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].