Kaposiform Lymphangiomatosis: Pathologic Aspects in 43 Patients.

Kaposiform lymphangiomatosis is an uncommon generalized lymphatic anomaly with distinctive clinical, radiologic, histopathologic, and molecular findings. Herein, we document the pathology in 43 patients evaluated by the Boston Children's Hospital Vascular Anomalies Center from 1999 to 2020. The most frequent presentations were respiratory difficulty, hemostatic abnormalities, and a soft tissue mass. Imaging commonly revealed involvement of some combination of mediastinal, pulmonary, pleural, and pericardial compartments and most often included spleen and skeleton. Histopathology was characterized by dilated, redundant, and abnormally configured lymphatic channels typically accompanied by dispersed clusters of variably canalized, and often hemosiderotic, spindled lymphatic endothelial cells that were immunopositive for D2-40, PROX1, and CD31. An activating lesional NRAS variant was documented in 9 of 10 patients. The clinical course was typically aggressive, marked by hemorrhage, thrombocytopenia, diminished fibrinogen levels, and a mortality rate of 21%.

Signaling pathways and inhibitors of cells from patients with kaposiform lymphangiomatosis.

BACKGROUND: Kaposiform lymphangiomatosis (KLA) is a rare lymphatic anomaly with significant morbidity and mortality. KLA is characterized by diffuse multifocal lesions comprised of focal areas of "kaposiform" spindled cells accompanying malformed lymphatic channels. The goal of this study was to identify activated signaling pathways in cells isolated from three KLA patients for the purpose of testing new therapies. PROCEDURE: Cells were obtained from the lungs of one patient isolated at autopsy and the spleen of two patients removed in surgery due to disease complications. A protein kinase array was performed on the KLA cell lysates and normal lymphatic endothelial cells. RESULTS: Higher activation of key signaling pathways in the KLA cells, including PRAS40, AKT1/2/3, and ERK-1/2, was identified by protein kinase array and confirmed by Western blot analysis. This indicated a role for highly activated PI3K-AKT and MAPK-ERK-1/2 signaling pathways in KLA cells. Cell proliferation studies assessed PI3K inhibitors (LY294002; BYL719), AKT inhibitor ARQ092, mTOR inhibitor rapamycin, and MAPK inhibitor U0126. These studies demonstrated that PI3K-AKT-mTOR and MAPK signaling are important mediators of KLA cell proliferation. BYL719 and rapamycin were more effective at inhibiting KLA cell proliferation than U0126. CONCLUSIONS: Our studies using cells from KLA patient lesions demonstrate that these cells are highly proliferative and the PI3K-AKT-mTOR and MAPK pathways are promising therapeutic targets. Development and clinical trials of PI3K, AKT, and MAPK inhibitors for cancer treatment and the data in this study lend support for early clinical trials assessing the efficacy of these inhibitors in KLA patients.

Preventing patient harm via adverse event review: An APSA survey regarding the role of morbidity and mortality (M&M) conference.

INTRODUCTION: Peer-review endeavors represent the continual learning environment critical for a culture of patient safety. Morbidity and mortality (M&M) conferences are designed to review adverse events to prevent future similar events. The extent to which pediatric surgeons participate in M&M, and believe M&M improves patient safety, is unknown. METHODS: A cross-sectional survey of the American Pediatric Surgical Association membership was conducted to evaluate participation in and perception of M&M conferences. Closed and open-ended questions were provided to gauge participation and perceptions of M&M effectiveness. Standard frequency analyses and tests of associations between M&M program attributes and surgeons' perceptions of effectiveness were performed. RESULTS: The response rate was 38% (353/928). Most surgeons (85%) reported that they always participate in M&M, but only 64% believe M&M is effective in changing practice or prevention of future adverse events. Effective M&Ms were more likely to emphasize loop closure, multidisciplinary participation, standardized assessment of events, and connection to quality improvement efforts. CONCLUSIONS: Most pediatric surgeons participate in M&M, but many doubt its effectiveness. We identified attributes of M&M conferences that are perceived to be effective. Further investigation is needed to identify how to optimally utilize peer-review programs to prevent adverse events and improve patient safety. LEVEL OF EVIDENCE: V.

Hepatic vascular tumors.

The most common hepatic vascular tumor in the pediatric population is the infantile hepatic hemangioma. Although these lesions have a spectrum of presentations, there are three main subtypes that have been described-focal, multifocal, and diffuse. An algorithm on the workup, treatment, and follow-up of these lesions can be based on this categorization. Recent shifts in the management of hemangiomas with beta-blockers (propranolol) have also influenced the treatment of hepatic hemangiomas. This article reviews the current understanding of hepatic hemangiomas and protocols in the management of these patients.