Historical and Contemporary Management of Infantile Hepatic Hemangioma: A 30-year Single-center Experience.

OBJECTIVE: To describe outcome of infants with hemangioma(s) of the liver. SUMMARY OF BACKGROUND DATA: Infantile hepatic hemangiomas exhibit a diverse phenotype. We report our 30-year experience and describe optimal management based on precise radiological classification. METHODS: Retrospective review of 124 infants (66 female) 1986-2016. Categorical analysis with Chi2 and nonparametric comparison. Data expressed as median (range) and P < 0.05 considered significant. RESULTS: Lesions classified as focal (n = 70, 56%); multifocal (n = 47, 38%) or diffuse (n = 7, 6%) and of these 80(65%) were symptomatic (eg, cardiac failure n = 39, 31%; thrombocytopenia n = 12, 10%).Increased hepatic artery velocity was seen in 63 (56%). Median hepatic artery velocity was greatest in diffuse lesions [245 (175-376) cm/s vs focal 120 (34-242) cm/s vs multifocal 93 (36-313) cm/s; P = 0.0001]. Expectant management alone was followed in 55 (44%). Medical therapy was utilised in 57(46%) and sufficient for symptom control in 29/57 (51%). Propranolol therapy (from 2008) was sufficient for symptom control in 22/28 (79%). Surgery (hepatic artery ligation n = 26; resection n = 13; embolization n = 1) was required in 40 (32%). Median maximal lesion diameter was 3 (0.5-17.1) cm and greater in those requiring surgery (7 cm vs 4.9 cm; P = 0.04). The proportion requiring surgery decreased markedly in the propranolol era [pre-propranolol 25/48 (52%) vs post-propranolol 16/76 (21%) (P = 0.0003)]. Systematic follow-up with ultrasound to a median of 2.6 (0.02-16) years. CONCLUSIONS: A proportion of infantile hepatic hemangiomas remain asymptomatic permitting observation until resolution but the majority require complex multi-modal therapy. First-line pharmacotherapy with propranolol has reduced but not abolished the need for surgery.

Radiomics-based classification of hepatocellular carcinoma and hepatic haemangioma on precontrast magnetic resonance images.

BACKGROUND: To evaluate the feasibility of using radiomics with precontrast magnetic resonance imaging for classifying hepatocellular carcinoma (HCC) and hepatic haemangioma (HH). METHODS: This study enrolled 369 consecutive patients with 446 lesions (a total of 222 HCCs and 224 HHs). A training set was constituted by randomly selecting 80% of the samples and the remaining samples were used to test. On magnetic resonance (MR) images of HCC and HH obtained with in-phase, out-phase, T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) sequences, we outlined the target lesions and extracted 1029 radiomics features, which were classified as first-, second-, higher-order statistics and shape features. Then, the variance threshold, select k best, and least absolute shrinkage and selection operator algorithms were explored for dimensionality reduction of the features. We used four classifiers (decision tree, random forest, K nearest neighbours, and logistic regression) to identify HCC and HH on the basis of radiomics features. Two abdominal radiologists also performed the conventional qualitative analysis for classification of HCC and HH. Diagnostic performances of radiomics and radiologists were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Valuable radiomics features for building a radiomics signature were extracted from in-phase (n = 22), out-phase (n = 24), T2WI (n = 34) and DWI (n = 24) sequences. In comparison, the logistic regression classifier showed better predictive ability by combining four sequences. In the training set, the area under the ROC curve (AUC) was 0.86 (sensitivity: 0.76; specificity: 0.78), and in the testing set, the AUC was 0.89 (sensitivity: 0.822; specificity: 0.714). The diagnostic performance for the optimal radiomics-based combined model was significantly higher than that for the less experienced radiologist (2-years experience) (AUC = 0.702, p < 0.05), and had no statistic difference with the experienced radiologist (10-years experience) (AUC = 0.908, p>0.05). CONCLUSIONS: We developed and validated a radiomics signature as an adjunct tool to distinguish HCC and HH by combining in-phase, out-phase, T2W, and DW MR images, which outperformed the less experienced radiologist (2-years experience), and was nearly equal to the experienced radiologist (10-years experience).

Proposed Classification System for Retinal Capillary Angiomatosis.

Retinal angiomas are rare tumors that develop within the vascular bed of the retina. Their occurrence may be sporadic or as part of the multisystem disorder called von Hippel-Lindau disease. It is well established in literature that retinal angiomas have a natural history of evolving as small aneurysmal dilatations and progressing to vision-threatening retinal detachments. Several approaches to the management of these angiomas have been reported in the literature, but it is difficult to decipher which modality is best suited for which type of angioma. A classification of retinal angiomas is proposed herein. A classification system may help in developing future guidelines for the study, screening, treatment, and prognostication of patients with retinal angiomas.

Guidance Document for Hepatic Hemangioma (Infantile and Congenital) Evaluation and Monitoring.

OBJECTIVE: To define the types of hepatic hemangiomas using the updated International Society for the Study of Vascular Anomalies classification and to create a set of guidelines for their diagnostic evaluation and monitoring. STUDY DESIGN: We used a rigorous, transparent consensus protocol defined by an approved methodology, with input from multiple pediatric experts in vascular anomalies from hematology-oncology, surgery, pathology, radiology, and gastroenterology. RESULTS: In the first section, we define the subtypes of hepatic hemangiomas based on the clinical course, histology, and radiologic characteristics. We recommend against using the term "hemangioma" for any vascular malformations affecting the liver or any hypervascular tumors that are not characterized by the approved definitions. We recommend against using the term "hemangioendothelioma" for infantile or congenital hemangioma. The following 2 sections dedicated to infantile hepatic hemangioma and to congenital hepatic hemangioma individually describe these subtypes in further detail, including complications to be considered during monitoring and respectively recommended screening evaluations. CONCLUSIONS: Although institutional variations may exist for specific clinical details, a clear understanding of the diagnosis of hepatic hemangiomas affecting children and the possible complications that require screening during the monitoring period should be standard. As children with hepatic hemangiomas are managed by different medical and surgical specialties, we offer an expert opinion multidisciplinary consensus based on current literature and on data extracted from the liver hemangioma registry.

An update of 77 cases diagnosed as oral hemangiomas based on GLUT-1 positivity.

OBJECTIVES: To evaluate cases diagnosed as "oral hemangiomas" based on the immunohistochemical expression of human glucose transporter protein (GLUT-1) and on histopathological features, and to investigate whether the classification proposed by the ISSVA was used correctly to classify these lesions. MATERIAL AND METHODS: All cases stored in the archives of an Oral Pathology Service and diagnosed as "oral hemangiomas" were reviewed. Seventy-seven cases were analyzed regarding the expression of GLUT-1. GLUT-1(+) specimens were classified as true infantile hemangioma (IH) and GLUT-1(-) specimens were reclassified based on their histopathological features. The nomenclature of these lesions was evaluated and some cases were reclassified. RESULTS: Only 26 (33.8%) of the specimens were indeed IHs. Among the GLUT-1(-) specimens, 20 (26.0%) were reclassified as pyogenic granulomas (PGs) and 31 (40.2%) as vascular malformations. Considering the previously applied nomenclature, only 47.5% of the cases initially diagnosed as "hemangiomas" were IHs. In the group of "capillary hemangiomas", most cases (56.2%) were PGs. Among the three "cellular hemangiomas", two were PGs and one was IH. Most (88.8%) "cavernous hemangiomas" were vascular malformations. CONCLUSION: Careful and parameterized review of cases of vascular anomalies is necessary using auxiliary tools such as GLUT-1, since the exclusive use of histopathological findings might be insufficient to differentiate some anomalies. CLINICAL RELEVANCE: Accurate clinical examination and the use of biomarkers such as GLUT-1 are essential for the diagnosis.

[Cutaneous vascular anomalies in children]. / Les anomalies vasculaires cutanées chez l'enfant.

INTRODUCTION: Vascular anomalies, which are erroneously categorized under the term angiomas, are a highly heterogeneous group of lesions that are poorly understood and affect a mean of 5 to 10 % of children. The fortuitous discovery of propranolol's efficacy in one of these entities has made them a topical issue. OBJECTIVES: The paper's main objective is to inform family doctors of the various types of vascular anomalies, clarify their classification, and provide a common terminology. Its secondary objective is to provide a decision tree that enables primary care doctors to avoid diagnostic pitfalls, successfully detect cases, and optimize management. METHODS: Systematic review. CONCLUSIONS: According to a recent study, 71,3 % of publications use the term hemangioma erroneously, regardless of the authors' field. The key for family doctors is to use one international classification only, that of the International Society for the Study of Vascular Anomalies (ISSVA), in order to facilitate management and comprehension between the different healthcare levels. The diagnosis of vascular anomalies is clinical in 90 % of cases, so all family doctors can, whilst using a decision tree, diagnose a vascular anomaly and refer only those that are complex for specialist care. The most common vascular anomaly is infantile hemangioma in infants, which spontaneously regresses around the age of 5-7 years in 90 % of cases. Watchful waiting and regular follow-up suffice, therefore, in such settings.

[Extracranial vascular anomalies (hemangiomas and vascular malformations) in children and adolescents--diagnosis, clinic, and therapy]. / Extrakranielle vaskuläre Fehlbildungen (Hämangiome und vaskuläre Malformationen) im Kindes- und Jugendalter--Diagnostik, Klinik und Therapie.

The field of extracranial vascular anomalies is considered as special focus of pediatric otolaryngology and it has shown a rapid development during the last years. The reason for this interest is finally also due to the global acceptance of the classification introduced by the ISSVA (International Society for the Study of Vascular Anomalies). Hemangiomas are the most frequently observed vascular tumors. Today the systemic propranolol therapy is mostly used for therapy of hemangiomas requiring treatment. Increasingly, the topical application of beta blocker is discussed while the benefit in the head and neck seems to be limited. Vascular malformations are classified according to the morphology of the affected part of the vascular system in arterial, venous, arterio-venous, lymphatic, capillary, and combined vascular malformations. Conventional surgery, sclerosing therapy, and laser treatment are invasive options for the treatment of lymphatic malformations. The options for the treatment of venous malformations could be significantly improved during the last years. In this context, the use of Nd:YAG laser, the conservative treatment of the localized disseminated intravascular coagulation with low-molecular weight heparin, the re-discovery of bleomycin as effective sclerosing agent, and the improvement of alcohol-based embolization agents must be mentioned. Today the treatment with dye laser is the preferred therapy for capillary malformations and it is superior to other therapeutic options as for example photodynamic therapy. Arterio-venous malformations as representatives for high-flow lesions are the high-risk lesions. Frequently they are compared to malignant head and neck tumors, in particular when a curative treatment can no longer be assured because of diffuse or multifocal extent and when the disease shows a progressive course. The combined treatment of embolization and surgical resection and if necessary consecutive defect reconstruction have turned out to be appropriate for arterio-venous malformations. Incurable findings are still a major challenge. Despite the introduction of antiangiogenetic drugs in oncology, the medicamentous therapeutic approach could not be established for arterio-venous malformations up to now.

Vertebral Hemangiomas: Yucesoy-Yilmaz Classification System with Corresponding Therapeutic Options.

OBJECTIVE: Vertebral hemangiomas (VHs) are relatively common, symptomatic benign tumors of the spine with a reported estimated incidence up to 11%. They usually appear in the body of the vertebrae; however, they can extend into pedicles, laminae, and epidural space. They may cause pain, neurologic deficits. and fractures. METHODS: In this retrospective, single-center study, we reviewed our cases with VH and we propose the novel classification system that evaluates these lesions per their views on magnetic resonance imaging and clinical findings under 4 main categories. RESULTS: Our novel classification system proposes that grade I lesions occupy less than 50% of the vertebral body, whereas grade II lesions occupy more than 50% and grade III lesions occupy the whole corpus. Grade IV lesions show an epidural and pedicular extension. We propose that grade I lesions may not be worthwhile for follow-up, whereas asymptomatic grade II (a) lesions to be worthy for a biannual imaging and symptomatic thoracolumbar grade II (b) and thoracolumbar grade III lesions to be considered for percutaneous vertebroplasty. We imply that decompression, posterior spinal instrumentation, and open vertebroplasty may be performed for thoracolumbar grade IV lesions. We further consider cervical grade IIb, III, and grade IV lesions as operable because of the disadvantages of percutaneous vertebroplasty. CONCLUSIONS: We suggest that our novel classification system may be useful for the determination of diagnostic and therapeutic procedures in the management of VH. Further multicentric trials on larger series are warranted to validate this system and popularize its utility in larger populations.

Hemangioma: review of literature.

Hemangiomas are tumors identifed by rapid endothelial cell proliferation in early infancy, followed by involution over time. All other abnormalities are malformations resulting from anomalous development of vascular plexuses. The malformations have a normal endothelial cell growth cycle that affects the veins, the capillaries or the lymphatics and they do not involute. Hemangiomas are the most common tumors of infancy and are characterized by a proliferating and involuting phase. They are seen more commonly in whites than in blacks, more in females than in males in a ratio of 3:1.

Rare non-epithelial primary breast neoplasms: a ten-year experience at a Greek University Hospital.

PURPOSE: Non-epithelial breast neoplasms cover a large spectrum of histopathological entities. The demographics and clinical features are similar to epithelial breast lesions but the diagnosis, prognosis and management options are often very different. METHODS: During 2001-2010, 1362 patients were examined at the Pathology Department of the Aretaieion General Hospital for various breast lesions. All specimens were processed routinely and slides stained with hematoxylin-eosin were re-examined. The patient clinical records were examined for demographics, clinical presentation and therapeutic approach. RESULTS: In 23/1362 cases (1.68%) pathological examination showed non-epithelial lesions: in 12/1362 cases (0.8%) haemangiomas (11 women, one man), in 4 /1362 cases (0.3%) myofibroblastomas (MFB), in 2/1362 cases (0.1%) primary breast non-Hodgkin's lymphoma (NHL), in 3 /1362 cases (0.2%) granular cell tumor (GCT), and in 2/1362 cases (0.1%) angiosarcomas (one developed after radiotherapy for breast cancer). CONCLUSIONS: Non-epithelial primary breast tumors are rare (1.68%) and present significant difficulty in accurate preoperative diagnosis and in certain cases in pathological diagnosis as well, which is necessary for the selection of the appropriate treatment. Avoidance of inappropriate therapies requires a multidisciplinary management approach.

Hobnail hemangioma reclassified as superficial lymphatic malformation: a study of 52 cases.

BACKGROUND: Hobnail hemangioma (HH) is currently classified as a benign vascular tumor, although it is not well understood whether this lesion differentiates toward blood or lymphatic endothelial cells. Immunostaining with the endothelial marker Wilms tumor 1 (WT1) helps distinguish between vascular neoplasms and malformations, being positive in the former and negative in the latter. OBJECTIVE: We sought to investigate WT1, human herpesvirus 8 latent nuclear antigen, D2-40, and Ki-67 immunoprofile in HH, to gain further insight into its histogenesis. METHODS: We evaluated 52 HHs collected in Dermatohistopathologische Gemeinschaftslabor, Friedrichshafen, Germany. Immunohistochemical expression of WT1 was performed in all cases. Ten of 52 lesions were also studied for D2-40 and Ki-67 staining and 12 lesions were stained for human herpesvirus 8 latent nuclear antigen. RESULTS: All 52 HHs were completely negative for WT1 immunostaining. Immunohistochemistry performed in 10 HHs showed diffuse and strong positive staining for D2-40 in 8 lesions and focal positivity in two. All cases tested showed negative staining for Ki-67 and human herpesvirus 8 latent nuclear antigen. LIMITATIONS: There are no limitations. CONCLUSIONS: Although the exact histogenesis of HH is unknown, most of the performed immunohistochemical studies support a lymphatic line of differentiation. However, on the basis of the WT1 negativity, we believe that HH is better considered as a lymphatic malformation rather than a lymphatic neoplasm.

Classification of vascular disorders in the skin and selected data on new evaluation and treatment.

Cutaneous vascular disorders are common. They include arteries, veins, and lymphatic vessels, or a mixture of them. In this review, we discuss classification, new developments in understanding and treatment of vascular diseases. We focus on infantile hemangiomas and drug therapy, vasculitides with new vasculitic syndromes, yellow nail syndrome and localized lymphatic malformations. Benign cutaneous vascular lesions may be a sign of severe internal diseases. In many cases multidisciplinary treatment is important. The dermatologist can often act as a pilot for these patients.

Histopathology of vascular anomalies.

Vascular anomalies may be appropriately classified into two broad categories, vascular tumors and vascular malformations, which are distinguished by the presence of cellular proliferation in contrast to aberrations in morphogenesis, respectively. This system of classification is based upon histological features that may in large part be differentiating, but nevertheless, may show morphological overlap. Advances in immunophenotyping allow for more precise diagnoses as well as further delineation of cell origins. In the discussion, we present the clinical, histological, and, when applicable, the immunophenotypic presentation of vascular anomalies commonly seen in infancy and early childhood.

[Therapeutic options for haemangiomas of infancy]. / Überblick der Therapiemöglichkeiten im Management von Säuglingshämangiomen.

The necessity of haemangioma treatment in infants has been controversially discussed for years. One reason is the favoured clinical observation of a potential spontaneous involution without any therapeutic approach or medical treatment, thus avoiding their specific risks. On the other hand, there are several reports on serious cases with -rapidly growing haemangiomas including severe consequences. There are potential complications such as loss of visus in cases of periorbital manifestation. A basic problem is the lack of a unique systematic classification, on the basis of which -diagnostic measures, therapeutic indications and modes could be compared. Such a classification would be much more competent including a sufficient comparison of treatment results. The basic aim in management is to achieve control of the haemangioma growth and induction of its sub-sequent involution back to only a cosmetic detraction. Each threatening functional loss can be classified as an urgent indication for treatment. There is a need to consider the treatment options and their values; in particular, cryotherapy or laser therapy in localised manifestations are mostly -favoured because of the convincing evidence from available data. In the case of a more disseminated haemangioma manifestation, the initiation of propranol medication is possible, a novel drug for this indication. However, there are no follow-up data on the mid-term or long-term outcome available at this time. Further studies on the subject are therefore required.

[Hereditary vascular malformations: classification, symptoms, diagnostics and prognosis]. / Angeborene Gefäßmalformationen: Klassifikation, Symptome, Diagnostik und Prognose.

The understanding of hereditary vascular anomalies was hampered for a long time by unclear und unspecific terminology. Today, the classification of the International Society for the Study of Vascular Anomalies (ISSVA) differentiates between vascular tumours (mostly infantile haemangioma) with active endothelial proliferation and regression and vascular malformations (VM), which are defects of the vascular morphogenesis and are distinguished in predominantly venous, arterial, capillary, lymphatic, arteriovenous or combined VM. Symptoms are pain, swelling and restricted movement, accompanied by skin signs like dys-plastic veins and capillary VM (naevus flammeus). Thrombophlebitis and chronic venous insufficiency are related to venous VM. Arteriovenous VM are progressive and can cause ischaemic necroses, in rare cases even a high-output cardiac fail-ure. Lymphatic VM lead to localised swelling, in the long run often to recurrent erysipelas and lymphorroea. Primary imaging is provided by -ul-trasound including flow measurements. Mor-phol-ogy and organ involvement is best delineated by magnetic resonance imaging. Phlebography is used to image deep venous system anomalies and is always accompanied by varicography of the dysplastic parts of the venous VM. Digital subtraction angiography is performed to demon-strate the flow pattern in feeding arteries, the nidus and the drainage veins of arteriovenous VM. Besides size and localisation the prognosis of the patients is determined by the pressure (the high-er the pressure, the poorer the prognosis) and the flow rate (the higher the flow rate, the poorer the prognosis) in the VM. Diagnosis and treatment of these rare diseases are best performed in special-ised, interdisciplinary centres.

[On the classification of vascular structures in children].

Vascular structures are a common childhood pathology that may cause not only the development of extensive cosmetic defects but also functional disorders of respiration, swallowing, vision, and hearing. These conditions not infrequently lead to severe disability and sometimes have a fatal outcome. The choice of the treatment modality depends on the type of the so-called "hemangiomas", the classification of these tumours remaining poorly developed. Our experience with the treatment of the children with these vascular structures (including those of "critical" localization) enabled us to propose a classification of vascular lesions according to which all vascular structures are subdivided into vascular hyperplasias, vascular malformations, and vascular tumour-like structures (both benign and malignant). It is believed that the rational use of this classification may be helpful for the choice of the adequate treatment strategies.

Hemangiomas revisited: the useful, the unusual and the new. Part 1: overview and clinical and imaging characteristics.

Hemangiomas are common vascular tumors occurring in children. Though most of the lesions present in infants and young children with a typical appearance, it is important to understand that they all do not behave in the same way. Rather, they are a group of vascular lesions with different clinico-pathological subtypes, with their clinical behavior varying with the stage of the tumor as well. As such, they can and do have a varied clinical, imaging and pathological appearance according to the location of the tumor and also the stage at which the patient is seen. In this pictorial essay, the classification, pathogenesis, clinical appearance, natural history and imaging characteristics of hemangiomas are reviewed and illustrated.

[Classification of the formations from blood vessels of maxillofacial region and neck in children].

Multidisciplinary group of investigators basing upon special literature study, analysis of their own observation (1168 cases) including retrospective for 20 years and with the help of several following methods - clinical, roentgenological, pathomorphological,immunohistochemical - picked out from wide group of the so called hemangiomas 3 types of lesions: hyperplasia, malformation, tumour and suggested their clinical biological classification. To each of lesion types characteristic was given.