Pulmonary and pleural lymphatic endothelial cells from pediatric, but not adult, patients with Gorham-Stout disease and generalized lymphatic anomaly, show a high proliferation rate

Abstract

BackgroundGorham-Stout disease (OMIM 123880) and generalized lymphatic anomaly are two rare disorders of lymphendothelial growth in which thoracic involvement with chylothorax is a feared complication. Currently it is believed that both disorders are prenatal malformations that progress slowly after birth. Several pharmaceuticals with antiproliferative properties, including interferon-α-2b, rapamycin and propranolol, have however been shown to affect the disease course in some patients. Deeper knowledge of the growth characteristics of these malformations are therefore needed to guide the clinical approach.MethodsLymphatic vessels in lung and pleural tissue from both children and adult patients with generalized lymphatic anomaly or Gorham-Stout disease were studied using an immunohistochemical approach, targeting lymphendothelial markers (D2-40/Prox-1) and a proliferation marker (Ki-67).ResultsWe found significant proliferation and growth in these lesions in pediatric patients but not in adults. Furthermore, the data may suggest that the disease process is at least partly reversible.ConclusionsThese malformations of the lymphatic system proliferate at a significant rate long after birth, which could suggest that the clinical approach for children should be different from adults.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0449-4) contains supplementary material, which is available to authorized users.

Generalized Lymphatic Anomaly and Gorham–Stout Disease: Overview and Recent Insights

“…One report described how LM proliferation during childhood is different from that in adults and that these LMs proliferate at a significant rate. 37 The common characteristics of these diseases are lymphatic tissue lesions, including osteolytic lesions, thoracic lesions (chylothorax, pleural effusion, pericardial effusion, mediastinal mass, and retroperitoneal soft-tissue mass), abdominal lesions (ascites, splenic lesions, and retroperitoneal mass), and skin lesions (lymphedema and lymphorrhea). However, to achieve a precise diagnosis, a variety of assessments, clinical, imaging, histological, and hematological examinations, are needed.…”

Lymphatic Changes in Respiratory Diseases: More than Just Remodeling of the Lung?

“…In one study, these anomalies have been associated with increased lung lymphatic area compared with healthy controls (0.6 versus 3.5%). Furthermore, the percentage of lymphatic vessels with robustly proliferating LECs was significantly higher than control subjects, and markedly more elevated in the pediatric compared with the adult population (11).…”

“…In addition, generalized lymphatic anomaly and Gorham-Stout disease are both characterized by systemic lymphatic malformations that can affect the lung and present with chylothorax (11). In one study, these anomalies have been associated with increased lung lymphatic area compared with healthy controls (0.6 versus 3.5%).…”

Rapamycin reversal of VEGF-C–driven lymphatic anomalies in the respiratory tract

“…Rapamycin and related mTORC1 inhibitors are being used with promising results in the treatment of lymphatic malformations (4,(80)(81)(82), which build on what is known from the treatment of patients with LAM (27,83). Favorable responses provide incentive for learning more about the actions of mTORC1 inhibitors in the treatment of lymphatic anomalies.…”