Complex Lymphatic Anomalies: Report on a Patient Registry Using the Latest Diagnostic Guidelines.

Abstract

Background: Generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), kaposiform lymphangiomatosis (KLA), and central conducting lymphatic anomaly (CCLA) are rare, multisystem lymphatic disorders, referred to as complex lymphatic anomalies (CLAs). Their etiology remains poorly understood; however, somatic activating mutations have recently been discovered, and the results of targeted treatments are promising. This study aimed to elaborate on the phenotypic description of CLA. Methods: Thirty-six consecutive patients were recruited for the "GLA/GSD Registry" of the University Hospital of Freiburg, Germany (2015-2021). Clinical data were prospectively collected provided that a signed informed consent form was obtained. The latest proposed diagnostic guidelines were retrospectively applied. Results: Thirty-two patients (38% males) were included in the study; 15 GLA, 10 GSD, 3 KLA, and 4 CCLA patients were identified. Eighty-four percent already had symptoms by the age of 15 years. Osteolysis and periosseous soft-tissue infiltration were associated with GSD (p < 0.001 and p = 0.011, respectively), ascites and protein-losing enteropathy with CCLA (p = 0.007 and p = 0.004, respectively), and consumption coagulopathy with KLA (p = 0.006). No statistically significant differences were found in organ involvement, distribution of osteolytic lesions, number of affected bones and fractures. Twenty-five patients had complications; one patient with GLA died despite multimodal treatment. Spontaneous regression was seen in one patient with untreated KLA. Conclusions: CLA are rare, and their overlapping clinical presentations make differential diagnosis difficult. The characterization of our case series contributes to the phenotypic description and differentiation of these four clinical entities. A further understanding of their pathogenesis is crucial for evaluating targeted therapies and optimizing medical care.