trombóticas , Niño , Humanos , Japón , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inactivadores del Complemento/efectos adversos , Microangiopatías Trombóticas/tratamiento farmacológico , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/diagnóstico , Vigilancia de Productos ComercializadosRESUMEN
Background: The natural history of venous malformation (VM) and Klippel-Trenaunay Syndrome (KTS) has not been quantitatively studied. To obtain benchmarks to guide designing clinical trials to assess safety and efficacy of novel drug candidates, the clinical course of the patients was followed for 6 months. Methods and Results: This is a multicenter prospective observational study evaluating the change rate in lesion volume from baseline with magnetic resonance images, as the primary endpoint. In addition, disease severities, performance status (PS), pain visual analog scale (VAS) score, quality of life (QoL), infections, and coagulation markers were also evaluated. Thirty-four patients (VM = 17, KTS = 17, 1-53 of age; median 15.9 years) with measurable lesion volume were analyzed. There was no statistically significant difference in the lesion volume between baseline and day 180, and the mean change rate (standard deviation) was 1.06 (0.28). There were no baseline characteristics that affected the change in lesion volume over 6 months. However, there were patients who showed more than 20% volume change and it was suggested that the lesion volume was largely impacted by local infection. There were no statistically significant changes in pain VAS score, severity, PS, QoL score, D-dimer, and platelet count over 6 months within all patients analyzed. Conclusion: The results showed the representative natural course of VM and KTS for a 6-month period with objective change of lesion volume and other factors, suggesting that it is scientifically reasonable to conduct a Phase 2 proof-of-concept study without a placebo arm, using the results of this study as the control. Clinical Trial Registration: NCT04285723, NCT04589650.
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Síndrome de Klippel-Trenaunay-Weber , Malformaciones Vasculares , Humanos , Síndrome de Klippel-Trenaunay-Weber/diagnóstico , Síndrome de Klippel-Trenaunay-Weber/diagnóstico por imagen , Dolor , Estudios Prospectivos , Calidad de Vida , Malformaciones Vasculares/diagnóstico , Malformaciones Vasculares/diagnóstico por imagen , Ensayos Clínicos como AsuntoRESUMEN
Introduction: Acute acquired comitant esotropia (AACE) is an acquired strabismus with uncrossed sudden-onset diplopia due to esodeviation, comitant esotropia without accommodation factor, or paretic eye movement. The diagnosis of AACE entails differentiation from incomitant esotropia caused by abnormalities in the central nervous system. We present 2 pediatric patients with AACE as the first symptom of brainstem tumor. Case Presentation: The 2 patients were aware of their diplopia and had no other neurological abnormalities. There were no special findings in the anterior segment, ocular media, or fundus. Esotropia with a difference of no more than 10Δ between distant and near fixations was observed. Eye movements were normal, and Hess red-green test under prism neutralization did not reveal abduction restriction. The presumed cause of AACE in both patients was excessive use of digital displays, and brain magnetic resonance imaging (MRI) was performed to confirm the absence of neurological abnormality. Using MRI, a definitive diagnosis of AACE was made based on comitant esotropia associated with diffuse median glioma and medullary pilocytic astrocytoma without abducens nerve palsy. Conclusion: Although the incidence of AACE caused by brainstem tumors may be low, it is necessary to perform head imaging to confirm etiology. Furthermore, Hess red-green test under prism neutralization is considered important for the differentiation of abducens nerve palsy.
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BACKGROUND: Transient abnormal myelopoiesis (TAM) is characterized by leukocytosis with increased circulating megakaryoblasts that harbor N-terminal truncating mutations in the GATA1 gene. Approximately 10% of affected patients experience early death. OBSERVATIONS: A 2-month-old boy with Down syndrome was diagnosed with TAM and followed without treatment. Although the blasts in the peripheral blood disappeared, liver failure progressed. A pathological examination revealed liver fibrosis, and double-immunostaining for full-length GATA1 and CD42b identified megakaryocytes with a GATA1 mutation. CONCLUSIONS: This simple and cost-effective method can be applied in routine practice to detect TAM blasts during assessment in a TAM crisis.
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Síndrome de Down , Masculino , Humanos , Lactante , Leucocitos , Biopsia , Hígado , Factor de Transcripción GATA1RESUMEN
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.
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Trastornos de la Coagulación Sanguínea , Trombocitopenia , Lactante , Humanos , Masculino , Trombocitopenia/complicaciones , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/diagnóstico , Hemorragia Gastrointestinal/complicaciones , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Sirolimus/uso terapéutico , Prednisolona/uso terapéuticoRESUMEN
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.
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Fosfatidilinositol 3-Quinasas , Malformaciones Vasculares , Humanos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Malformaciones Vasculares/genética , Malformaciones Vasculares/metabolismo , Malformaciones Vasculares/patología , Secuenciación de Nucleótidos de Alto Rendimiento , MutaciónRESUMEN
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.
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Hemangioma Capilar , Hemangioma , Hipoglucemia , Neoplasias Cutáneas , Antagonistas Adrenérgicos beta/efectos adversos , Niño , Femenino , Hemangioma/tratamiento farmacológico , Hemangioma Capilar/tratamiento farmacológico , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/uso terapéutico , Lactante , Propranolol/efectos adversos , Estudios Retrospectivos , Convulsiones/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Resultado del TratamientoAsunto(s)
Hemangioendotelioma , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Hemangioendotelioma/diagnóstico , Hemangioendotelioma/tratamiento farmacológico , Humanos , Síndrome de Kasabach-Merritt/diagnóstico , Síndrome de Kasabach-Merritt/tratamiento farmacológico , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/tratamiento farmacológico , Sirolimus/uso terapéuticoRESUMEN
RATIONALE: McCune-Albright syndrome (MAS) is a rare disorder characterized by clinical findings, which includes fibrous dysplasia (FD). FD is a benign tumor that leads to increased rates of bone fracture. In some MAS cases with FD, facial deformities, severe pain, and orbital neuropathies are complicated. Aneurysmal bone cyst (ABC) is a benign bone tumor and rare complication of FD. PATIENT CONCERNS: A 9-year-old boy was admitted to our hospital because of acute visual disturbance. DIAGNOSIS AND INTERVENTIONS: The patient was clinically diagnosed as ABC complicated with MAS, and he underwent surgery. OUTCOMES: After the surgery, his sight became normal. Recurrence of ABC and visual disturbance was not observed in 3âyears. Genetic analysis of a tissue sample from the ABC lesion by next-generation sequencing revealed a somatic activating GNAS mutation. LESSONS: To the best of our knowledge, this is the first case report of MAS causing optic neuropathy complicated with ABC. ABC complicated with MAS is extremely rare, but it should be considered as a possible diagnosis in patients with acute visual loss and facial swelling. In addition, our case had OAS, which is an uncommon syndrome and a rare complication in ABC with MAS, and rapid decompression of the ABC was effective in improving the patient's eyesight.
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Quistes Óseos Aneurismáticos/complicaciones , Displasia Fibrosa Ósea/complicaciones , Enfermedades del Nervio Óptico/diagnóstico , Trastornos de la Visión/etiología , Niño , Cromograninas , Displasia Fibrosa Poliostótica/complicaciones , Displasia Fibrosa Poliostótica/genética , Subunidades alfa de la Proteína de Unión al GTP Gs , Pruebas Genéticas , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades del Nervio Óptico/complicacionesRESUMEN
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.
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Cordoma , Neuroblastoma , Tumor Rabdoide , Teratoma , Femenino , Niño , Humanos , Preescolar , Cordoma/genética , Cordoma/diagnóstico , Proteína SMARCB1/genética , Tumor Rabdoide/diagnóstico , Fosa Craneal Posterior/metabolismo , Biomarcadores de TumorRESUMEN
BACKGROUND: Fibro-adipose vascular anomaly (FAVA) is a rare and new entity of vascular anomaly. Activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene were identified at a frequency of 62.5% in FAVA cases. The PIK3CA mutations excessively activate mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis, implying that PIK3CA mutations may act as drivers of FAVAs. This study investigated the correlations between PIK3CA mutational status, clinicopathological features and immunohistochemical expression of the mTOR pathway in a series of FAVA. METHODS: We retrospectively evaluated the clinical and pathological findings of four FAVA cases. We performed next-generation sequencing (NGS) with a custom panel of genes associated with the mTOR pathway and genes responsible for other vascular anomalies; followed by direct sequencing and immunohistochemical analysis of the mTOR pathway. RESULTS: Two PIK3CA-mutation cases and two PIK3CA-wild-type (wt) cases exhibited similar typical clinical features of FAVA. Histological analysis revealed venous malformation, lymphatic malformation, nerves containing enlarged abnormal vessels and fibrofatty tissue were observed regardless of PIK3CA mutational status. In contrast to clinical and histological findings, the immunohistochemical expression of activated AKT and mTOR that are upstream of the mTOR pathway was detected in abnormal vessels of PIK3CA-mutation cases but not in those of PIK3CA-wt cases. However, activated eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1), both of which are downstream effectors of the mTOR pathway, were expressed in abnormal vessels of both PIK3CA-mutation and PIK3CA-wt cases. Furthermore, targeting NGS did not find any common genetic mutations involved in the mTOR pathway among PIK3CA-wt cases. CONCLUSIONS: There was no significant association between the presence of PIK3CA mutations and the clinicopathological features of FAVA, suggesting that the PIK3CA gene is not necessarily involved in the onset of FAVA. FAVAs lacking PIK3CA mutations may be caused by other gene mutations that activate 4EBP1 and S6K1.
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Fosfatidilinositol 3-Quinasa Clase I , Serina-Treonina Quinasas TOR , Malformaciones Vasculares , Fosfatidilinositol 3-Quinasa Clase I/genética , Humanos , Mutación , Proteínas Proto-Oncogénicas c-akt/genética , Estudios Retrospectivos , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Malformaciones Vasculares/genéticaRESUMEN
OBJECTIVES: This study aimed to evaluate the CT and MRI findings of focal splenic lesions and ascites in generalized lymphatic anomaly (GLA), kaposiform lymphangiomatosis (KLA), and Gorham-Stout disease (GSD). MATERIAL AND METHODS: Twenty-three patients (10 with GLA, 5 with KLA, and 8 with GSD) who underwent abdominal CT and/or MRI before treatment were included in this study, and their imaging findings were retrospectively evaluated. RESULTS: Focal splenic lesions were observed in nine patients; these lesions were observed frequently in GLA (n = 5; 50%) or KLA (n = 3; 60%) compared with GSD (n = 1; 13%); however, no significant differences were found between the three groups (P = 0.190). On CT images among eight patients (4 with GLA, 3 with KLA, and 1 with GSD) with focal splenic lesions who underwent CT, the number of focal splenic lesions per patient ranged from 2 to 189 (mean, 42) and the maximum diameter of focal splenic lesions ranged from 2 to 39 mm (mean, 8 mm), while more than 30 focal splenic lesions per patient were observed in 2 (50%) GLA and focal splenic lesions with maximum diameters of ≥10 mm were observed in 4 (100%) GLA but not in KLA or GSD. Ascites was observed in five patients; significant differences were observed among KLA (n = 4; 80%), GLA (n = 1; 10%), and GSD (n = 0; 0%) (P < 0.01). Ascites was significantly more frequent in KLA than in GSD (P < 0.05). CONCLUSION: More than 30 focal splenic lesions per patient and/or focal splenic lesions with maximum diameters of ≥10 mm were observed only in GLA. Focal splenic lesions tended to be less frequent in GSD, whereas ascites tended to be frequent in KLA.