Complex lymphatic anomalies

https://doi.org/10.1053/j.sempedsurg.2014.07.006Get rights and content

Abstract

Complex lymphatic anomalies include several diagnoses with overlapping patterns of clinical symptoms, anatomic location, imaging features, hematologic alterations, and complications. Lymphatic malformations likely arise through anomalous embryogenesis of the lymphatic system. Analysis of clinical, imaging, histologic, and hematologic features is often needed to reach a diagnosis. Aspiration of fluid collections can readily define fluid as chylous or not. The presence of chyle indicates dysfunction at the mesenteric or retroperitoneal level or above the cisterna chyli due to reflux. The imaging patterns of generalized lymphatic anomaly (GLA) and Gorham–Stout disease have been segregated with distinctive bone lesions and peri-osseous features. More aggressive histology (spindled lymphatic endothelial cells), clinical progression, hemorrhage, or moderate hematologic changes should raise suspicion for kaposiform lymphangiomatosis. Biopsy may be needed for diagnosis, though avoidance of rib biopsy is advised to prevent iatrogenic chronic pleural effusion. Lymphangiography can visualize the anatomy and function of the lymphatic system and may identify dysfunction of the thoracic duct in central conducting lymphatic anomalies. Local control and symptom relief are targeted by resection, laser therapy, and sclerotherapy. Emerging data suggest a role for medical therapies for complications of complex lymphatic anomalies. Outcomes include recurrent effusion, infection, pain, fracture, mortality, and rarely, malignancy. Complex lymphatic anomalies present significant diagnostic and therapeutic challenges. Results from a phase 2 study of sirolimus in these and other conditions are expected in 2014. Improved characterization of natural history, predictors of poor outcomes, responses to therapy, and further clinical trials are needed for complex lymphatic anomalies.

Introduction

The lymphatic system initially develops as blind-ending sacs, which coalesce to form a delicate plexus of vessels. These peripheral lymphatics then drain into the central lymphatic channels, including the cisterna chyli. Chyle is a mixture of lymph and chylomicrons absorbed from the intestine and conducted centrally via lacteals. Mesenteric chyle then mixes with clear lymph from the pelvis and lower extremities. The central conducting channels eventually drain into the venous system via the thoracic duct.

Lymphatic dysfunction and hypertension lead to expansion of the interstitial spaces with lymphatic fluid, also known as lymphedema. Obstruction or anomalies of the lymphatic system can result in leakage, manifesting as pleural effusions and ascites. The fluid may be clear lymph or chylous depending on the site of obstruction, leakage, and reflux. Chyle accumulation in or leakage from caudal structures such as the vagina, scrotum, urinary tract, and lower extremities may also be seen as a result of chylous reflux.1

Section snippets

Diagnostic investigations and clinical patterns

Whether chylous or not, the fluid collections are usually anechoic by ultrasonography, although mild internal echoes and fluid levels may be seen in chylous effusions and ascites. It is similarly difficult to differentiate between simple and chylous fluid on CT, although lower attenuation and fluid–fluid levels suggest the presence of chyle.3 The diagnosis can be confirmed by aspiration. A high lymphocyte count will be seen in both, while milky white fluid with a high triglyceride level is

Treatment

Treatment of complex lymphatic anomalies varies by mechanism of lymphatic dysfunction and location of active complications. Unfortunately, for the majority of children with engorged lymphatics, dysmotility, and reflux, interventional and surgical treatments are largely palliative. Procedures such as pleurodesis or sclerotherapy are primarily aimed at providing symptomatic relief and local control. For symptoms related to reflux of lymphatic fluid, diversion of fluid by embolization or surgical

Outcomes and prognosis

While natural history studies are lacking in these conditions, some patterns of outcomes and prognosis are emerging from clinical experience. Uncorrected, chronic lymphedema leads to dermal hypertrophy, cutaneous leak, and chronic infection. In severe cases of chronic lymphedema, chronic ulceration and angiosarcoma (Stewart–Treves syndrome)27 development are reported. Patients with lytic bone disease, as in GLA, may present with pathologic fractures. Osteolysis in Gorham–Stout disease leads to

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