[Orbital hemangiomas: capabilities of modern neuroradiological diagnostics]. / Gemangiomy orbity: vozmozhnosti sovremennoi neiroradiologicheskoi diagnostiki.

MATERIAL AND METHODS: In the period from 2010 to 2016. 14 patients with cavernous hemangioma (CH) and 2 patients with capillary hemangioma (CapH) of the orbit were examined. The age of CH patients varied from 17 to 67 years (median, 53 years); 8 females and 6 males. The age of CapH patients was 35 and 54 years. All patients underwent surgery with subsequent histological verification. CT-perfusion was performed in 10 CH patients and 2 CapH patients according to a developed low-dose protocol (80 kV, 200 mAs, tscan=40 s) with allowance for a target localizer (80 kV, 120 mAs) and at a maximum radiation dose of not more than 4.0 mZv. Neoplasm microcirculation was quantitatively assessed by calculating hemodynamic parameters: blood flow velocity (BFV), blood volume (BV), and mean transit time (MTT). MRI without and with contrast enhancement was performed in 11 CH patients and 2 CapH patients according to the ophthalmologic protocol (Signa GE, 3.0 T) accepted at the Institute: without contrast enhancement - T1, T2, and T2-FLAIR modes, T1 and T2 with a Fat Sat technique at a scan thickness of 3 mm, and DWI MRI; contrast enhancement - T1 (three projections) mode, including the Fat Sat technique. SWAN (n=2) and non-contrast MR perfusion ASL (n=3) were also used. Diffusion-weighted images (DWI) were processed with calculation of the apparent diffusion coefficient (ACD). RESULTS: In all CH patients, CT-perfusion revealed low perfusion parameters of blood flow: BVCH=0.86±0.37 mL/100 g, BFVCH= 4.89±2.01 mL/100 g/min with a high mean transit time MTTCH=10.13±3.05 s compared to the same parameters of blood flow in the normal white matter: CBVNormWM=1.63±2.22 mL/100 g, CBFVNormWM=9.72±3.13 mL/100 g/min, and MTTNormWM=6.76±2.78 s. In CapH cases, significantly increased blood flow velocity and volume values and a low MTT value in the tumor were observed: BVCapH=10.30±4.10 mL/100 g, BFVCapH=119.72±53.13 mL/100 g/min, and MTTCapH=4.35±1.79 s. In the case of orbital hemangiomas, optimal MRI modes were T1 and T2 with the Fat Sat technique, a scan thickness of 3 mm, and intravenous contrast enhancement. The revealed pattern of contrast agent accumulation by CH, initially in the central part and then in the periphery, may be a useful radiographic sign in the differential diagnosis with other orbital tumors. CONCLUSION: Modern CT- and MRI-based diagnostics of orbital hemangiomas provides not only the exact location, size, and spread of the lesion but also reveals the characteristic structural features of these tumors, and the use of perfusion techniques visualizes hemodynamics of the tumors. CT-perfusion-based hemodynamic parameters of cavernous hemangiomas typical of this type of hemangiomas may be used in the differential diagnosis with other tumors of this location. The use of contrast enhancement and the Fat Sat technique with a scan thickness of not more than 3 mm is optimal for MRI diagnostics of orbital hemangiomas.

Intravitreal bevacizumab and feeder vessel laser treatment for a posteriorly located retinal capillary hemangioma.

Retinal capillary hemangioma (RCH) is strongly associated with von Hippel-Lindau (VHL) disease. Treatment of this sight-threatening condition is often unsatisfactory despite multiple treatment options available. We here describe an interesting case of a 50-year-old male with RCH located in the perifoveal region of the left eye. Subretinal bleed, exudation, and macular edema resulted in progressive deterioration of visual acuity. Fundus photography, fluorescein angiography, and optical coherence tomography (OCT) were used to serially monitor the lesion. After ruling out systemic lesions of VHL disease, the patient was subjected to direct laser photocoagulation of the lesion which resulted in further loss in vision with increase in bleed and exudation. Subsequently, the patient was given 2 monthly intravitreal injections of bevacizumab followed by laser photocoagulation of feeder arteriole. This combination therapy resulted in resolution of exudation, bleed, and macular edema with improvement in visual acuity. Thus, vision-threatening RCH may be safely and effectively treated by means of a combination therapy comprising of intravitreal bevacizumab and feeder vessel treatment.

Effect of topical propranolol gel on plasma renin, angiotensin II and vascular endothelial growth factor in superficial infantile hemangiomas.

The effect of topical propranolol gel on the levels of plasma renin, angiotensin II (ATII) and vascular endothelial growth factor (VEGF) in superficial infantile hemangiomas (IHs) was investigated. Thirty-three consecutive children with superficial IHs were observed pre-treatment, 1 and 3 months after application of topical propranolol gel for the levels of plasma renin, ATII and VEGF in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants of the same age from out-patient department. The clinical efficiency of topical propranolol gel at 1st, and 3rd month after application was 45%, and 82% respectively. The levels of plasma renin, ATII and VEGF in patients pre-treatment were higher than those in healthy infants (565.86 ± 49.66 vs. 18.19 ± 3.56, 3.20 ± 0.39 vs 0.30 ± 0.03, and 362.16 ± 27.29 vs. 85.63 ± 8.14, P < 0.05). The concentrations of VEGF and renin at 1st and 3rd month after treatment were decreased obviously as compared with those pre-treatment (271.51 ± 18.59 vs. 362.16 ± 27.29, and 405.18 ± 42.52 vs. 565.86 ± 49.66 P < 0.05; 240.80 ± 19.89 vs. 362.16 ± 27.29, and 325.90 ± 35.78 vs. 565.86 ± 49.66, P < 0.05, respectively), but the levels of plasma ATII declined slightly (2.96 ± 0.37 vs. 3.20 ± 0.39, and 2.47 ± 0.27 vs. 3.20 ± 0.39, P > 0.05). It was indicated that the increased renin, ATII and VEGF might play a role in the onset or development of IHs. Propranolol gel may suppress the proliferation of IHs by reducing VEGF.

[Capillary hemangioma in renal hilum; a case report].

A 76-year-old woman with a capillary hemangioma in renal hilum is reported. She was referred to our hospital with left cystic renal tumor detected by ultrasonography during the hepatitis C follow-up. Computed tomography revealed a retroperitoneal tumor in the left renal hilum with contrast effect. A hypervascular tumor in the renal hilum with severe fibrous adhesion was observed with laparoscopy and open tumorectomy was indicated. However, left radical nephrectomy was required because of severe adhesion. Histopathologic examination revealed capillary hemangioma without malignancy. Because preoperative diagnosis of capillary hemangioma was challenging, surgical excision was selected as a treatment for this rare entity.

Haemangiomas in kidneys with end-stage renal disease: a novel clinicopathological association.

AIMS: The study of haemangiomas in end-stage renal disease (ESRD). METHODS AND RESULTS: Twenty ESRD nephrectomies from 16 patients (aged 9 months-68 years) were due to hypertension (four), focal segmental glomerulosclerosis (four), lupus nephritis (three), diabetes (one), IgA nephropathy (one), hereditary nephritis (one), congenital nephrotic syndrome (one) and unknown cause (one). Haemangiomas appeared as a single mass (15), two masses (one), three masses (one), four masses (two) and eight masses (one) per kidney. Tumours measured 0.2-3.5 cm. Four patients had bilateral haemangiomas. All tumours were in the medulla and often abutted renal sinus fat. All except one of the tumours were anastomosing haemangiomas, showing isolated or interconnected sinusoidal capillary-sized vascular channels lined by a single layer of benign cuboidal CD34(+) , CD31(+) , D2-40(-) endothelial cells, separated by loose stroma with spindle cells. One tumour was a cellular capillary haemangioma. Intravascular growth was seen in nine specimens. All haemangiomas had extramedullary haematopoiesis. Acquired cystic kidney disease (ACKD) was seen in 11 kidneys (nine patients), renal cell carcinoma (RCC) in five, ACKD-associated RCC precursors in three, Wilms' tumour in one and papillary adenomas in five. CONCLUSIONS: Anastomosing haemangioma appears as a distinctive clinicopathological entity developing in kidneys with ESRD, with or without ACKD.

An experimental study on the therapy of infantile hemangioma with recombinant interferon γ.

BACKGROUND/PURPOSE: The purpose of this investigation was to study the effect of interferon γ (IFN-γ) in the treatment of infantile hemangioma. METHODS: Hemangioma tissue excised from a 4-month-old female infant who underwent surgery were separated into small nubs (4 × 4 × 5mm(3)) and implanted subcutaneously into nude mice (2 nubs per mouse). Thirty-two surviving hemangioma nubs were randomly divided into 2 groups, an IFN-γ-administered group (16) and a control group (16). Interferon γ or saline solution was injected subcutaneously, and the growth of hemangioma in the nude mice was monitored. Proliferation and apoptosis of hemangioma were tested by immunohistochemistry and real-time polymerase chain reaction. RESULTS: Seven days after IFN-γ injection, the hemangiomas in the IFN-γ-administered group were significantly smaller than that in the control group (P < .01). The proliferation cytokine Ki-67 mRNA in the IFN-γ group was significantly lower than that in the control group (P < .05). DAPK-1 mRNA in the IFN-γ group was significantly higher than that in the control group (P < .05). Cell apoptosis expression in the IFN-γ group was significantly more than that in controls (P < .05). CONCLUSIONS: Exogenous IFN-γ can treat hemangioma effectively in a nude mice model. Its mechanism was closely related to both inhibition of hemangioma proliferation and acceleration of its apoptosis.

59-year old female with suprasellar mass.

Intracranial capillary hemangiomas are extremely rare. Only 14 histologically proven cases have been reported in the literature. A 59-year-old-female presented with a severe headache for 3 weeks. Brain MRI revealed a homogeneous contrast enhancing round mass lesion in the pituitary stalk and infundibular recess. We performed endoscopic biopsy. In the operative field, a reddish, well-circumscribed mass from the infundibular recess protruded into the third ventricle and it was separated from the optic chiasm. The tumor appeared a highly vascular. Histopathological examination demonstrated an aggregation of thin-walled capillaries, consistent with capillary hemangioma.

Eosinophilic globules in 3 cases of glomeruloid hemangioma of the head and neck: a characteristic offering more evidence for thanatosomes with or without POEMS.

Glomeruloid hemangiomas (GHs) are glomeruli-like capillary tufts lined by endothelial cells that contain periodic acid-Schiff (PAS) positive eosinophilic globules (EGs). These hemangiomas are characteristic cutaneous manifestation of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). Hemangiomas histologically identical to GHs but not associated with POEMS have recently been designated as papillary hemangiomas. In this report, we present solitary head and neck GHs in 3 patients, 2 without POEMS, with particular attention to the characteristic EGs. We performed immunostains for hemoglobin A, kappa and lambda light chains, factor VIII-related antigen, CD31 and CD34, PAS stain after diastase digestion (PASD), and electron microscopic examinations on routinely fixed tissues containing EGs. Eosinophilic globules stained uniformly positive for PASD but only peripherally positive for hemoglobin and light chains on surfaces, with interiors negative for antigens. Factor VIII-related antigen and CD31 and CD34 confirmed cells containing EGs to be endothelial. Electron microscopic examination suggested that EGs are enlarged secondary lysosomes (thanatosomes). These features fail to support red blood cells or immunoglobulins as EG constituents. Glomeruloid hemangiomas may be vascular proliferations stimulated by endothelial cells' protein phagocytosis but not by phagocytosis of either hemoglobin-containing red blood cells or immunoglobulins. The vascular lesions in POEMS syndrome appear identical to papillary hemangioma in cases without the other syndromic manifestations.

Differential expression of decorin by human malignant and benign vascular tumors.

An increasing amount of evidence indicates that a small extracellular chondroitin/dermatan sulfate proteoglycan, decorin, is indirectly involved in angiogenesis. Given that angiogenesis is a sine qua non for tumor growth and progression, we attempted to examine whether human malignant vascular tumors differ from human benign vascular tumors in terms of their decorin expression and synthesis. CD31 immunostaining demonstrated that the human malignant vascular tumors Kaposi's sarcoma and angiosarcoma were filled with capillary-like structures, whereas in benign cavernous and capillary hemangiomas, blood vessels were not as abundantly present. By utilizing in situ hybridization and immunocytochemical assays for decorin, we showed that there was no detectable decorin mRNA expression or immunoreactivity within the tumor mass in the Kaposi's sarcoma or angiosarcoma group. Instead, decorin was expressed in the connective tissue stroma lining the sarcoma tissue. In contrast to sarcomas, in hemangiomas, decorin mRNA expression and immunoreactivity were observed also within the tumor mass, particularly in the connective tissue stroma surrounding the clusters of intratumoral blood vessels. Finally, distribution of type I collagen was found to be similar to that of decorin in these tumor tissues. Our findings can be explained with different states of angiogenesis in dissimilar growths. In sarcomas, angiogenesis is extremely powerful, whereas in hemangiomas, angiogenesis has ceased. Thus, decorin is likely to possess a suppressive effect on human tumor angiogenesis in vivo, as previously described by studies using different experimental models. Decorin certainly provides a usable biomarker for distinguishing between benign and malignant vascular tumors in patients.

The effect of intralesional steroid injections on the volume and blood flow in periocular capillary haemangiomas.

AIM: To examine the effect of steroid therapy on the volume estimates and blood flow characteristics of childhood periorbital capillary haemangiomas. PATIENTS AND METHODS: Children at risk of amblyopia due to periorbital haemangiomas were treated with intralesional steroid injections (between 1 and 4 courses) and serial assessment of the volume and blood-flow characteristics of the lesions measured using colour Doppler ultrasonography. The characteristics of the haemangiomas in these children were compared with a cohort of untreated cases. RESULTS: Eight of nine treated children were female, this proportion being significantly different from the equal sex distribution of an untreated cohort (p < 0.05). All children in the steroid-treated group presented within 1 month of birth, compared to the untreated children, who presented at an average of 2.1 months of age (range 0-14, median 2.9 months) (p = 0.04) and they required significantly longer follow-up in the Orbital service (mean 65 months, range 26-105), compared with an average of 35 months (range 4-92, median 23) in the untreated group (p = 0.002). The maximum estimated volume of the lesions were significantly larger in the treated group (treated group mean 8.9 ml, untreated group mean 4.1 ml; p = 0.016), with a trend towards higher maximum measured blood velocities in the treated group (treated mean 64 cm compared with untreated mean 52 cm; p = 0.1). Steroid injections appear to reduce the volume and blood flow of haemangiomas, this suppression persisting for several months (between 5 and 20) before the lesion later displays the cyclic fluctuations in volume and flow seen with untreated lesions. All treated haemangiomas had some residual vascular anomaly, detectable on ultrasonography, at last follow-up--this being despite absence of clinical signs in most cases. CONCLUSION: Periorbital capillary haemangiomas requiring steroid therapy for risk of amblyopia were significantly commoner in females, were larger lesions and presented at an earlier age. Intralesional steroids appear to cause a reduction of blood flow, with a transient reduction in volume and a suppression of the natural cyclic variation seen without treatment. The changes after a course of steroid therapy appear to last for between 5 and 20 months, this period of suppression of the lesion probably being particularly useful during infancy and early childhood when the child is at greatest risk of amblyopia.

Capillary vascular malformation response to increased ambient temperature is dependent upon anatomical location.

BACKGROUND: It has been documented that capillary malformations (CMs) located on the limbs tend to respond less well to laser treatment than those sited on the head and neck. However, there is little evidence available to explain this observation. OBJECTIVES: To investigate potential differences between CMs located on the head and neck with those on the limbs, by comparing their response to increasing ambient temperature. METHODS: Fifteen previously untreated subjects with CMs were compared as the ambient temperature was increased from 20 degrees C to 28 degrees C. These included 10 with head and neck CMs and 5 with limb CMs. The following measurements were taken at 2 degrees C intervals: cutaneous blood flow, capillary diameter, density and depth, CM color, skin and core temperatures. RESULTS: There were no statistically significant differences in mean capillary depth, diameter, density, or CM color between groups. Cutaneous blood flow increased with ambient temperature in the head and neck CMs (P = 0.009) and was significantly higher than that in the limb CMs at all temperatures (P < 0.001), while the limb CMs did not demonstrate any increase in cutaneous blood flow with temperature. CONCLUSIONS: These results suggest a possible reason for the poorer response to laser treatment seen in limb CMs: since cutaneous blood flow is a product of the blood flow velocity and hemoglobin concentration, malformations with lower blood perfusion would have less chromophore available and therefore be less suitable for laser destruction.

Natural history of periocular capillary haemangiomas: changes in internal blood velocity and lesion volume.

AIM: Although the clinical characteristics of childhood periocular capillary haemangiomas are well known, serial measurements of blood velocity and lesion size are unknown. This investigation was designed to measure the changes in maximum blood velocity and estimated size of lesion in children with capillary haemangioma not requiring active intervention. STUDY DESIGN: Retrospective case-note review for a cohort of children with capillary haemangioma involving the eyelid and orbit. PATIENTS AND METHODS: Children with periocular capillary haemangioma, under the care of the Orbital unit at Moorfields Eye Hospital between 1996 and 2005, were monitored clinically and with repeated ultrasonographic examination. Volume estimates were calculated as an ovoid based on the three maximum orthogonal measurements for the haemangioma, and blood velocity was assessed by Colour Flow Mapping, Colour Doppler Energy Imaging, and Spectral Doppler techniques using a Sequoia 512 Acuson scanner. RESULTS: Twenty-four children (12 boys) had initial assessment by 18 months of age, and the haemangioma increased in size in 14/24 (58%), the increase being between 4 and 931% of initial volume estimate. The largest measured size for an individual haemangioma appears inversely related to the child's age at measurement, this mirroring a similar trend in measurements for the maximum blood velocity. Blood velocity measurements also tend to decrease with time, the peak velocity being before 1 year of age in the majority (15/24; 62%). In many children, both volume estimates and blood velocities show a cyclic variation-this occurring with increasing intervals between the maxima, before a final decay in both parameters. Although, for the whole group, there was no correlation (correlation coefficient=0.29) between estimated size and measured blood velocity, some individual children showed a significant correlation between the two parameters. The age at maximum blood velocity appeared to precede the age at maximum volume in most children, and in many there was an orbital anomaly detectable on ultrasonographic examination, even with complete clinical resolution of the haemangioma. CONCLUSIONS: Ultrasonographic examination of periocular capillary haemangiomas show that these lesions have a very high blood velocity in feeding vessels-about 2-3 orders of magnitude greater than normal capillary beds-and that the velocity and volume of such lesions undergo a cyclic variation during their natural history. Evidence suggests that both velocity and volume decrease with time, although often not returning to zero on ultrasonography (unlike the clinical resolution of the lesions). In most children, blood velocity peaks before volume estimates and this might suggest that decreasing perfusion leads to later tissue atrophy and involution of the haemangioma.

Photodynamic therapy for vasoproliferative retinal tumors.

PURPOSE: To report our experience with photodynamic therapy (PDT) with verteporfin for patients with vasoproliferative retinal tumors (VPRTs). METHODS: Three patients with VPRTs who presented with macular exudative changes were treated with one session of PDT with 6 mg/m body surface area of verteporfin and a light dose of 100 J/cm at 689 nm delivered in 166 seconds. Biomicroscopy, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; visual acuity was measured using Early Treatment Diabetic Retinopathy Study criteria. RESULTS: At the 1-year follow-up, all tumors responded with a reduction in size (mean height: pretreatment, 2.96 mm; posttreatment, 1.32 mm), and optical coherence tomography showed complete resolution of macular exudates. For all patients, fluorescein angiography evidenced reduction of leakage from the lesion, and indocyanine green angiography verified nonperfusion of the vascular channels. An improvement in visual acuity (average, 4.7 Early Treatment Diabetic Retinopathy Study letters) was observed. No retreatment was needed. CONCLUSION: PDT may represent an effective and safe modality of treatment for VPRTs because of its selectivity. Our study supports the application of a light dose of 100 J/cm, although further studies with larger numbers of cases and longer follow-ups are required.

Colour Doppler ultrasound patterns and clinical follow-up of incidentally found hypoechoic, vascular tumours of the spleen: evidence for a benign tumour.

Between January 1990 and January 2005, incidental hypoechoic, vascular tumours of the spleen were identified in 13 patients using B-mode and colour Doppler ultrasound (CDS). All lesions found were well demarcated, intrasplenically located, and ranged in size between 1 cm and 4 cm. The increased vascular pattern on CDS was confirmed in 9 of the 13 cases by contrast enhanced ultrasound (CES), while two patients showed reduced vascularity on CES. In 10 patients, lesions were confirmed by contrast enhanced CT. Histological examination was performed in three patients with the diagnosis of capillary haemangioma (n = 2) and hamartoma (n = 1). In the remaining cases, ultrasound follow-up was performed (range 4 months to 13 years) and demonstrated no evidence of tumour growth in all but one patient. During a 4 year follow-up, one lesion increased in size from 1.0 cm to 1.5 cm and in the same patient an additional 0.5 cm sized hypoechoic increased vascular lesion was also found. In the spleen a hypoechoic lesion with an increased vascular pattern incidentally found by ultrasound most likely indicates a benign tumour with capillary haemangioma/hamartoma as the most likely diagnosis. However, it should be emphasised that in all cases a careful ultrasound follow-up is warranted.

Endothelial nitric oxide synthase expression in pulmonary capillary hemangiomatosis.

Pulmonary capillary hemangiomatosis (PCH) is an unusual disorder characterized by the proliferation of capillaries in the alveolar septa and pulmonary interstitium. Originally conceived as a primary idiopathic disorder of the pulmonary microcirculation, recent studies have demonstrated that PCH may be associated with other pathologies. Nitric oxide (NO) is a gaseous free radical with protean biological effects that is released during the intracellular conversion of arginine to citrulline. Nitric oxide synthases (NOS) mediate the production of NO and the release of NO in the microvasculature is specifically catalyzed by endothelial NOS (NOS-III). As NOS contributes to angiogenesis and is reduced in the hypertensive pulmonary microcirculation, we examined the expression of NOS-III protein in situ in the lungs of patients with PCH. Reduced microvascular expression of NOS-III protein by endothelial cells was observed in 4/6 (67%) cases of PCH, and all of these showed concomitant pulmonary vascular hypertensive remodeling. In 2/6 (33%) cases of PCH with no morphologic evidence of pulmonary hypertensive arteriopathy, endothelial expression of NOS-III protein was judged to be either minimally reduced or normal. These findings suggest that NOS-III is specifically reduced in PCH when pulmonary arterial hypertensive remodeling is concomitantly present.

The HIF-2alpha/VEGF pathway activation in cutaneous capillary haemangiomas.

AIM: To investigate the pathogenesis of capillary haemangiomas, a common form of vascular malformation. METHODS: Twenty-five cutaneous capillary haemangiomas, excised from patients under 14 years of age, were studied immunohistochemically for endothelial cells, the angiogenic factors thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF), the proliferation index Ki-67, and the hypoxia inducible factors-1alpha (HIF-1alpha) and -2alpha (HIF-2alpha). RESULTS: Endothelial-lined channels reacted strongly with CD31 in all cases, clearly definining capillary spaces. Between 5 and 20% of the endothelial cells were Ki-67 positive, indicating an intense proliferative activity; more importantly, they consistently expressed VEGF and HIF-2alpha, and in many cases TP, but failed to react with HIF-1alpha. CONCLUSION: It is suggested that the activation of the HIF-2alpha pathway and the consequent overexpression of VEGF by the endothelial cells are involved in the pathogenesis of cutaneous capillary haemangiomas.

Pathophysiology of capillary haemangioma growth after birth.

Capillary haemangiomas (CHs) are the most common soft tissue tumours of infancy. It is generally believed that the primary defect in CHs is intrinsic to endothelial cells, but their pathogenesis is yet poorly understood. The relatively low oxygen environment, in which the human foeto-placental unit develops, during the first trimester, is necessary to induce vasculo-angiogenesis via embryonic endothelial cells proliferation, since these cells are sensitive to hypoxia and acidosis. In newborn infants with haemangioma, persistent embryonic primitive endothelial cells trapped in the intimae underneath the developing vessels, and representing "leader" endothelial cells, can stabilise the labile vascular endothelial growth factor mRNA (VEGF mRNA), produce other angiogenic factors, degrade the underlying basement membrane and invade into the stroma of the neighbouring tissue. With bearing down, the transition from intra- to extra-uterine life is accompanied by more or less pronounced hypoxia. Consequently, in babies with haemangioma, hypoxia can act as a switch to activate these "leader" endothelial cells and thereby initiate a cascade of reactions leading to CH proliferation. As they are regulated by embryonic cells, the haemangioma growth mechanisms pursue the pathway of embryonic angiogenesis and it will stop at the end of the embryonic endothelial cell cycle. Addressing this mechanism in vivo has partly been done (the angiogenic peptide bFGF varies with haemangioma growth). Thus, early treatment seems necessary in infants with haemangioma, before the endothelial cells achieve their proliferative stage. The use of an antibody to interfere with VEGF receptors provides a particular attractive strategy.

Thoracic intradural extramedullary capillary hemangioma.

We report a case of a thoracic intradural extramedullary capillary hemangioma. The MR imaging appearance was nonspecific for this lesion, and it could not be distinguished from more common spinal intradural extramedullary lesions. The presence of subtly enlarged abnormal vessels on contrast MR images should, however, lead one to consider a vascular mass and order preoperative spinal arteriography.

Localized arteriole formation directly adjacent to the site of VEGF-induced angiogenesis in muscle.

We have shown previously that implantation of myoblasts constitutively expressing the VEGF-A gene into nonischemic mouse skeletal muscle leads to overgrowth of capillary-like blood vessels and hemangioma formation. These aberrant effects occurred directly at the implantation site. We show here that these regions result from angiogenic capillary growth and involve a change in capillary growth pattern and that smooth muscle-coated vessels similar to arterioles form directly adjacent to the implantation site. Myoblasts genetically engineered to produce VEGF were implanted into mouse leg muscles. Implantation sites were surrounded by a zone of dense capillary-sized vessels, around which was a second zone of muscle containing larger, smooth-muscle-covered vessels but few capillaries, and an outer zone of muscle exhibiting normal capillary density. The lack of capillaries in the middle region suggests that the preexisting capillaries adjacent to the implantation site underwent enlargement and/or fusion and recruited a smooth muscle coat. Capillaries at the implantation site were frequently wrapped around VEGF-producing muscle fibers and were continuous with the circulation and were not observed to include bone-marrow-derived endothelial cells. In contrast with the distant arteriogenesis resulting from VEGF delivery described in previous studies, we report here that highly localized arterioles also form adjacent to the site of delivery.