Neonatal haemangiomatosis in identical twins with twin-twin transfusion syndrome

INTRODUCTION: Benign natal haemangiomatosis is characterised by the presence of multiple congenital haemangiomas restricted to the skin. It is differentiated from diffuse neonatal haemangiomatosis in which there is both cutaneous and visceral involvement, with higher morbidity and mortality. PATIENTS AND METHODS: Two identical twins, I and II (monochorionic placenta, biamniotic), born prematurely at 30 weeks' amenorrhoea, presented twin-transfusion syndrome resulting in retarded intrauterine growth in twin I, the donor, and incipient anasarca in twin II, the recipient. Twin I weighed 960 g while twin II weighed 1 200 g. At birth, miliary haemangiomatosis was observed in both infants (16 haemangiomas in I, 19 in II). Abdominal ultrasound and whole-body MRI performed in the two children revealed multiple angiomatous hepatic nodular lesions in I. Subsequent routine clinical and ultrasound monitoring (hepatic and cardiac) showed increased size of the haemangiomatous lesions over the first 4 months followed by stabilisation and gradual regression. No systemic therapy was required. In twin I an episode of ulceration of a neck haemangioma occurred at 5 months and a favourable outcome was obtained on administration of topical hydrocolloid therapy. DISCUSSION: Twin-transfusion syndrome affects 15 to 30% of monochorionic biamniotic pregnancies. It is a serious complication of twin pregnancies resulting from a dynamic process of interfoetal blood transfusion as a result of venous-venous or arteriovenous vascular anastomoses. In the present case, which appears to be the first reported case, it seems that these monochorionic twins, who shared the same placenta, presented haemangiomatosis simultaneously in utero, if we accept the hypothesis of grafting of emboli of placental microvessels in the formation of congenital haemangiomas.     

Endothelial cells in infantile haemangiomas originate from the child and not from the mother (a fluorescence in situ hybridization-based study)

BACKGROUND: Infantile haemangiomas are benign vascular tumours of infancy of unknown origin. Their aetiological relationship to maternal cells has been questioned given that they develop during the neonatal period. OBJECTIVES: As endothelial cells in the placenta may be of maternal or fetal origin, we questioned whether vascular haemangioma cells originated from fetal or maternal tissue. METHODS: We aimed to detect, by using fluorescence in situ hybridization, maternal XX cells in the male XY tissue in four specimens of infantile haemangiomas obtained from boys. A sample of a female infantile haemangioma was used as a positive control and a male specimen of melanocytic naevus as a negative control. RESULTS: In one case of infantile haemangioma, a single XX female - probably maternal - cell was detected in the infantile haemangioma. All the other cells from this male as well as the three other informative specimens were uniformly negative for XX cell detection. CONCLUSION: Our results support the hypothesis that endothelial cells of infantile haemangiomas appear to derive from the child itself, in accordance with other studies.     

Expression of allograft inflammatory factor-1 and CD68 in haemangioma: implication in the progression of haemangioma

Background Recent studies revealed that immune and immune‐mediated inflammatory events may contribute to the pathogenesis of haemangioma. As a modulator of immune responses, the allograft inflammatory factor‐1 (AIF‐1) is involved in immune dysfunction and macrophage activation. Objective To investigate the possible role of AIF‐1 in the progression of haemangioma. Methods In a retrospective study of haemangiomas in the oral and facial regions, we assessed lesional immunoreactivities for AIF‐1, CD68 and Ki67. Negative controls were similarly confirmed, including 24 pyogenic granulomas, 26 vascular malformations, five samples of normal skin, 10 squamous cell carcinomas of the tongue and three placentas. Immunostaining for each antigen in the haemangiomas was compared with control tissues. Results Out of all the samples, intense immunoreactivity for AIF‐1 was detected in 17 of 19 (89%) haemangioma specimens, with a specific location in the endothelial cells. The intensity of AIF‐1 immunostaining did not show remarkable difference among proliferating, involuting and involuted haemangiomas. CD68‐positive endothelial cells were found in the neovessels of haemangiomas, as well as in pyogenic granulomas and squamous cell carcinoma. Conclusions The exclusive expression of AIF‐1 on endothelial cells of haemangiomas suggests that it may play a significant role in the pathophysiology and progression of haemangiomas. AIF‐1 can be used as an additional biomarker for infantile haemangiomas. CD68‐positive cells participate in the neovessel formation during proliferative haemangioma and contribute to the promotion of haemangioma growth.     

NDRG1 and FOXO1 regulate endothelial cell proliferation in infantile haemangioma

The etiopathogenesis of infantile haemangioma has not been well understood, and it is accepted that angiogenic mediator dysregulation is the main contributor to the abnormal haemangioma capillary formation. The role of NDRG1, a hypoxia‐inducible protein; FOXOs, which are tumor suppressor proteins; and the mTOR complex 2 pathway in infantile haemangioma have not been studied yet. The purpose of this study was to investigate NDRG1 and FOXO1 expression in the infantile haemangioma and the correlation of these proteins with proliferation and involution. Primary endothelial cells were obtained, with parental agreement, from 12 infantile haemangioma patients during surgery; 6 patients had proliferating infantile haemangiomas and 6 had involuting IHs. We compared the infantile haemangioma tissues and primary endothelial cells with human vein endothelial cells using microarrays, real‐time PCR, Western blotting and immunohistochemical staining. Our data indicated that FOXO1 expression was downregulated in proliferating infantile haemangioma tissue. We found that the expression of NDRG1, a molecule upstream of the FOXO1 pathway, increased during haemangioma proliferation. NDRG1 knockdown decreased haemangioma endothelial cell proliferation and downregulated c‐MYC oncoprotein levels. Our findings suggest that NDRG1 positively regulates haemangioma proliferation. FOXO1 dysregulation plays an important role in infantile haemangiomas pathogenesis.     

Treatment of ulcerated haemangiomas with a non‐coherent pulsed light source: Brief initial clinical report

Background: Ulceration is the most common complication of infantile haemangiomas and constitutes an authentic therapeutic challenge because of associated pain, infection, haemorrhage and subsequent scarring. Objective: To report our experience with an intense pulsed light (IPL) system in the treatment of ulcerated haemangiomas. Methods: Case 1: A 4‐month‐old girl, with haemangioma affecting the entire cutaneous surface of the left limb, developed four ulcerations on the inner aspect of this extremity. Two sessions with an IPL system using a triple pulse mode, a 570‐nm lower cut‐off filter and a fluence of 38?J/cm² were performed. Case 2: A 5‐month‐old girl with ulcerated labial haemangioma that previously failed to respond to intralesional corticoids was treated with an IPL system device. Three sessions using a triple pulse mode with a 570‐nm lower cut‐off filter and a fluence of 48?J/cm² were realized. Results: Good results were rapidly obtained after two and four sessions of IPL treatment, respectively. Pain was soon relieved and complete epithelization was obtained by between 1 and 2 months in both patients. Conclusion: Although our experience is rare, we believe that IPL devices may be an effective alternative treatment of ulcerated haemangiomas.     

Unusual presentation of GLUT-1 positive infantile haemangioma

Infantile haemangiomas are usually not present at birth. This is a case of a female infant with an atypical congenital vascular tumour present at birth which ulcerated in the first few days of life, involuted over several months and showed histopathological features in keeping with either an involuting GLUT-1 positive infantile haemangioma or a reticular haemangioma of infancy. The initial clinical presentation was atypical for an infantile haemangiomas and for a congenital haemangioma, however the histopathology and immunohistochemistry assisted with confirmation of the diagnosis. Vacuum-assisted closure (VAC) therapy aided in the complete healing of the ulcerated infantile haemangioma which was not achievable with conventional dressings.     

Small facial haemangioma and supraumbilical raphe—a forme fruste of PHACES syndrome?

We report two female infants with congenital midline supraumbilical raphes who subsequently developed haemangiomas on the lower lip and gingiva within the first 2 months of life. One was found to have a subglottic haemangioma during laryngoscopy. The infants were otherwise well and had normal chest X-ray, echocardiogram, cranial ultrasound, magnetic resonance imaging/angiography (head, neck, chest) and ophthalmological examination. Both received oral prednisolone 1-2 mg kg(-1) daily and four sessions of flashlamp pulsed-dye laser therapy to the lip lesions, with significant improvement. The initial presentation of these two infants with supraumbilical raphes, who were otherwise healthy and without other cutaneous stigmata, suggested the diagnosis of isolated congenital sternal malformation. However, lower lip and gingival haemangiomas developed 4-6 weeks later, consistent with the diagnosis of PHACES syndrome. Children with sternal malformation and haemangioma may also have intracranial and/or cardiovascular anomalies. All previously reported patients were females who had either craniofacial and/or multiple haemangiomas. We propose guidelines for the evaluation and management of a neonate presenting with a sternal fusion defect at birth.     

Blue rubber bleb naevus

A 35 year old female had multiple progressive painful, tender, soft, bluish compressible nodules with the feel of rubber nipples. There was no evidence of gastrointestinal haemangiomas or other systemic abnormalities. Histopathologically, cavernous haemangioma with prominent smooth muscle outline proved the clinical diagnosis of blue rubber bleb naevus. Only cutaneous lesions were seen in the patient.     

Epidemiology of strawberry haemangioma in low birthweight infants

The prevalence of cutaneous haemangiomas in a representative population of low birthweight infants was determined by tracing and assessing survivors of pre-school age. Data from hospital case-notes and follow-up assessments were used to investigate whether prevalence of haemangiomas was related to perinatal factors and childhood morbidity. Eleven point one per cent of 615 infants developed a haemangioma. Haemangiomas were more common in girls than boys, and in infants of lower gestational age. Hypothermia in the first hours of life and neonatal illness were associated with lower prevalence, suggesting that neonatal skin perfusion influences haemangioma development; this is consistent with a tendency for haemangiomas to be distributed centripetally. However, the major aetiological determinants are unknown. Children with a haemangioma were more likely to have had a febrile convulsion than those without a haemangioma.     

Absent/reduced glucose transporter-1 protein expression in infantile subglottic haemangiomas

BACKGROUND: Positive immunohistochemical staining for glucose transporter-1 protein (GLUT1) is a characteristic of cutaneous infantile haemangiomas. OBJECTIVES: To examine GLUT1 expression in subglottic haemangiomas. METHODS: Review of clinical notes and biopsy tissue with immunostaining for GLUT1 in 14 patients with subglottic haemangiomas. RESULTS: GLUT1 immunostaining was negative in 11 cases, and focally positive in three. No subglottic haemangiomas demonstrated the intense diffuse positive GLUT1 staining seen in cutaneous infantile haemangiomas. Five patients had cutaneous as well as subglottic haemangiomas, one of whom had a GLUT1-negative subglottic haemangioma and a GLUT1-positive cutaneous haemangioma of the lip. CONCLUSIONS: Subglottic haemangiomas appear immunohistochemically different from cutaneous infantile haemangiomas, which may reflect differences in endothelial cell differentiation or underlying aetiology.     

Glomeruloid haemangioma with cerebriform morphology in a patient with POEMS syndrome

A 40-year-old Chinese man presented with sensorimotor polyneuropathy, IgAlambda paraprotein, osteosclerotic bone lesions, hypertrichosis, and impotence with decreased testosterone and raised prolactin level. POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome was diagnosed and he was treated with melphalan and prednisolone. After chemotherapy, other manifestations of POEMS syndrome developed, such as multiple haemangiomas over the chest and neck region, splenomegaly and generalized oedema. One haemangioma had a peculiar clinical morphology, similar to the appearance of cerebral gyri. Skin biopsy confirmed the diagnosis of glomeruloid haemangioma. Chemotherapy was then switched to cyclophosphamide and prednisolone, resulting in further improvement in muscle power and hypertrichosis. To our knowledge, this is the first report on a clinically distinctive morphology of glomeruloid haemangioma, and its recognition may increase the index of suspicion for early skin biopsy.     

A case of unilateral dermatomal cavernous haemangiomatosis

We report a 39-year-old man with unilateral dermatomal cavernous haemangiomatosis (UDCH). Clinically, three haemangiomas were unilaterally distributed in the C6 dermatome. Histologically, these haemangiomas were distinct from routine cavernous haemangioma in that hyperplasia of smooth muscle cells on the vascular wall was observed, and electron microscopy showed that smooth muscle cells contained myofilaments and a crystal-like structure in the endothelial cells. This is distinct from Weibel-Palade bodies, which are rod-shaped cytoplasmic organelles measuring approximately 0.1 microm in diameter with a parallel linear structure. In UDCH, the haemangiomas occur only in the skin. They are clinically and histologically similar to those of blue rubber bleb naevus syndrome (BRBNS), but in BRBNS there are multiple haemangiomas in the digestive tract and other organs. UDCH is distinct from Maffucci syndrome in that enchondromata and malignant tumours are absent. To our knowledge, this is the second case of UDCH reported in the literature.     

Solitary glomeruloid haemangioma without POEMS syndrome

BACKGROUND: The term 'glomeruloid haemangioma' was coined by Chan et al. for a histologically distinctive cutaneous haemangioma, which they considered a specific cutaneous marker for POEMS syndrome. Glomeruloid haemangiomas appear to be specific to POEMS syndrome, because they have not been reported in patients without this syndrome. METHODS: We report on an 86-year-old man without POEMS syndrome and with a solitary red papule on the face. RESULTS: A cutaneous biopsy showed histological findings consistent with a glomeruloid haemangioma. Physical examination of the skin did not show any other cutaneous lesion and laboratory and radiological studies ruled out the presence of POEMS syndrome. CONCLUSIONS: Glomeruloid haemangiomas could exceptionally be present as solitary vascular tumours and out of the context of POEMS syndrome. To our knowledge, this is the first case reported of glomeruloid haemangioma without POEMS syndrome. Moreover, the presentation on the face is also highly unusual.     

Benign neonatal hemangiomatosis with early regression of skin lesions: A case report and review of the published work

A 2-day-old Japanese male infant was referred to our outpatient clinic for multiple cutaneous hemangiomas present since birth. Physical examination revealed 14 small, well-circumscribed red papules, scattered over the head, face, dorsum of the right hand, trunk, lower extremities, buttocks and penis. Ultrasound examination revealed no evidence of visceral involvement. Histological examination of a cutaneous lesion was consistent with infantile hemangioma, resulting in the final diagnosis of benign neonatal hemangiomatosis (BNH). The hemangiomas enlarged by 1 month of age and began to resolve at 2 months of age. Within the next month, the lesions had almost completely disappeared. BNH is a rare, non-heritable, self-limited, benign disease characterized by multiple cutaneous infantile hemangiomas and no or unremarkable visceral lesions. Generally, BNH lesions spontaneously regress within the first 1–2 years of life or within 4 months of onset. However, there have been no detailed reports about the time course of BNH. To our knowledge, 31 cases of BNH without hepatic hemangiomas, excluding this case, have been reported so far. Twenty-one of these cases demonstrated spontaneous regression of the cutaneous hemangiomas without treatment. In all cases, the cutaneous hemangiomas were present at birth. The median age at the beginning of spontaneous regression was 6.0 months (range, 1–12) and the median age at complete or almost complete regression was 15 months (range, 3–28). Cutaneous hemangiomas in BNH without hepatic hemangiomas undergo spontaneous regression within the first year of life.     

Síndrome de Maffucci

.—The Maffucci's syndrome is mesodermic dysplasia characterized for the coexistence of subcutaneous vascular lesions (fundamentally haemangiomas) and enchondromas. The enchondromas is bony tumours characterized by the cartilage persistence in your metaphysic and epiphysic. This tumour can be cause of the deformity and the reduction of the member due to the expansion of the cartilage inside the bone.The haemangioma are a deep vascular tumours, histological appearance is a spindle-cell haemangioma.On the basis of a 26 year-old woman with multiple vascular lesions (haemangioma) and bony (enchondromas) characteristic of the Maffucci's syndrome, we review the clinical characteristics, histologic, epidemiologic and associated features or the process.     

Multiple, genital lobular capillary haemangioma (pyogenic granuloma) in a young woman: a diagnostic puzzle

A 21 year old woman presented with multiple lobulated lesions on the labia majora. The surface of most of the lesions was ulcerated revealing a glistening surface. All lesions were excised. The histopathology revealed features suggestive of lobular capillary haemangioma (pyogenic granuloma). Pyogenic granuloma is considered as a reactive hyperproliferative vascular response to trauma or other stimuli. A literature search revealed reports of a few cases of lobular capillary haemangioma of the glans penis but not on the female genitalia. This case is presented to help physicians become aware that lobular capillary haemangiomas (pyogenic granuloma) may occur at this site.     

Multiple neonatal haemangiomatosis with liver haemangiomas and anaemia

A 5-month-old girl presented with six cutaneous haemangiomas that appeared over a 1-month period. Investigations revealed anaemia and multiple liver haemangiomas. After 3 months follow up, there has been some further enlargement of the cutaneous lesions but no increase in number, while the liver lesions have remained stable, without any other systemic complications.     

Pulse methylprednisolone therapy for threatening periocular haemangiomas of infancy

Periocular haemangiomas of infancy can cause severe and rapid ocular damage. Oral corticosteroids remain the front-line treatment to minimize the consequences of these haemangiomas. The aim of this report is to summarize our experience with pulse intravenous methylprednisolone as an alternative therapy for periocular haemangioma when visual prognosis is engaged. Fifteen infants, who presented periocular haemangioma with functional impact on vision, received 2 mg/kg methylprednisolone intravenously twice a day for 2 days. Following pulse therapy, 2 mg/kg/day prednisolone was given orally with gradual tapering. No further visual impact was noticed following pulse therapy. Two patients relapsed, needing new pulses or, in one case, vincristine. No serious side-effects were recorded. Pulse methylprednisolone therapy permitted a particularly rapid shrinkage of haemangiomas and a complete disappearance of their visual impact within 2 days. Apparently more rapid than the usual oral corticosteroids, pulse intravenous methylprednisolone decreases the risk of ocular complications, which correlates with the duration of the influence of haemangiomas.     

Thermographic evaluations of haemangiomas.

Strawberry hacmangiomas, benign haemangioendotheliomas with Kasabach-Merritt's syndrome, and cavernous haeniangiomas with arterio-venous fistulas demonstrated hot thermograms with the maximum temperatures often exceeding 2°C above the surrounding or symmetrical normal skin level. Hot vascular radiating patterns were also frequent in the cavernous haemangiomas with arterio-venous fistulas. Cavernous haemangiomas without arterio-venous fistulas, portwine and telangiectatic naevi showed cold or insignificant thermograms. The infra-red thermography was valuable in evaluating the types of haemangioma and in determining the therapeutic effects.