Outcome of bleomycin electrosclerotherapy of slow-flow malformations in adults and children.

OBJECTIVES: To evaluate the safety and clinical outcome of bleomycin electrosclerotherapy (BEST) for treating extracranial slow-flow malformations. METHODS: In this retrospective investigation of a multicenter cohort presenting symptomatic slow-flow malformations, patient records were analyzed with respect to procedural details and complications. A treatment-specific, patient-reported questionnaire was additionally evaluated, obtained 3-12 months after the last treatment, to assess the subjective outcomes, including mobility, aesthetic aspects, and pain, as well as the occurrence of postprocedural skin hyperpigmentation. All outcome parameters were compared according to patients' age. RESULTS: Overall, 325 BEST treatments were performed in 233 patients after intralesional and/or intravenous bleomycin injection. The total complication rate was 10.2% (33/325), including 29/352 (8.9%) major complications. Patient-reported mobility decreased in 10/133 (8.8%), was stable in 30/113 (26.5%), improved in 48/113 (42.5%), and was rated symptom-free in 25/113 (22.1%) patients. Aesthetic aspects were rated impaired compared to baseline in 19/113 (16.8%), stable in 21/133 (18.6%), improved in 62/113 (54.9%), and perfect in 11/133 (9.7%) patients. Postprocedural skin hyperpigmentation occurred in 78/113 (69%) patients, remaining unchanged in 24/78 (30.8%), reduced in 51/78 (65.5%), and completely resolved in 3/78 (3.8%) patients. The median VAS pain scale was 4.0 (0-10) preprocedural and 2.0 (0-9) postprocedural. Children/adolescents performed significantly better in all parameters compared to adults (≥ 16 years) (mobility, p = 0.011; aesthetic aspects, p < 0.001; pain, p < 0.001). CONCLUSIONS: BEST is effective for treating slow-flow vascular malformations, with few but potentially significant major complications. Regarding patient-reported outcomes, children seem to benefit better compared to older patients, suggesting that BEST should not be restricted to adults. CLINICAL RELEVANCE STATEMENT: Bleomycin electrosclerotherapy is a safe and effective approach and therapy should not be restricted to adults due to good clinical outcomes in children.

Reconstruction after ablative treatment of arteriovenous malformations of the head and neck.

Arteriovenous malformations are high-flow congenital vascular malformations that are characterized by abnormal connections between arteries and veins across an abnormal capillary bed. The head and neck region is the most common location for extracranial arteriovenous malformations. Due to their highly invasive, aggressive, and locally destructive nature, arteriovenous malformations are difficult to treat, and management through a multimodal, multidisciplinary approach is recommended. The mainstay of treatment is embolization and surgical excision. With the advent of genetic research, adjuvant targeted medical therapy is starting to play a larger role. Successful surgical treatment with or without embolization requires removal of the nidus. Large, focal, or diffuse lesions involving multiple anatomic areas usually necessitates surgical reconstruction. Free tissue transfer has many advantages over more conservative methods with restoration of function and contour. Herein, the authors describe the surgical treatment and reconstruction in head and neck arteriovenous malformations.

SECg Staging System: A New Approach to the Management of Arteriovenous Malformations of the Head and Neck.

OBJECTIVES: Arteriovenous malformations (AVM) are the most troublesome vascular malformations to deal with. They tend to behave like low-grade malignancies with infiltrative and disruptive growth. Crucially, the clinical course of an AVM that has been improperly managed is usually characterized by a recurrence that is much more aggressive than the original disease. As in oncology, a comprehensive staging system is highly desirable and is to date lacking in the literature. The authors present a new comprehensive staging system. METHODS: A multicentric multidisciplinary team of experts in the field of vascular anomalies has created this new staging system. The SECg staging system defines the local extension of the disease (S1-S4), the vascular architecture of the malformation (E1, E2, E3), the severity of the symptoms (C0-C3) and the presence or absence of growth of the AVM (g+, g-). RESULTS: This staging system allows to address all the aspects of AVMs and, more importantly, to help building an appropriate, individualized treatment plan for affected patients. After being staged an AVM can be defined as (a) healable, (b) healable with predicted sequelae, or (c) unhealable. Then, the SECg system allows to outline (a) absolute indications, (b) relative indications, and (c) no indications for treatment. The purpose of the treatment (radical, palliative) is furthermore taken into consideration. CONCLUSIONS: This multicentric, the SECg staging system that this multidisciplinary group of Authors has defined allows for a comprehensive staging of the disease which in turn has enabled to outline an algorithm to properly manage AVMs.

One-Stage Supramaximal Full-Thickness Wedge Resection of Vascular Lip Anomalies.

PURPOSE: Vascular lip anomalies include infantile hemangiomas, venous malformations, and arteriovenous malformations. Surgical management can be complicated by alterations in horizontal length, vertical height, and lip thickness from the underlying pathology. Additional reconstructive challenges include preservation of oral continence, vermillion definition, and the sublabial sulcus. This report describes a technique of supramaximal single-stage full-thickness wedge resection of these lesions. MATERIALS AND METHODS: A retrospective study approved by the institutional review board of patients who underwent full-thickness resection of vascular lip anomalies from December 2007 through February 2013 was performed. Patient demographics, final diagnosis, preoperative treatment, examination findings (pre- and postoperative), intraoperative management, and follow-up findings were reviewed. RESULTS: Eighteen patients (9 female) with a mean age of 25 ± 19.8 years (range, 3 to 70 yr) were identified. Underlying pathologies were arteriovenous malformation (6), port wine stain with secondary soft tissue hypertrophy (6), capillary malformation (1), venous malformation (3), and infantile hemangioma (2). Prior treatments included embolization, lasers, surgical excision, steroids, and propranolol; 8 patients were treatment naive. All patients underwent a single or double pentagonal-shaped wedge resection of the involved upper or lower lip. An average of 3.75 cm (41.7%; range, 20 to 70%) of horizontal lip length was excised. Four patients required additional concomitant debulking of the vermillion. No intraoperative complications were noted. Postoperatively, 1 patient developed wound dehiscence at 12 days and another had a midline depression with mild oral incontinence. Follow-up averaged 1,074 days (range, 371 to 1,777 days) and patients and their parents reported a high degree of satisfaction with the improvement in lip appearance and symmetry except for 1 patient who required further debulking. The sublabial sulcus and vermillion and cutaneous definition were preserved in all cases. CONCLUSION: Despite the traditional recommendation that no more than 30% of lip length be surgically removed, vascular lip anomalies result in tissue hypertrophy, horizontal elongation, ectropion labii, and tissue expansion that allow up to 70% of the lip to be excised.

The Natural History of Soft Tissue Hypertrophy, Bony Hypertrophy, and Nodule Formation in Patients With Untreated Head and Neck Capillary Malformations.

BACKGROUND: A percentage of patients with capillary malformation (CM) develop soft tissue hypertrophy, bony hypertrophy, and/or nodule formation. OBJECTIVE: To determine the incidence, age of onset, anatomic distribution of soft tissue/bony hypertrophy, and nodule formation in patients with untreated CM. METHODS: A retrospective medical records review of head and neck CM patients presenting to a tertiary referral center over a 7-year period (2004-2011) was performed. RESULTS: Of the 160 patients with CM, 96 demonstrated progression of disease to include either soft tissue/bony hypertrophy or nodule formation. Of these, 87 patients had not received previous treatment and met the inclusion criteria for analysis. On average, soft tissue hypertrophy began at 9 years of age. The V2/maxillary segment was most commonly involved with upper lip hypertrophy being the most prominent. Fourteen percent of the patients also presented with bony hypertrophy, which began at an average age of 15 years. Nodules were present in 38/87 (44%) of patients with an average age of onset of 22 years. CONCLUSION: This study demonstrates the nature progression of CM and quantifies the clinical characteristics of hypertrophy and nodule formation with untreated head and neck CM. Early and continuous treatment is recommended in hopes of preventing CM progression.

Infantile hemangiomas exhibit neural crest and pericyte markers.

Infantile hemangiomas (IHs) are the most common benign tumors of infancy and occur with greater than 60% prevalence on the head and neck. Despite their prevalence, little is known about the pathogenesis of this disease. Given the predilection of hemangioma incidence on the face and its nonrandom distribution on embryological fusion plates, we postulated that IHs are derived from pericytes of the neural crest. We performed an analysis on 15 specimens at various stages of the IH progression. Experiments performed included immunohistochemical staining, immunofluorescent staining, quantitative real-time polymerase chain reaction, and flow cytometry. We analyzed a number of cell markers using these methods, including cell markers for the neural crest, pericytes, endothelial cells, stem cells, and the placenta. We observed that neural crest markers such as NG2 and nestin were expressed in the hemangioma samples, in addition tomultiple pericytes markers including δ-like kinase, smooth muscle actin, calponin, and CD90. Stem cell markers such as c-myc, oct4, nanog, and sox2 were also more highly expressed in hemangioma samples compared to controls. Our work demonstrates that hemangiomas express pericyte, neural crest, and stem cell markers suggesting a possible pathogenetic mechanism.

Expression Patterns of HIF-1α Under Hypoxia in Vascular Smooth Muscle Cells of Venous Malformations.

PURPOSE: The molecular pathophysiology of venous malformations (VMs), which are a type of vascular malformation, is poorly understood. Until now, it is known that VM lesions are related to the process of angiogenesis. Because angiogenesis is induced under hypoxic conditions, hypoxia is thought to be important in VM lesion formation. Therefore, we examined the implications of hypoxia on the biological behavior of VM vascular smooth muscle cells (VSMCs). In doing so, we investigated the expression patterns of hypoxia-inducible factor-1α (HIF-1α), which plays a key role in hypoxia-induced angiogenesis, to provide a further understanding of the molecular mechanisms involved in VM. METHODS: Vascular smooth muscle cells from 5 normal veins and 5 VM lesions were cultured under moderate hypoxic conditions (3% O2, 5% CO2). The effects of hypoxia on HIF-1α expression were measured by immunocytochemical staining, reverse transcription-polymerase chain reaction, and real-time reverse transcription-polymerase chain reaction. RESULTS: Overall, the expression of HIF-1α in cells was high after exposure to hypoxia for 6 or 12 hours, but decreased after 24 hours of hypoxia. HIF-1α expression in VM VSMCs was 2 times higher than that in normal VSMCs. Immunocytochemically, HIF-1α was mainly located in the nucleus and the intensity in VM VSMCs was stronger after 6 and 12 hours of hypoxia when compared to the expression pattern of HIF-1α in VSMCs from normal tissue. This suggested that VM tissue is more susceptible to the effects of hypoxia than normal tissue. CONCLUSIONS: These results indicate that the high expression of HIF-1α in VM VSMCs under hypoxic conditions could be an important factor for stimulating downstream angiogenesis in VM. Furthermore, the results of this investigation could provide the basis for future studies of VM pathophysiology, and ultimately lead to the development of new therapeutic approaches.

Surgical Management of Scalp Infantile Hemangiomas.

BACKGROUND: Scalp infantile hemangiomas (IHs) are usually focal lesions that can be both disfiguring and may lead to complications such as ulceration and bleeding. The clinical features of scalp IHs have not been previously studied. This study aims to identify the clinical characteristics associated with scalp IH, the indications for surgical intervention, and results of surgical treatment. METHODS: We performed a retrospective chart review of patients with scalp IH presenting to a tertiary care referral center over the past 7 years. Patients' demographics, clinical features, location, and treatment course were noted. RESULTS: One hundred fifty-one of 1916 total IH patients presented with a diagnosis of scalp IH (8%). The distribution of the scalp lesions was the following: 31.8% frontal, 46.7% parietal, 7.9% occipital, and 9.9% temporal. Fifty-eight percent were solitary and 42% were multifocal lesions. The size range of scalp IH is 1 × 1 cm to 8 × 6 cm. Two percent of patients with scalp IH presented with other facial IH. Primary indications for surgery were secondary to complications such as ulceration (23.2%) and alopecia (51.7%). Surgery included elliptical excision with primary closure (85.7%) or with rotational flap closure (14.3%). The average age of surgery was 3 years (1-8 years). Most patients had a good aesthetic outcome with satisfactory hair growth. CONCLUSION: Scalp IHs are morbid tumors which often cause alopecia and/or ulceration. In our experience, many scalp IHs eventually require surgical intervention. We find that early surgical excision is beneficial, as the tissues are easily manipulated secondary to scalp/soft tissue laxity and scarring is more favorable.

Advantages of Early Surgical Management of Periorbital Infantile Hemangiomas.

Background: Early evaluation and treatment of periorbital infantile hemangiomas (POIH) were associated with lower rates of ophthalmological complications. Objective: To evaluate age and characteristics associated with improved anisometropic astigmatism (anisoastigmatism) and eye symmetry measured by diopters and a 5-point scale, respectively, in patients with POIH treated with surgical excision. Methods: A retrospective study was performed on patients with POIH. Patient characteristics and eye symmetry were analyzed between patients with resolved and unresolved anisoastigmatism after surgery. Statistical analyses included the Mann-Whitney U tests, chi-square tests, and linear regression models. Results: In total, 54 patients were included (male: 20, female: 34). Upper medial eyelid was the most commonly affected site (resolved: 45%, unresolved: 43%), followed by upper lateral and upper central. Fifty-six percent (31/55) had postoperative resolution of anisoastigmatism, whereas 44% (24/55) did not. Earlier surgical evaluation (median: 4.5 vs. 6.0 months, p = 0.047) and excision (median: 5.0 vs. 12.0 months, p = 0.005) were associated with reversible anisoastigmatism. Good and suboptimal eye symmetry were not associated with earlier surgical excision (median: 6 vs. 6.5 months, p = 0.87). Follow-up ranged from 1 month to 12 years. Conclusion: Earlier surgical excision was associated with reversing anisoastigmatism but was not significant for improving eye symmetry.

Staged endovascular and surgical treatment of slow-flow vulvar venous malformations.

OBJECTIVE: The objective of the study was to report our experience in a rare series of treated symptomatic slow-flow vulvar venous malformations (VVMs) using a staged, multidisciplinary approach. STUDY DESIGN: Consecutive patients with symptomatic lesions treated over a 7 year period (2005-2012) were followed up for technical success, resolution of symptoms, aesthetic outcomes, and complications. Direct endovenous sclerotherapy (DEVS) using sodium tetradecyl sulfate (STS) foam was performed in all patients under ultrasound and contrast-enhanced fluoroscopic guidance. Surgical excision and layered primary closure was performed within 24 hours after the last DEVS session. RESULTS: Eleven patients (mean age, 25 years; range, 4-43 years) were treated. Presenting symptoms included pain (n = 11), soft tissue swelling (n = 11), local heaviness (n = 11), dyspareunia (n = 2), and dysmenorrhea (n = 2). Most were isolated lesions (n = 8). There were 2 cases of Klippel-Trénaunay syndrome and 1 case of Maffucci syndrome. The latter required Nd:YAG laser photocoagulation prior to sclerotherapy. On average, approximately 3 DEVS sessions were required prior to surgical excision (range, 1-6). Mean estimated surgical blood loss was 130 mL (range, 20-400 mL). Mean follow-up was 23 months (range, 3-55 months). Elimination of pain and soft tissue redundancy was achieved in all patients with satisfactory aesthetic outcomes. All patients experienced minor pain and swelling after DEVS. Following surgical excision, there was 1 case of hematoma and wound dehiscence requiring surgical evacuation. No other reinterventions, endovascular or surgical, were required. CONCLUSION: VVMs require increased awareness and appropriate preoperative evaluation for proper identification and treatment. A multidisciplinary approach can provide improvement in clinical signs and symptoms with satisfactory cosmesis and minimal complications.

Retrospective study of the treatment of infantile hemangiomas using a combination of propranolol and pulsed dye laser.

BACKGROUND: Infantile hemangioma (IH) clearance may be slow or incomplete in response to pulsed dye laser (PDL) or propranolol alone. OBJECTIVES: To evaluate whether IH treated with PDL and propranolol displayed more rapid and complete clearance than IH treated with propranolol alone. MATERIALS AND METHODS: Retrospective review of facial-segmental IH treated with propranolol and PDL and controls treated with propranolol was conducted. Blinded physicians used patient photographs to select clearance level and the earliest date of near-complete clearance. Days of propranolol, PDL sessions, and propranolol dose, each until date of near-complete clearance; total days of propranolol; and total propranolol dose were recorded. RESULTS: Infantile hemangiomas treated concurrently with propranolol and PDL achieved complete clearance (6/12) more often than IH treated with propranolol followed by PDL (2/5) or IH treated with propranolol alone (1/8; difference in clearance scores p = .01) and achieved near-complete clearance after fewer days of propranolol (mean 92 days for concurrent propranolol and PDL vs 288 days for propranolol; p < .001). Cumulative propranolol dose until near-complete clearance was lowest in the concurrent propranolol and PDL group (149.16 vs. 401.25 mg/kg for propranolol; p < .001). CONCLUSION: Facial-segmental IH treated with propranolol and PDL displayed morerapid and complete clearance and required a lower cumulative propranolol dose to achieve near-complete clearance.

Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells.

Diabetes mellitus is characterized by either the inability to produce insulin (type 1 diabetes) or as insensitivity to insulin secreted by the body (type 2 diabetes). In either case, the body is unable to move blood glucose efficiently across cell membranes to be used. This leads to a variety of local and systemic detrimental effects. Current treatments for diabetes focus on exogenous insulin administration and dietary control. Here, we describe a potential cure for diabetes using a cellular therapy to ameliorate symptoms associated with both reduced insulin secretion and insulin sensitivity. Using induced pluripotent stem (iPS) cells, we were able to derive beta-like cells similar to the endogenous insulin-secreting cells in mice. These beta-like cells secreted insulin in response to glucose and corrected a hyperglycemic phenotype in two mouse models of type 1 and 2 diabetes via an iPS cell transplant. Long-term correction of hyperglycemia was achieved, as determined by blood glucose and hemoglobin A1c levels. These data provide an initial proof of principle for potential clinical applications of reprogrammed somatic cells in the treatment of diabetes type 1 or 2.

Orbital development as a function of age in indigenous North American skeletons.

PURPOSE: Infants with orbital hemangiomas and vascular malformations often develop expanded orbits or regional hyperostosis. Treatment in these cases depends, in part, on the stage of orbital development at the time of intervention; yet, orbital development with respect to age is not well-known. The authors sought to determine the rate of orbital development and the age of orbital maturation in a single ethnic population. METHODS: Skeletons recovered in North America and housed at the Peabody Museum of Archaeology and Ethnology, Harvard University, were inspected. The age of specimen was determined by dentition. Orbital volume was measured using 1-mm glass beads and a graduated cylinder. Linear measurements were taken with calipers and paper rulers. The measurements were plotted against age, and statistical analysis was performed. Relevant literature was reviewed. RESULTS: Of the hundreds of skeletons examined, 42 were sufficiently intact for orbital measurement. The specimens represented a period of up to 1000 years. Thirty-two were pediatric (defined prenatal to 18 years) and 10 were adults. Mean adult orbital volume was 26.2 ml. Based on the regression analysis, 60% of adult orbital volume was achieved at 4.35 years, 75% at 9.36 years, and 90% at 17.13 years of age. Linear dimensions progressively increased with age. CONCLUSIONS: This largest direct-measure study of pediatric orbital volume suggests that orbital growth continually decelerates from birth until maturity at 22 years. With 50% of orbital growth occurring by 16 months of age, surgeons removing periocular vascular anomalies after that age should consider concurrent skeletal management.

Distribution and Clinical Characteristics of Periorbital Infantile Hemangiomas.

Background: Periorbital infantile hemangiomas (POIHs) are associated with a high incidence of visual complications. Objective(s): To analyze the sites of predilection of POIHs and to determine whether certain sites require earlier intervention due to their higher rate of visual complications. Methods: A retrospective case series study was conducted on patients from two tertiary care centers for 25 years. The location of POIHs was determined from clinical photographs, medical records, and radiological studies. The presence or absence of anisometropic astigmatism (anisoastigmatism) and amblyopia was recorded. Data were analyzed using a chi-square test. Results: There were 486 patients, of which 302 patients had ophthalmology evaluations and 245 patients had refractive error data. At presentation, 10% of patients already had amblyopia and 44% had anisoastigmatism. Medial eyelid lesions had the highest risk of developing anisoastigmatism (anisoastigmatism correlates with eyelid position, p = 0.0001). Segmental and upper medial lesions had the highest risk of amblyopia at initial evaluation. Conclusion: The site of POIH is an important indicator for developing clinically significant anisoastigmatism and amblyopia, underlining the need for early ophthalmologic assessment and management.

Percutaneous sclerotherapy of microcystic lymphatic malformations: the use of an innovative gravity-dependent technique.

BACKGROUND: In the last few decades there has been development of innovative therapies for the treatment of craniofacial lymphatic malformations. Percutaneous sclerotherapy has demonstrated efficacy in the management of macrocystic lymphatic lesions, but it is less suitable for microcystic lesions given their size. The gravity-dependent technique is a novel augmentation of standard percutaneous sclerotherapy: the technique enables a sclerosing agent to permeate the small microchannels seen in microcystic lesions that would otherwise be difficult to treat. METHODS: Between 2005 and 2021, 124 patients with microcystic or mixed lymphatic malformations were treated using a novel gravity-dependent sclerotherapy technique. Bleomycin at a maximum dose of 15 IU per session was used as the main sclerosing agent. Fluoroscopy and ultrasound were used to ensure proper positioning of the catheter prior to injecting the sclerosing agent. The response to treatment was assessed clinically and with cross-sectional imaging. RESULTS: Nearly all cases showed significant improvement after the gravity-dependent technique. There have been no permanent complications from sclerotherapy treatment. There was a mild transient adverse effect from bleomycin in one case of erythema and tenderness that lasted several weeks then ameliorated. CONCLUSIONS: The gravity-dependent sclerotherapy technique is a suitable treatment option for microcystic lymphatic malformations.

American society of pediatric otolaryngology vascular anomalies task force review of tongue venous malformations: Techniques, pearls, and pitfalls.

Management of tongue venous malformations can be challenging in the pediatric population due to their heterogeneity in presentation, extent of involvement and functional compromise. It is important to recognize the value of various treatment options in order to guide management of each patient in an individualized fashion. Here we describe a series of patients with tongue venous malformations that are managed using diverse modalities to illustrate the relative benefits and risks of each technique. The challenges of venous malformation treatment can be mitigated by tailoring the approach to each individual patient and malformation. This case series also emphasizes the need and importance of working in the setting of a multidisciplinary vascular anomalies team.

Preoperative sclerotherapy of facial venous malformations: impact on surgical parameters and long-term follow-up.

PURPOSE: To analyze the operative benefit of preoperative sclerotherapy of facial venous malformations and assess long-term patient outcome. MATERIALS AND METHODS: Preoperative sclerotherapy was performed in 24 consecutive patients referred before resection of facial venous malformation. Pretreatment imaging was reviewed for malformation dimensions (length, width, and height), and volumes were estimated. Sclerotherapy was performed with 3% sodium tetradecyl in the first 15 patients and 98% dehydrated alcohol in the remaining 9 patients. Operative blood loss, operative time, transfusion requirement, and hospital stay were recorded. Operative time per lesion volume and operative blood loss per lesion volume were calculated. Results were compared with 15 historical control patients who underwent resection of facial venous malformations without preoperative sclerotherapy. Long-term follow-up of study and control patients was performed. RESULTS: Compared with controls, patients undergoing preoperative venous sclerotherapy were significantly older (P = .0206) and had larger lesions in all three dimensions (height, P = .0002; length, P = .0010; width, P = .0004). Patients receiving sclerotherapy had shorter operative time per lesion volume (P < .0001) and reduced blood loss per lesion volume (P < .0001). Neither hospital stay nor the need for blood transfusion differed from the control patients (P = .2449 and P = .6857). Mild periprocedural complications were encountered in 12.5% of cases, and nerve paresis occurred in 8.3% of cases. Long-term follow-up revealed retreatment was required in 2 of 24 patients (8.3%). CONCLUSIONS: Preoperative sclerotherapy of venous malformations was associated with less operative time per lesion volume and less operative blood loss per lesion volume. Long-term follow-up revealed a low need for retreatment.

Differential expression of SKI oncogene protein in hemangiomas.

OBJECTIVE: The pathogenesis for benign tumorigenesis in hemangiomas is unknown. Oncogene proteins may be influential in this process. SKI proteins have been previously described in various malignancies. We investigated the differential expression of the SKI (sarcoma viral oncogene) protein in hemangiomas. STUDY DESIGN: Prospective basic science study. SUBJECTS AND METHODS: Paraffin-embedded hemangioma tissues were obtained from the senior author from 2005 to 2006. We created the first vascular tissue array composed of 12 hemangioma specimens at various stages of growth and anatomic location. Two cores were taken from each sample. Controls were also included. Immunohistochemical studies were performed using SKI, CD31, and Ki67. RESULTS: All 12 hemangioma tissues overexpressed the SKI protein. The staining pattern was perinuclear within the endothelial cells. The intensity of staining was inversely proportional to the growth stage. The endothelial cells that were SKI-positive were involved in active cell division. CONCLUSION: SKI oncogene protein is differentially and specifically expressed in hemangioma tissues. SKI acts as a transcriptional co-repressor and inhibits the TGF-beta pathway, thus leading to uncontrolled cellular proliferation and transformation. All vascular controls were negative for SKI staining. CLINICAL SIGNIFICANCE OF STUDY: The SKI oncogene protein is upregulated by hemangiomas and may play a role in hemangioma tumorigenesis.

Segmental hemangioma of infancy complicated by life-threatening arterial bleed.

Infantile hemangiomas (IHs) are the most common benign vascular tumors of childhood. IH of "segmental" morphology, are clusters of hemangiomas with a configuration involving a broad anatomic territory of skin. They are the least common of all types and generally larger than regular hemangiomas, morphologically characterized as plaque-like lesions. Head and neck segmental hemangiomas have a higher risk of causing life-threatening complications and of having associated structural anomalies, i.e., PHACES syndrome (Posterior fossa malformations, hemangiomas, arterial anomalies, coartation of the aorta and other cardiac defects, eye abnormalities and sternal clefting or supra abdominal raphe). We present a patient with a segmental IH over the right anterior neck complicated by ulceration and life threatening arterial bleeding. Although segmental hemangiomas of head and neck have high incidence of ulceration, fortunately life threatening bleeding events are rare with only 7 previously recorded cases. We recommend that large, neck IH be followed closely for evidence of ulceration and that MRI/MRA be performed to adequately assess their vascular supply. Direct extension of the ulceration into arterial vessels is a possibility and can lead to severe bleeding. Life-threatening bleeding is an unusual complication of IH and may represents a surgical emergency. In such cases we recommend a multidisciplinary approach to their treatment.