Pediatric lymphadenopathy: Which patients need evaluation by an oncologist?
Authors: Kathryn A. Six, Orlando Esparza, Gabriel Daniels, Inmaculada B. Aban, Matthew A. Kutny, Julie Wolfson, Jeffrey Lebensburger, Ana C. Xavier
Journal: Journal of Clinical Oncology (2021)

e13605 Background: While lymphadenopathy may be the first sign of cancer in children, it can also be a manifestation of non-malignant illness. Lymphadenopathy is a common reason for referral to a pediatric oncologist, which can result in significant anxiety for parents. Understanding which patients require an oncology referral for lymphadenopathy is key in order to streamline healthcare utilization for this common clinical entity. Methods: In this single institution study, we retrospectively reviewed the medical records of patients referred to pediatric oncology for lymphadenopathy between 2012 and 2020. A logistic regression model was fitted to examine the association between the maximum size of the lymph nodes and cancer diagnosis. We also obtained estimates of odds ratio and area under the ROC curve. Sensitivity and specificity were estimated using exact Clopper-Pearson method for proportion. SAS v9.4 was used to perform statistical analyses. Institutional IRB approved the study. Results: A total of 91 patients aged 1 to 19 years (median 14 years) were included. There was a statistically significant association between lymph node size and a diagnosis of malignancy. For every centimeter increase in maximal dimension of lymph node(s), there was an estimated 2.2-times increase in the odds of cancer (CI 95% 1.5-3.3; p = 0.0002). The estimated area under the curve for this model was 0.8 (95% CI 0.7-0.9) indicating that lymph node size correlated very well with cancer risk. We evaluated the model to find a threshold for lymph node size that provided a high sensitivity for screening purposes. A cut-off of 2 centimeters resulted in an estimated sensitivity of 0.95 (95%CI 0.7-0.99) and specificity of 0.6 (95%CI 0.5-0.7). Conclusions: This study provides preliminary evidence that the estimated odds of a cancer diagnosis doubles for each centimeter increase in lymph node size. This single institution retrospective study suggests that in patients with lymphadenopathy, the maximum lymph node size may be a predictor of malignancy. Our results demonstrate that the sensitivity for cancer increases at a lymph node size of two centimeters or larger. Navigating when to monitor a patient with lymphadenopathy in the primary care setting versus referring to the oncologist can be a challenge for primary care physicians. Our results are consistent with the practice that using a two centimeter cutoff is a good starting point for referrals; however, these results will need to be verified with a larger sample size before they are adopted into clinical guidelines. Further study is underway to evaluate lymphadenopathy referrals to both surgery and oncology in order to reduce potential bias that may be associated with oncology referrals, which may have a predilection for malignancy. This study underlines the importance of a physical examination by the primary care physician as the crucial step in determining if a patient requires an oncology referral.