Cutaneous Hemangiomas Research Articles

A rare case report of Maffucci syndrome in a 16-year-old girl

Maffucci syndrome is an extremely rare, sporadic disorder that primarily affects bone and skin. It is characterized by multiple enchondromas, especially in the bones of hands and feet, with cutaneous hemangiomas. Treatment consists of orthopedic and surgical intervention to minimize deformities and for cosmetic purposes. Careful surveillance for both skeletal and non-skeletal malignancies is needed. We report here a case of Maffucci syndrome in a 16-year-old girl.

Is the identification of multiple infantile cutaneous haemangiomas always a definitive diagnosis? A case report of an infant with multifocal hepatic haemangioma

Multifocal hepatic haemangiomas are the most common benign vascular tumours of the liver that are detected in children with concomitant multiple infantile haemangiomas. Reported lesions are usually undetectable at birth, which presents a diagnostic problem for general practitioners. Ultrasound should be the imaging examination performed in the first instance in search for vascular anomalies in children. In pharmacotherapy, the first-choice treatment is propranolol, administered orally. In the described case, a boy with multiple hepatic and skin haemangiomas, after treatment with propranolol, achieved a significant improvement in the ultrasound image of the liver. Skin lesions were also reduced. The importance of the physical examination should be emphasised in the context of detecting cutaneous haemangiomas, which usually accompany multifocal hepatic haemangiomas and should prompt the physician to regularly observe and repeat abdominal ultrasound examinations of the diagnosed and/or treated child.

GNA14 and GNAQ somatic mutations cause spinal and intracranial extra-axial cavernous hemangiomas

Extra-axial cavernous hemangiomas (ECHs) are complex vascular lesions mainly found in the spine and cavernous sinus. Their removal poses significant risk due to their vascularity and diffuse nature, and their genetic underpinnings remain incompletely understood. Our approach involved genetic analyses on 31 tissue samples of ECHs employing whole-exome sequencing and targeted deep sequencing. We explored downstream signaling pathways, gene expression changes, and resultant phenotypic shifts induced by these mutations, both invitro and invivo. In our cohort, 77.4% of samples had somatic missense variants in GNA14, GNAQ, or GJA4. Transcriptomic analysis highlighted significant pathway upregulation, with the GNAQ c.626A>G (p.Gln209Arg) mutation elevating PI3K-AKT-mTOR and angiogenesis-related pathways, while GNA14 c.614A>T (p.Gln205Leu) mutation led to MAPK and angiogenesis-related pathway upregulation. Using a mouse xenograft model, we observed enlarged vessels from these mutations. Additionally, we initiated rapamycin treatment in a 14-year-old individual harboring the GNAQ c.626A>G (p.Gln209Arg) variant, resulting in gradual regression of cutaneous cavernous hemangiomas and improved motor strength, with minimal side effects. Understanding these mutations and their pathways provides a foundation for developing therapies for ECHs resistant to current therapies. Indeed, the administration of rapamycin in an individual within this study highlights the promise of targeted treatments in treating these complex lesions.

An Infant with High-Output Heart Failure and Pulmonary Hypertension Resulting from a Giant Cutaneous Hemangioma.

We present the clinical course of an 8-month-old infant with a giant cutaneous hemangioma resulting in high-output heart failure and pulmonary hypertension. The lesion was successfully embolized and excised, with rapid resolution of heart failure and improvement in pulmonary hypertension.

Hemangiomatosis hepática de inicio neonatal

Infantile hemangioma is the most frequent pediatric benign tumor. The involvement is usually cutaneous, but it can be visceral too. Some presentations pose a diagnostic challenge and can even be life-threatening. We present two cases that consulted to our center. The first is a 13-day-old female newborn, who presents with an increase in the number and size of erythematous micromacules-papules, which she already had. She is diagnosed with infantile hemangiomatosis. In the extension study, the abdominal ultrasound shows multiple hepatic hemangiomas. The evolution is favorable without treatment, disappearing almost all hemangiomas within the first year. The second case is a 37-day-old infant, who presents with propulsive vomiting and abdominal distention. The physical exam is remarkable for cutaneous jaundice and 4cm hepatomegaly. Blood tests show cholestatic hepatitis without liver failure and hypothyroidism. Abdominal ultrasound shows diffuse hepatic hemangiomatosis, which is confirmed by MRI. Oral Propanolol and Levothyroxine are started. The evolution is favorable, with resolution of the hemangiomatosis. Hemangiomas are usually cutaneous but visceral involvement must be studied in the presence of more than 5 cutaneous hemangiomas or if they are large. Hepatic hemangiomas are the most common. They can be congenital (focal), which can involute spontaneously, or infantile (multifocal or diffuse), which can produce symptoms (cholestasis, hepatomegaly, heart failure, hypothyroidism…). The treatment is Propranolol and, in case of hypothyroidism, Levothyroxine. To conclude, we emphasize the importance of early diagnosis of hepatic hemangiomatosis because it has the possibility of specific and effective treatment.

68Ga-PSMA-11 PET/CT in Cherry Hemangiomas.

A 63-year-old man was remitted for a 68Ga-PSMA-11 PET/CT scan due to biochemical recurrence with a PSA of 0.32 ng/mL 1 year after radical prostatectomy of locally advanced Gleason 6 (3 + 3) ISUP 2 pT3a pN0 prostate cancer. 68Ga-PSMA-11 PET/CT showed multiple cutaneous and subcutaneous uptake foci in the upper body. Physical examination revealed numerous dome-shaped, ruby-red papules. These were consistent with a previous diagnosis of cutaneous hemangiomas. Cherry hemangiomas (also known as Campbell de Morgan spots) are the most common type of benign vascular proliferation of the skin. Due to the nonspecific 68Ga-PSMA-11 uptake of vascular lesions, careful interpretation should be considered in order to avoid a potential pitfall in nonmalignant conditions.

A rare presentation of pupillary block glaucoma and persistent tunica vasculosa lentis in Klippel–Trenaunay syndrome

Phacomatoses are a group of neurocutaneous disorders characterized by vascular and pigmentary birthmarks, often involving multiple organ systems. Klippel–Trenaunay syndrome (KTS), a rare phacomatosis, is characterized by the classical triad of cutaneous capillary hemangiomas, venous malformations, and soft tissue overgrowth. Glaucoma secondary to angle dysgenesis, raised episcleral venous pressure, or excess angle pigmentation is observed. We report a case of KTS that presented with cutaneous capillary hemangiomas and limb hypertrophy along with unilateral buphthalmos. This eye was noted to have persistent tunica vasculosa lentis and persistent pupillary membrane with pupillary block glaucoma that was treated with pupilloplasty. To the best of our knowledge, this mechanism of glaucoma in KTS has not been reported before. The purpose of this article is to document this rare presentation as well as highlight the importance of detecting the underlying mechanism for appropriate management.

Diagnóstico clínico de hemangiomatose neonatal disseminada: um relato de caso

Hemangioma is the most common vascular tumor of childhood. It may present as multiple cutaneous hemangiomas on rare occasions, with or without visceral involvement. The condition of lesions restricted to the skin is called benign neonatal hemangiomatosis, and in the case of visceral lesions associated with cutaneous lesions, the denomination is disseminated or diffuse neonatal hemangiomatosis (DNH). For the diagnosis of DNH, three criteria must be met: onset in the neonatal period, involvement of three or more organs, and absence of malignancy in hemangiomas. ASAS, a full-term, vaginally delivered newborn, weight: 3560g, length: 52cm, head circumference: 35cm, APGAR: 9/9. Maternal history of syphilis during pregnancy - mother adequately treated in pregnancy. At birth, she presented with purpuric lesions of variable size on the chest, limbs, feet, and hands, which discolored under digital pressure; larger lesions with relief, not scaly. He developed severe heart failure and was admitted to the Neonatal Intensive Care Unit (NICU) in a secondary hospital in the Federal District. Imaging tests were performed: Computed tomography of the skull, thorax, and total abdomen, which revealed the presence of a possible hemangioma in the left frontal lobe, telangiectasias in the lungs, and multiple hepatic hemangiomas. He had a clinical diagnosis of DNH. The case described corroborates the fact that knowledge about the disease is relevant, as early diagnosis can lead to more accurate approaches that may reduce morbidity and mortality from the disease.

Interesting case of subglottic hemangioma presented with stridor

Subglottic hemangioma is a very rare infantile form of hemangioma as compared to cutaneous hemangioma but if left undiagnosed or untreated can be life-threatening. Here we report one case of preterm who presented with sudden onset of inspiratory stridor and respiratory distress in OPD in a previously normal child. The patient was initially misdiagnosed as croup which did not improve after nebulized adrenaline and steroids later on direct laryngobrochoscopy showed subglottic stenosis. A CT scan was done later which revealed subglottic hemangioma which showed complete remission in symptoms after starting oral propranolol. A careful approach towards diagnosing and managing the sudden onset of stridor with probable structural cause is necessary for a favorable outcome.

Clinical and morphological characteristics and diagnosis of external haemangiomas in children

Background. The relevance lies in the increasing occurrence of haemangiomas in children under 1 year old when diagnosis confirmation through morphological methods is necessary. The purpose of the research is to characterise the histological initial and final changes of cutaneous haemangiomas and to present the main clinical manifestations of haemangiomas in children. Materials and methods. Several clinical (for detailed diagnosis of the disease), morphological (histological examination of the material) and statistical methods were used in the work. The object of the research was 98 children with haemangiomas of the facial skin aged 6 months to 16 years. Results. The morphological study demonstrated that in 49 cases (50 %), the typical simple capillary structure of haemangioma was identified, in 35 cases (35.7 %) — cavernous type of neoplasm. Only 18.3 % of the children had combined haemangiomas. Capillary-type haemangiomas contain many small capillaries with a narrow lumen, covered by adhering fleshy epithelium. Conclusions. During the phase of the active growth of haemangiomas, there is a predominance of massive endothelial cells, suggesting that the vascular component, particularly proliferating epithelium-lined capillaries, makes up the main and largest part of the hyperplasia.

Hemangiomatosis of the spleen in a patient with Klippel-Trenaunay syndrome: A case report.

Hemangiomatosis of the spleen is a benign vascular condition occurring as a manifestation of systemic angiomatosis. It is usually associated with Klippel-Trenaunay syndrome (KTS), which is a rare congenital malformation characterized by a triad of varicose veins, bony and soft tissue hypertrophy, and cutaneous and visceral hemangiomas and/or venous malformations. The association of splenic hemangiomatosis with KTS is less documented in the literature. In this report, we describe a 63-year-old female who presented with massive splenomegaly, the histopathology of which showed features of diffuse hemangiomatosis. Based on the histopathological diagnosis, a retrospective evaluation of the patient was carried out and she was diagnosed as KTS. To the best of our knowledge, this is the first report in the Indian literature describing splenic hemangiomatosis in a patient with KTS.

Clinical features of cutaneous infantile hemangioma combined with asymptomatic infantile hepatic hemangioma and efficacy of propranolol treatment.

Infantile hepatic hemangioma (IHH) is a common liver tumor in infants and shares the same characteristics as cutaneous infantile hemangioma (IH). Propranolol is effective for symptomatic IHH. The clinical features between cutaneous IH and IHH, and treatment efficacy of IHH (smaller than 4 cm) is unclear. To evaluate the correlation of clinical features between cutaneous IH and IHH, as well as efficacy of systemic propranolol in the treatment of cutaneous IH combined with IHH. The clinical data of infants with complicated cutaneous IH combined with IHH treated with systemic propranolol (1.5 ~ 2 mg/(kg d)) from January 2011 to October 2020 were retrospectively analyzed. Forty-five cases with IHH combined with complicated cutaneous IH were reviewed. Single cutaneous IH is more likely to be combined with focal IHH, cutaneous IH greater than 5, more likely to be combined with multiple IHH (Pearson = 0.546, p < 0.01). The mean age of focal and multiple IHH regression was 11.93 ± 14.42 months and 10.20 ± 9.15 months, respectively. The number of cutaneous IH were correlated with the number of IHH. There was no difference in the age of complete remission for focal and multiple IHH.

Efficacy and safety of PD-1/PD-L1 inhibitor plus platinum-based chemotherapy vs. platinum-based chemotherapy alone in patients with previously untreated advanced large-cell neuroendocrine cancer of the lung.

9066 Background: Large-cell neuroendocrine carcinoma (LCNEC) is a rare tumor with a poor prognosis and limited treatment options. The efficacy of first-line therapies for LCNEC has not yet been established. This study evaluated the efficacy and safety of the combination of PD-1/PD-L1 inhibitor and platinum-based chemotherapy in treatment-naïve patients with advanced LCNEC. Methods: We retrospectively analyzed patients with advanced LCNEC who were treated with a PD-1/PD-L1 inhibitor plus platinum-based chemotherapy (PD-1/PD-L1 inhibitor group) or with platinum-based chemotherapy alone (chemotherapy group) based on data obtained from electronic databases of three participating cancer centers from January 2015 to August 2022. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were evaluated for each group. Safety was assessed in all patients who received at least one dose of their assigned treatment. Results: Among the 75 enrolled patients, 25 were allocated to receive PD-1/PD-L1 inhibitor plus platinum-based chemotherapy and 50 were allocated to receive platinum-based chemotherapy alone (patients were matched 1:2 on baseline characteristics). The median PFS was 15.1 months (95% confidence interval [CI], 7.1–23.2) in the PD-1/PD-L1 inhibitor group and 5.3 months (95% CI, 4.4–6.2) in the chemotherapy group (hazard ratio [HR], 0.26; 95% CI, 0.113–0.428; p &lt; 0.0001). The 12-month OS was 88.0% (95% CI, 67.7–96.9) in the PD-1/PD-L1 inhibitor group and 56.0% (95% CI, 41.4–69.7) in the chemotherapy group ( p = 0.0056). The ORRs in the two groups were 40% and 16%, respectively ( p = 0.022), and the DCRs were 96% and 70%, respectively ( p = 0.010). Regarding safety, the most common incidences of grade ≥ 3 adverse events involved neutropenia, leukopenia, anemia, and fatigue. There were no significant differences between the two groups. Immune-related adverse events (irAEs) in the PD-1/PD-L1 inhibitor group included cutaneous hemangiomas, hypothyroidism, anaphylaxis, and pneumonitis. Grade 3 or 4 irAEs were not observed. No new safety signals were noted. Conclusions: First-line PD-1/PD-L1 inhibitor plus platinum-based chemotherapy significantly improved PFS in patients with advanced LCNEC compared with platinum-based chemotherapy alone.

Topical Application of 0.5% Timolol Maleate Hydrogel for the Treatment of Superficial Infantile Hemangiomas.

Oral propranolol is considered the first line therapy in the treatment of infantile hemangiomas (IHs). However, there are considerable side effects due to its ability to penetrate the blood brain barrier. Alternatively, topical timolol, a non-selective beta blocker, has resulted in fewer side effects and is 4&ndash;10 times more potent in comparison to oral propranolol. This study evaluates the efficacy of 0.5% timolol maleate hydrogel for the treatment of IH. This study was conducted via a quasi-experimental design from October 30, 2020 &ndash; April 29, 2021, at the Department of Dermatology Benazir Bhutto Hospital, Rawalpindi. 145 infants between 1&ndash;12 months in age diagnosed with superficial cutaneous hemangiomas were included in the study with a male to female ratio of 2.4:1. A thin layer of timolol maleate 0.5% hydrogel was applied to the entire surface of the patient&rsquo;s IH three times daily. Digital photographs and measurements of the hemangiomas were taken at one-month intervals for a maximum of 6 months. The age range in this study was from 1&ndash;12 months with a mean age of 6.10 &plusmn; 2.52 months. The majority of the patients 89 (61.4%) were between 1&ndash;6 months of age. Of the 145 patients, 89 (61.4%) showed an excellent response, 44 (30.3%) showed a good response, and 12 (8.3%) showed no response to the topical 0.5% timolol maleate hydrogel treatment. The use of topical 0.5% timolol maleate hydrogel is a promising therapeutic option for the treatment of superficial IHs. Anwar F, Mahmood E, Sharif S, et al. Topical application of 0.5% timolol maleate hydrogel for the treatment of superficial infantile hemangiomas. J Drugs Dermatol. 2023;22(6):594-598. doi:10.36849/JDD.7054.

Infantile hepatic hemangioendothelioma associated with pulmonary arterial hypertension and cardiac insufficiency successfully treated with oral propranolol—a rare case report

BackgroundInfantile hepatic hemangioendothelioma (IHHE) is a benign liver tumor associated with a varied spectrum of presentations ranging from asymptomatic hepatomegaly and cutaneous hemangiomas to some life-threatening complications like cardiac failure, consumptive hypothyroidism, pulmonary arterial hypertension, gastrointestinal bleeding, and coagulopathy. Hypothyroidism results from increased activity of type 3 iodothyronine deiodinase in the liver. Clinico-radiological correlation is essential for a definite diagnosis. Although children with asymptomatic lesions may experience spontaneous regression within a year, those with symptomatic lesions require aggressive management due to the risk of mortality once the symptoms commence. Treatment modalities can be either pharmacologic or interventional depending on the clinical presentation, with propranolol being considered the first-line agent.Case presentationHere, we describe a 2-month-old female infant with progressive abdominal distension, signs of congestive cardiac failure, and pulmonary arterial hypertension, confirmed as IHHE by abdominal ultrasonography and contrast-enhanced MRI. It was complicated by consumptive hypothyroidism and coagulopathy. The child was successfully treated with oral propranolol, levothyroxine, and supportive measures.ConclusionEarly aggressive treatment in a symptomatic patient is linked to successful outcomes. Hypothyroidism should be focused on and managed earlier to prevent intellectual and growth retardation.

Effect of 32P Application Combined with Timolol Maleate on Circulating Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor in Children with Cutaneous Hemangioma

Effect of 32P Application Combined with Timolol Maleate on Circulating Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor in Children with Cutaneous Hemangioma

Propranolol for Vascular Anomalies: Efficacy and Complications in Pediatric Patients.

Congenital vascular anomalies are classically subdivided into vascular tumors and vascular malformations. The role of propranolol in the regression of infantile hemangioma (IH), a vascular tumor, is well establishe. This study aimed to analyze the therapeutic efficacy and complications associated with oral propranolol and adjuvant therapy in the treatment of vascular anomalies. A prospective interventional study was undertaken over 10 years duration extending from 2012 to 2022 at a tertiary care teaching institute. All children with cutaneous hemangiomas and lymphatic and venous malformations under 12 years of age, except those with contraindications for administration of propranolol, were included in the study. Out of 382 patients, there were 159 males and 223 females (male: female = 1:1.4). The majority (53.66%) were between ≥3 months and 1 year. There were 481 lesions in 382 patients. There were 348 patients with IH, and 11 were congenital hemangiomas (CHs). There were 23 patients with vascular malformations; lymphatic malformation (n = 19) and venous malformation (n = 4) were present. The size of the lesions ranged from 5 mm to 20 cm; 50.73% were 2-5 cm in size. Ulceration (>5 mm) was the most common complication present in 20/382 (5.24%) patients. Complications related to oral propranolol were seen in 23 (6.02%) patients. Drugs were given for a mean period of 10 months (range from 5 months to 2 years). At the end of the study, 282 (81.03%) out of 348 patients with IH showed an excellent response; 4 (36.36%) patients in the case of CH (n = 11) and 5 (21.74%) patients with vascular malformation (n = 23) showed excellent response. The study validates the use of propranolol hydrochloride as the first-line agent for the treatment of IHs and congenital hemangiomas. It may have an additive role in lymphatic malformations, and venous malformations, as a part of a multimodality treatment approach for vascular malformations.

Use of Propanolol versus Intralesional Bleomycin in the Management of Infantile Hemangioma: A Comparative Study

Abstract Background: Infantile haemangiomas (IHs) are widespread vascular tumours having incidence of 10% and most of them involute spontaneously. However, they are known to be located in proximity of vital organs and can have poor cosmetic and functional sequel if left untreated. The aim of the study is to assess the efficacy of oral propranolol and intraleisonal bleomycin in the treatment of infantile cutaneous haemangioma in terms of size regression. Materials and Methods: IH patients presenting in the outpatient department in PIMS were divided randomly by stratified random sampling in two groups. Out of 90 patients, 45 patients had treatment with oral propranolol and other 45 patients received intralesional bleomycin. Baseline size of haemangiomas was taken and regression in size was noted again at 3 and 6 months. Mean and standard deviation were calculated for the age and size of haemangioma in both groups. The mean size regression for both treatments was compared using independent t-test taking P &lt; 0.05 as significant. Results: Out of 90 cases included in this study, the mean age of patients was 10.9 ± 6.1 months in Bleomycin group compared to 10.2 ± 6.9 months in propranolol group. The average size of haemangioma at baseline was 9.5 cm2 in bleomycin group compared to 8.9 cm2 in propranolol group. At 3 months after the intervention, the mean size regression was 3.5 cm2 in bleomycin group compared to 5.3 cm2 in propranolol group and after 6 months of treatment with bleomycin group the mean size of haemangioma was 0.45 cm2, whereas in the propranolol group, it was 2.8 cm2 and difference in the two was found statistically highly significant (P &lt; 0.001). Conclusion: The present study concluded that treatment with intralesional injection Bleomycin for IHs helps in size reduction more efficiently with minimal side effects as compared to oral propranolol for comparable sized haemangiomas.

Prenatal ultrasound evaluation of fetal cutaneous hemangioma and related complications

Objectives Congenital hemangiomas are rare benign vascular tumors but can lead to serious adverse pregnancy outcomes. Its prenatal diagnosis is a challenge. We explored the clinical applications of prenatal ultrasound for evaluating fetal cutaneous hemangioma and associated complications. Methods A retrospective observational study was conducted comprising a population of pregnant women with fetal cutaneous hemangioma, the latter diagnosed by prenatal ultrasound, between January 2016 and December 2020. The clinical characteristics, sonographic images, complications, and pregnancy outcomes were documented and analyzed. Results We identified 20 cases of fetal cutaneous hemangioma diagnosed by prenatal ultrasound and confirmed by postpartum examinations. Most hemangiomas were in the head and neck (55%), with either solid isoechoicity (25%) or solid mildly hyperechoic (25%), and well-circumscribed (80%) mass. Eight (40%) fetuses experienced complications, which often occurred in fetuses with large hemangiomas (67% with maximum diameter ≥5 cm; 100% with a volume ≥40 cm3). The most common complications were cardiac-related (88%), including elevated cardiothoracic area ratio, atrioventricular valve regurgitation, and fetal hydrops. A large hemangioma was usually associated with advanced gestational age and a fast hemangioma growth rate. In five (25%) cases, the pregnancy was terminated; these involved hemangioma of the head or neck. One newborn developed Kasabach–Merritt phenomenon, pulmonary hemorrhage and respiratory distress, and died 3 days after birth. Among the 14 (70%) fetuses that survived birth, all hemangiomas disappeared or regressed after treatments with propranolol, interventional surgery, or observed routinely. Conclusions Prenatal ultrasound examination can accurately diagnose fetal cutaneous hemangioma and related complications to facilitate appropriate management during the pregnancy. Rationale Prenatal diagnosis of cutaneous hemangiomas is a clinical challenge. Prenatal ultrasound examination could be a method to accurately diagnose and monitor these hemangiomas.

Retinal vascular abnormalities in a patient with an overgrowth syndrome

AbstractPurpose: To present a case report of unilateral vascular abnormalities on the retina of a patient with an overgrowth syndrome.Methods: A 26‐year‐old male who presents hemihypertrophy, hemimegaloencephaly, cutaneous haemangiomas and intellectual disability who underwent a complete ophthalmological examination. A detailed retinal imaging was performed as well as a fluorescein angiography (FA) and optical coherence tomography (OCT).Results: Fundus examination of the right eye revealed retinal vascular tortuosity while on the left eye there was fibrovascular proliferative tissue with new vessels from the optic nerve to retinal temporal vessel arcades and an area of chorioretinal atrophy in the superior‐temporal sector. FA illustrated diffuse retinal vascular leakage around temporal arcades which was more evident in late‐phase fluorescein angiograms, but no ischemic areas were found. An extrafoveal epiretinal membrane was seen by OCT on the left eye. As his visual acuity was adequate (20/20 vision in both eyes), initially a conservative management was considered, with visits every 6 months.Conclusions: Patients with an overgrowth syndrome can present different ocular abnormalities as optic nerve hypoplasia, strabismus, and high myopia but it is not frequent to find retinal vascular abnormalities. These patients would require a strict follow‐up by an ophthalmologist. This case also led us to think of the importance of a multidisciplinary work and how useful is to have a genetic testing and a differential diagnosis from all types of overgrowth disorders associated with ocular manifestations.