Generalized Lymphatic Anomaly

Generalized lymphatic anomaly (GLA) (formerly known as lymphangiomatosis) is a rare multisystem disorder characterized by diffuse or multifocal lymphatic malformations, often associated with osseus involvement [25]. Lung involvement is not uncommon, and can include chylous effusions, peribronchovascular pulmonary in ltrates, and pleural disease. GLA is present at birth but occasionally is recognized later in young adults or even middle-aged patients.

Etiopathogenesis

GLA can arise from somatic mutations in PIK3CA (similar to Klippel-Trenaunay Syndrome (KTS)) and is associated with congenital lipomatous overgrowth, vascular malformations, epidermal nevi and spinal (scoliosis), and/or skeletal

anomalies (CLOVES), vascular malformations (VM) and lymphangiomas [26, 27]. GLAs are characterized by multifocal, well-circumscribed lesions within the lung, pleura, pericardium, spleen, soft tissue, bone, peritoneum, and other visceral organs. The malformed lymphatic channels are microcystic (<1 cm), lined by a single layer of bland endothelial cells, with no atypia (Fig. 21.10). These channels may lack smooth muscle investment or show partial muscularization of the vessel wall. The endothelial cells are immunoreactive to vascular and lymphatic markers. Organizing thrombi can be seen. Bone may show osteopenia and secondary fracture changes. Staining of PROX-1 and D2–40 reveals dilated lymphatic lumens containing pink proteinaceous material consistent with lymphatic fuid [25, 28–30]. GLA has recently been found to be associated with sporadic somatic activating mutations in PIK3CA gene [27], which interestingly have also been also detected in isolated LMs and several overgrowth syndromes.

Fig. 21.10  Generalized Lymphatic Anomaly (GLA). (a) H&E section of mature lung tissue demonstrates excessive, irregular thin-walled vascular channels within the septa, pleura, and bronchoalveolar bundles. (b) H&E of the pleural, (c) septa, and (d) bronchoalveolar bundles at

higher magni cation highlight irregular vascular channels which are immunoreactive to an anti-podoplanin antibody, D2–40 (b and d, insert), a lymphatic marker