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1.
Semin Pediatr Surg ; 33(3): 151422, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38833763

ABSTRACT

The lymphatic system is one of the most essential and complex systems in the human body. Disorders that affect the development or function of the lymphatic system can lead to multi-system complications and life-long morbidity. The past two decades have seen remarkable progress in our knowledge of the basic biology and function of the lymphatic system, the molecular regulators of lymphatic development, and description of disorders associated with disrupted lymphangiogensis. In this chapter we will touch on the clinical features of complex lymphatic anomalies, new molecular knowledge of the drivers of these disorders, and novel developmental therapeutics for lymphatic disease.

2.
Pediatr Blood Cancer ; 71(7): e31032, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38711167

ABSTRACT

BACKGROUND: Angiopoietin-2 (Ang-2) is increased in the blood of patients with kaposiform lymphangiomatosis (KLA) and kaposiform hemangioendothelioma (KHE). While the genetic causes of KHE are not clear, a somatic activating NRASQ61R mutation has been found in the lesions of KLA patients. PROCEDURE: Our study tested the hypothesis that the NRASQ61R mutation drives elevated Ang-2 expression in endothelial cells. Ang-2 was measured in human endothelial progenitor cells (EPC) expressing NRASQ61R and a genetic mouse model with endothelial targeted NRASQ61R. To determine the signaling pathways driving Ang-2, NRASQ61R EPC were treated with signaling pathway inhibitors. RESULTS: Ang-2 levels were increased in EPC expressing NRASQ61R compared to NRASWT by Western blot analysis of cell lysates and ELISA of the cell culture media. Ang-2 levels were elevated in the blood of NRASQ61R mutant mice. NRASQ61R mutant mice also had reduced platelet counts and splenomegaly with hypervascular lesions, like some KLA patients. mTOR inhibitor rapamycin attenuated Ang-2 expression by NRASQ61R EPC. However, MEK1/2 inhibitor trametinib was more effective blocking increases in Ang-2. CONCLUSIONS: Our studies show that the NRASQ61R mutation in endothelial cells induces Ang-2 expression in vitro and in vivo. In cultured human endothelial cells, NRASQ61R drives elevated Ang-2 through MAP kinase and mTOR-dependent signaling pathways.


Subject(s)
Angiopoietin-2 , Membrane Proteins , Animals , Humans , Angiopoietin-2/genetics , Angiopoietin-2/metabolism , Mice , Membrane Proteins/genetics , Membrane Proteins/metabolism , GTP Phosphohydrolases/genetics , GTP Phosphohydrolases/metabolism , Disease Models, Animal , Endothelial Cells/metabolism , Mutation , Signal Transduction , Mice, Transgenic
3.
Am J Med Genet A ; 194(1): 64-69, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37705207

ABSTRACT

Turner syndrome (45,X) is caused by a complete or partial absence of a single X chromosome. Vascular malformations occur due to abnormal development of blood and/or lymphatic vessels. They arise from either somatic or germline pathogenic variants in the genes regulating growth and apoptosis of vascular channels. Aortic abnormalities are a common, known vascular anomaly of Turner syndrome. However, previous studies have described other vascular malformations as a rare feature of Turner syndrome and suggested that vascular abnormalities in individuals with Turner syndrome may be more generalized. In this study, we describe two individuals with co-occurrence of Turner syndrome and vascular malformations with a lymphatic component. In these individuals, genetic testing of the lesional tissue revealed a somatic pathogenic variant in PIK3CA-a known and common cause of lymphatic malformations. Based on this finding, we conclude that the vascular malformations presented here and likely those previously in the literature are not a rare part of the clinical spectrum of Turner syndrome, but rather a separate clinical entity that may or may not co-occur in individuals with Turner syndrome.


Subject(s)
Cardiovascular Abnormalities , Lymphatic Abnormalities , Turner Syndrome , Vascular Malformations , Humans , Turner Syndrome/complications , Turner Syndrome/genetics , Mosaicism , Lymphatic Abnormalities/genetics , Vascular Malformations/complications , Vascular Malformations/genetics , Class I Phosphatidylinositol 3-Kinases/genetics
4.
Pediatr Blood Cancer ; 71(3): e30779, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38073018

ABSTRACT

BACKGROUND AND OBJECTIVES: Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first-line therapy in the absence of available prospective clinical trials. METHODS: Patients from 17 institutions diagnosed with KHE/TA between 2005 and 2020 with more than 6 months of follow-up were included. Response rates to sirolimus and vincristine were compared at 3 and 6 months. Durability of response and response to other treatment modalities were also evaluated. RESULTS: Of 159 unique KHE/TA subjects, Kasabach-Merritt phenomenon (KMP) was present in 64 (40.3%), and only two patients were deceased (1.3%). Over 60% (n = 96) demonstrated treatment response at 3 months, and more than 70% (n = 114) by 6 months (no significant difference across groups). The vincristine group had higher radiologic response at 3 months compared to sirolimus (72.7% vs. 20%, p = .03), but there were no differences between these groups at 6 months. There were no differences in rates of recurrent or progressive disease between vincristine and sirolimus. CONCLUSIONS: In this large, multicenter cohort of 159 patients with KHE/TA, rates of KMP were consistent with historical literature, but the mortality rate (1.3%) was much lower. Overall treatment response rates were high (>70%), and there was no significant difference in treatment response or durability of disease comparing sirolimus to vincristine. Our results support individualized treatment decision plans depending on clinical scenario and patient/physician preferences. Response criteria and response rates reported here will be useful for guiding future treatment protocols for vascular tumors.


Subject(s)
Hemangioendothelioma , Hemangioma , Kasabach-Merritt Syndrome , Sarcoma, Kaposi , Skin Neoplasms , Vascular Neoplasms , Child , Humans , Kasabach-Merritt Syndrome/drug therapy , Kasabach-Merritt Syndrome/pathology , Vincristine , Prospective Studies , Hemangioendothelioma/drug therapy , Hemangioendothelioma/pathology , Sarcoma, Kaposi/pathology , Sirolimus/therapeutic use
5.
Addiction ; 119(1): 137-148, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37766508

ABSTRACT

AIM: To measure the association between cannabis use disorder (CUD) and adverse cardiovascular disease (CVD) outcomes. DESIGN AND SETTING: We conducted a matched, population-based retrospective cohort study involving five linked administrative health databases from Alberta, Canada. PARTICIPANTS: We identified participants with CUD diagnosis codes and matched them to participants without CUD codes by gender, year of birth and time of presentation to the health system. We included 29 764 pairs (n = 59 528 individuals in total). MEASUREMENTS: CVD events were defined by at least one incident diagnostic code within the study period (1 January 2012-31 December 2019). Covariates included comorbidity, socio-economic status, prescription medication use and health service use. Using mortality-censored Poisson regression models, we computed survival analyses for time to incident CVD stratified by CUD status. In addition, we calculated crude and stratified risk ratios (RRs) across various covariates using the Mantel-Haenszel technique. FINDINGS: The overall prevalence of documented CUD was 0.8%. Approximately 2.4% and 1.5% of participants in the CUD and unexposed groups experienced an incident adverse CVD event (RR = 1.57; 95% confidence interval = 1.40-1.77). CUD was significantly associated with reduced time to incident CVD event. Individuals who appeared to have greater RRs for incident CVD were those without mental health comorbidity, who had not used health-care services in the previous 6 months, who were not on prescription medications and who did not have comorbid conditions. CONCLUSIONS: Canadian adults with cannabis use disorder appear to have an approximately 60% higher risk of experiencing incident adverse cardiovascular disease events than those without cannabis use disorder.


Subject(s)
Cannabis , Cardiovascular Diseases , Marijuana Abuse , Substance-Related Disorders , Adult , Humans , Retrospective Studies , Marijuana Abuse/complications , Alberta/epidemiology , Cardiovascular Diseases/epidemiology , Substance-Related Disorders/epidemiology , Cohort Studies
6.
Genet Med ; 25(12): 100969, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37634128

ABSTRACT

PURPOSE: PIK3CA-related overgrowth spectrum (PROS) encompasses several rare conditions resulting from activating variants in PIK3CA. Alpelisib, a PI3Kα-selective inhibitor, targets the underlying etiology of PROS, offering a novel therapeutic approach to current management strategies. This study evaluated the safety and efficacy of alpelisib in pediatric and adult patients with PROS. METHODS: EPIK-P1 (NCT04285723) was a non-interventional, retrospective chart review of 57 patients with PROS (≥2 years) treated with alpelisib through compassionate use. Patients had severe/life-threatening PROS-related conditions and confirmed PIK3CA pathogenic variant. The primary end point assessed patient response to treatment at Week 24 (6 months). RESULTS: Twenty-four weeks (6 months) after treatment initiation, 12 of 32 (37.5%) patients with complete case records included in the analysis of the primary end point experienced a ≥20% reduction in target lesion(s) volume. Additional clinical benefit independent from lesion volume reduction was observed across the full study population. Adverse events (AEs) and treatment-related AEs were experienced by 82.5% (47/57) and 38.6% (22/57) of patients, respectively; the most common treatment-related AEs were hyperglycemia (12.3%) and aphthous ulcer (10.5%). No deaths occurred. CONCLUSION: EPIK-P1 provides real-world evidence of alpelisib effectiveness and safety in patients with PROS and confirms PI3Kα as a valid therapeutic target for PROS symptom management.


Subject(s)
Thiazoles , Adult , Humans , Child , Retrospective Studies , Mutation , Thiazoles/adverse effects , Class I Phosphatidylinositol 3-Kinases/genetics
8.
Nat Med ; 29(6): 1530-1539, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37264205

ABSTRACT

Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.


Subject(s)
Lymphatic Abnormalities , Vascular Malformations , Humans , Mutation , Genetic Testing/methods , Vascular Malformations/diagnosis , Vascular Malformations/genetics , Vascular Malformations/therapy , Alleles , Lymphatic Abnormalities/genetics , Genomics
9.
Pediatr Blood Cancer ; : e30419, 2023 May 17.
Article in English | MEDLINE | ID: mdl-37194624

ABSTRACT

Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.

10.
Ecology ; 104(7): e4106, 2023 07.
Article in English | MEDLINE | ID: mdl-37259174

ABSTRACT

Historical horticultural plant sales influence native and nonnative species assemblages in contemporary ecosystems. Over half of nonnative, invasive plants naturalized in the United States were introduced as ornamentals, and the spatial and temporal patterns of early introduction undoubtedly influence current invasion ecology. While thousands of digitized nursery catalogs documenting these introductions are publicly available, they have not been standardized in a single database. To fill this gap, we obtained the names of all plant taxa (species, subspecies, and varieties) present in the Biodiversity Heritage Library's (BHL) Seed and Nursery Catalog Collection. We then searched the BHL database for these names and downloaded all available records. We combined BHL records with data from an encyclopedia of heirloom ornamental plants to create a single database of historical nursery sales in the US. Each record represents an individual taxon offered for sale at an individual time in a specific nursery's catalog. We standardized records to the current World Flora Online (http://worldfloraonline.org) accepted taxonomy and appended accepted USDA code, growth habit, and introduction status. We also appended whether taxa were reported as invasive in the Global Plant Invaders (GPI) data set or the Global Invasive Species Database (GISD) or regulated in the conterminous US. Lastly, we geocoded all reported publication locations. The data set contains 2,445,875 records from nurseries in at least 2795 unique locations, with the majority of catalogs published between 1890 and 1950. Nurseries were located in all conterminous states but were concentrated in the eastern US and California. We identified 19,140 unique horticultural taxa, of which 8642 matched taxa in the USDA Plants database. The USDA Plants database is limited to native and naturalized taxa in the US. Native or introduced status was listed in USDA Plants for 7018 of included taxa, while 1642 had an unknown status. The remaining 10,498 taxa are not naturalized according to USDA Plants or are of varieties of native and introduced taxa that did not match USDA Plants taxonomy. The majority of taxa in the Historical Plant Sales (HPS) database with an identified status are native (65.5%; 4596 of 7018 taxa), of which 393 taxa are reported as invasive outside of the US. Of the 2381 introduced taxa, 1103 (46.3%) are reported as invasive somewhere globally. Despite a richer pool of native taxa, most cataloged plant records with an identified status were of introduced taxa (54.1%; 1,045,684 of 1,933,925 records). Plants reported as invasive somewhere globally comprised a large portion of records with an identified status (38.7%; 747,953 of 1,933,925 records) underscoring the large role of ornamental introductions in facilitating plant invasions. The HPS database provides a consolidated and standardized perspective on the history of native, introduced, and invasive plant sales in the US. We release these data into the public domain under a Creative Commons Zero license waiver (https://creativecommons.org/share-your-work/publicdomain/cc0/). Individuals who use these data for publication may cite the associated data paper.


Subject(s)
Commerce , Plants , Humans , Biodiversity , Ecology , Ecosystem , Introduced Species , United States
11.
Pediatr Blood Cancer ; 70(4): e30219, 2023 04.
Article in English | MEDLINE | ID: mdl-36683202

ABSTRACT

Kaposiform lymphangiomatosis (KLA) is a life-threatening rare disease that can cause substantial morbidity, mortality, and social burdens for patients and their families. Diagnosis often occurs long after initial symptoms, and there are few centers in the world with the expertise to diagnose and care for patients with the disease. KLA is a lymphatic anomaly and significant advancements have been made in understanding its pathogenesis and etiology since its first description in 2014. This review provides multidisciplinary, comprehensive, and state-of-the-art information on KLA patient presentation, diagnostic imaging, pathology, organ involvement, genetics, and pathogenesis. Finally, we describe current therapeutic approaches, important areas for research, and challenges faced by patients and their families. Further insights into the pathogenesis of KLA may advance our understanding of other vascular anomalies given that similar signaling pathways may be involved.


Subject(s)
Lymphatic Abnormalities , Humans , Signal Transduction
12.
Pediatr Blood Cancer ; 70(4): e30215, 2023 04.
Article in English | MEDLINE | ID: mdl-36651691

ABSTRACT

BACKGROUND: Capillary lymphatic venous malformations (CLVM) and associated syndromes, including Klippel-Trenaunay syndrome (KTS) and congenital lipomatous overgrowth, vascular malformation, epidermal nevi, skeletal, and spinal syndrome (CLOVES), are underrecognized disorders associated with high morbidity from chronic pain, recurrent infections, bleeding, and clotting complications. The rarity of these disorders and heterogeneity of clinical presentations make large-scale randomized clinical drug trials challenging. Identification of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [gene]) mutations in CLVM has made targeted medications, such as sirolimus, attractive treatment options. The aim of this study was to investigate the safety and efficacy of sirolimus therapy in CLVM. PROCEDURE: A combined prospective and retrospective cohort of pediatric and young adult patients with CLVM treated with sirolimus was evaluated for disease response, including symptom improvement, quality of life (QOL), and radiologic response. Sirolimus dosing regimens and toxicities were also assessed. RESULTS: Twenty-nine patients with CLVM, including KTS and CLOVES, were included. Ninety-three percent of patients reported improved QOL, and 86% had improvement in at least one symptom. Most significantly, improvement was noted in 100% of patients with bleeding and 89% with thrombotic complications with corresponding decreases in mean D-dimer (p = .008) and increases in mean fibrinogen (p = .016). No patients had progressive disease on sirolimus. Most common side effects included neutropenia, lymphopenia, infection, and aphthous ulcers/stomatitis. No toxicities were life-threatening, and none required long-term discontinuation of sirolimus. CONCLUSION: Sirolimus appears to be effective at reducing complications and improving QOL in patients with CLVM and associated syndromes. In this patient cohort, sirolimus was well tolerated and resulted in few treatment-related toxicities.


Subject(s)
Klippel-Trenaunay-Weber Syndrome , Vascular Malformations , Child , Humans , Young Adult , Klippel-Trenaunay-Weber Syndrome/diagnosis , Klippel-Trenaunay-Weber Syndrome/genetics , Prospective Studies , Quality of Life , Retrospective Studies , Sirolimus , Vascular Malformations/diagnosis
13.
Pediatr Res ; 94(6): 1911-1915, 2023 Dec.
Article in English | MEDLINE | ID: mdl-35246606

ABSTRACT

BACKGROUND: Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy. METHODS: The NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay. RESULTS: Trametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib. CONCLUSIONS: Trametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies. IMPACT: This is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.


Subject(s)
Endothelial Cells , Lymphatic Abnormalities , Child , Humans , Phosphatidylinositol 3-Kinases , Mutation , Treatment Outcome , Mitogen-Activated Protein Kinase Kinases/genetics , Membrane Proteins/genetics , GTP Phosphohydrolases/genetics
14.
Lymphat Res Biol ; 21(2): 135-140, 2023 04.
Article in English | MEDLINE | ID: mdl-35984928

ABSTRACT

Background: To describe the dynamic contrast magnetic resonance lymphangiography (DCMRL) findings of three patients with complicated lymphatic anomaly (CLA) and protein losing enteropathy. We further discuss the importance of a multicompartment (intrahepatic [IH], intramesenteric [IM], and intranodal [IN]) DCMRL in delineating central lymphatic flow pathologies. Methods and Results: This is a retrospective study of three patients-one adult and two children who individually underwent the three-compartment DCMRL, namely IN-DCMRL, IH-DCMRL, and IM-DCMCRL. Findings from the results of the DCMRL for these three patients were obtained from the medical records and compared. Using the multicompartment imaging modalities, chylous fluid leakage into the peritoneum was observed using IM-DCMRL and IH-DCMRL but not IN-DCMRL for one of the patients in the case series. In contrast, leakage of chyle into the mediastinum was noted using IN-DCMRL but not IH-DCMRL and IM-DCMRL on another patient in this case series. Conclusion: Owing to the variability in outlining lymphatic flow pathologies, multicompartment imaging gives a more global picture of individual conduction disorders, has the potential to improve clinical assessment, and in some cases leads to a diagnosis of the abnormality and thus provides a better understanding of lymphatic flow anomalies in patients with CLAs.


Subject(s)
Lymphatic Abnormalities , Lymphography , Child , Adult , Humans , Lymphography/methods , Retrospective Studies , Contrast Media , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy
15.
Pediatr Res ; 93(6): 1470-1479, 2023 05.
Article in English | MEDLINE | ID: mdl-36180586

ABSTRACT

BACKGROUND: We report a 3-month-old female with cardiovascular anomalies and diffuse intestinal infantile hemangioma (IIH) of the small bowel suggesting possible diagnosis of PHACE syndrome (posterior fossa anomalies, hemangioma, arterial lesions, cardiac abnormalities/coarctation of the aorta, eye anomalies). The GI symptoms persisted under treatment with propranolol, whereas the addition of sirolimus led to regression of the IIH. METHODS: A systematic review was conducted using PubMed, EMBASE, and Ovid MEDLINE databases between 1982 and 2021. RESULTS: A total of 4933 articles were identified; 24 articles met inclusion criteria with 46 IIH cases. The most common GI presentations were unspecified GI bleed (40%) and anemia (38%). The most common treatments were corticosteroids (63%), surgical resection (32.6%), and propranolol (28%). Available outcomes were primarily bleeding arrest (84%). Nine cases (19.5%) were diagnosed with definite PHACE, 5 (11%) with possible PHACE, and 32 (69.5%) no PHACE. Our case presented with symptoms most consistent with those of possible PHACE and definite PHACE. No cases in this review underwent treatment with sirolimus. CONCLUSIONS: This is the first reported case of successful treatment of IIH with sirolimus. Our case, along with other patients who present with IIH and PHACE features, suggests consideration of IIH as a diagnostic criterion for PHACE syndrome. IMPACT: This is the first reported case in which sirolimus showed regression of an intestinal infantile hemangioma. This study serves to demonstrate the presentation, treatment, outcomes of intestinal infantile hemangioma, and correlation with PHACE. The potential correlation between intestinal infantile hemangioma and PHACE deserves more study in consideration of intestinal infantile hemangioma as a diagnostic criterion of PHACE.


Subject(s)
Aortic Coarctation , Eye Abnormalities , Hemangioma, Capillary , Hemangioma , Humans , Female , Infant , Propranolol/therapeutic use , Aortic Coarctation/diagnosis , Eye Abnormalities/diagnosis , Hemangioma/diagnosis , Hemangioma/drug therapy , Hemangioma/pathology , Syndrome
16.
Radiol Cardiothorac Imaging ; 4(5): e220035, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36339058

ABSTRACT

The lymphatic system plays an integral part in fluid homeostasis. Disturbances in lymphatic pathways are congenital, posttraumatic, or posttreatment related, such as after Fontan palliation. Lymphatic pathway evaluation is challenging because of the difficulty in introducing contrast material into the lymphatics. Intranodal, intramesenteric, and intrahepatic dynamic contrast-enhanced MR lymphangiography (DCMRL) offer better visualization of major lymphatic pathways. However, these techniques exclude pathways outside the central conduction system, preventing the visualization of abnormalities and, thus, administration of treatment. The authors describe alternative imaging of an axillary pathway via DCMRL in a patient with a symptomatic chylous effusion not previously assessed with current techniques. Keywords: Lymphatic, MR-Dynamic Contrast Enhanced, Pediatrics, Thorax, Pleura Supplemental material is available for this article. © RSNA, 2022.

17.
Pediatrics ; 150(5)2022 11 01.
Article in English | MEDLINE | ID: mdl-36193691

ABSTRACT

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor of childhood resulting from abnormal angiogenesis and lymphangiogenesis. Most commonly, KHE presents as a single tissue mass, ranging from an erythematous papule to a violaceous indurated tumor. Definitive diagnosis requires tissue sampling with the demonstration of ill-defined nodules and fascicles of spindle-shaped D2-40 positive endothelial cells, forming slit-like vascular channels. This newborn presented with multifocal cutaneous Kaposiform hemangioendothelioma associated with Kasabach-Merritt phenomenon confirmed on histopathology with immunostaining.


Subject(s)
Hemangioendothelioma , Kasabach-Merritt Syndrome , Sarcoma, Kaposi , Infant, Newborn , Humans , Kasabach-Merritt Syndrome/diagnosis , Kasabach-Merritt Syndrome/complications , Endothelial Cells , Hemangioendothelioma/diagnosis , Hemangioendothelioma/complications , Sarcoma, Kaposi/diagnosis , Sarcoma, Kaposi/complications
19.
J Neurosurg Spine ; : 1-7, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35364593

ABSTRACT

OBJECTIVE: Clinical manifestations of blue rubber bleb nevus syndrome (BRBNS) and multifocal venous malformation (MVM) vary depending on the location of the lesions. The aim of this study was to assess the risk of developing CSF leaks in patients with epidural venous malformations (VMs). METHODS: The authors retrospectively investigated the relationship between the development of a CSF leak and the presence of epidural VMs. RESULTS: Nine patients (5 females) had epidural VMs and presentation that was confirmatory or suggestive of a CSF leak: 4 had BRBNS, 4 had MVMs, and 1 had a solitary VM. Of 66 patients with BRBNS, clinical and imaging features of CSF leak were noted in 3 (4.5%) with epidural VMs at the age of 11-44 years. A fourth patient had suggestive symptoms without imaging confirmation. An epidural blood patch was ineffective in 2 patients, both with more than one source of leakage, requiring surgical repair or decompression. Symptomatic downward displacement of the cerebellar tonsils was noted in 3 patients with MVM and 1 with a solitary VM; 3 required surgical decompression. CONCLUSIONS: These findings suggest an increased risk of CSF leak in patients with epidural VM, including BRBNS, MVMs, and solitary VMs. Awareness of the association between epidural VM and CSF leakage may facilitate earlier diagnosis and therapeutic intervention.

20.
Am J Surg Pathol ; 46(7): 963-976, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35385405

ABSTRACT

Kaposiform lymphangiomatosis is an uncommon generalized lymphatic anomaly with distinctive clinical, radiologic, histopathologic, and molecular findings. Herein, we document the pathology in 43 patients evaluated by the Boston Children's Hospital Vascular Anomalies Center from 1999 to 2020. The most frequent presentations were respiratory difficulty, hemostatic abnormalities, and a soft tissue mass. Imaging commonly revealed involvement of some combination of mediastinal, pulmonary, pleural, and pericardial compartments and most often included spleen and skeleton. Histopathology was characterized by dilated, redundant, and abnormally configured lymphatic channels typically accompanied by dispersed clusters of variably canalized, and often hemosiderotic, spindled lymphatic endothelial cells that were immunopositive for D2-40, PROX1, and CD31. An activating lesional NRAS variant was documented in 9 of 10 patients. The clinical course was typically aggressive, marked by hemorrhage, thrombocytopenia, diminished fibrinogen levels, and a mortality rate of 21%.


Subject(s)
Endothelial Cells , Lung , Boston , Child , Humans
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