1 INTRODUCTION
Complex lymphatic anomalies (CLA) are rare conditions that occur due to embryonal errors in lymphangiogenesisis and are associated with significant morbidity. CLA include Gorham-Stout disease, generalized lymphatic anomaly, kaposiform lymphangiomatosis, and central collecting lymphatic anomaly [1]. These conditions have phenotypic heterogeneity as well as overlapping symptoms, imaging features and complications of these disorders. Management of complex lymphatic anomalies is often challenging, requiring multimodal and interdisciplinary approach.
Gorham-Stout Disease
Gorham-Stout disease (GSD) or “vanishing bone disease” is a multifocal lymphatic malformation (LM) that classically affects bone but may also involve soft tissue and viscera. GSD is characterized by progressive osteolysis and proliferation of lymphatic vessels, leading to the destruction and absorption of bone. The most commonly affected bones include the vertebrae, ribs, skull, jaw, and clavicle [2]. Multiple bones may become involved, often in a contiguous distribution. In addition to frequently causing pain and functional impairment, GSD may cause significant morbidity. Complications may include pathologic fractures, pleural and pericardial effusions, CSF leaks, deformity and neurologic deficits secondary to osteolysis of the spine and/or skull. Computed tomography (CT) and magnetic resonance imaging (MRI), along with a thorough medical history, are usually sufficient for diagnosis. On imaging, evidence of destruction of the bone cortex is critical for diagnosis [3]. Histology reveals abnormal, dilated lymphatic channels with endothelial cells that stain positive for the lymphatic markers, PROX-1 and D2-40, as well as increased osteoclast activity in bone [4]. No causative genetic mutations have been identified.
Generalized Lymphatic Anomaly
Generalized lymphatic anomaly (GLA) is characterized by multifocal LM that involves the bones, viscera, thoracic and abdominal cavities. Although GLA has similar areas of anatomic involvement and complications as GSD, the disorder is distinctively different. In contrast to GSD, the lytic bone lesions in GLA are confined to the medullary cavity and do not cause destruction of bone cortex. GLA favors the appendicular skeleton and typically involves multiple body sites in a non-contiguous pattern [1, 2]. Lesions in the spleen and liver are commonly seen on imaging [5]. Pathology appears similar to that of GSD with exception of bone cortex disruption [4]. Somatic PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutations were recently discovered in individuals with GLA [6].