Distinguishing soft-tissue hemangiomas from vascular malformations using technetium-labeled red blood cell scintigraphy.

Soft-tissue vascular lesions in children can be classified as either hemangiomas or vascular malformations. The distinction between the two has important prognostic and therapeutic implications. Over the past 8 years, we have evaluated 64 vascular lesions with the technetium-labeled red blood cell (Tc-RBC) scan. Twenty-eight lesions imaged as hemangiomas with intense focal uniform uptake. This diagnosis was confirmed in 27 lesions, or 96 percent. Thirty-six lesions imaged as vascular malformations with abnormal vessels or diffusely increased activity. This diagnosis was confirmed in 35 lesions, or 97 percent. Overall, the Tc-RBC scan was 97 percent accurate in distinguishing hemangiomas from vascular malformations. It is particularly useful when the clinical diagnosis of the lesion may not be evident. Not only can biopsy be avoided, but parents can be reassured at an earlier age and given accurate information regarding prognosis.     

Local serum levels of vascular endothelial growth factor in infantile hemangioma: Intriguing mechanism of endothelial growth

The pathogenesis of hemangiomas still remains poorly understood. Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of our study was to determine the peripheral and local serum levels of VEGF in patients with hemangiomas and vascular malformations. Material and methods: The study group consisted of 52 children with infantile hemangioma (33 with proliferative lesions, 19 with involuting lesions), 14 children with vascular malformations and 36 healthy children. VEGF serum levels were analyzed by an ELISA assay and the values between the groups were compared. Results: The serum peripheral VEGF concentrations in children with proliferative hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and controls. There was no correlation between the measured cytokine level, hemangioma size, and the age of the patients. The local serum VEGF levels in 29 children with hemangiomas were distinctly lower than in the peripheral blood, both in 20 proliferating hemangiomas (p < 0.0001) and 9 involuting ones (p = 0.007); and the difference between females and males was non-significant (NS p = 0.06). Conclusions: (1) VEGF serum levels vary in the different phases of hemangioma growth and may help to distinguish hemangiomas from vascular malformations; (2) obtained local results may support the intrinsic theory of endothelial cell proliferation in hemangiomas.     

Vascular anomalies: hemangiomas

Mulliken and Glowacki categorized vascular anomalies as either hemangiomas or malformations, with the former being the most common tumor of infancy. Despite distinct clinical, radiologic, and histologic findings, the two major types of vascular lesions are often confused. This complicates both patient care and interpretation of the medical literature. A thorough understanding of the presentation, natural history, treatment, and complications of vascular tumors (hemangiomas) and vascular malformations is essential to their proper management. A comprehensive review outlining the diagnosis and treatment of hemangiomas in presented.     

Intralesional corticosteroid therapy for infantile hemangiomas

Intralesional corticosteroid injections were performed in 31 hemangiomas in 30 infants aged 1 to 10 months at first injection. One to five injections were given, spaced 6 weeks apart. Lesions were located throughout the head and neck region, except one that was on the buttock. A mixture of betamethasone acetate and triamcinolone acetonide was used. Four lesions (13 percent) virtually disappeared, ten (32 percent) showed greater than 50 percent reduction in volume, ten (32 percent) showed definite but less than 50 percent reduction in volume, and seven (23 percent) showed little or no decrease in size. None showed further growth. All injections were performed without anesthesia, and there were not significant complications. We conclude that intralesional corticosteroid injections are safe and effective in properly selected infants with hemangiomas.     

Surgical management of parotid hemangioma

Hemangiomas represent one of the most common childhood neoplasms. They are often managed conservatively, requiring numerous years for spontaneous involution. No effective medical treatment has been reported for children with large, deforming hemangiomas of the parotid gland and overlying cheek. The authors retrospectively studied 17 children who underwent surgical resection of parotid hemangiomas at Childrens Hospital Los Angeles from 1997 to 2003. All 17 patients had improvements in facial asymmetry and deformity. There were no major complications. Minor complications included hematoma (11.8 percent), transient facial nerve palsy (11.8 percent), and blood transfusion (5.9 percent). All operations were performed on an outpatient basis. Surgical resection of parotid hemangiomas provides an aesthetic benefit to young children with low associated morbidity. Early resection by an experienced surgeon should be considered as a treatment option for these disfiguring lesions.     

Vascular malformations

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the nomenclature and classification system of vascular malformations. 2. Evaluate these patients diagnostically. 3. Outline the surgical and nonsurgical options for treating these lesions. SUMMARY: Vascular anomalies can be classified into two unique groups-hemangiomas and vascular malformations-based on their endothelial properties. The present review focuses on vascular malformations rather than hemangiomas. The authors address capillary malformations, lymphatic malformations, venous malformations, and arteriovenous malformations. Diagnostic and therapeutic modalities are discussed with relevant case examples. A MEDLINE search was performed to gather all pertinent references. The physician treating these challenging lesions should ideally use a multidisciplinary team-based approach with multispecialty experience in diagnostic and therapeutic modalities for the management of vascular malformations.     

Management of parotid hemangioma in 100 children

Most problematic infantile hemangiomas are successfully treated with pharmacological therapy. However, there are reports that hemangioma of the parotid gland responds poorly to corticosteroid and interferon. To better clarify the management of parotid hemangioma, the authors retrospectively studied the records of 100 consecutive patients, seen between 1975 and 2002. The characteristics of the tumor, including sex ratio, presence at birth, size, side, complications, and involvement of adjacent structures, were recorded. The indications for and response to treatment and the need for surgical procedures were documented and statistically analyzed. The female-to-male ratio was 4.5:1. Forty percent of parotid hemangiomas were on the right side, 36 percent were on the left, and 24 percent were bilateral. Forty-five percent of patients had a premonitory cutaneous lesion at birth. Fifty-nine percent of parotid hemangiomas ulcerated during the early proliferative phase. Eighty-eight percent involved nearby structures (ear, 70 percent; lip, 34 percent; subglottic region, 21 percent; eye, 18 percent; and nose, 3 percent). Seven percent of patients required tracheostomy, and 3 percent had signs of congestive heart failure. Seventy infants received pharmacological treatment. Sixty-seven patients were initially managed with corticosteroids; regression or stabilization was noted in 83 percent of tumors (56 of 67 tumors). Twenty-one patients received interferon: 11 in whom corticosteroid therapy had failed, seven in whom the tumor stabilized with corticosteroid therapy but further regression was needed, and three who had interferon as primary therapy. Ninety-five percent of the lesions that were resistant to corticosteroid subsequently responded to interferon alfa-2a or -2b. The overall response rate to pharmacological therapy was 98 percent. A reconstructive procedure was necessary during the involuting or involuted phase in 66 percent of patients: 92 percent had preauricular excision of redundant skin and/or fibrofatty tissue and 37 percent of patients had auricular revision. In summary, drug therapy was effective in the majority of infants with parotid hemangioma, whether given because the tumor was large, deforming, ulcerated, or involved nearby structures with functional consequences. Infantile hemangioma in the parotid gland responded to pharmacological treatment in a similar manner as hemangioma in other locations.     

Complications of systemic corticosteroid therapy for problematic hemangioma.

Systemic corticosteroid therapy has been used to treat hemangiomas for 30 years; yet, there are no studies of possible complications. We reviewed the database of the Vascular Anomalies Center at the Boston Children's Hospital and gathered information on short- and long-term side effects in children who were given systemic corticosteroids for problematic hemangiomas. In addition, a questionnaire regarding early and late consequences was sent to the families of children who were treated with corticosteroids from 1983 to 1997. Of 300 patients with hemangiomas, 80 children were identified as having received a full course of systemic corticosteroids for problematic tumors. Complete data were collected on 62 of these children. The response rate to the questionnaire was 78 percent (n = 62 of 80). The initial dose of corticosteroid varied from 2 to 3 mg/kg/ day. Duration of therapy ranged from 2 to 21 months (mean, 7.9 months; median, 6.5 months). The follow-up interval from the cessation of therapy ranged from 6 months to 15 years (mean, 4 years; median, 3 years). Short-term complications included cushingoid facies (n = 44; 71 percent), personality changes (n = 18; 29 percent), gastric irritation (n = 13; 21 percent), fungal (oral or perineal) infection (n = 4; 6 percent), and diminished gain of height (n = 22; 35 percent) and weight (n = 26; 42 percent). A total of 91 percent of children who had diminished gain of height (n = 20) returned to their pretreatment growth curve for height by 24 months of age. One child, who was treated at another institution with a dose of 20 mg/kg/day for 6.5 months that was slowly tapered over 18 months, was petite 6 years after ending therapy. Another child treated with an initial dose of 2 mg/kg/day for 5 months was smaller than predicted at the age of 6 years, but she was born prematurely and was on ventilatory support for respiratory distress. Three children treated with the standard dose and duration were at a low percentile for weight 4, 5, and 10 years after the cessation of therapy. Statistical analysis showed a correlation between diminished gain of height with duration of therapy and age at initiation of treatment. One child had corticosteroid myopathy that resolved with cessation of therapy. We found no evidence for immunologic suppression, i.e., there was no increase in the number of bacterial infections during corticosteroid administration. In conclusion, systemic corticosteroids can be safely given to treat endangering hemangiomas in infants at doses of 2 to 3 mg/kg/day, which are slowly tapered and stopped before the age of 1 year. Short-term side effects were minor and transient, and no serious long-term complications occurred.     

Molecular pathogenesis of vascular anomalies: classification into three categories based upon clinical and biochemical characteristics

Vascular tumors and malformations can be challenging to diagnose. Although they can resemble one another, their classification into tumors, such as hemangiomas of infancy, and malformations, such as venous or arteriovenous malformations, is based not only on their divergent biological behavior, but also on their pathogenesis. This review examines the molecular pathobiology of the processes involved in the development of these vascular birthmarks as they are currently understood. The terms hemangioma, hemangiosarcoma, and vascular proliferation are often used interchangeably, even though these entities are clinically and biochemically distinct. A more precise classification is necessary to facilitate communication between basic scientists and clinicians. Vasculogenesis, the in situ differentiation of blood vessels, occurs very early in the developing embryo. In vivo and in vitro studies, as well as knockout models, seem to indicate that this mechanism is unlikely to be involved in the development of either vascular malformations or hemangiomas of infancy. Recent advances in embryonic angiogenesis, especially explorations of mechanisms of vascular remodeling, have brought new understanding of the pathogenesis of vascular malformations. Vascular remodeling, an integral part of angiogenesis that centers upon the interactions between pericytes and endothelial cells, has been shown to be defective in certain experimental models and in some familial cases of vascular malformation. The occurrences of arteriovenous malformations in territories susceptible to increased remodeling also point towards epigenetic events in the development of vascular malformations.     

The treatment of periorbital infantile hemangioma with intralesional corticosteroid

A series of 25 patients with periorbital hemangiomas was treated with intralesional corticosteroid injection. This resulted in a marked involution of the tumor in 16 patients, a moderate involution in 5 patients, and a minimal response in 4. No local or systemic complications were noted. The overall incidence of ocular complications in the form of amblyopia or strabismus secondary to the hemangiomas was 16 percent.     

Lower auricular malformations: their representation, correction, and embryologic correlation

Seventy-seven lower auricular malformations in 74 patients treated during the last 6 years were analyzed. Sixty cases (77.9 percent) were of malformations involving the earlobe; 54 cases involved the earlobe alone, and 6 cases were of complex deformities involving the earlobe and adjacent helix and/or tragus. Cleft earlobe was the most common lower auricular malformation (49 cases, 63.6 percent); four subtypes and their corrective methods are described. Cases of complex earlobe malformations, corrected by fabricated costal cartilage and expanded skin flap, are presented. A question mark ear (5 cases, 6.5 percent), a malformation with an ectopic anthelical fold (5 cases, 6.5 percent), and a malformation with a lower conchal stria (5 cases, 6.5 percent) are considered to be major lower auricular malformations. An attempt has been made to correlate the presented malformations with the embryologic-fetal development of the auricle. It is suggested that "clefting" ear malformations such as the cleft earlobe, the question mark ear, and the ectopic anthelical fold deformity may provide clues to understanding the embryologic-fetal development of the human auricle. It appears that hillocks 1 and 6 produce the earlobe and that hillock 4 or 5 produces the anthelix or helix.     

Argon Laser Management of Cutaneous Vascular Deformities: A Preliminary Report

Twenty-two patients with cutaneous vascular malformations were treated with an argon laser. Promising results were obtained in patients with port-wine stains, hemangiomas, telangiectasia and varicose veins. The argon laser shows promise as an effective clinical tool in the treatment of all such cutaneous vascular abnormalities. However, further study of clinical as well as laboratory data is necessary over a long period of time before this modality can be definitely recommended as the treatment of choice for vascular deformities of the skin.     

Frontonasal tumors: their diagnosis and management.

Fifty-three patients with frontonasal tumors were seen in a 17 -year period. Of these patients, 33 were females (62 percent) and 50 were caucasians (94 percent). The correct diagnosis was made preoperatively in 87 percent of the cases. Eighty-five percent of the patients were children, and most of the lesions (83 percent) were developmental anomalies rather than true neoplasms. The most common lesions were dermoids (17), hemangiomas (16), and encephaloceles (9), but 13 different types of lesions were encountered. The treatment of all is surgical excision, and a cooperative effort by the neurosurgeon and the plastic surgeon is required in some cases.     

婴儿期Klippel-Trenaunay综合征并精神运动发育迟缓病例报道及文献复习

Klippel-Trenaunay综合征(KTS)又称先天性静脉畸形骨肥大综合征,好发于儿童及青少年。临床以多发性皮肤血管瘤、肢体静脉曲张、骨及软组织肥大为特征。其病因尚不清楚,可能为遗传性血管壁间质组织发育异常所致。目前尚无特异的治疗方法,手术及介入治疗主要是减轻症状和治疗并发症。对于婴儿期出现偏侧肢体肥大并血管瘤的患儿应长期随访,早期诊断,早期干预以防止并发症。近年来有报道利用超声进行产前诊断,对及时发现和处理有重要意义。本文报道1例婴儿期KTS,以口腔黏膜血管瘤伴出血、颜面及肢体不对称性肥大为特点,并伴精神运动发育迟缓,CT见侧脑室、三脑室扩张。     

Congenital malformations and maternal smoking during pregnancy

The relationship between smoking during pregnancy and congenital malformations was studied in prospective studies of 33,434 live births in the Kaiser-Permanente Birth Defects Study and 53,512 live births in the Collaborative Perinatal Project (CPP). In the Kaiser study, statistically significant positive associations (P less than .05) were observed for ventral hernias, omphaloceles, and "other major gut abnormalities," but, for each comparison the estimates were based on one or two unexposed cases. Statistically significant negative associations were found for ventricular septal defects (odds ratio, 0.5 [95% confidence interval, 0.2-0.96]), hydroceles (0.7 [0.6-0.9]), clubfoot (0.7 [0.6-0.9]), pigmented nevi (0.7 [0.6-0.9]), hemangiomas (0.8[0.7-0.98]) and Down syndrome (0.2 [0.1-0.9]). To determine if the findings noted above were an artifact of multiple comparisons, seven of these nine malformations were analyzed by smoking status for women in the CPP. All but one of the associations were not confirmed in the CPP. Previously described associations between smoking and specific congenital malformations were also tested using data from the CPP. We conclude that smoking is unlikely to be responsible for a large increase in malformations at birth.     

UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers

We report on the first untargeted UPLC-MS study of 2nd trimester maternal urine and amniotic fluid (AF), to investigate the possible metabolic effects of fetal malformations (FM), gestational diabetes mellitus (GDM) and preterm delivery (PTD). For fetal malformations, considerable metabolite variations were identified in AF and, to a lesser extent, in urine. Using validated PLS-DA models and statistical correlations between UPLC-MS data and previously acquired NMR data, a metabolic picture of fetal hypoxia, enhanced gluconeogenesis, TCA activity and hindered kidney development affecting FM pregnancies was reinforced. Moreover, changes in carnitine, pyroglutamate and polyols were newly noted, respectively, reflecting lipid oxidation, altered placental amino acid transfer and alterations in polyol pathways. Higher excretion of conjugated products in maternal urine was seen suggesting alterations in conjugation reactions. For the pre-diagnostic GDM group, no significant changes were observed, either considering amniotic fluid or maternal urine, whereas, for the pre-PTD group, some newly observed changes were noted, namely, the decrease of particular amino acids and the increase of an hexose (possibly glucose), suggesting alteration in placental amino acid fluxes and a possible tendency for hyperglycemia. This work shows the potential of UPLC-MS for the study of fetal and maternal biofluids, particularly when used in tandem with comparable NMR data. The important roles played by sampling characteristics (e.g. group dimensions) and the specific experimental conditions chosen for MS methods are discussed.     

Magnetic resonance imaging findings of vascular malformations of the lower extremity

Vascular malformations are congenital lesions resulting from a defect during embryogenesis. Magnetic resonance imaging (MRI) is a very effective method for demonstrating detailed information regarding involved structures, extent, and flow characteristics of vascular malformations. In previous MRI studies, most of the emphasis is laid on the difference between high- and low-flow lesions, whereas little detailed information is available about the extent of local tissue involvement. These additional characteristics may influence the approach in treating these malformations and improve understanding of the pathogenesis. We retrospectively reviewed MRI scans of 40 patients with vascular malformations of the lower extremity. Thirty-four patients had low-flow lesions, and six had high-flow lesions. Of the low-flow lesions, 23 patients (67.6 percent) had muscle infiltration, with four of the six high-flow lesions having muscle infiltration. Nine of the 11 male patients (81.8 percent) with low-flow lesions had associated muscle infiltration, in comparison with 14 of the 23 female patients (60.9 percent) with low-flow lesions (p = 0.206). Eighty percent of the vascular malformations located on the thigh with muscle involvement had involvement of the anterior muscle group, whereas 86.6 percent of the patients with a vascular malformation located on the leg and with associated muscle involvement had at least the posterior muscle group involved (p = 0.0049). Ten patients (25 percent) of the whole group had bone infiltration. Low-flow lesions often had multifocal lesions (20.6 percent), whereas associated muscle atrophy was visible in 10 low-flow lesions and in two high-flow lesions. In low-flow lesions with muscle infiltration (n = 23), 43 percent (n = 10) had associated surrounding muscle atrophy (p = 0.009). Hypertrophy of the subcutaneous tissue was visible in 11 low-flow patients (32.4 percent). The high amount of muscle and bone involvement in vascular malformations of the lower extremity is emphasized with this study. Of particular interest was the difference in affected muscle groups. The angiosome concept is used to explain this preponderance, and we feel the angiosome concept could also be used when assessing possible intervention. The surrounding muscle atrophy and multifocal nature of these anomalies are further important considerations when assessing the possibility of intervention.     

Venous malformations of skeletal muscle

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 Children's 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.     

Mammographic changes following reduction mammaplasty

Mammographic findings after reduction mammaplasty may be similar to those seen with carcinoma. A knowledge of the expected mammographic alterations would be helpful in differentiating postoperative changes from those seen with carcinoma of the breast. Accordingly, the clinical records and mammograms of patients who underwent reduction mammaplasty at the Dartmouth-Hitchcock Medical Center between March of 1977 and July of 1985 were analyzed. Forty-two patients had at least one mammographic examination following reduction mammaplasty. Periareolar soft-tissue changes and inferior pole alterations were present in almost all examinations of patients during the first 6 months after operation, but they decreased during the next few years. Asymmetrical densities were present in approximately half the patients throughout the follow-up period but decreased in degree. Parenchymal calcifications occurred later; few x-rays showed these calcifications during the first year, but 50 percent were apparent after 2 years. Evidence of fat necrosis occurred in approximately 10 percent. Four patients had biopsies for suspicious densities. Chronic inflammation and inclusion cyst were reported. We believe that changes after reduction mammaplasty are predictable and can usually be differentiated from those associated with cancer.     

Secretion of SPARC by endothelial cells transformed by polyoma middle T oncogene inhibits the growth of normal endothelial cells in vitro.

Endothelioma cells expressing the polyoma virus middle T oncogene induced hemangiomas in mice by the recruitment of nonproliferating endothelial cells from host blood vessels (Williams et al. 1989). I now report that SPARC, a Ca(2+)-binding glycoprotein that perturbs cell-matrix interactions and inhibits the endothelial cell cycle, is produced by endothelioma cells and is in part responsible for the alterations in the morphology and growth that occur when nontransformed bovine aortic endothelial cells are cocultured with endothelioma cells. Normal endothelial cells cocultured with two different middle T-positive endothelial cell lines, termed End cells, exhibited changes in shape that were accompanied by the formation of cell clusters. Media conditioned by End cells repressed proliferation of normal endothelial cells, but enhanced that of an established line of murine capillary endothelium. Radiolabeling studies revealed no apparent differences in the profile of proteins secreted by aortic or capillary cells cultured in End cell conditioned media. Characterization of proteins produced by End cells led to the identification of type IV collagen, laminin, entactin, and SPARC as major secreted products. Although SPARC did not affect the morphology of End or capillary cells, it was associated with overt changes in the shape of aortic endothelial cells. Moreover, SPARC and a synthetic peptide from SPARC domain II inhibited the incorporation of [3H]thymidine by aortic cells, but had minimal to no effect on the capillary endothelial cell line. The inhibition of growth exhibited by aortic endothelial cells cultured in End cell conditioned media could be partially reversed by antibodies specific for SPARC and SPARC peptides. These studies indicate a potential role for SPARC in the generation of hemangiomas by End cells in vivo, a process that requires normal (host) endothelial cells to disengage from the extracellular matrix, withdraw from the cell cycle, migrate, and reassociate into the disorganized cellular networks that comprise cavernous and capillary hemangiomas.