Prenatal Diagnosis and Management of Kaposiform Hemangioendothelioma With Kasabach-Merritt Phenomenon: Imaging Features and First Experience With Maternal Sirolimus Therapy.

Aggressive vascular tumor mimicking posttraumatic hematoma: A case report of kaposiform hemangioendothelioma on the nose

Kaposiform hemangioendothelioma is a rare, benign, locally destructive vascular tumor. Kasabach-Merritt phenomenon, a consumptive coagulopathy, is a life-threatening complication associated with kaposiform hemangioendothelioma. We describe a case of kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon in a neonate born with a large facial mass with deep extension toward the cranium and airway. The mass was not identified prenatally. The patient was a 37-week gestation age female neonate born via spontaneous vaginal delivery and noted to have a large left-sided facial mass that was not noted on the most recent prenatal ultrasound at 22 weeks gestation age. At birth, the patient was in respiratory distress and required continuous positive airway pressure support. Imaging revealed a large highly vascularized soft tissue mass adjacent to the airway with intracranial extension and bony destruction. Fine needle aspiration confirmed kaposiform hemangioendothelioma. On day of life 6, the patient was noted to have thrombocytopenia, elevated d-dimer, anemia, and hypofibrinogenemia, consistent with Kasabach-Merritt phenomenon, which resolved at day of life 12. Given the location and extent of the mass, medical therapy with single agent oral sirolimus was chosen over surgery. At 13-month follow-up, the infant is well on sirolimus therapy, and the mass has decreased in size, both clinically and on imaging. This case highlights the importance of prompt diagnosis and management of kaposiform hemangioendothelioma with extensive craniofacial and bony involvement with Kasabach-Merritt phenomenon with single oral therapy of sirolimus. Fibrinogen concentrate may be considered in the Kasabach-Merritt phenomenon refractory to cryoprecipitate.

Analysis of Risk Factors for Kasabach Merritt Phenomenom in Children With Kaposiform Hemangioendothelioma

Few studies have reported the clinical features, complications and predictors of Kasabach-Merritt phenomenon (KMP) associated with Kaposiform haemangioendothelioma (KHE). To determine the clinical characteristics present at diagnosis and to identify features that may aid clinicians in managing KHE. We conducted a cohort study of 146 patients diagnosed with KHE. 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. 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.

Kaposiform hemangioendothelioma (KHE) is a unique locally aggressive vascular tumor with poor prognosis. The aim of this study is to assess the clinical and imaging features of KHE, and to compare the differences between solitary and diffusive infiltrative subtype further. The clinical and radiological findings of a cohort of 25 cases with histologically proven KHE, between June 2011 and June 2016, were reviewed retrospectively. 7 solitary and 18 diffusive infiltrative subtypes KHE were included. The differences of clinical and imaging features between these two subtypes were compared statistically by Wilcoxon rank sum test and Fisher exact test. The median age was 4 months old. 20 cases (80%) were accompanied by Kasabach-Merritt phenomenon (KMP). Most KHE located in trunk and/or extremity. The masses showed inhomogeneous echogenicity and were rich in vascularity on ultrasound; showed isoattenuation relative to muscle on unenhanced CT, isointense(n=15) or slightly hyperintense (n=7) T1 weighted imaging (T1WI) signal relative to muscle, mainly heterogeneous hyperintense or slightly hyperintense with speckled hypointense (n=17) T2WI signal (77%) relative to muscle, and notable (n=15) and moderate (n=3) enhancement. Feeding and draining vessels were revealed in 15 cases. Five masses with DWI showed slightly restricted diffusivity, with average apparent diffusion coefficient value of (1.28±0.09) ×10-3mm2s-1. Necrosis and hemorrhage were also found. Compared with solitary ones, diffusive infiltrative KHE were larger, more commonly accompanied by KMP and reticular lymphedema, and more frequently located in trunk and/or extremity. Five masses with DWI showed slightly restricted diffusivity. A hypervascular mass accompanied by KMP and reticular lymphedema, with speckled hypointense signal T2WI signal, especially in pediatric patients, is highly suggestive of the diagnosis of KHE. Advances in knowledge: Speckled hypointense signal T2WI signal, and notable enhancement were unique features of KHE. KHE showed slightly restricted diffusivity on DWI, commonly accompanied by KMP and reticular lymphedema.

Background/Objectives: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor of infancy, often complicated by Kasabach-Merritt phenomenon (KMP), a consumptive coagulopathy characterized by severe thrombocytopenia and hypofibrinogenemia. Airway involvement at birth is exceptionally rare and can be life-threatening. This study reports the clinical presentation and treatment course of a full-term male neonate with severe airway obstruction caused by KHE with KMP. Case Presentation: The patient had unremarkable prenatal imaging but presented at birth with severe respiratory distress requiring emergent intubation. Physical examination revealed firm violaceous swelling over the right cervicothoracic region. Laboratory tests showed profound thrombocytopenia (22,000/μL), hypofibrinogenemia (75 mg/dL), and coagulopathy. Imaging findings were consistent with KHE complicated by KMP. Due to bleeding risk, the biopsy was not performed. Initial treatment included platelet and plasma transfusions, intravenous immunoglobulin (IVIG), corticosteroids, and antithrombin III replacement. Vincristine was discontinued owing to gastrointestinal toxicity. Sirolimus therapy was initiated on day 14. Following sirolimus initiation, rapid platelet recovery was observed. At three months, marked tumor regression was documented. After mild recurrence, sirolimus was reintroduced, and the patient remained stable at 16-month follow-up. Conclusions: This case underscores the critical importance of prompt airway stabilization, early recognition of consumptive coagulopathy, and sirolimus-based therapy in managing neonatal KHE with airway involvement.

Mammalian target of rapamycin inhibitors have shown promising results in the management of kaposiform hemangioendothelioma (KHE). The purpose of this study was to present our experience involving sirolimus therapy for KHE. A retrospective study was conducted to review the medical documents of 26 patients with KHE who were treated with sirolimus at our hospital between March 2012 and December 2016. Fifteen males and 11 females manifested KHE in infancy with an average age of 2.9±1.8months. Multiple anatomical sites were involved. Four patients had multifocal lesions, while 22 patients had solitary lesions. Twenty-five patients had Kasabach-Merritt phenomenon (KMP). Twenty patients completed sirolimus therapy in 28.3±12.5months. Nineteen KHE lesions reduced to small residuals with platelet counts reaching normal levels 3.7±2.8weeks after treatment; one KHE lesion had no response to therapy. One patient with multifocal lesions died due to a severe infection, although the patient had previously responded to sirolimus. Five patients remained in treatment and had good responses with normal platelet counts. Nineteen patients with anemia had normal hemoglobin levels after 3.5±1.9weeks of treatment. Mild side effects were observed. The median follow-up time was 32months (26-60months), with no evidence of recurrences. Sirolimus was shown to be efficacious in the management of KHE with an average course of 28months. The time-to-response was variable, with an average of 1week. After 4weeks of treatment, the platelet count and hemoglobin level had normalized. Multifocal KHE with KMP is more severe than solitary KHE.

Treatment with sirolimus, an inhibitor of the mammalian target of rapamycin pathway, has improved the prognosis of patients with kaposiform hemangioendothelioma (KHE). However, the efficacy, durability and tolerability of long-term sirolimus treatment in patients with KHE have not been well elucidated. We performed efficacy and safety assessments based on more than 4.5 years of follow-up in patients receiving sirolimus therapy for KHE. One hundred sixty-seven patients were analyzed, including 102 (61.1%) patients with the Kasabach-Merritt phenomenon (KMP). Follow-up was conducted after a median of 56.0months. A total of 154 (92.2%) patients had a durable response to sirolimus treatment. No difference in durable response was found between patients without KMP and patients with KMP (95.4% vs 90.2%; difference, 5.2%; 95% confidence interval [CI], -4.0% to 13.1%). Rebound growth occurred in 17.3% of patients upon sirolimus discontinuation. Early treatment discontinuation (odds ratio [OR]: 3.103; 95% CI: 1.529-6.299; P=.002) and mixed lesion type (OR: 2.271; 95% CI: 0.901-5.727; P=.047) were associated with tumor rebound growth. No KHE-related deaths occurred in this cohort. At the last follow-up, approximately 17.4% of patients had active disease and/or changes in body structures to a variable extent. Serious adverse events occurred most commonly during the first year of sirolimus therapy. Follow-up of almost 4.5 years demonstrated that the efficacy of sirolimus persisted over time and that long-term treatment with sirolimus was not associated with unacceptable cumulative toxicities. However, nonresponse, tumor relapse and long-term sequelae remained challenges despite intensified and prolonged sirolimus therapy.

Sirolimus for treatment of kaposiform hemangioendothelioma associated with Kasabach-Merritt phenomenon

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor with a high risk of mortality. Few studies with large samples of KHE have been reported. KHE may develop into the Kasabach-Merritt phenomenon (KMP), which is characterized by thrombocytopenia and consumptive coagulopathy. The features of severe symptomatic anemia and life-threatening low platelets make the management of KHE associated with KMP challenging. The aim of this study was to examine the clinical characteristics of patients with KHE and discuss the treatment experience for different risk groups of KHE. Through a retrospective review of 70 patients diagnosed with KHE between 2017 and 2022 in our center, we classify lesions into three clinicopathological stages based on the tumor involving depth, and divided the severity of KHE into three levels by estimating clinicopathological stages and severity of thrombocytopenia. Treatments of different severity groups were estimated with sufficient data. In our cohort, 27% were neonates, and KHE lesion occurred at birth in 84% of patients. There was a slight male predominance (32 girls and 38 boys). Common clinical characteristics included associated coagulation disorder (100%), locally aggressive cutaneous blue-purple mass (89%), thrombocytopenia (78%), and local pain or joint dysfunction (20%). The lower extremities were the dominant location (35%), followed by the trunk (29%), the maxillofacial region and neck (24%), and the upper extremities (10%). Of the total cohort, 78% developed KMP; the median age at which thrombocytopenia occurred was 27.8 days. The median platelet count of patients who were associated with KMP was 24,000/µL in our cohort. Ninety-two percent of patients were given surgery treatment and 89% of these patients were given high-dose methylprednisolone (5-6 mg/kg daily) before surgery. In 55 patients with KMP, 36% were sensitive to high-dose corticosteroid therapy. Patients from the low-risk group (eight cases) underwent operation, all of whom recovered without recurrence after a maximum follow-up of 5 years. Out of 26 patients from the high-risk group, 25 underwent surgery treatment, with 1 case undergoing secondary surgery after recurrence and 1 case taking sirolimus. Out of 36 cases from the extremely high-risk group, 32 underwent surgery (including 2 cases who underwent external carotid artery ligation and catheterization), 3 of whom underwent secondary operation after recurrence, and the remaining 4 cases took medicine. The mean length of having sirolimus was 21 months; two cases stopped taking sirolimus due to severe pneumonia. Two cases died at 1 and 3 months after discharge. Our study describes the largest assessment of high-risk patients with KHE who have undergone an operation to date, with 5 years of follow-up to track recovery, which provides invaluable knowledge for the future treatment of patients with KHE and KMP from different risk groups: Early surgical intervention may be the most definitive treatment option for most patients with KHE; multimodality treatment is the best choice for the extremely high-risk group.

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor, typically affecting infants. Kasabach-Merritt phenomenon (KMP) is a frequent and serious complication of KHE. The study aimed to analyze clinical manifestations, treatment strategies, and outcomes in children with KHE treated in Poland between 2007 and 2024. Clinical data of 42 children with KHE treated in 15 Polish pediatric hematology/oncology and surgery centers between 2007 and 2024 were analyzed retrospectively. KMP was present in 27/42 children (64.3%). The median age at diagnosis in children with and without KMP was 2.5 and 8 months, respectively. A male predilection was observed (61.9%), particularly in patients without KMP (13/15, 86.7%). Diagnosis of KHE required a tumor biopsy in 20 patients, including 14/15 (93.3%) of patients without KMP. Treatment strategies varied significantly between patients, institutions, and treatment periods. Systemic treatment was administered in 39 (92.9%) children, with predominating role of chemotherapy and glucocorticoids in the first period (2007-2013), and with gradually increasing importance of sirolimus in the years 2014-2018 and 2019-2024. Three children were successfully treated with surgery only. Salvage therapies ultimately controlled KHE progression/relapse in 14/17 (82.4%) patients. Only one child with metastatic, treatment-resistant cardiac KHE died of disease progression. Management of childhood KHE is challenging since no unified treatment recommendations exist. To optimize KHE therapy in Poland, the Section of Childhood Vascular Anomalies was established in June 2021 as part of the Polish Society of Pediatric Oncology and Hematology. Its aim is to standardize therapeutic guidelines and provide education on vascular anomalies in Poland.

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor with high morbidity and mortality. The aim of this study was to evaluate ultrasonographic findings associated with KHE.The clinical and ultrasonographic findings of a cohort of 64 cases with pathologically proven KHE were retrospectively reviewed and analyzed between November 2014 and February 2021. Two subtypes were divided according to the presence or absence of the Kasabach-Merritt phenomenon (KMP). The KMP risk factors in patients with KHE were analyzed statistically.Among the 64 cases of KHE, 43 (67.2%) were accompanied by KMP. There was a positive correlation between the appearance of KMP and tumor size. KHEs had an increased risk of developing KMP if the lesions measured were >6 cm and if they belonged to the deep or mixed subtype. On ultrasonography, all KHE lesions were heterogeneous, and 81.3% were hypoechoic; 93.8% of KHEs exhibited ill-defined margins, 68.7% had strands branching into the adjacent tissue, and 84.4% presented marked hypervascularity. Elastography showed that central hypoechogenic lesion areas were hard, and surrounding hyperechogenic lesion areas were soft.KHEs can occur in different parts of childrens' bodies. On ultrasonography, the main findings are heterogeneous low erosions, indistinct margins, branching strangulation into adjacent tissues, and obvious hypervascularity. Patients with lesions larger than 6 cm or belonging to deep or mixed subtypes (musculoskeletal infiltrates) are at risk for developing KMP, and clinicians should be vigilant.

Kaposiform Hemangioendothelioma: Atypical Features and Risks of Kasabach-Merritt Phenomenon in 107 Referrals

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor in children, which can be accompanied by life-threatening thrombocytopenia, referred to as Kasabach-Merritt phenomenon (KMP). The mTOR inhibitor sirolimus is emerging as targeted therapy in KHE. As the sirolimus effect on KHE occurs only after several weeks, we aimed to evaluate whether additional transarterial embolization is of benefit for children with KHE and KMP. Seventeen patients with KHE and KMP acquired from 11 hospitals in Germany were retrospectively divided into two cohorts. Children being treated with adjunct transarterial embolization and systemic sirolimus, and those being treated with sirolimus without additional embolization. Bleeding grade as defined by WHO was determined for all patients. Response of the primary tumor at 6 and 12 months assessed by magnetic resonance imaging (MRI), time to response of KMP defined as thrombocyte increase >150 × 103 /μL, as well as rebound rates of both after cessation of sirolimus were compared. N = 8 patients had undergone additive embolization to systemic sirolimus therapy, sirolimus in this group was started after a mean of 6.5 ± 3 days following embolization. N = 9 patients were identified who had received sirolimus without additional embolization. Adjunct embolization induced a more rapid resolution of KMP within a median of 7 days vs 3 months; however, tumor response as well as rebound rates were similar between both groups. Additive embolization may be of value for a more rapid rescue of consumptive coagulopathy in children with KHE and KMP compared to systemic sirolimus only.

Kaposiform hemangioendothelioma (KHE) is a rare intermediate-grade malignant vascular tumor that is frequently associated with the Kasabach–Merritt phenomenon (KMP). Cases without KMP are less common and, therefore, prone to misdiagnosis. We report a case of superficial KHE in a 6-month-old male infant without associated KMP. Magnetic resonance imaging revealed a poorly demarcated lesion with T1 hypointensity and T2 hyperintensity, demonstrating marked enhancement and an arterial flow void. The patient was hospitalized because KHE was suspected and received a single course of intralesional pingyangmycin therapy. One week later, histopathological examination showed proliferating spindle-shaped endothelial cells in a glomeruloid pattern. The immunohistochemical results revealed CD31 and CD34 positivity and GLUT1 and D2–40 negativity. GLUT1 negativity helped exclude infantile hemangioma, whereas D2–40 negativity ruled out lymphatic malformation. Upon confirming KHE diagnosis, we initiated a combined sirolimus and prednisone treatment. At the 3-month follow-up, clinical observation showed regression of the lesion, prompting prednisone discontinuation while continuing sirolimus maintenance therapy. In this report, we also discuss the clinical manifestations, imaging features, histopathological characteristics, and treatment options for this KHE subtype and review relevant literature. This case highlights the diagnostic features and therapeutic considerations of superficial KHE without KMP, emphasizing the importance of multidisciplinary evaluation.