Background and Objectives: Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first line therapy in the absence of available prospective clinical trials. Methods: Patients from 17 institutions diagnosed with KHE/TA between 2005-2020 with > 6 months follow-up were included. Response rates to sirolimus and vincristine were compared at 3 and 6 months. Durability of response and response to other treatment modalities were also evaluated. Results: Of 159 unique KHE/TA subjects, Kasabach-Merritt phenomenon (KMP) was present in 64 (40.3%) and only 2 patients were deceased (1.3%). Over 60% (n=96) demonstrated treatment response at 3 months and >70% (n=114) by 6 months (no significant difference across groups). The vincristine group had higher radiologic response at 3 months compared to sirolimus (72.7% vs 20%, p=0.03) but there was no differences between these groups at 6 months. There were no differences in rates of recurrent or progressive disease between vincristine and sirolimus. Conclusions: In this large, multicenter cohort of 159 patients with KHE/TA, rates of KMP were consistent with historical literature but the mortality rate (1.3%) was much lower. Overall treatment response rates were high (>70%) and there were no significant difference in treatment response or durability of disease comparing sirolimus to vincristine. Our results support individualized treatment decision plans depending on clinical scenario and patient/physician preferences. Response criteria and response rates reported here will be useful for guiding future treatment protocols for vascular tumors.

Background: Intra-abdominal lymphatic malformations are rare entities without a clear consensus on management or prognosis. These malformations are medically and surgically complex and often require a sophisticated, multi-disciplinary approach to treatment. Methods: A single quaternary institutional, retrospective chart review between January 2000-December 2019 was performed on all patients with an initial diagnosis of a non-solid organ intra-abdominal lymphatic malformation. Demographics, presentation, treatment, and outcome were reviewed. Results: 24 patients were identified, 62.5% were male. Median age at time of diagnosis was 2.5 years old, 33% were present at birth, 50% presented before 2 years old, and 29% presented ≥10 years of age. 75% were lymphatic (majority macrocystic), 20.8% were mixed lymphatic-venous malformations (LVM). 54% had other associated lymphatic or vascular malformations including 4 patients with PIK3CA-Related Overgrowth Spectrum (PROS), 3 with Generalized Lymphatic Anomaly, and 2 with Capillary Venous Lymphatic malformation (CVLM). Patients most often presented with abdominal pain (50%). 95.8% required an intervention. 87.5% were managed initially with sclerotherapy. Most interventions were performed for abdominal symptoms either before three years of age or during adolescence. 41.7% underwent laparoscopic or open surgery. 8.3% underwent surgery as their primary therapy. Conclusion: Intra-abdominal lymphatic malformations have a bimodal distribution pattern of presentation; shortly after birth and again at puberty. Most patients present with abdominal symptoms and have other associated vascular anomalies. MRI appears to be the most accurate modality for treatment planning. Interventional procedures such as sclerotherapy and medical therapy with sirolimus are safe and effective and should be considered first line therapies. Surgical resection is often required when the diagnosis is in question or when more conservative therapies are no longer efficacious.

Complex lymphatic anomalies are congenital diseases of the lymphatic circulation system that are associated with significant morbidity and early mortality. While guidelines for the comprehensive evaluation of the complex lymphatic anomalies were recently published, the diagnostic approach and medical management are not standardized. The current manuscript presents the clinical features of 4 complex lymphatic anomalies: Gorham-Stout disease, generalized lymphatic anomaly, kaposiform lymphangiomatosis, and central collecting lymphatic anomaly. We also offer three cases from the authors’ practice and our views on diagnostic testing and disease management including supportive care, medical therapies and other interventions.