Treatment experience for different risk groups of Kaposiform hemangioendothelioma

BackgroundKaposiform 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.ObjectiveThe 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.MethodsThrough 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.ResultsIn 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.ConclusionsOur 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

Circular RNA profile of infantile hemangioma by microarray analysis

<div><p>Background</p><p>Circular RNAs (circRNAs) are a recently identified class of noncoding RNAs that participate in several physiological processes. However, the expression of circRNAs in infantile hemangioma (IH) remains unknown.</p><p>Methods</p><p>The profile of circRNAs was assessed by microarray in four pairs of IH and adjacent skin tissues. The expression of circRNAs was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, circRNA-microRNAs (miRNA)-mRNA networks were constructed using bioinformatics tools.</p><p>Results</p><p>234 up- and 374 down- regulated circRNAs were identified in IH by microarray. Among them, the expression of two up-regulated circRNAs (hsa_circRNA_100933 and hsa_circRNA_100709) and one down-regulated circRNA (hsa_circRNA_104310) was confirmed by qRT-PCR. In addition, 3,019 miRNA response elements (MREs) of circRNAs were predicted, and two circRNA-miRNA-mRNA networks were constructed, including 100 and 94 target genes of hsa_circRNA_100933 and hsa_circRNA_104310, respectively. GO and pathway analysis showed that both networks participated in angiogenesis and vascular development-related biological processes.</p><p>Conclusions</p><p>This is the first study to reveal the profiling of circRNAs in IH and pave the way for further characterization of the role of circRNAs in the pathogenesis of IH.</p></div

Clinicopathological characteristics of IH patients.

<p>Clinicopathological characteristics of IH patients.</p

Top 25 down-regulated circRNAs in IH.

<p>Top 25 down-regulated circRNAs in IH.</p

Networks of circRNA-miRNA-mRNA in IH.

<p>(A) Hsa_circRNA_100933 with 5 MREs and 94 target genes. (B) Hsa_circRNA_104310 with 5 MREs and 100 target genes. Red represents up-regulation in IH, yellow represents down-regulation in IH, blue represents miRNAs, green represents mRNAs.</p

Differential expression of circRNAs between IH and adjacent skin tissues by microarray.

<p>(A) Box plot showed that all the 8 samples were normalized. (B) Scatter-Plot was used for assessing the variation of circRNA expression between IH and adjacent skin tissues. The circRNAs above the top and below the bottom green lines indicated > 2.0-fold change in circRNAs between the two groups. (C) Volcano Plots were displayed for visualizing the differential expression of circRNAs. The red points in the plot represent the differentially expressed circRNAs with statistical significance. (D) Hierarchical cluster analysis of all the deregulated circRNAs.</p

Top 25 up-regulated circRNAs in IH.

<p>Top 25 up-regulated circRNAs in IH.</p

Circular RNA profile of infantile hemangioma by microarray analysis - Fig 7

<p>GO (A) and pathway analysis (B) of hsa_circRNA_104310 targeted genes.</p

A snippet of detailed annotation for circRNA/miRNA interaction.

<p>(A) has_circRNA_100933. (B) has_circRNA_104310.</p

Quantitative real-time PCR validation of selected circRNAs.

<p>The relative expression of selected circRNAs (circRNA_100709, circRNA_100933, circRNA_104310, circRNA_102116, circRNA_051239 and circRNA_102039) in IH as compared to paired skin samples.</p