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The diagnosis of vascular anomalies remains challenging due to significant clinical heterogeneity and uncertain etiology. Evaluation using biopsy and/or genetic testing for somatic variants is invasive, expensive, and prone to sampling error. There is great need for noninvasive and easily measured blood laboratory biomarkers that can aid not only in diagnosis, but also management of treatments for vascular anomalies. Angiopoietin-2, a circulating blood angiogenic factor, is highly elevated in patients with kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon and kaposiform lymphangiomatosis. Here, we describe our clinical experience using serum angiopoietin-2 as a biomarker for diagnosis and monitoring response to treatment., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor that often occurs in infants and young children. The goal of this study was to analyze the clinical characteristics of KHE patients with bone destruction and provide clinical guidance for diagnosis and treatment., Methods: We conducted a descriptive cohort study with follow-up from January 2007 to January 2023 to collect demographic information and tumor-related clinical information from KHE patients with bone destruction., Results: A total of 269 KHE patients were included in the study, of whom 70 (26.0%) patients had tumors with bone destruction. The median age at diagnosis of patients with bone destruction was 19.0 months, which was much later than that of patients without bone destruction (P < 0.001). Patients with bone destruction were more likely to have a decreased range of motion (ROM) (P < 0.001). Metaphysis involvement was more likely to occur in the lower limb bones (P = 0.039), and the lower limb bones were more likely to be associated with decreased ROM (P = 0.001). Tumors involving extracompartmental bone were more likely to have decreased ROM (P = 0.003) and exhibit the Kasabach-Merritt phenomenon (P = 0.006)., Conclusions: Based on the rarity and significant heterogeneity of KHE patients with bone destruction, we should give full play to the role of multidisciplinary teams in addressing disease to reduce the long-term complications of KHE with bone destruction and improve the quality of life of patients., Type of Study: Prognostic Study., Level of Evidence: Level II., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy that is commonly associated with a life-threatening thrombocytopenic condition, Kasabach-Merritt phenomenon (KMP). Platelet CLEC-2, tumor podoplanin interaction is considered the key mechanism of platelet clearance in these patients. Here, we aimed to assess platelet functionality in such patients. Three groups of 6 to 9 children were enrolled: group A with KHE/KMP without hematologic response (HR) to therapy; group B with KHE/KMP with HR; and group C with healthy children. Platelet functionality was assessed by continuous and end point flow cytometry, low-angle light scattering analysis (LaSca), fluorescent microscopy of blood smears, and ex vivo thrombi formation. Platelet integrin activation in response to a combination of CRP (GPVI agonist) and TRAP-6 (PAR1 agonist), as well as calcium mobilization and integrin activation in response to CRP or rhodocytin (CLEC-2 agonist) alone, were significantly diminished in groups A and B. At the same time, platelet responses to ADP with or without TRAP-6 were unaltered. Thrombi formation from collagen in parallel plate flow chambers was also noticeably decreased in groups A and B. In silico analysis of these results predicted diminished amounts of CLEC-2 on the platelet surface of patients, which was further confirmed by immunofluorescence microscopy and flow cytometry. In addition, we also noted a decrease in GPVI levels on platelets from group A. In KHE/KMP, platelet responses induced by CLEC-2 or GPVI activation are impaired because of the diminished number of receptors on the platelet surface. This impairment correlates with the severity of the disease and resolves as the patient recovers., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Some vascular anomalies can present with challenging hematologic aberrations. Kaposiform hemangioendothelioma (KHE) may be complicated with Kasabach-Merritt phenomenon (KMP) and stagnant blood flow in slow-flow malformations can promote activation and consumption of coagulation factors, which results in bleeding and clotting known as localized intravascular coagulopathy (LIC). These patients can experience significant morbidity secondary to pain due to thrombosis and are at higher risk of hematologic complications during surgical procedures. No standard of care has been established to prevent or manage these complications. This review focuses on the management of coagulopathy in children and adults with vascular anomalies., (© 2021 Wiley Periodicals LLC.)

Competing Interests: Conflicts of interest None disclosed.

A 3-y-3-mo old male child presented with massive hypertrophy and bluish-purple discoloration of the left upper limb and adjacent chest wall of 3 mo duration. There was no h/o fever, weight loss, painful large joint swelling, or any bleeding manifestations. He had spindle like nonprogressive, painless swelling of all fingers of the left hand since infancy. The child was moribund with microangiopathic hemolytic anemia, thrombocytopenia, and consumptive coagulopathy without sepsis. He received multiple transfusions of fresh frozen plasma (FFP), platelets, and packed RBC. Paradoxical worsening of symptoms with platelet transfusions and radiological evidences led to the diagnosis of a very rare congenital multifocal vascular tumor, kaposiform hemangioendothelioma (KHE) with Kasabach-Merritt phenomenon (KMP). The index case of KHE was multifocal with cutaneous lesions, osteolytic bony lesions of all phalanx and metacarpals of the left hand, and intrathoracic extension. It was successfully managed with a combination of steroid, vincristine and sirolimus., (© 2021. Dr. K C Chaudhuri Foundation.)

Purpose: The management of hepatic hemangioendothelioma (HHE) may be challenging. We aimed to review a large cohort of children who presented to our centers with symptomatic HHE in the last 16 years., Methods: We collected age at presentation, clinical features, histology, diagnostic process, management and outcome., Results: Twenty seven patients (male/female 5/22), median age 13 days (1-1530) presented with hepatomegaly (24/27), cardiac failure (10/27), cutaneous hemangiomas (8/27), fever and anemia (6/27 each), vomiting (5/27), splenomegaly (4/27). The lesion was focal, multifocal, or diffuse in 9 patients of each group. The management included medical treatment (8/27), embolization (8/27), resection (3/27), observation (6/27), transplantation (2/27). After 16 months' follow-up (30 days-11 years), 23/27 (85%) were alive. Diffuse lesions (4/4), cardiac failure (4/4), type II histology (4/4), age older than 6 months at diagnosis (3/4) predicted mortality (all p < 0.01). Histology showed type 1 lesion in 3/8, type 2 in 3/8, and type 3 in 2/8 with foci of angiosarcoma., Conclusion: Most patients with symptomatic HHE can be managed successfully with a combination of medical, radiological and surgical treatments. Patients with diffuse lesions, late presentation, cardiac failure and type II histology have a poor outcome., Level of Evidence: Diagnostic level IV. Therapeutic level IV.

Vascular tumors are a rare subset of vascular anomalies. These are classified based on their malignant potential or local destruction potential. Classification has been historically difficult and treatment recommendations are based on case series. The purpose of this chapter is to review the presentation, pathologic and imaging characteristics. Treatment recommendations are summarized based on the current literature. Congenital and infantile hemangiomas are covered separately in a separate chapter in this issue., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose, (Copyright © 2020. Published by Elsevier Inc.)

Kaposiform lymphangiomatosis (KLA) is a rare, life-threatening congenital lymphatic malformation. Diagnosis is often delayed due to complex indistinct symptoms. Blood angiopoietin-2 (ANG2) levels are elevated in KLA and may be useful as a biomarker to monitor disease status. We report a 7-year-old male child with easy bruising, inguinal swelling, and consumptive coagulopathy, diagnosed with KLA. A multimodal treatment regimen of prednisone, sirolimus, vincristine, and adjunctive zoledronate was used. Plasma ANG2 levels were highly elevated at diagnosis but decreased during treatment. The patient showed significant clinical improvement over a 38-month period and normalization of ANG2 levels correlated with resolution of the coagulopathy., (© 2020 Wiley Periodicals, Inc.)

Competing Interests: Competing interests: None declared.

Purpose: Infantile hepatic hemangioendothelioma (IHHE) is the most common hepatic vascular tumor in children. We report on the treatment outcome of our large single-center experience of patients with IHHE over a 9-year period., Materials and Methods: A retrospective analysis of all IHHE patients treated at the Children Cancer Hospital Egypt from April 2008 through April 2017., Results: In total, 28 patients (18 females, 10 males) were diagnosed with IHHE with a median age at diagnosis of 3 months. The lesions were multifocal (n=12), focal (n=10), and diffuse (n=6). Six (21.4%) patients initially had low T3 and T4. Eleven patients did not receive any treatment, whereas 1 patient underwent resectional surgery. Sixteen patients received drug treatment, 9 of whom responded well to first-line propranolol/prednisolone, whereas 7 patients needed salvage treatment. Twenty-five patients are alive, whereas 3 patients have died., Conclusions: Overall, patients with IHHE do well, a significant percentage of whom do not require drug therapy, particularly for those with small focal lesions. In patients with multifocal/diffuse disease, there is a high incidence of low T3 and T4 and while some of these patients did well without additional therapy, those with rapidly progressive lesions during treatment may do poorly.

Background: Endothelial cell malignancies are extremely rare in childhood. New identification of genetic abnormalities (WWTR1:CAMTA1 translocation) helps to recognize potential therapeutic targets. Little is known about treatment and outcome of these patients., Methods: Clinical course, treatment, and outcome in patients with endothelial cell malignancies treated within the Cooperative Weichteilsarkom Studiengruppe (CWS) trials CWS-91, -96, -2002P, and the Soft-Tissue Sarcoma Registry (SoTiSaR) were analyzed (1991-2019)., Results: Patients had angiosarcoma (AS) (n = 12), malignant epithelioid hemangioendothelioma (EHE) (n = 16), and kaposiform hemangioendothelioma (KHE) (n = 13). The median age was 5.39 years (range, 0.8-17.34); 33 patients had localized disease (LD), and 8 patients had metastatic disease. Therapy consisted of chemotherapy (CHT) (AS n = 8, EHE n = 9, KHE n = 5), interferon or new agent therapy (EHE n = 5, 2 KHE n = 2), microscopically or macroscopically complete resection (AS n = 3, EHE n = 6, KHE n = 3), and radiotherapy (AS n = 6, EHE n = 2, KHE n = 1). Two patients (KHE) had watch-and-wait strategy resulting in stable disease. Complete remission (CR) was achieved in AS (10/12; 83%), EHE (10/16; 63%), and KHE (5/13; 38%). The five-year EFS and OS for patients with AS was 64% (± 29 CI 95%) and 80% (± 25, CI 95%), with EHE 62% (± 24, CI 95%) and 78% (± 23, CI 95%), with KHE 33% (± 34, CI 95%) and 92% (± 15, CI 95%), respectively. Complete resection was a significant prognostic factor for AS, LD for EHE., Conclusions: Endothelial cell malignancies in childhood have a fair outcome with multimodal treatment. New treatment options are needed for metastic disease., (© 2019 Wiley Periodicals, Inc.)

A vascular mass localized in the face and the neck was displayed by ultrasonography in a 38-week-old male fetus. At birth, the mass was bulky and purplish. The newborn breathed spontaneously but with severe desaturation. During laryngoscopy, we observed an obstruction of the larynx with a left-shift caused by the hemorrhagic mass. Blood analysis revealed anemia, severe thrombocytopenia, and coagulation disorders. The diagnosis of kaposiform hemangioendothelioma (KHE) complicated by a Kasabach-Merritt phenomenon (KMP) was put forward and treatment with propranolol, corticoids, and vincristine was initiated. Platelets were transfused daily for 8 days but did not resolve the thrombocytopenia. At day 8, we added sirolimus to the treatment and noted a rapid response with the normalization of the platelet count within 1 week and a significant regression of the mass. In this paper, we review the clinical and biological features of hemangioendothelioma associated with KMP and discuss its current and future treatment. Sirolimus seems to be very promising., (Copyright © 2019 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon, rarely metastasizing vascular neoplasm with predilection to affect young adults. The tumors often present as multiple nodules involving various tissue planes, including superficial and deep soft tissues as well as bone. Recurrent SERPINE1-FOSB gene fusions have been reported as the hallmark genetic abnormality in PHE, however, in our experience, a number of cases with typical histology lack this genetic abnormality. In this study, we identify a novel ACTB-FOSB gene fusion, which is as prevalent as the initial translocation reported. We selected 15 consecutive cases of PHE with typical morphologic features which had material for molecular testing. The cohort included 10 males and 5 females, ranging in age from 17 to 58 years (median age: 33 y; mean age: 35.3 y). Eight (53%) cases were located in the lower extremities (foot, calf, tibia, thigh), 5 (33%) were located in the trunk, abdomen or pelvis (abdominal wall-2, shoulder, back, ischium) and 2 (13%) were located in the upper extremity (humerus and hand). Ten (67%) cases had multifocal presentation and 5 (33%) presented as solitary lesions. Three (20%) cases were located only in the superficial dermis and subcutaneous tissues, 4 (27%) involved the superficial and deep soft tissue and 8 (53%) cases involved only the deep soft tissue and bone. Using fluorescence in situ hybridization and ARCHER fusionplex analysis we identified a novel ACTB-FOSB gene fusion in 7 cases, while the remaining 8 had the previously described SERPINE1-FOSB fusion. The clinicopathologic features and behavior of PHE associated with the ACTB-FOSB gene fusion were similar to those harboring the SERPINE1-FOSB; except that tumors with the ACTB variant were more often associated with solitary presentation. In conclusion, our results expand the spectrum of genetic alterations in PHE with a novel gene fusion identified in half of the cases. We speculate that some of the novel targeted therapies that have shown promise in SERPINE1-FOSB-positive PHE might also be beneficial in this molecular subset.

Purpose: We sought to characterize the clinical features and management of patients diagnosed as Kaposiform hemangioendothelioma (KHE) without cutaneous involvement., Methods: The electronic patient chats at six Triple A hospitals in China were searched to find all patient diagnoses with KHE without cutaneous involvement., Results: Of 30 patients (mean age at diagnosis, 55.6 months), 17 (56.7%) were male. Fourteen (46.7%) patients were associated with Kasabach-Merritt phenomenon (KMP). Patients with KMP were significantly more likely to have lesions involving truck compared to patients without KMP (odds ratio 10.000; 95% confidence interval 1.641-60.921; P = 0.011). Other common complication included severe anemia and decreased range of motion. In the majority of cases (93.3%), the lesions were highly infiltrative and locally invasive with ill-defined margins. Histological examination was required in all patients without KMP for precise diagnosis. In all, 16 (53.3%) patients received corticosteroid treatment, 19 (63.3%) received oral sirolimus treatment, 7 (23.3%) received intravenous vincristine, and 5 (16.7%) patients used propranolol. Patients had varied responses to conventional drugs, whereas all patients receiving sirolimus treatment had better response. In all, three patients (10%) died of disease, all presented with KMP. Feature of these recalcitrant cases (death) included young age, visceral location, extensive involvement, and lack of improvement with high-dose corticosteroids., Conclusions: Our study clearly demonstrated that KHE without cutaneous involvement could be associated with important complication, which might result in death or severe morbidity. Increased awareness of KHE without cutaneous involvement is required for early diagnosis and aggressive therapy in an attempt to prevent complication.

Background: Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor affecting infants and young children. Although benign, it can be associated with an aggressive locally growing tumor and/or a life-threatening Kasabach-Merritt phenomenon (KMP). To date, only reviews of limited cases have been performed. We, therefore, conducted a comprehensive literature search to collect relevant data and make recommendations for future treatment trials., Methods: Review of the available literature between 1993 and 2017 revealed a total of 105 publications involving 215 patients of less than 21 years of age. To this, we added 12 from our department and 4 from the Cooperative Weichteilsarkomstudie database., Results: We found that KMP was present in 79% of the infants, in 47% of the 1-5-year olds, in 43% of the 6-12-year olds, and in 10% of the 13-21-year-old patients. KMP was present in nearly all (94%) patients with retroperitoneal tumors and in all patients with extra-regional tumors. The median size of a KHE without KMP was 12 cm 2 as compared to 49 cm 2 when associated with a KMP. With complete (not further classifiable if R0 or R1) resection, all patients were cured. If inoperable, response regarding KMP/regression of tumor size was seen in 29/28% with steroid-, 47/39% with vincristine-, 44/43% with interferon alpha-, 65/61% with anti-platelet agents-, and in 97/100% with sirolimus-containing therapies., Conclusions: Patients with progressive KHE should undergo resection whenever it is considered a safe option. If inoperable, sirolimus should be the first choice for treating KMP and reducing tumor size.

Background: Few studies have reported the clinical features, complications and predictors of Kasabach-Merritt phenomenon (KMP) associated with Kaposiform haemangioendothelioma (KHE)., Objectives: To determine the clinical characteristics present at diagnosis and to identify features that may aid clinicians in managing KHE., Methods: We conducted a cohort study of 146 patients diagnosed with KHE., Results: KHE precursors or lesions were present at birth in 52·1% of patients. In 91·8% of patients, lesions developed within the first year of life. The median age at diagnosis of KHE was 2·3 months (interquartile range 1·0-6·0). The extremities were the dominant location, representing 50·7% of all KHEs. Among KHEs in the cohort, 63·0% were mixed lesions (cutaneous lesions with deep infiltration). Approximately 70% of patients showed KMP. A KHE diagnosis was delayed by ≥ 1 month in 65·7% of patients with KMP. Patients with KMP were more likely to have major complications than patients without KMP (P = 0·023). Young age (< 6 months), trunk location, large lesion size (> 5·0 cm) and mixed lesion type were associated with KMP in a univariate analysis. In the multivariate analysis, only age [odds ratio (OR) 11·9, 95% confidence interval (CI) 4·07-34·8; P < 0·001], large lesion size (OR 5·08, 95% CI 2·24-11·5; P < 0·001) and mixed lesion type (OR 2·96, 95% CI 1·23-7·13; P = 0·016) were associated with KMP., Conclusions: Most KHEs appeared before 12 months of age. KHEs are associated with various major complications, which can occur in combination and develop early in the disease process. Young age, large lesion size and mixed lesion type are important predictors of KMP., (© 2018 British Association of Dermatologists.)

Pseudomyogenic hemangioendothelioma (PMH) is a rare, mostly indolent vascular tumor. Extensive cases are treated with amputation as chemotherapy seems to be ineffective. Recently, promising results were published using mammalian target of rapamycin (mTOR) inhibitors in tumors of vascular origin. Here, we present a case of a child with advanced PMH relapsing after surgery and chemotherapy. Sirolimus achieved significant clinical improvement and stabilization of the lesions without any remarkable toxicity. This case contributes to the growing evidence regarding the efficacy of mTOR inhibitors, such as sirolimus, in multifocal PMH., (© 2017 Wiley Periodicals, Inc.)

Congenital and acquired vascular anomalies are common in childhood. In addition to predominantly harmless vascular skin alterations there are others which must be immediately treated due to the potentially threatening complications. As examples three anomalies and the typical complications are presented. Hemangiomas in infancy can make urgent treatment necessary because they can be complicated by obstruction or painful ulceration. Kaposiform hemangioendothelioma can lead to a life-threatening consumption coagulopathy. Klippel-Trenaunay syndrome can be complicated by thrombosis, localized coagulopathy, and superinfections.

Kaposiform hemangioendothelioma (KHE) is a rare aggressive vascular tumor of skin and deep soft tissues that typically presents in infancy and may be associated with a potentially life-threatening coagulopathy known as Kasabach-Merrit phenomenon (KMP). Recent advances in medical therapy have successfully treated many patients. However, our knowledge regarding the natural history of these lesions and optimum surveillance strategies remains rudimentary. We report two young women who had KHE with KMP treated in infancy and presented in adolescence with comorbidities related to their KHE tumor. This presentation supports the need for long-term surveillance in these patients., (© 2016 Wiley Periodicals, Inc.)

This meta-analysis was to evaluate the efficacy of current treatment modalities for kaposiform hemangioendothelioma and tufted angioma. A systematic review was performed using PubMed (Medline), Web of Science and Embase for clinical studies. The outcome was measured by pooled response rate with 95% confidence intervals (CIs), together with heterogeneity, subgroup analysis, sensitivity analysis and publication bias. Fifteen studies with 244 participants were included in this analysis. Vincristine therapy exhibited a relatively higher response rate (0.72; 95%CI, 0.64-0.79) compared with other therapies including systemic corticosteroid (0.27; 95%CI, 0.17-0.36), interferon (0.36; 95%CI, 0.24-0.48), radiotherapy (0.49; 95%CI, 0.26-0.73), embolization (0.66; 95%CI, 0.48-0.83), aspirin/ticlopidine (0.42; 95%CI, 0.06-0.78) and sirolimus (0.57; 95%CI, 0.00-0.10), in treating KHE/TA. Subgroup analysis indicated that the efficacy of systemic corticosteroids therapy was age-related. The pooled response rate was 0.15 (95%CI, 0.08-0.23) for participants 3.5 months of age and older compared with 0.35 (95% CI, 0.26-0.44) for participants less than 3.5 months. Regarding side effects, systemic corticosteroids treatment was 0.32 (95%CI, 0.15-0.50), vincristine modality was 0.16 (95%CI, 0.08-0.24) and interferon therapy was 0.28 (95%CI, 0.13-0.43). In conclusion, as one of the first reviews evaluating the effect of common therapies in the treatment of KHE/TA, our meta-analysis displayed that vincristine was more effective. Thus, vincristine was the most effective, providing evidence supporting the use of vincristine as a first-line therapy for KHE/TA., (© 2016 UICC.)

Kasposiform hemoangioendothelioma (KHE) and tufted angioma (TA) are classifed as vascular tumors with locally aggressive and benign growth potential, respectively, within the classification schema proposed by the International Society for the Study of Vascular Anomalies. A unique feature of these vascular tumors is the risk of Kasabach-Merritt phenomenon (KMP), a severe thrombocytopenia with mild to moderate coagulopathy resulting from intralesional platelet trapping. As with many vascular anomalies, accurate description of clinical course, responses to therapy, and long-term outcomes have been hindered by lesion misidentification, imprecise nomenclature, and lack of prospective, randomized clinical trials to assess therapeutic efficacy. The classic dermatologic features of these lesions can facilitate diagnosis for the astute provider; however, the absence of or unusual integumentary involvement or presentation in a less common age group (adolescents/adults) poses a diagnostic challenge. Current approaches to the management of KHE/TA are often informed by lesion features such as presence of KMP, extent and location of the tumor, and symptomatology. Evidence-based treatment guidelines are limited. Corticosteroids, vincristine, interferon, multi-agent regimens and newer therapies, such as sirolimus, have demonstrated efficacy in patient series. The use of surgical excision and interventional radiology guided therapies have been described with mixed clinical benefit. Collaboration among emerging vascular anomaly centers and an increasing number of providers across subspecialties with interest in this field are facilitating the development of standardized approaches to diagnosis and management. The rarity of KHE-spectrum lesions and the heterogeneity of clinical manifestations necessitate rationally designed, multisite clinical trials to investigate risk stratification schemas and formally evaluate the short and long-term efficacy of available and novel therapies., (©2016 Frontline Medical Communications.)

Background: Kaposiform haemangioendothelioma (KHE) is a tumor of intermediate malignant potential derived from vascular endothelial cells. Due to rarity of head neck KHE (HN-KHE) this comprehensive review aims to compile, analyze and present details to develop a consensus and augment available literature on HN-KHE., Materials and Methods: A comprehensive literature search was performed on PUBMED/MEDLINE, EMBASE, CINAHL and Science Citation Index for HN-KHE using MeSH words. Statistical analysis was performed using a variety of tests., Results: Common sites of involvement were neck 41.5%, face and scalp 32.0% and tympanomastoid region in 13.2% patients. Kasabach-Merritt phenomenon was seen in 58.5% patients. Surgical excision was performed in 37.7% patients while 39.6% patients underwent medical management/chemotherapy (CT). Significantly better disease free survival (DFS) was seen in patients undergoing surgical excision vs. CT (p=0.001), without recurrence vs. with recurrence (p=0.001) and those presenting within 0-1year of life vs. 1-5 years (p=0.021)., Conclusion: Recurrence and metastasis were seen in 35.8% and 20.0% patients respectively. Complete surgical excision with clear margins remains the treatment of choice., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Retiform hemangioendothelioma (RH) is a locally aggressive vascular tumor. Wide surgical excision with tumor-free margins is the standard treatment strategy. However, surgical excision is not an option for lesions near critical anatomical structures, such as those on the face. We report the case of a patient with retiform hemangioendothelioma that responded to non-surgical treatments., Methods: We describe the case of a 72-year-old male patient with a retiform hemangioendothelioma on the face that responded to a combination of pulsed dye laser, local corticosteroid injection, and application of imiquimod cream. In addition, we reviewed past case reports of patients with retiform hemangioendothelioma., Results: Thirty-five cases that describe the management of RH, including the present case, have been reported. Review of the cases indicate a relatively low disease-free survival rate in cases that underwent surgical excision as the initial therapy for retiform hemangioendothelioma., Conclusion: Surgical excision might not be the best therapeutic option. Local control with conservative therapy is an acceptable strategy for lesions in anatomical regions including the face., (© 2015 The International Society of Dermatology.)

Kasabach-Merritt phenomenon (KMP) is a rare life-threatening vascular condition of infancy. Prognosis factors and long-term follow-up data are lacking. We retrospectively analysed the records of 24 infants (10 females, 14 males) treated for KMP in the Department of Dermatology of Necker-Enfants Malades Hospital, Paris, France, from 1984 to 2012. Mean duration of thrombocytopaenia (2,000-38,000 platelets/mm3, mean 10,500/µl) was 8.8 months (range 3 days-84 months), which correlated with tumour infiltration depth on imaging. D-dimer levels were always elevated, even before KMP onset. Each patient received a mean of 4.8 different treatments (range 1-10). Median follow-up was 6.5 years (range 2 months-22 years). All infants had residual cutaneous lesions, along with inflammatory manifestations (n = 9), elevated D-dimer (n = 5) and orthopaedic sequelae (n = 5). The permanent coagulopathy (elevated D-dimer) even after resolution of KMP suggests the presence of chronic low-grade platelet trapping, with possible sudden worsening, and raises the possibility of prophylactic anti-platelet therapy.

Infantile hepatic hemangioendothelioma (IHH) is rare which can regress spontaneously. Arteriovenous shunts within hemangiomas, however, may result in pulmonary artery hypertension (PAH) and congestive heart failure (CHF).The authors report 2 young infants suffering from multifocal IHH associated with CHF were both treated with glucocorticoid and transcatheter arterial embolization (TAE), but had different outcomes. The PAH decreased immediately and the symptoms of CHF were alleviated after TAE for both of them. For the Tibetan infant, the development was normal with tumor regression by follow-up. For the Han ethnic neonate, PAH increased again in the seventh day with progressive cardiovascular insufficiency. Ultrasound showed a persisting perfusion caused by collateralization around occluded main feeders. Furthermore, a pulmonary infection occurred and ventilation was performed. As a result, the infant died from multiorgan failure caused by CHF and infection.TAE is a treatment of reducing shunting for hemangiomas. Fistula recanalization in multifocal IHH, however, might be an important risk factor affecting the outcome of TAE. TAE should be further evaluated with special attention to anatomy of feeding and draining vessels, and cardiopulmonary conditions. In addition, the patients were susceptible to secondary pulmonary infection because of lung congestion. As well, the infant from the high altitude area showed better adaptability to hypoxia., Competing Interests: The authors have no conflicts of interest to disclose.

A 20-year-old man presented with proptosis, nasal obstruction, vision loss and cavernous sinus syndrome, ongoing for 6 years. Imaging and biopsy confirmed a middle skull base epithelioid hemangioendothelioma arising from the left sphenopetroclival region with infratemporal fossa and intracranial-intradural extension into the left temporal lobe. Preoperative embolization of the left internal maxillary artery followed by a combined neurosurgical (front-temporal orbito-zygomatic craniotomy) and otorhinolaryngology (maxillary swing) approach was performed for tumor debulking. Postoperative radiotherapy and maintenance interferon chemotherapy was given to achieve a favorable outcome at 6 months follow-up. We describe the pertinent clinical, genetic, radiological and histopathological features, along with the available therapeutic modalities for a primary giant skull base hemangioendothelioma., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Kaposiform lymphangiomatosis (KLA) is a rare proliferation of abnormal lymphatic vessels often complicated by pleural/pericardial effusions and a consumptive coagulopathy that may lead to life threatening hemorrhage. Establishing the diagnosis is challenging due to the clinical heterogeneity and variable findings in laboratory values, radiographic features, and pathologic characteristics. We report three patients who had slowly progressive symptoms and presented with pleural or pericardial effusions, evidence of a consumptive coagulopathy and anemia. Despite being a rare and challenging diagnosis, KLA should be considered in patients presenting with non-specific indolent symptoms, pleural or pericardial effusions and laboratory evidence of a consumptive coagulopathy., (© 2014 Wiley Periodicals, Inc.)

Neonatal vascular tumours present particular difficulties in their diagnosis and treatment. The special behaviour of neonatal hemangioma and the aggressive but benign nature of kaposiform hemangioendothelioma provide examples of a modern need for a conservative approach. Recent advances in their pharmacological management have dramatically changed the therapeutical scope of this group of tumors with surgery playing a minor role in their treatment. Multidisciplinary teams management involving neonatology, pediatric surgery, dermatology, pathology, genetics and radiology specialists among others remains the best option for an optimal outcome.

The therapy of complicated Kaposiform hemangioendothelioma (KHE) is still difficult. We present the first case of laryngomalacia with simultaneous mammalian target of Rapamycin (mTOR)-positive KHE of the neck and thoracic inlet and concurrent Kasabach-Meritt Phenomenon (KMP) in an 11-month-old boy suffering life-threatening progress despite intravenous vincristine, corticosteroids, propranolol and local interstitial laser-application. The laryngomalacia restored after laser-supraglottoplasty. Successfully treatment of the prior fatal course of the KHE with KMP was initiated not till adding the mTOR inhibitor sirolimus to therapy. After 16 months single therapy of KHE with oral sirolimus the boy presented free of symptoms with minimal residual disease and excellent functional long-term results. Thus we stopped sirolimus therapy. The results are stable for 9 months without therapy. The special features including full report of histopathologic findings of this utmost complicated case are demonstrated in detail underlining the effectiveness of sirolimus for KHE., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Kasabach-Merritt phenomenon (KMP) is characterized by thrombocytopenia, microangiopathic hemolytic anemia, consumptive coagulopathy, and an enlarging vascular lesion. It is a rare and life-threatening disease of vascular tumor. The purpose of this study was to assess the effectiveness of absolute ethanol in the treatment of KMP., Methods: We treated 8 pediatric patients with KMP by using absolute ethanol injections, whose cases failed previously when applied steroid therapy. We reviewed the clinical and laboratory data of these 8 cases at Nanjing Children's Hospital in China., Results: Eight pediatric patients (5 female and 3 male) showed tumor regression after treatments. Core needle biopsy had been performed on the 8 patients, and the results included 7 kaposiform hemangioendotheliomas and one tufted angioma. All patients had an increase in platelet count. All coagulopathies were corrected. Complications included one patient with flush on face, one patient with needle scars, and one patient with a small area of local tissue necrosis., Conclusion: Absolute ethanol therapy presents a safe option in the treatment of KMP. Treatment-associated complications seemed to be reversible and acceptable by severity levels. Direct intralesional injection of absolute ethanol provides a simple and reliable alternative treatment for KMP among infants and may be used as the second-line therapy.

A 16-month-old previously healthy boy was admitted to the hospital with respiratory distress and thrombocytopenia. Initial workup demonstrated large pleural and pericardial effusions. The patient had no cutaneous abnormality on physical examination, and his initial chest CT (computed tomography) was nondiagnostic. He required multiple platelet transfusions, chest tube placement, and pericardiocentesis. Sixteen days after admission, a chest MRI (magnetic resonance imaging) revealed a large infiltrative mass of the superior mediastinum, consistent with kaposiform hemangioendothelioma (KHE). The patient's thrombocytopenia was due to associated Kasabach-Merritt phenomenon (KMP). The patient now has complete resolution of KMP after medical treatment with prednisolone, aminocaproic acid, vincristine, and aspirin.

Objective: To describe the clinical and imaging characteristics of a new lymphatic disorder with a unique histological pattern and poor prognosis., Study Design: An observational, retrospective study identified and characterized 20 patients with distinct lymphatic histopathology referred to the Vascular Anomalies Center at Boston Children's Hospital between 1995 and 2011., Results: The median age at onset was 6.5 years (range, birth to 44 years). Clinical and radiologic findings suggested a generalized process. The most common presentations were respiratory symptoms (50%), hemostatic abnormalities (50%), and an enlarging, palpable mass (35%). All patients had mediastinal involvement; 19 patients developed pericardial (70%) and/or pleural effusions (85%). Extrathoracic disease manifested in bone and spleen and less frequently in abdominal viscera, peritoneum, integument, and extremities. Despite aggressive procedural and medical therapies, the 5-year survival was 51% and the overall survival was 34%. Mean interval between diagnosis and death was 2.75 years (range, 1-6.5 years)., Conclusions: We describe a clinicopathologically distinct lymphatic anomaly. We propose the term kaposiform lymphangiomatosis (KLA) because of characteristic clusters or sheets of spindled lymphatic endothelial cells accompanying malformed lymphatic channels. The intrathoracic component is most commonly implicated in morbidity and mortality; however, extrathoracic disease is frequent, indicating that KLA is not restricted to pulmonary lymphatics. The mortality rate of KLA is high despite aggressive multimodal therapy., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Liver transplantation is a lifesaving treatment for patients suffering from end-stage liver disease. Rarely, acute congestion of the inferior vena cava (IVC) is being encountered because of tumor compression. MELD allocation does not reflect severity of this condition because of lack of organ failure. Herein, a patient is being presented undergoing urgent living-donor liver transplantation (LDLT) with IVC reconstruction for a fast-growing hepatic epithelioid hemangioendothelioma (HEH). IVC reconstruction using a venous graft recovered from a 25-h after circulatory-death prior transplantation became necessary to compensate severe venous congestion. Additionally, a systematic review of the literature searching MEDLINE/PubMed was performed. Protocol and eligibility criteria were specified in advance and registered at the PROSPERO registry (CRD42013004827). Published literature of IVC reconstruction in LDLT was selected. Two reports describing IVC reconstruction with cryopreserved IVC grafts and one IVC reconstruction using a deceased after-circulatory-death-donor IVC graft were included. Follow-up was at 12 and 13 months, respectively. Regarding the graft recovery in the setting of living-related donation, this graft remained patent during the nine-month follow-up period. This is the first report on the use of a venous graft from a circulatory-death-donor, not eligible for whole organ recovery. We demonstrate in this study the feasibility of using a size and blood-group-compatible IVC graft from a cold-stored donor, which can solve the problem of urgent IVC reconstruction in patients undergoing LDLT., (© 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Many dermatologic conditions may be present on a newborn infant's upper extremity that can evoke concern for parents and/or primary caregivers. Although the pediatrician typically remains the first care provider, often these children are referred to specialists to diagnose and treat these lesions. Hand surgeons should be familiar with different infantile skin lesions on an upper extremity. Some lesions are best observed, whereas others require treatment with nonoperative measures, lasers, or surgical interventions. A 2-part series is presented to aid the hand surgeon in becoming familiar with these lesions. This part 1 article focuses on vascular neoplasms and malformations. Particular attention is paid to the multiple types of hemangiomas and hemangioendotheliomas, telangiectasias, angiokeratomas, as well as capillary, venous, and lymphatic malformations. Diagnostic tips and clinical photographs are provided to help differentiate among these lesions. In addition, the recommended treatment for each is discussed., (Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Blueberries are amongst the most commonly consumed berries in the United States. Berries in general are rich in phenolic compounds, which are known for their high antioxidant capacity. Specifically, evidence from in vitro, in vivo and a few clinical studies suggest that blueberries and their active constituents show promise as effective anti-cancer agents, both in the form of functional foods and as nutritional supplements. Some of the mechanisms by which blueberries have been shown to prevent carcinogenesis include inhibition of the production of pro-inflammatory molecules, oxidative stress and products of oxidative stress such as DNA damage, inhibition of cancer cell proliferation and increased apoptosis. This review will focus on the preclinical and clinical evidence that supports blueberries as an anti-cancer fruit, as well as expressing the need for more preclinical studies and the conduction of clinical studies with respect to the cancer preventive ability of blueberries.

Infantile hepatic hemangioendothelioma (IHHE) is the most common benign hepatic tumor in children (12% of hepatic tumors), that usually responds well to therapy and has low mortality rates. In extremely rare cases of diffuse tumors resistant to therapy, size and blood flow can lead to cardiorespiratory failure and death. A 3-month-old male infant presented with respiratory infections and an abdominal mass, with frequent broncho-obstructive attacks. The CT, MRI and DSA exams showed typical morphology of hemangiendothelioma that was proven on histopathological biopsy. The tumor was resistant to standard medical therapy, and its volume led to cardiopulmonary arrest and death at 13 months of age. In rare cases of diffuse therapy-resistant IHHE a liver transplantation should be considered as an earlier treatment.

Background: Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy and childhood. This tumor results in poor prognosis, and therefore, development of a more effective treatment is needed., Methods and Results: We describe an 11-year-old boy presenting with left facial palsy caused by aggressive KHE of the left temporomastoid region. He was treated with paclitaxel-based chemotherapy, because of the difficulty with complete surgical resection for anatomic factor, multiple lung metastases on diagnosis, and no response to conventional treatments. This treatment reduced the volume of primary tumor and lung metastatic lesions, but the efficacy was transitory., Conclusions: Paclitaxel-based chemotherapy for aggressive KHE may be effective, therefore the multimodality therapy including paclitaxel of aggressive KHE, particularly in the head and neck, needs to be investigated in further studies., (Copyright © 2012 Wiley Periodicals, Inc.)

: Pseudomyogenic hemangioendothelioma is a recently described vascular tumor that occurs predominantly in the distal extremities of young adults. Because of multifocal presentation, epithelioid morphology, and strong cytokeratin expression, the tumor was frequently misdiagnosed as epithelioid sarcoma. However, substantial immunohistochemical studies revealed an endothelial nature. It has been currently considered a tumor of intermediate malignancy with frequent local recurrence but low risk of distant metastasis. In this report, we describe a case of pseudomyogenic hemangioendothelioma occurring in a 22-year-old man who presented with multifocal disease in the lower extremity and developed bilateral pulmonary metastases within a short period.

A hemangioma that rapidly increases in size has the potential to trap platelets and cause a consumptive coagulopathy. We describe the case of an 18-week-old boy who was brought to a local emergency department with ecchymosis on his nasal bridge and medial epicanthi, as well as a subconjunctival hemorrhage. He was noted to be anemic and thrombocytopenic. Packed red blood cells and platelets were transfused. However, despite hematologic correction, the ecchymosis and petechiae worsened, and a mass became evident in the right posterior triangle of the patient's neck. Computed tomography demonstrated a lobular soft-tissue-density mass in the right posterior triangle that extended to the level of the skull base. Histologic analysis of a biopsy specimen revealed that the lesion was a giant kaposiform hemangioma. The patient was diagnosed with Kasabach-Merritt syndrome, and prednisolone was commenced as a first-line treatment. However, the mass continued to grow, resulting in inspiratory stridor. Magnetic resonance imaging revealed encroachment into the thecal sac and compression of the spinal cord. The lesion was embolized, and vincristine therapy was commenced. Following a second embolization, the size of the lesion decreased and no further blood products were required. The hemangioma was deemed to be unresectable. The successful treatment in this case was dependent on the maintenance of hemostasis, the initial medical treatment with a corticosteroid, repeat embolization, and longer-term control with vincristine.

Vascular tumors are the most common of the vascular anomalies affecting children. The management of these neoplasms has changed over the years as our knowledge of their pathophysiology has increased, available technology has evolved, and our clinical experience has widened. Medical, laser, and surgical therapies are used concurrently to treat these tumors., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)