Kaposiform lymphangiomatosis: a distinct aggressive lymphatic anomaly

Abstract

Objective: To describe the clinical and imaging characteristics of a new lymphatic disorder with a unique histological pattern and poor prognosis.

Study design: An observational, retrospective study identified and characterized 20 patients with distinct lymphatic histopathology referred to the Vascular Anomalies Center at Boston Children's Hospital between 1995 and 2011.

Results: The median age at onset was 6.5 years (range, birth to 44 years). Clinical and radiologic findings suggested a generalized process. The most common presentations were respiratory symptoms (50%), hemostatic abnormalities (50%), and an enlarging, palpable mass (35%). All patients had mediastinal involvement; 19 patients developed pericardial (70%) and/or pleural effusions (85%). Extrathoracic disease manifested in bone and spleen and less frequently in abdominal viscera, peritoneum, integument, and extremities. Despite aggressive procedural and medical therapies, the 5-year survival was 51% and the overall survival was 34%. Mean interval between diagnosis and death was 2.75 years (range, 1-6.5 years).

Conclusions: We describe a clinicopathologically distinct lymphatic anomaly. We propose the term kaposiform lymphangiomatosis (KLA) because of characteristic clusters or sheets of spindled lymphatic endothelial cells accompanying malformed lymphatic channels. The intrathoracic component is most commonly implicated in morbidity and mortality; however, extrathoracic disease is frequent, indicating that KLA is not restricted to pulmonary lymphatics. The mortality rate of KLA is high despite aggressive multimodal therapy.

Keywords: GLA; Generalized lymphatic anomaly; KHE; KLA; Kaposiform hemangioendothelioma; Kaposiform lymphangiomatosis; MRI; Magnetic resonance imaging.

Figure 1

KLA histopathology (A-C) and radiologic (D-F) features of KLA. A, Pulmonary parenchyma with dilated lymphatic channels (asterisks), accompanying airway (Aw), pulmonary artery (PA), and focus of spindled cells (H&E stain). B, Focus of spindled cells some with cytoplasmic hemosiderin granules (black arrows); interspersed red blood cells present (black open arrow heads) (H&E stain). C, Spindled lymphatic endothelial cells immunopositive for lymphatic marker D2-40. D, MRI of chest. T2 axial thoracic image demonstrates pleural effusion (star), pulmonary interlobular septal thickening (white arrows), and retroperitoneal soft tissue mass (arrow heads). E, MRI of abdomen. T2 axial abdominal image shows heterogeneous, infiltrative, hyperintense retroperitoneal soft tissue mass (arrow heads), splenic cysts (asterisks), and pulmonary interlobular septal thickening (white arrow). F, Plain film illustrates multiple lucent bony lesions of the humerus (red arrows).

Figure 2

Clinical Phenotype of KLA. A, Patient age at initial symptoms compared with age at diagnosis of lymphatic anomaly. Median age with interquartile range indicated; mean interval between onset of symptoms and diagnosis of lymphatic anomaly was 2 years. B, Frequency of presenting features. C, Hemorrhagic plaques on thoracic visceral pleura. D, Dilated tortuous blood vessels coursing the surface of the mediastinum. E, Frequency of involvement of anatomical sites. F, Cutaneous manifestations of KLA with red-purple discoloration and scattered lymphatic vesicles.

Figure 3

Kaplan-Meier curve. Overall survival of patients compared from three time points: emergence of first symptoms (black), development of first respiratory symptoms (blue), and from time of lymphatic anomaly diagnosis (red).