Patricia E. Burrows

Sclerotherapy of craniofacial venous malformations: complications and results.

Of all vascular anomalies, venous malformations are the most common, and they have a propensity for the head and neck. The authors retrospectively analyzed 40 patients with craniofacial venous malformations who underwent sclerotherapy between October of 1994 and June of 1996 to determine (1) the results of sclerotherapy with ethanol and/or sodium tetradecyl sulfate, (2) the types and rate of complications, and (3) whether outcome correlated with age, sex, location, size, tissues involved, morphology (lobular or varicose), venous outflow, or number of sclerotherapy sessions. The authors also reviewed the results after sclerotherapy and contour resection (n = 18). Comparisons between the results with ethanol and sodium tetradecyl sulfate and between sclerotherapy alone and sclerotherapy and resection combined were not done. The study was composed of three parts. They were (1) a review of records and imaging studies, (2) a panel evaluation of pretreatment and posttreatment photographs, and (3) a questionnaire that determined the patients (or parent of the patients) impression of therapy. Interrater and intrarater agreement were analyzed. Sclerotherapy was performed in an angiographic suite, under general anesthesia, using absolute ethanol and/or sodium tetradecyl sulfate. Complications of the treatment included acute blistering (50 percent), hemoglobinuria (28 percent), deep ulceration (13 percent), and nerve injury (7.5 percent). Two patients suffered transient facial paresis, and one had permanent unilateral vocal cord paralysis. Thirty patients (75 percent) were rated as having marked improvement or as being cured by all three members of the panel; 10 patients (25 percent) were rated as having no change or only slight improvement by one or more members of the panel. Interrater reliability was moderately positive, and intrarater reliability was highly positive. Thirty-seven patients or parents of patients (93 percent) responded to the questionnaire. The outcome was considered to be marked improvement or cured in 28 patients (76 percent), and nine respondents (24 percent) described only minor improvement or no change. Logistic regression analysis revealed that only male sex and number of sclerotherapeutic procedures were significant multivariate predictors of outcome. Size, location, tissues involved, morphology, or venous outflow were not determinant. In conclusion, sclerotherapy with ethanol or sodium tetradecyl sulfate is an effective and safe treatment for craniofacial venous malformations. Often, sclerotherapy has to be repeated. For extensive perioral malformations, combined sclerotherapy and resection give the best result.

Thrombocytopenic coagulopathy (Kasabach-Merritt phenomenon) is associated with kaposiform hemangioendothelioma and not with common infantile hemangioma

&NA; Children with a large vascular tumor and associated Kasabach‐Merritt coagulopathy respond inconsistently to therapy and have a high mortality rate. For this reason, we undertook a retrospective study of 21 such patients, and focused on clinical, radiographic, and histopathologic features. The male to female ratio was 1:1.6. Tumor was noted at birth in 50 percent of patients; the remainder appeared throughout infancy. The location was cervicofacial (n = 2), shoulder/upper limb (n = 4), trunk including retroperitoneum (n = 11), and lower limb (n = 4). These tumors grew rapidly to large size and were characterized by cutaneous purpura, edema, and an advancing ecchymotic margin. In contrast to common hemangioma, magnetic resonance imaging showed diffuse enhancement with ill‐defined margins, cutaneous thickening, stranding of subcutaneous fat, hemosiderin deposits, and small feeding and draining vessels. All tumors were Kaposiform hemangioendothelioma (KHE); none were infantile hemangioma. Light microscopy showed irregular lobules or sheets of poorly formed, small vascular channels infiltrating and entrapping normal tissues. Characteristic features included spindleshaped endothelial cells, diminished pericytes and mast cells, microthrombi, and hemosiderin deposits. Wide endothelial intercellular gaps and incomplete basement membranes were seen by electron microscopy. Dilated, hyperplastic, lymphaticoid channels were prominent in one tumor. KHE in 14 infants was treated with interferon alpha‐2a: 6 had accelerated regression; 2 had stabilization of growth; and 6 evidenced no response. The mortality rate was 24 percent (5 of 21); this included three infants with retroperitoneal KHE. Kasabach‐Merritt phenomenon does not occur with common hemangioma. Rather it is associated with the more aggressive KHE and rarely with other vascular neoplasms. Variable response to current pharmacologic therapy underscores our inadequate knowledge of the pathogenesis of thrombocytopenia in KHE. (Plast. Reconstr. Surg. 100: 1377, 1997.)

DIAGNOSTIC IMAGING IN THE EVALUATION OF VASCULAR BIRTHMARKS

This article reviews the role of modern diagnostic imaging in the evaluation of patients with vascular birthmarks. There are two main categories of vascular anomalies: hemangiomas and vascular malformations. The findings on plain radiography, sonography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, and the appropriate sequence of investigation for the different vascular anomalies are discussed.

Rapidly Involuting Congenital Hemangioma: Clinical and Histopathologic Features

We define the histopathologic findings and review the clinical and radiologic characteristics of rapidly involuting congenital hemangioma (RICH). The features of RICH are compared to the equally uncommon noninvoluting congenital hemangioma (NICH) and common infantile hemangioma. RICH and NICH had many similarities, such as appearance, location, size, and sex distribution. The obvious differences in behavior served to differentiate RICH, NICH, and common infantile hemangioma. Magnetic resonance imaging (MRI) of the three tumors is quite similar, but some RICH also had areas of inhomogeneity and larger flow voids on MRI and arterial aneurysms on angiography. The histologic appearance of RICH differed from NICH and common infantile hemangioma, but some overlap was noted among the three lesions. RICH was composed of small-to-large lobules of capillaries with moderately plump endothelial cells and pericytes; the lobules were surrounded by abundant fibrous tissue. One-half of the specimens had a central involuting zone(s) characterized by lobular loss, fibrous tissue, and draining channels that were often large and abnormal. Ancillary features commonly found were hemosiderin, thrombosis, cyst formation, focal calcification, and extramedullary hematopoiesis. With one exception, endothelial cells in RICH (as in NICH) did not express glucose transporter-1 protein, as does common infantile hemangioma. One RICH exhibited 50% postnatal involution during the 1st year, stopped regressing, was resected at 18 months, and was histologically indistinguishable from NICH. In addition, several RICH, resected in early infancy, also had some histologic features suggestive of NICH. Furthermore, NICH removed early (2–4 years), showed some histologic findings of RICH or were indistinguishable from RICH. We conclude that RICH, NICH, and common infantile hemangioma have overlapping clinical and pathologic features. These observations support the hypothesis that these vascular tumors may be variations of a single entity ab initio. It is unknown whether the progenitor cell for these uncommon congenital vascular tumors is the same as for common infantile hemangioma.

Developmental venous anomalies (DVA): the so-called venous angioma.

SummaryFollowing a review of the literature it is possible to demonstrate the “normality” of the so called venous angiomas. They should be named Developmental Venous Anomaly (DVA). They illustrate in their two extreme types (superfical and deep) the hemodynamic equilibrium of the transcortical venous drainage in the periependymal zones. Venous ectasias and varices which can be encountered, associated with DVA constitute an acquired feature in relation to a venous outlet obstacle.The sinus pericranii represents an extracerebral DVA, but also corresponds to a normal variation. As any extreme anatomical variant, each DVA corresponds to a weak situation which may express itself clinically; only rare situations justify a radical treatment.

Percutaneous treatment of low flow vascular malformations

Low flow vascular malformations, especially venous and macrocystic lymphatic malformations, are effectively treated by percutaneous intralesional injection of sclerosant drugs, such as ethanol and detergent sclerosant drugs. Good to excellent results are possible in 75%-90% of patients who undergo serial sclerotherapy. Most adverse effects are manageable, but severe complications can result from the intravascular administration of ethanol. It is generally recommended that the treatment of vascular malformations be performed in a multidisciplinary setting by practitioners with appropriate training and support.

Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast‐flow vascular anomalies are caused by RASA1 mutations

Capillary malformation‐arteriovenous malformation (CM‐AVM) is a newly recognized autosomal dominant disorder, caused by mutations in the RASA1 gene in six families. Here we report 42 novel RASA1 mutations and the associated phenotype in 44 families. The penetrance and de novo occurrence were high. All affected individuals presented multifocal capillary malformations (CMs), which represent the hallmark of the disorder. Importantly, one‐third had fast‐flow vascular lesions. Among them, we observed severe intracranial AVMs, including vein of Galen aneurysmal malformation, which were symptomatic at birth or during infancy, extracranial AVM of the face and extremities, and Parkes Weber syndrome (PKWS), previously considered sporadic and nongenetic. These fast‐flow lesions can be differed from the other two genetic AVMs seen in hereditary hemorrhagic telangiectasia (HHT) and in phosphatase and tensin homolog (PTEN) hamartomatous tumor syndrome. Finally, some CM‐AVM patients had neural tumors reminiscent of neurofibromatosis type 1 or 2. This is the first extensive study on the phenotypes associated with RASA1 mutations, and unravels their wide heterogeneity. Hum Mutat 29(7), 959–965, 2008.

Hepatic vascular anomalies in infancy: A twenty-seven-year experience

OBJECTIVE Infantile hemangioma and arteriovenous malformation (AVM) of the liver have a similar presentation but a different natural history, and therefore require different treatment. This study was undertaken to clarify differential diagnosis and management of these two biologically distinct vascular disorders. STUDY DESIGN We retrospectively analyzed the records of 43 children with hepatic vascular anomalies treated during the past 27 years. RESULTS Ninety percent were hemangiomas (n = 39); 10% were AVM (n = 4). Infants with AVM or large solitary hemangioma had hepatomegaly, congestive heart failure, and anemia as presenting symptoms at birth. Multiple hepatic hemangiomas manifested at 1 to 16 weeks of age with the same clinical triad, plus multiple cutaneous lesions (19/23). The mortality rate after treatment of hepatic AVM was 50% (2/4). The mortality rates after treatment of liver hemangiomas were as follows: resection of solitary lesions, 20% (2/10); embolization, 43% (3/7); corticosteroids, 30% (3/10); and interferon alfa-2a, 15% (2/13). CONCLUSION Solitary hepatic hemangioma cannot always be distinguished from hepatic AVM without radiologic studies. Multiple hepatic hemangiomas are differentiated from hepatic AVM by coexistence of multiple cutaneous hemangioma and by radiologic imaging. We recommend combined embolization and surgical resection for hepatic AVM and for solitary symptomatic hemangioma, if drug therapy fails. Pharmacologic treatment is used for symptomatic multiple liver hemangiomas. Embolization allows interim control of heart failure. A decreased mortality rate after interferon alfa-2a therapy is encouraging.

Venous malformations of skeletal muscle.

&NA; Intramuscular venous malformations are often mistaken for tumors because of a similar presentation and improper nomenclature. This is a review of 176 patients with venous malformations localized to skeletal muscle compiled from the Vascular Anomalies Center at Childrens Hospital from 1980 through 1999. The female‐to‐male ratio was 2:1. Two‐thirds of skeletal muscle venous malformations were noted at birth; the remainder manifested in childhood and adolescence. Venous malformations occurred in every muscle group, most often in the head and neck and extremities. Pain and swelling were the usual presenting complaints. Skeletal problems, such as fracture, deformation, or growth abnormalities, were rare. Hormonal exacerbation and intralesional bleeding were infrequent. Magnetic resonance imaging showed the lesions to be isointense to surrounding muscle on T1‐weighted sequences and hyperintense on T2‐weighted images. Characteristic tubular or serpentine components were oriented along the muscular long axis. Thrombi were hyperintense on T1‐weighted and hypointense on T2‐weighted sequences; phleboliths were seen as signal voids on all sequences. Gross examination of resected specimens revealed multicolored tissue with dilated vascular channels, frequently containing phleboliths. Light microscopy showed aggregates of primarily medium‐sized, thin‐walled vascular channels with flat endothelium and variable smooth muscle, most closely resembling dysplastic veins. Three lesions had a different histologic appearance consisting predominantly of small vessels with capillary structure and proliferative activity admixed with large feeding and draining vessels, similar to a lesion called intramuscular capillary hemangioma in the literature. The endothelium in these three lesions was negative for glucose transporter‐1 by immunostaining. Eight percent of the patients, who had minor or no symptoms, were not treated. Twenty‐four percent of the patients were managed conservatively (with aspirin and compressive garments); for 17 of these patients (10 percent of 176), noninvasive therapy was not successful, and they proceeded to sclerotherapy, excision, or both. A total of 31 percent of the patients had sclerotherapy, 20 percent had excision, and 27 percent had combined sclerotherapy and excision. Sclerotherapy was used for diffuse lesions, except for those with multiple intralesional thromboses, neurologic impairment, or compressive signs and symptoms. Resection was preferred for venous malformations well localized to a single muscle or muscle group, particularly if the muscles are expendable. Therapeutic outcomes were recorded in the charts or obtained by telephone interview in 122 of the patients (69 percent). Of these, compression garment and aspirin, resection, sclerotherapy, or combined excision and sclerotherapy improved symptoms in 121 patients (92 percent); no change was noted in 10 patients (8 percent). Only one patient was worse (self‐reported) after intervention. (Plast. Reconstr. Surg. 110: 1625, 2002.)

The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management

Background: Mutations in the PTEN gene cause two disorders that predispose to cancer, Bannayan–Riley–Ruvalcaba and Cowden syndromes. Some patients with a PTEN mutation have only macrocephaly and autism, but they may still be at risk for neoplasms. Vascular anomalies occur in patients with a PTEN mutation, but they have not been systematically studied or precisely defined. Method: We analysed the clinical and radiological features of the vascular anomalies in 26 patients with PTEN mutations who were either seen or had their medical records reviewed at Children’s Hospital Boston. Results: All 23 patients who had their head circumference measured were macrocephalic, and all 13 male patients who were fully examined had penile freckling. Vascular anomalies were found in 14/26 (54%) of patients: 8/14 (57%) had multiple lesions and 11/13 (85%) who had cross-sectional imaging had intramuscular vascular lesions. Radiographic studies showed that 12/14 (86%) were fast-flow vascular anomalies, and angiography typically showed focal segmental dilatation of draining veins. Excessive ectopic fat in the vascular anomalies was present in 11/12 (92%) of patients on CT or MRI. Intracranial developmental venous anomalies (DVAs) were found in 8/9 (89%) of patients who had brain MRI with contrast. Conclusions: Vascular anomalies in patients with a PTEN mutation are typically multifocal intramuscular combinations of fast-flow channels and ectopic fat. Cerebral DVAs are very common. PTEN mutational analysis should be considered for all macrocephalic patients with fast-flow vascular anomalies or multiple intracranial DVAs.