Congenital plaque-type glomuvenous malformations presenting in childhood

BACKGROUND: Glomuvenous malformations (GVMs) are now considered a separate entity from venous malformations. The rarest type of GVM is the generalized congenital plaque-type GVM. OBSERVATIONS: We present 10 new cases of congenital plaque-type GVM and describe their clinical progression and treatment. Mutations in the glomulin gene were found in those patients who participated in the genetic study. CONCLUSIONS: Congenital plaque-type GVMs are unique in their congenital nature, extensive distribution, difficult to diagnose and treat, and progressive involvement after birth. Most cases are familial, yet affected relatives usually have only minor lesions. The lesions of congenital plaque-type GVM are severe, visible at birth, and usually mistaken for extensive venous malformations. Vascular malformations are divided by hemodynamic type into slow-flow and fast-flow lesions. Slow-flow lesions are subcategorized as capillary, lymphatic, and venous.(1) Capillary malformations are flat, sharply demarcated, red-pink vascular stains of the skin commonly referred to as port-wine stains. These persist throughout life and are characterized histologically by dilated capillaries within the dermis. They slowly increase in size with age. Lymphatic malformations are spongelike collections of abnormal channels and spaces that contain clear lymphatic fluid, causing an excess of fluid to accumulate and dilate the lymphatic channels. This results in swelling of the affected area and, if extensive, can cause enlargement of soft tissues and bones.     

A novel mutation of the glomulin gene in an Italian family with autosomal dominant cutaneous glomuvenous malformations

Glomuvenous malformations (GVM) are hamartomas characterized histologically by glomus cells, which should be distinguished from glomus tumors. Familial GVM are rare, often present as multiple lesions, and exhibit familial aggregation, with autosomal dominant transmission. GVM are caused by mutations of the glomulin (GLMN) gene on chromosome 1p21-p22. Their development is thought to follow the 'two-hit' hypothesis, with a somatic mutation required in addition to the inherited germline mutation. We describe a novel GLMN mutation in an Italian family with GVM in which some members present with the less commonly observed phenotype of solitary lesions. A second somatic 'hit' mutation in GLMN was not discovered in our family. We further provide histological, immunohistochemical and electron microscopic data exhibiting the classic features of GVM. The diagnosis of GVM is critical because of distinction from venous malformations and blue rubber bleb nevus syndrome, which may demonstrate clinical similarities but require different treatment.     

Large plaque-like glomuvenous malformation (glomangioma) simulating venous malformation

Glomuvenous malformations and venous malformations are vascular lesions that can be distinguished on the basis of clinical and pathological features. A vascular lesion of the skin and superficial and deep soft tissues of a lower limb in a 5-year-old child is described. The clinical and radiological features, including skeletal muscle involvement, were typical of venous malformation, whereas the histopathological features were those of a glomuvenous malformation. The clinical and histopathological features are briefly discussed.     

Giant multifocal venous malformation with monomelic predominance

INTRODUCTION: Venous malformations are usually easy to recognise. We describe one case in which the clinical aspect was suggestive of Maffucci's syndrome. OBSERVATION: A 44-year-old male, had numerous angiomatous nodules which could be emptied by pressure since infancy. The progressive increase in volume of these lesions on the arms and forearms led to enormous deformation and major disability. The thoracic area and the right foot were also affected to a lesser degree. Two endobuccal lesions were also found on the clinical examination The cutaneous lesions were tender and occasionally hyperhidrosis was present. The presence of phleboliths on Xray and the presence of venous and capillary cavities with numerous thrombi confirmed the diagnosis of venous malformation. Following the failure of the Ethibloc(R) embolization, eight excisions were made in a two-year-period with a good functional result. Elastic strapping was then applied. DISCUSSION: The diagnosis of venous malformation was based on clinical, radiological and histological findings. The absence of chondroma excluded the diagnosis of Maffucci's syndrome. Spindle cell hemangioendothelioma, "blue rubber bleb nevus" and glomangiomatosis were confirmed by the histological findings. The absence of port-wine stain or bone hypertrophy and the presence of multiple nodules excluded Klippel-Trenaunay syndrome. The presence of multifocal involvement with oral lesions, the severity of the deformation and the relative success of the surgical procedure make this case unusual.     

Mutation analysis in Irish families with glomuvenous malformations

BACKGROUND: Glomuvenous malformations (GVMs) are rare bluish lesions that can affect the skin and mucosal surfaces. They represent defects in vasculogenesis. Lesions can occur sporadically or in an autosomal dominant mode of inheritance. Recent studies have shown that mutations in the glomulin gene (GLMN) on chromosome 1p21-22 are responsible for familial GVMs. OBJECTIVES: To search for mutations in GLMN in Irish families with GVMs. METHODS: We identified four Irish families with GVMs and confirmed linkage to chromosome 1p21-22 in these cases. We sequenced the glomulin gene in all affected and unaffected members of the families. Results Linkage analysis showed that affected individuals from the families shared a common haplotype. Mutation analysis revealed a delAAGAA mutation in exon 3 of the glomulin gene in all four families with GVMs. CONCLUSIONS: We confirm that mutations in the glomulin gene are responsible for GVMs and suggest a founder Irish mutation in the glomulin gene in four Irish families.     

Diagnosis and management of extensive vascular malformations of the lower limb: part I. Clinical diagnosis

There is significant confusion in the literature when describing vascular anomalies, and vascular malformations are often misnamed or incorrectly classified. Part I of this two-part series on the diagnosis and management of extensive vascular malformations of the lower limbs will discuss the dermatologist's role in the diagnosis of these lesions. At least nine types of vascular malformations with specific clinical and radiologic characteristics must be distinguished in the lower limbs: Klippel-Trénaunay syndrome, port-wine stain with or without hypertrophy, cutis marmorata telangiectatica congenita, macrocephaly-capillary malformation, Parkes Weber syndrome, Stewart-Bluefarb syndrome, venous malformation, glomuvenous malformation, and lymphatic malformation. This article highlights the differences in clinical appearance and discusses the differential diagnosis of extensive vascular malformations in an attempt to ensure earlier diagnosis and better outcomes for these patients.     

Diagnosis and management of extensive vascular malformations of the lower limb: part II. Systemic repercussions [corrected], diagnosis, and treatment

At least nine types of vascular malformations with specific clinical and radiologic characteristics must be distinguished in the lower limbs: Klippel-Trénaunay syndrome, port-wine stain with or without hypertrophy, cutis marmorata telangiectatica congenita, macrocephaly-capillary malformation, Parkes Weber syndrome, Stewart-Bluefarb syndrome, venous malformation, glomuvenous malformation, and lymphatic malformation. Extensive vascular malformations are often more complex than they appear and require a multidisciplinary therapeutic approach. Vascular malformations may be associated with underlying disease or systemic anomalies. Part II of this two-part series on the diagnosis and management of extensive vascular malformations of the lower limb highlights the systemic repercussions [corrected] (bone, articular, visceral, and hematologic involvement), diagnosis, and treatment of these lesions.     

Facial "glomangiomas": large facial venous malformations with glomus cells.

BACKGROUND: "Glomangiomas" are benign cutaneous vascular lesions consisting of convoluted, abnormally formed venous channels lined by cuboidal and oval epithelioid, alpha-actin-positive, glomus cells. Three different clinical variants of glomangioma have been recognized: solitary, multiple, and nodular, or plaquelike. Inheritable forms are common. OBJECTIVE: We describe in 7 patients (2 of them having a familial glomangiomatosis) the rare facial location of glomangiomas to differentiate this type from common facial venous malformation (VM). METHODS: We analyzed clinical data (photographs), course, investigations (computed tomographic scans in 4 patients, magnetic resonance imaging in 6, arteriography in 2, direct puncture phlebography in 4, and pathologic examinations in all 7), and outcome with treatment. RESULTS: Lesions were soft, composed of multiple nodules, confluent and plaquelike, deep blue or blue-to-purple, sometimes sagging, one-sided in a cheek, extending to the lips in 5 patients, to the chin in 4, and to the lower eyelid in 4. They were poorly compressible, a finding different from common facial VMs. In a young man extensive back involvement was associated. Among radiologic investigations, only magnetic resonance imaging after gadolinium enhancement offered some differential features with common VMs. However, histopathologic examination clarified the differential diagnosis: although the large tortuous venous channels were reminiscent of capillary-venous malformation, in many vessels the walls contained one or several rows of glomus cells. CONCLUSION: Multiple plaquelike facial "glomangiomas" mimic a common venous malformation because of their blue hue. However, with experience, one can clinically recognize them, and their pathologic aspect is distinctive. Management should differ slightly from that for common facial VM because sclerotherapy has proven to be less effective. Therefore surgical treatment is the only helpful therapeutic option.     

Congenital plaque-type glomuvenous malformations associated with fetal pleural effusion and ascites

Glomuvenous malformations are hereditary vascular anomalies, usually without extracutaneous involvement. We report two cases of extensive thoracic plaque-type glomuvenous malformation in newborns who had previously been diagnosed in utero with pleural effusion and ascites, suggesting a pathogenic link between the two conditions.     

Laser surgical planning with magnetic resonance imaging-based 3-dimensional reconstructions for intralesional Nd:YAG laser therapy of a venous malformation of the neck

BACKGROUND: Three-dimensional (3-D) imaging using computed tomography or magnetic resonance imaging data is well known for surgical planning of complex lesions in neurosurgery. In dermatology, percutaneous and intralesional Nd:YAG laser therapy is well established for numerous types of vascular malformations. Diagnostic imaging using ultrasound, computed tomography, or magnetic resonance imaging is necessary to plan the laser therapy of those malformations. The therapeutic problem is to localize the venous malformation exactly before treatment on sectional 2-dimensional images. OBSERVATIONS: We describe a 27-year-old woman with a venous malformation of the neck. The data of diagnostic magnetic resonance imaging were used for a 3-D reconstruction of the venous malformation to demonstrate the anatomical extent and subcutaneous involvement for laser surgical planning. Percutaneous and intralesional laser therapy was performed at 3-month intervals with the Nd:YAG laser using the 3-D reconstruction as a road map for the Nd:YAG laser. Eight weeks after the last laser treatment, the bulky lesions of the neck showed regression. Using the 3-D reconstruction for laser surgical planning, physicians could perform intralesional laser treatment more exactly. The complex anatomy of the venous malformation could be elucidated by studying the 3-D images before and during laser surgery. CONCLUSION: The use of magnetic resonance imaging-based 3-D reconstructions for laser surgical planning can demonstrate the often unexpected extent and improve the intralesional laser therapy in the treatment of venous malformations.     

Early Versus Later Presentations of Venous Malformations: Where and Why?

Venous malformations (VMs) are congenital anomalies of the venous vasculature, but not all are evident at birth. The factors that lead to presentation later in life are not well understood. The objective of this retrospective cohort study of patients with VMs evaluated at the University of California at San Francisco Birthmarks and Vascular Anomalies Center from 2005 to 2009 was to investigate the clinical presentation of VMs and correlate these features with different types of tissues (e.g., skin, subcutis, intramuscular). Main outcomes included the age at which lesions were first noticed, tissue type involved, presenting signs and symptoms, aggravating factors, and morbidities. A total of 115 subjects was included. The mean age when VM was first noted was 6.7 ± 0.9 years. Tissue types involved included skin/subcutaneous (46%); intramuscular (40%); and bone, tendon, or joint (14%). Presenting signs/symptoms included soft tissue swelling (44%), discrete mass (34%), pain (33%), and skin discoloration (26%). When compared with VMs limited to the skin or subcutis, those restricted to the intramuscular compartment were less likely to present at birth (27% vs 53%, p < 0.05) but were more frequently painful (79% vs 60%, p < 0.05) and contained more phleboliths (28% vs 11%, p < 0.05), and were associated with more exercise limitation (35% vs 16%, p < 0.05). VMs differ in age of onset, clinical features, and complications based on differing tissues and sites of involvement, with isolated intramuscular involvement associated with later presentation and greater morbidity.     

A collection of rare anomalies: multiple digital glomuvenous malformations,epidermal naevus,temporal alopecia,heterochromia and abdominal lipoblastoma

Glomuvenous malformations are a subtype of venous malformations, which present in infancy or childhood. We describe a teenage girl who presented with multiple digital glomuvenous malformations from birth. In addition, she had an epidermal naevus on the upper lip, an area of congenital alopecia of the scalp, heterochromia irides and an abdominal lipoblastoma. We are unaware of any reports of the association of multiple glomuvenous malformations with the other uncommon developmental anomalies seen in our patient, and a common link eludes us.     

Verrucous lymphovascular malformation versus verrucous hemangioma: controversial nomenclature

The International Society for the Study of Vascular Anomalies (ISSVA) divides congenital vascular anomalies into malformations and tumors and subclassified hemangiomas under tumors. However, evidence shows this accepted classification has not been widely employed. Particularly troublesome is the use of the term hemangioma, commonly used to describe a variety of vascular lesions (both malformations and tumors). The term verrucous hemangioma has been used to describe a congenital vascular anomaly with a progressive verrucous epidermal surface persisting throughout life unless surgically excised. Recent evidence suggests that some of these lesions may share histologic features of both hemangiomas and malformations, thereby causing nosologic confusion. We report a 15-year-old adolescent girl with such a lesion and review the literature and controversy of verrucous hemangiomas. In our case, the most appropriate diagnosis is verrucous lymphovascular malformation. Further testing of similar lesions will be necessary to fully understand the nature and classification of these lesions.     

Ecografía Doppler color en malformaciones glomuvenosas con correlación clínica e histológica

Glomuvenous malformations are hamartomatous lesions characterized by the presence of glomus cells in the vascular smooth muscle. We present the clinical and color Doppler ultrasound features of a series of 13 cases of histologically confirmed glomuvenous malformations. In all cases, the ultrasound study revealed moderately delimited superficial dermal and hypodermal pseudonodular structures of mixed echogenicity, with hypoechoic and heterogeneous areas and anechoic, pseudocystic tubular and lacunar zones. Arterial and venous vessels, mainly with a low flow (≤ 15 cm/s) were observed in 85% of patients, but no arteriovenous shunts were present. Deeper structures were not affected and no phleboliths were detected. The clinical and ultrasound findings could facilitate diagnosis, surgical planning, and noninvasive follow-up in these tumors.     

Pseudo-Kaposi's sarcoma secondary to superficial arteriovenous malformation: Stewart-Bluefarb syndrome

BACKGROUND: Pseudo-Kaposi's sarcoma or Stewart-Bluefarb subtype acroangiodermatitis is uncommon and is caused by arteriovenous fistula and malformation. We report a new case. CASE REPORT: A 33-year-old man presented with painful red-violet plaque on the dorsum of the toes with angiomatous nodules on the sole. Histological and immunohistochemical studies for CD34 were consistent with Kaposi's sarcoma. Doppler ultrasonography and femoral angiography showed multiple distal arteriovenous shunts. Free-flow embolisation with fragments of Ethibloc gelatin sponge was performed and arteriography, performed immediately afterwards, showed delayed venous drainage. The outcome was good with complete drainage of the angiomatous lesions. DISCUSSION: Pseudo-Kaposi's sarcoma Stewart-Bluefarb subtype begins early in life in male subjects, with unilateral skin lesions. It bears clinical and histological resemblance to Kaposi's sarcoma. Doppler ultrasonography and angiography show arteriovenous fistulas that classically develop at shunts, explaining the role of traumatism and high vascular pressure in the genesis of this disease.     

血管性胎记相关综合征的遗传学研究进展

血管性胎记主要有婴幼儿血管瘤和血管畸形,婴幼儿血管瘤有家族聚集性发病倾向,部分患儿与特应性皮炎等过敏性疾病伴发,患儿在瘤体增生期和消退期均存在基因突变。血管畸形可表现为散发或常染色体显性遗传,动静脉畸形常因RASA1突变导致。静脉畸形可散发,可呈不完全显性遗传或常染色体显性遗传。常染色体显性遗传性静脉畸形基因Tie2/Tek突变导致。此外,约1,2散发静脉畸形会出现Tie2体细胞突变。有关血管性胎记分子水平的研究能为临床诊治提供新的思路。     

Characteristic appearance of spindle cell hemangiomatosis,often misdiagnosed as venous malformation: A retrospective study of 11 cases

Spindle cell hemangiomatosis is a benign multifocal vascular proliferation that mostly occurs in the distal extremities. It is a relatively rare disease and causes difficulties in clinical diagnosis and differential diagnosis of venous malformation. We retrospectively assessed the medical history, and clinical features, imaging features, pathological features and follow up of 11 patients diagnosed pathologically with spindle cell hemangiomatosis after surgery. There are two types of clinical appearances in spindle cell hemangiomatosis in the distal extremities: bleb-like nodules and varix-like nodules. Bleb-like nodules are mostly superficially located in the palm or interphalangeal joints with obvious hemorrhage in lesions and mainly composed of cavernous spaces rather than spindle cells. Varix-like nodules are located in the back of the hands or arms with normal skin color and mainly composed of solid areas of accumulated spindle cells. Surgery is the standard therapy for spindle cell hemangiomatosis, while sclerotherapy is invalid. Despite the tendency to develop new lesions, there are no residual lesions at the surgical site during follow up. Bleb-like nodules in the palm and interphalangeal joints are a typical clinical appearance in spindle cell hemangiomatosis which can help make clinical and a differential diagnosis of venous malformation. Surgery is the standard therapy for spindle cell hemangiomatosis with no residual lesions remaining at the surgical sites.     

Glomuvenous Malformation in a Boy with Transposition of the Great Vessels: A Case Report and Review of Literature

Abstract:   We report a case of glomuvenous malformation (GVM) in an 11-year-old boy with a history of transposition of the great vessels. The glomulin gene was discovered in 1999, and multiple mutations have been identified with some of the mutations resulting in GVM. The molecular genetics, clinical presentation, histopathology, differential diagnosis, and management of GVM are reviewed. To our knowledge, no case of glomuvenous malformation in the setting of transposition of the great vessels has ever been reported in the literature.     

Oral 11, Potential life-threatening complications of vascular malformations

We present two patients with vascular anomalies which illustrate important learning points.
Patient 1 was a 7-year-old girl who was being followed up for a vascular malformation which had been present at birth and had slowly enlarged over the years. It was located midline, overlying her thoracic spine. Magnetic resonance (MR) imaging revealed the lesion to be an arteriovenous malformation. An MR angiogram, performed to delineate further the extent of involvement around the spine, surprisingly revealed multiple pulmonary arteriovenous malformations. The patient admitted to having regular nosebleeds but was otherwise asymptomatic and had no telangiectasia on her face or in her mouth. There was no family history of bleeding disorders. Genetic testing has confirmed hereditary haemorrhagic telangiectasia. We present this girl to highlight the significance of midline vascular lesions, which should be treated with suspicion and physicians should have a low threshold for investigation.
Patient 2 was an 18-year-old man attending the multidisciplinary vascular anomalies clinic with an extensive lymphatic venous malformation present since birth. Imaging showed this involved the bladder and rectum, and extended the whole way down the left leg to include the foot. Over the years he was troubled with haematuria, rectal bleeding, and recurrent painful episodes. D-dimers were elevated. His condition was complicated by bilateral extensive pulmonary emboli and he was started on low-molecular-weight heparin. Despite this he went on to suffer a fatal pulmonary embolus 2 months later.
These cases highlight the associated risks of vascular malformations.