Risk of disease progression in pediatric lymphatic malformations: predictors and a clinical risk score

Lymphatic malformations (LMs) in children are characterized by a prolonged and fluctuating clinical course with a risk of continued growth or recurrent enlargement after treatment. Identification of independent predictors and development of a clinically applicable risk score may improve treatment planning and long-term follow-up strategies.

Purpose of the study. To identify independent clinical and anatomical predictors of continued growth or recurrent enlargement of lymphatic malformations in children after initiation of surgical treatment using multivariable analysis.

Patients and methods. A retrospective single-center cohort study was conducted between 2012 and 2022. A total of 115 patients aged 17 years or younger were included who underwent surgical treatment (including extensive resection procedures), sclerotherapy, or combined treatment. The primary endpoint was the first episode of continued growth or recurrent enlargement of LM, defined predominantly by contrast-enhanced magnetic resonance imaging findings. Receiver operating characteristic analysis was used to determine the optimal lesion volume threshold. Multivariable logistic regression with bootstrap validation and time-to-event analysis using Kaplan–Meier and Cox methods were performed.

Results. The median follow-up after the index intervention was 11.0 (3.2–27.0) months. The event occurred in 22 of 115 patients (19.1 %). At the last follow-up visit, a ≥50 % reduction in lesion volume or complete response was observed in 95 of 115 patients (82.6 %), a <50 % reduction in 15 of 115 patients (13.0 %), and ongoing growth in 5 of 115 patients (4.3 %). Independent risk factors included prenatal or neonatal onset (OR 4.08; 95 % CI 1.10–15.05; p = 0.035), preoperative lesion volume ≥ 90 cm³ (OR 4.06; 95 % CI 1.09–15.15; p = 0.037), and previous surgery outside a referral center (OR 5.93; 95 % CI 1.73–20.36; p = 0.005). Aggressive anatomical spread demonstrated a trend toward increased risk (OR 2.82; p = 0.092). Model discrimination was high (AUC 0.812; 95 % CI 0.708–0.916) and remained stable after internal validation (AUC_0.632+ = 0.812). The additive score stratified the risk of the event as 6.0 % (95 % CI 1.9–17.4) for patients with ≤1 point, 10.3 % (95 % CI 3.2–28.7) for those with 2 points, and 44.4 % (95 % CI 28.8–61.2) for those with ≥ 3 points. Median event-free survival was 65.2 months. No significant differences were observed between treatment approaches (log-rank p = 0.699).

Conclusion. In this cohort, the risk of continued growth in pediatric lymphatic malformations was primarily associated with early disease onset, baseline lesion volume, and previous surgery outside a referral center, whereas extensive anatomical involvement demonstrated a trend toward increased risk. The proposed risk stratification score may support individualized follow-up and treatment planning; however, external validation is required.

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