Evaluation of qualitative and quantitative imaging features of hepatic hemangiomas with and without pseudo-washout sign on gadoxetic acid-enhanced MRI: a descriptive and comparative study.

BACKGROUND: Hepatic hemangiomas are the most common benign liver tumors. It is important to know the imaging features of hemangiomas on gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI). PURPOSE: To evaluate the qualitative and quantitative imaging features of hemangiomas on GA-enhanced MRI, and to compare imaging features of hemangiomas with and without pseudo-washout sign (PWS). MATERIAL AND METHODS: We retrospectively included 93 cases of hemangioma that underwent GA-enhanced MRI. The presence of an enhancement pattern in the arterial phase (AP) and PWSs in the transitional phase (TP) were evaluated. Signal-to-norm ratios (SINorm) of hemangiomas, liver parenchyma, and portal vein (PV) as well as contrast-to-norm ratio (CNorm) were assessed. Additionally, hemangiomas with and without PWSs were defined as two separate subgroups, and imaging features were compared. RESULTS: Of the 93 cases of hemangiomas, 49 (52.6%) had PWSs in the TP. The mean SINorms of hemangiomas showed the highest value in the AP (P < 0.05). The mean CNorms showed positive values in the AP, and gradually decreased (P < 0.05). Hemangiomas with PWSs were significantly rapidly enhanced and smaller in size (P < 0.05), and the mean SINorms was lower in the TP (P = 0.023). While the mean CNorms showed a significant difference in the AP between subgroups (P < 0.001), the enhancement pattern was equal to that of the PV. CONCLUSION: When evaluating GA-enhanced MRI, radiologists should utilize quantitative measures in addition to qualitative assessment and should be aware that SI matching with PV in all phases can be a distinguishing finding in the diagnosis of hemangioma.

Non-beta blocker enantiomers of propranolol and atenolol inhibit vasculogenesis in infantile hemangioma.

Propranolol and atenolol, current therapies for problematic infantile hemangioma (IH), are composed of R(+) and S(-) enantiomers: the R(+) enantiomer is largely devoid of beta blocker activity. We investigated the effect of R(+) enantiomers of propranolol and atenolol on the formation of IH-like blood vessels from hemangioma stem cells (HemSCs) in a murine xenograft model. Both R(+) enantiomers inhibited HemSC vessel formation in vivo. In vitro, similar to R(+) propranolol, both atenolol and its R(+) enantiomer inhibited HemSC to endothelial cell differentiation. As our previous work implicated the transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18) in propranolol-mediated inhibition of HemSC to endothelial differentiation, we tested in parallel a known SOX18 small-molecule inhibitor (Sm4) and show that this compound inhibited HemSC vessel formation in vivo with efficacy similar to that seen with the R(+) enantiomers. We next examined how R(+) propranolol alters SOX18 transcriptional activity. Using a suite of biochemical, biophysical, and quantitative molecular imaging assays, we show that R(+) propranolol directly interfered with SOX18 target gene trans-activation, disrupted SOX18-chromatin binding dynamics, and reduced SOX18 dimer formation. We propose that the R(+) enantiomers of widely used beta blockers could be repurposed to increase the efficiency of current IH treatment and lower adverse associated side effects.

Inflammatory lobular hemangioma: A vascular proliferation with a prominent lymphoid component. Review of a series of 19 cases.

In the last 30 years, there has been a strong interest in vascular proliferations. Pyogenic granuloma was not only renamed lobular capillary hemangioma, but also the conceptual interpretation was also changed from an overgrowth of granulation tissue to a genuine hemangioma (or benign vascular neoplasm). We describe 19 cases of patients who presented clinically with a vascular lesion, characteristically a pyogenic granuloma or lobular hemangioma, where the histopathological findings led to the pathologic concern for a lymphoma of the skin. These benign lesions with a dense lymphoid infiltrate were further defined on the basis of different vascular and lymphoid immunohistochemical markers as inflammatory lobular hemangiomas. We propose that given the considerable histopathological overlap between acral pseudolymphomatous angiokeratoma, T-cell rich angiomatoid polypoid pseudolymphoma of the skin, and other designations of some of these vascular proliferations with a rich and dense lymphoid infiltrate, they might constitute a spectrum of vascular lesions with varying clinical presentations.

Case 276: Pulmonary Veno-Occlusive Disease and Pulmonary Capillary Hemangiomatosis Disease.

HistoryA 34-year-old man presented to the emergency department of our hospital for progressive shortness of breath and worsening productive cough of 2 weeks duration. He reported a 10-kg weight loss over 4 months but denied experiencing fever, chills, night sweats, or gastrointestinal, musculoskeletal, or neurologic symptoms. His medical history was unremarkable. Although he was a native of Morocco, he had lived in Europe for many years and worked as a truck driver. The patient had a smoking history but had quit smoking 5 years prior to presentation. He denied alcohol abuse or recreational drug use. He did not have any allergies. Besides bilateral clubbing, the physical examination findings were normal. At the time of admission, he had an oxygen (O2) saturation of 87% at ambient air, which increased to 100% with 1 L of O2 administered via a nasal cannula. The blood sample revealed a slight increase in his hemoglobin concentration (18.7 g/dL; normal range, 13.6-17.2 g/dL) and hematocrit level (50.8%; normal range, 39%-49%). His inflammatory parameters were normal, as were his hepatic and renal function. The arterial blood gas test showed partially compensated pulmonary alkalosis (pH, 7.43; normal range, 7.35-7.42; PCO2, 26 mmHg; normal range, 38-42 mmHg; PO2, 89 mmHg; normal range, 75-100 mmHg; bicarbonate level, 17 mEq/L [17 mmol/L]; normal range 22-26 mEq/L [22-26 mmol/L]). The results of the pulmonary function tests were expressed as the percentage of predicted values and were 92% for forced vital capacity, 93% for forced expiratory volume in 1 second, 116% for total lung capacity, and 60% for diffusing capacity of carbon monoxide. Anteroposterior chest radiography and enhanced chest CT were also performed at admission.

Hepatic hemangioma supplied by abnormal portal vein: A case report.

Hepatic hemangioma is the most common hepatic tumor with a prevalence of approximately 3%. It is typically supplied by the hepatic artery as evident from findings of abdominal angiography, contrast-enhanced ultrasonography (CEUS), contrast-enhanced computed tomography (CT), and contrast-enhanced magnetic resonance imaging. However, few cases of hepatic hemangioma supplied by the portal vein have been reported. In this paper, we report a rare case of hepatic hemangioma supplied by the portal vein as shown on CEUS and CT arterioportography.

Infantile Hepatic Hemangioma.

Infantile hepatic hemangioma (IHH) historically called "hemangiomaendothelioma" refers to visceral manifestation of infantile hemangioma. The diagnosis of infantile hepatic hemangioma is primarily based on the radiological features. We present a case of 4 month old infant who presented with abdominal distention. Contrast enhanced CT demonstrated typical features of diffuse infantile hepatic hemangiomas.

Pigment epithelium-derived factor/vascular endothelial growth factor ratio plays a crucial role in the spontaneous regression of infant hemangioma and in the therapeutic effect of propranolol.

Infantile hemangioma (IH) is a benign tumor that is formed by aberrant angiogenesis and that undergoes spontaneous regression over time. Propranolol, the first-line therapy for IH, inhibits angiogenesis by downregulating activation of the vascular endothelial growth factor (VEGF) pathway, which is hyperactivated in IH. However, this treatment is reportedly ineffective for 10% of tumors, and 19% of patients relapse after propranolol treatment. Both pro-angiogenic and anti-angiogenic factors regulate angiogenesis, and pigment epithelium-derived factor (PEDF) is the most effective endogenous anti-angiogenic factor. PEDF/VEGF ratio controls many angiogenic processes, but its role in IH and the relationship between this ratio and propranolol remain unknown. Results of the present study showed that the PEDF/VEGF ratio increased during the involuting phase of IH compared with the proliferating phase. Similarly, in hemangioma-derived endothelial cells (HemEC), which were isolated with magnetic beads, increasing the PEDF/VEGF ratio inhibited proliferation, migration, and tube formation and promoted apoptosis. Mechanistically, the VEGF receptors (VEGFR1 and VEGFR2) and PEDF receptor (laminin receptor, LR) were highly expressed in both IH tissues and HemEC, and PEDF inhibited HemEC function by binding to LR. Interestingly, we found that propranolol increased the PEDF/VEGF ratio but did so by lowering VEGF expression rather than by upregulating PEDF as expected. Furthermore, the combination of PEDF and propranolol had a more suppressive effect on HemEC. Consequently, our results suggested that the PEDF/VEGF ratio played a pivotal role in the spontaneous regression of IH and that the combination of PEDF and propranolol might be a promising treatment strategy for propranolol-resistant IH.

Oral superficial haemosiderotic lymphovascular malformation: a rare presentation.

We present an extremely rare case of a 53-year-old woman with an intraoral superficial haemosiderotic lymphovascular malformation (SHLM), also known as hobnail haemangioma. SHLM is a rare, benign, vascular tumour first described as targetoid haemosiderotic haemangioma, with only a handful of cases reported to present in the oral cavity. The diagnosis was established following complete surgical excision of the lesion, and after 14 months, there are still no signs of recurrence. Although SHLM is an uncommon condition, accurate and timely diagnosis is valuable in distinguishing these lesions from their more serious competing differential diagnoses.

INFRARED IMAGING OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMAS.

PURPOSE: To describe the features of choroidal tumors on infrared (IR) imaging and to determine the diagnostic sensitivity and specificity of intratumoral choroidal vascular loops on IR imaging for circumscribed choroidal hemangioma (CCH). METHODS: Infrared and indocyanine green images of CCH, choroidal metastases, and choroidal melanomas were reviewed. The main outcome measure was the presence of intratumoral choroidal vascular loops and tufts on IR images. The secondary outcome measure was the presence of peritumoral vascular expansion on indocyanine green images. RESULTS: Intratumoral CCH vessels appear as dark beaded spaces on IR imaging; 95.5% of CCH had vascular loops compared with the controls of 65% in choroidal melanomas and 64% in choroidal metastases. The sensitivity of intratumoral vessels on IR for CCH was 95.4%. Subanalysis of six patients with CCH showed the presence of peritumoral vascular expansion on indocyanine green images. CONCLUSION: Infrared imaging delineates intratumoral vessels in choroidal tumors appearing as dark beaded loops and tufts. Vascular loops on IR imaging showed a high diagnostic sensitivity for CCH. The absence of these loops on IR can help rule out the diagnosis of CCH. Peritumoral vascular expansion on indocyanine green is an additional diagnostic tool that is helpful in the diagnosis of CCH.

Hiperplasia angiolinfoide com eosinofilia: um caso raro em cavidade oral / Angiolymphoid hyperplasia with eosinophilia: a rare case in the oral cavity

Resumo A hiperplasia angiolinfoide com eosinofilia (HALE) é considerada uma lesão vascular benigna rara que acomete, principalmente, o tecido cutâneo e subcutâneo da região de cabeça e pescoço, mas incomum na cavidade oral. Sua etiopatogenia permanece indefinida, sendo descrita como proliferação vascular reacional, malformação vascular ou neoplasia. Tem como principal diagnóstico diferencial a doença de Kimura. Este trabalho relata um caso de um paciente do sexo masculino, de 50 anos, que exibia aumento de volume nodular na mucosa do lábio superior, com 3 cm de dimensão e 7 anos de evolução. Após a biópsia excisional, o exame histopatológico mostrou lesão bem encapsulada multilobulada com proliferação de capilares sanguíneos com células endoteliais de aspecto epitelioide, infiltrado inflamatório difuso com linfócitos, plasmócitos, inúmeros eosinófilos e presença de folículos linfoides. A análise imuno-histoquímica revelou positividade para CD34 e Ki-67, o que, juntamente com o exame morfológico, direcionou o diagnóstico para HALE.

Abstract Angiolymphoid Hyperplasia with eosinophilia (ALHE) is considered a rare, benign vascular lesion that mainly affects the skin and subcutaneous tissues of the head and neck, but is uncommon in the oral cavity. Its etiology remains unclear and it has been described as a reactive vascular proliferation, vascular malformation or neoplasm. Kimura's disease is the primary entity to consider in differential diagnosis. Here we report on a rare case of ALHE involving the upper lip of a 50-year-old male patient that had a nodular swelling with approximately 3 cm, 7 years after initial onset. An excisional biopsy was performed and histopathologic examination revealed a well-encapsulated, multi-lobed lesion with proliferation of blood capillaries, displaying endothelial cells of epithelioid appearance, diffuse inflammatory infiltrate with lymphocytes, plasma cells, numerous eosinophils, and presence of lymphoid follicles. Immunohistochemical tests were positive for the markers CD34 and Ki-67 that, in combination with the results of morphological examination, were suggestive of a diagnosis of ALHE.

Superb microvascular imaging technology for ultrasound examinations: Initial experiences for hepatic tumors.

PURPOSE: To explore whether superb microvascular imaging (SMI) technology could be helpful for the evaluation of hepatic tumors. MATERIALS AND METHODS: Our institutional review board approved this study, and informed consent was obtained from all of the patients. Twenty-three patients with 29 hepatic tumors were enrolled in our study. The tumors consisted of hemangiomas (n=15), focal nodular hyperplasias (FNHs) (n=7), and hepatocellular carcinomas (n=7). All lesions were pathologically (n=2) or radiologically (n=27) confirmed. The mean tumor diameter was 1.9cm (range, 0.9cm to 5.0cm). Using SMI technology, all lesions were scanned and categorized into subgroups according to the flow pattern on the SMI. RESULTS: The hemangiomas exhibited nodular rim patterns (33%) and spotty dot-like patterns (20%), and both of these findings were very specific for the diagnosis of hemangioma. The FNHs exhibited spoke-wheel patterns (43%) and radiating vessel patterns (29%) that were very specific findings for the diagnosis of FNH. The other tumors did not exhibit any specific patterns on SMI. CONCLUSION: Evaluations of the inner vascularities of hepatic tumors with the SMI technique were feasible, and the SMI features were significantly different between the different types of hepatic tumors. These differences could aid the diagnoses of hepatic tumors with US.

Use of three-dimensional color power doppler in imaging of liver cancer.

We aimed to assess the role of three-dimensional color power Doppler (3D-CPD) imaging in diagnosis of liver cancer. First of all, we performed 2D- and 3D-CPD imaging on 96 cases of liver tumors with a total of 106 lesions to examine the characteristics of the vascular distribution patterns of the tumors, and in turn, compare the sensitivity and specificity. Also, with the use of three-dimensional volumetric measurement, we calculated the volume of tumors, quantity of intra-tumor blood vessels, and the ratio of the quantity of intra-tumor blood vessels to tumor volumes (vascular index, VI). Finally, we statistically analyzed the vascular index between benign and malignant tumors. We found that the sensitivity/specificity were 21.3%/100% for 2D-CPD, and 81.3%/100% for 3D-CPD, based on the use of type-III of blood vessels for diagnosis of the malignant lesions. In 3D-CPD, the type-III of blood vessels along with VI of > 0.3/cm3 can be used as the criteria for the diagnosis of liver cancer since we found that average VI was 0.38/cm3 in 75 malignant tumors, but 0.18/cm3 in 31 benign tumors (p less than0.05). The sensitivity and specificity in determining malignancy in the liver based on VI > 0.3/cm3 were 78.7% and 87.1%, respectively.

Altered ratios of pro- and anti-angiogenic VEGF-A variants and pericyte expression of DLL4 disrupt vascular maturation in infantile haemangioma.

Infantile haemangioma (IH), the most common neoplasm in infants, is a slowly resolving vascular tumour. Vascular endothelial growth factor A (VEGF-A), which consists of both the pro- and anti-angiogenic variants, contributes to the pathogenesis of IH. However, the roles of different VEGF-A variants in IH progression and its spontaneous involution is unknown. Using patient-derived cells and surgical specimens, we showed that the relative level of VEGF-A165 b was increased in the involuting phase of IH and the relative change in VEGF-A isoforms may be dependent on endothelial differentiation of IH stem cells. VEGFR signalling regulated IH cell functions and VEGF-A165 b inhibited cell proliferation and the angiogenic potential of IH endothelial cells in vitro and in vivo. The inhibition of angiogenesis by VEGF-A165 b was associated with the extent of VEGF receptor 2 (VEGFR2) activation and degradation and Delta-like ligand 4 (DLL4) expression. These results indicate that VEGF-A variants can be regulated by cell differentiation and are involved in IH progression. We also demonstrated that DLL4 expression was not exclusive to the endothelium in IH but was also present in pericytes, where the expression of VEGFR2 is absent, suggesting that pericyte-derived DLL4 may prevent sprouting during involution, independently of VEGFR2. Angiogenesis in IH therefore appears to be controlled by DLL4 within the endothelium in a VEGF-A isoform-dependent manner, and in perivascular cells in a VEGF-independent manner. The contribution of VEGF-A isoforms to disease progression also indicates that IH may be associated with altered splicing. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Hemangioma: descrição de um caso clínico e sua importância no diagnóstico diferencial / Hemangioma: description of a clinical case and the importance in the differential diagnosis

O hemangioma infantil é um tumor vascular benigno que ocorre devido a uma proliferação anormal dos vasos sanguíneos. O quadro clínico apresenta três fases bem definidas: proliferativa, involutiva e involuída. O diagnóstico é realizado basicamente por meio da anamnese e do exame físico, e quando necessário preconiza-se avaliação histopatológica. O presente trabalho, descreve um caso clínico de um hemangioma presente em um bebê de 3 meses de idade que foi, de principio, diagnosticado como mucocele ou fibroma. A cirurgia excisional foi realizada eo material encaminhado para análise histopatológica, confirmando o diagnóstico de hemangioma. Nessas situações, vale ressaltar a importância do diagnostico diferencial, manobra cirúrgica adequada e a avaliação das características clínicas da lesão para evitar possíveis complicações cirurgicas.

The infantile hemangioma is a benign vascular tumor which occurs due to an abnormal proliferation of blood vessels. The clinical features three well-defined phases: proliferative, involution,and involuted. The diagnosis is made primarily by clinical history and physical examination, but when necessary, help to close the histopathological diagnosis. This paper describes a clinical case of a gift hemangioma in a baby three months old who was, in principle, diagnosed as mucocele or fibroma. The excisional surgery was performed and material sent for histopathological confirmation hemangioma. It is worth emphasizing the importance of differential diagnosis, appropriate surgical maneuver, assessment of clinical characteristics of the lesion to prevent potential surgical complications possible.