Cutaneous Vascular Anomalies Associated With Neural Tube Defects: Nomenclature and Pathology Revisited

Abstract BACKGROUND: Lumbosacral cutaneous vascular anomalies associated with neural tube defects are frequently described in the literature as “hemangiomas.” The classification system for pediatric vascular anomalies developed by the International Society for the Study of Vascular Anomalies provides a framework to accurately diagnose these lesions. OBJECTIVE: To apply this classification to vascular cutaneous anomalies overlying myelodysplasias. METHODS: A retrospective analysis of patients with neural tube defects and lumbosacral cutaneous vascular lesions was performed. All eligible patients had detailed histopathologic analysis of skin and spinal cord/placode lesions. Clinical and radiologic features were analyzed. Conventional histology and GLUT-1 immunostaining were performed to differentiate infantile capillary hemangiomas from capillary vascular malformations. RESULTS: Ten cases with cutaneous lesions associated with neural tube defects were reviewed. Five lesions were diagnosed as infantile capillary hemangiomas based upon histology and positive GLUT-1 endothelial reactivity. These lesions had a strong association with dermal sinus tracts. No reoperations were required for residual intraspinal vascular lesions, and overlying cutaneous vascular anomalies involuted with time. The remaining 5 lesions were diagnosed as capillary malformations. These occurred with both open and closed neural tube defects, did not involute, and demonstrated enlargement and darkening due to vascular congestion. CONCLUSION: The International Society for the Study of Vascular Anomalies scheme should be used to describe the cutaneous vascular lesions associated with neural tube defects: infantile capillary hemangiomas and capillary malformations. We advocate that these lesions be described as “vascular anomalies” or “stains” pending accurate diagnosis by clinical, histological, and immunohistochemical evaluations.

Download Full-text

Glut 1, S-100, and Nerve Bundle Study in Vascular Anomalies

Indian Journal of Surgery ◽

10.1007/s12262-021-02972-2 ◽

2021 ◽

Author(s):

Ajay K. Khanna ◽

Akhilesh Kumar ◽

Soumya Khanna ◽

Amrita Kar ◽

Puneet Kumar ◽

...

Keyword(s):

Vascular Malformation ◽

Vascular Malformations ◽

Vascular Anomalies ◽

Vascular Lesions ◽

Histological Evaluation ◽

Vascular Tumors ◽

Nerve Bundle ◽

Glut 1 ◽

S 100 ◽

Hematoxylin And Eosin

Abstract Vascular anomalies grouped into vascular tumors (hemangioma) (HI) and vascular malformation (VM) are benign vascular lesions that are difficult to distinguish from one another clinically and often confused with each other at histopathology. This confusing terminology leads to improper diagnosis, illogical treatment, and misdirected research. This study aimed to study GLUT 1, S-100, and nerve bundle to differentiate hemangioma and vascular malformation. Thirty two cases of vascular lesions (26 vascular malformations and 6 hemangiomas) were taken into the study. For histological evaluation and immunohistochemistry (IHC), samples of vascular lesions were collected in formalin. All the hematoxylin and eosin-stained slides were evaluated under light microscope for histology and nerve bundles. Immunohistochemical staining was performed by streptavidin–biotin method for GLUT 1 and S-100. GLUT 1 was positive in all 6 cases of hemangiomas (100%) and only in 1 case of vascular malformation. Nerve bundle was present in 24 cases of vascular malformation (92.3%) out of 26 cases but not in any cases of hemangioma and S-100 was found positive in all vascular malformation cases (100%) but not in hemangioma. So GLUT 1 expression, S-100, and presence of nerve bundle in vascular lesions can help to differentiate hemangioma and vascular malformation.

Download Full-text

Is There an Association Between Hemangioma and Syndromes With Dysmorphic Features?

PEDIATRICS ◽

10.1542/peds.88.6.1257 ◽

1991 ◽

Vol 88 (6) ◽

pp. 1257-1267

Author(s):

A. Jay Burns ◽

Lawrence C. Kaplan ◽

John B. Mulliken

Keyword(s):

Aortic Arch ◽

Vascular Malformations ◽

Vascular Anomalies ◽

Vascular Lesions ◽

Dysmorphic Features ◽

Vascular Birthmarks ◽

Neonatal Tumor ◽

Nevus Flammeus ◽

Genitourinary Defects

Most vascular birthmarks can be categorized, based on clinical and cellular criteria, as either (1) a hemangioma, or (2) a malformation, or (3) a macular stain. Macular stains are commonly seen in newborns, and they consist of faint vascular stains of the glabella, eyelids, and nuchal region called "nevus flammeus," "stork bite," "salmon patch," etc. Unfortunately, the term "hemangioma" is frequently applied to all three types of cutaneous vascular lesions. Usually, these disparate vascular anomalies are listed in association with various malformative syndromes and are generically labeled "hemangioma." This study attempts to define accurately the specific vascular anomalies seen in children born with syndromes with dysmorphic features. This review of five standard textbooks of genetics showed that the majority of vascular anomalies reported in syndromic newborns are not hemangiomas. Rather, they are macular stains, and the vast majority of these fade with time. Congenital telangiectasias and other vascular malformations (capillary, lymphatic, venous, arterial, and combinations thereof) also occur in association with dysmorphic syndromes. contrast, hemangioma, the most common neonatal tumor, is seen only incidentally with rare dysmorphic conditions. Specifically, hemangioma was found to occur only in association with midline (sternal, abdominal) clefting, right-sided aortic arch coarctation, and with a constellation of sacral and genitourinary defects.

Download Full-text

2014 Revised Classification of Vascular Lesions from the International Society for the Study of Vascular Anomalies: Radiologic-Pathologic Update

Radiographics ◽

10.1148/rg.2016150197 ◽

2016 ◽

Vol 36 (5) ◽

pp. 1494-1516 ◽

Cited By ~ 68

Author(s):

Arnold C. Merrow ◽

Anita Gupta ◽

Manish N. Patel ◽

Denise M. Adams

Keyword(s):

International Society ◽

Vascular Anomalies ◽

Vascular Lesions

Download Full-text

Loci C677T and A1298C of the methylenetetrahydrofolate reductase gene and the risk of neural tube defects in the Kyrgyz population

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2019.09.3-8 ◽

2019 ◽

pp. 3-8

Author(s):

Н.М. Алдашева ◽

Э.М. Мамбетсадыкова ◽

Э.Т. Талайбекова ◽

С.Дж. Боконбаева ◽

Х.М. Сушанло ◽

...

Keyword(s):

Neural Tube ◽

Neural Tube Defects ◽

Methylenetetrahydrofolate Reductase ◽

Strong Association ◽

Mthfr Gene ◽

Control Group ◽

Increased Risk ◽

Pcr Rflp ◽

1298C Allele ◽

Kyrgyz Population

Цель. Изучить ассоциацию полиморфных локусов С677Т и А1298С гена MTHFR с развитием дефектов нервной трубки (ДНТ) у детей киргизской национальности. Методы. В исследование включены 76 детей и их матери. В основную группу вошли 30 детей с пороками невральной трубки, чаще всего в виде изолированной спиномозговой грыжи или в сочетании с другими врожденными пороками развития, а также их матери. 46 детей без ДНТ и их матери составили контрольную группу. Идентификация генотипов полиморфных локусов С677Т и А1298С гена MTHFR проводилась методом анализа полиморфизма длин рестрикционных фрагментов (ПДРФ). Результаты. При анализе распределения генотипов и аллелей полиморфизма А1298С гена MTHFR выявлено, что среди детей с ДНТ статистически значимо чаще встречались гетерозиготный генотип А1298С (χ²=9,67; р=0,0079) и аллель 1298С (χ²=4,17; р=0,04). При наличии генотипа А1298С риск развития ДНТ повышается в 4,71 раза (OR=4,71; p=0,0079), а при наличии аллеля 1298С - в 2,2 раза (OR=2,20; p=0,04). Полиморфный локус С677Т гена MTHFR самостоятельно не был ассоциирован с ДНТ, однако гетерозиготность по двум полиморфным аллелям ассоциирована с ДНТ (χ²=5,60; p=0,018) и существенно повышает относительный риск развития ДНТ (OR=9,75; p=0,018). Заключение. У детей киргизской национальности полиморфный локус А1298С гена MTHFR ассоциирован с развитием дефекта нервной трубки. Комбинированная гетерозиготность (С677Т/А1298С) по обоим полиморфизмам является дополнительным отягощающим фактором. Aim. The aim of the study was to investigated whether polymorphisms С677Т and А1298С of the MTHFR gene are associated with neural tube defects (NTDs) in the Kyrgyz population. Methods. The study included 76 children and their mothers. The study group included 30 children and their mothers, where the child had a neural tube defect, most commonly in the form of an isolated spina bifida or in combination with congenital anomalies. Control group - 46 children without congenital malformations. С677Т and А1298С polymorphisms analysis in the MTHFR gene were performed by PCR-RFLP method. Results. The frequency of the heterozygous A1298C genotype (χ²=9,67; p=0,0079) and 1298C allele (χ²=4,10; p=0,041) of the MTHFR gene was higher in cases than in controls. Child with heterozygous A1298C genotype had a 4,71- fold (OR=4,71; p=0,0079) higher risk of NTDs when compared with those who had the AA genotype. Child carriers of the 1298C allele had a 2,2-fold higher risk of NTDs (OR=2,20; p=0,041). С677Т/А1298С genotypes are more frequent among cases than controls (χ²=5,00; p=0,025). We showed that the combinations of С677Т/А1298С is strong association with NTDs (χ²=5,60; p=0,018). Subjects carriers of the combinations of С677Т/А1298С genotypes had a significant 9,7-fold higher risk of NTDs (OR=9,75; p=0,018). Conclusion. There is significant association between С677Т and А1298С polymorphism in MTHFR gene and neural tube defects in the Kyrgyz population. An increased risk of neural tube defects associated with heterozygous A1298C genotype, 1298C allele and combinations of С677Т/А1298С in MTHFR gene.

Download Full-text

Vascular Birthmarks as a Clue for Complex and Syndromic Vascular Anomalies

Frontiers in Pediatrics ◽

10.3389/fped.2021.730393 ◽

2021 ◽

Vol 9 ◽

Author(s):

Andrea Diociaiuti ◽

Guglielmo Paolantonio ◽

Mario Zama ◽

Rita Alaggio ◽

Claudia Carnevale ◽

...

Keyword(s):

Vascular Malformation ◽

Early Recognition ◽

Vascular Malformations ◽

Clinical Signs ◽

Vascular Anomalies ◽

Vascular Lesions ◽

Vascular Tumors ◽

Capillary Malformation ◽

Wide Range ◽

Vascular Birthmarks

Vascular birthmarks are common in neonates (prevalence: 20–30%) and mostly incidental findings sometimes with spontaneous regression (salmon patch and nevus simplex). Capillary malformations are found in about 1% and infantile hemangiomas are found in 4% of mature newborns. Vascular malformations are classified according to their most prominent vessel type. The term “capillary malformation” (port wine stain) includes a wide range of vascular lesions with different characteristics; they may be isolated or part of specific syndromic conditions. Part of the infantile hemangiomas and of the vascular malformations may require treatment for functional or cosmetic reasons, and in rare cases, investigations are also necessary as they represent a clue for the diagnosis of complex vascular malformation or tumors associated with extracutaneous abnormalities. Complex vascular malformations are mostly mosaicism due to early somatic mutations. Genetic advances have led to identify the main pathogenic pathways involved in this disease group. Diffuse capillary malformation with overgrowth, Klippel–Trenaunay syndrome, CLAPO syndrome, CLOVES syndrome, and megalencephaly-capillary malformation belong to the PIK3CA-related overgrowth. Capillary malformation–arteriovenous malformation underlies a fast-flow vascular malformation, sometimes manifesting as Parkes–Weber syndrome. Recognition of these different types of capillary vascular stains is sometimes difficult; however, associated findings may orient the clinicians while genetic testing may confirm the diagnosis. Lymphatic malformation frequently manifests as large masses that compress and/or infiltrate the surrounding tissues, representing a neonatal emergency when airways are involved. Infantile hemangiomas may cause functional and/or permanent esthetical damage, depending on their localization (such as periorbital area, lip, nose); large (more than 5 cm) infantile hemangiomas with a segmental distribution can be associated with obstruction or malformations of the underneath organs with complications: PHACE syndrome, LUMBAR/SACRAL syndrome, and beard infantile hemangioma. In our review, we discuss controversies regarding the international classification and emerging concepts in the field of vascular anomalies. Finally, we discuss potential developments of new, non-invasive diagnostic techniques and repurposing of target therapies from oncology. Complex and/or life-threatening vascular tumors and malformations are extremely rare events and they represent a considerable therapeutic challenge. Early recognition of clinical signs suggestive for a specific disease may improve therapeutic outcomes and avoid severe complications.

Download Full-text

Vascular and Perivascular Lesions of Skin and Soft Tissues in Children and Adolescents

Pediatric and Developmental Pathology ◽

10.2350/11-11-1119-pb.1 ◽

2012 ◽

Vol 15 (1_suppl) ◽

pp. 26-61 ◽

Cited By ~ 27

Author(s):

Elisabeth Bruder ◽

Rita Alaggio ◽

Harry P. W. Kozakewich ◽

Gernot Jundt ◽

Louis P. Dehner ◽

...

Keyword(s):

Children And Adolescents ◽

Soft Tissues ◽

Vascular Malformations ◽

Classification Systems ◽

Vascular Anomalies ◽

Vascular Lesions ◽

Malignant Neoplasms ◽

Clinical Expertise ◽

Full Spectrum ◽

Specific Diagnosis

Vascular anomalies in children and adolescents are the most common soft tissue lesions and include reactive, malformative, and neoplastic tumefactions, with a full spectrum of benign, intermediate, and malignant neoplasms. These lesions are diagnostically challenging because of morphologic complexity and recent changes in classification systems, some of which are based on clinical features and others on pathologic findings. In recent decades, there have been significant advances in clinical diagnosis, development of new therapies, and a better understanding of the genetic aspects of vascular biology and syndromes that include unusual vascular proliferations. Most vascular lesions in children and adolescents are benign, although the intermediate locally aggressive and intermediate rarely metastasizing neoplasms are important to distinguish from benign and malignant mimics. Morphologic recognition of a vasoproliferative lesion is straightforward in most instances, and conventional morphology remains the cornerstone for a specific diagnosis. However, pathologic examination is enhanced by adjunctive techniques, especially immunohistochemistry to characterize the type of vessels involved. Multifocality may cause some uncertainty regarding the assignment of “benign” or “malignant.” However, increased interest in vascular anomalies, clinical expertise, and imaging technology have contributed greatly to our understanding of these disorders to the extent that in most vascular malformations and in many tumors, a diagnosis is made clinically and biopsy is not required for diagnosis. The importance of close collaboration between the clinical team and the pathologist cannot be overemphasized. For some lesions, a diagnosis is not possible from evaluation of histopathology alone, and in a subset of these, a specific diagnosis may not be possible even after all assembled data have been reviewed. In such instances, a consensus diagnosis in conjunction with clinical colleagues guides therapy. The purpose of this review is to delineate the clinicopathologic features of vascular lesions in children and adolescents with an emphasis on their unique aspects, use of diagnostic adjuncts, and differential diagnosis.

Download Full-text

Vascular anomalies of the tympanic membrane

The Journal of Laryngology & Otology ◽

10.1017/s0022215106001782 ◽

2006 ◽

Vol 120 (9) ◽

pp. 796-799

Author(s):

L O Redaelli de Zinis ◽

C Galtelli ◽

M G Barezzani

Keyword(s):

Tympanic Membrane ◽

Rare Case ◽

Vascular Malformations ◽

Incidental Finding ◽

Vascular Anomalies ◽

Vascular Lesions

Benign vascular lesions include various forms whose classification has created some controversies in the literature. The observation of a rare case of vascular bulge of the eardrum in a 57-year-old man prompted us to analyse the essential features of these lesions. This was an incidental finding and the mass was removed by a transcanal approach. The patient is free of disease four years later. Vascular malformations can be differentiated from vascular tumours since they are present at birth, are generally stable, do not involute, and do not necessitate treatment unless symptoms occur.

Download Full-text

Blue Rubber Bleb Nevus Syndrome

Journal of Pediatric Neurology ◽

10.1055/s-0038-1667178 ◽

2018 ◽

Vol 16 (05) ◽

pp. 288-296

Author(s):

Federica Sullo ◽

Angela D'Ambra ◽

Agata Polizzi ◽

Maria Garozzo ◽

Flavia Mendola ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Gastrointestinal Bleeding ◽

Vascular Malformations ◽

Mammalian Target Of Rapamycin ◽

Clinical Problem ◽

Vascular Lesions ◽

Oral Drug ◽

Venous Malformations ◽

Cutaneous Lesions ◽

Curative Therapy

AbstractBlue rubber bleb nevus syndrome (BRBNS) is a rare congenital disorder characterized by multifocal venous malformations mainly of the skin, soft tissue, and gastrointestinal tract. However, it may occur in any tissue including the nervous system. This syndrome most commonly occurs sporadically but can be associated with an autosomal dominant inheritance. Among the cases reported in the literature, the female/male ratio was ∼1:1. The diagnosis of BRBNS is based on the presence of characteristic cutaneous lesions with or without gastrointestinal bleeding and/or the involvement of other organs. Typical skin manifestations consist of soft, easily compressive, bluish papules similar to rubber-like nipples. Aside the skin, vascular lesions are usually found in the gastrointestinal tract, anywhere from the oral to the anal mucosa, but predominantly in the small bowel. Endoscopy provides the opportunity to treat and diagnose the lesions. BRBNS should be differentiated from hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu syndrome), Klippel–Trenaunay syndrome, and Maffucci syndrome. The prognosis of BRBNS depends on which organs are involved and the extent of involvement. Most patients can live a long life with the disease, but the quality of life is limited due to gastrointestinal bleeding, oral drug therapy, and blood transfusions. Sudden massive gastrointestinal hemorrhage remains the most frequent cause of death. No curative therapy is currently available for this syndrome. The cutaneous lesions are usually asymptomatic and do not require treatment. The most important clinical problem is the management of acute or chronic bleeding from the multiple gastrointestinal venous malformations: a conservative approach should be instituted whenever the clinical features and the bleeding episodes are mild and only in a life-threatening situation surgery may be required. In the recent years, however, molecular targeted therapy with the mammalian target of rapamycin inhibitor sirolimus has been anecdotally employed with reduction in bleeding and shrinkage of vascular malformations.

Download Full-text