Malignancy Risk Markers in a Cohort of Referrals for Lymphadenopathy; An Evaluation of Clinical Features Including Lymph Node Size
Authors: Esparza Orlando , Xavier Ana , Kutny Matthew A. , Wolfson Julie A. , Lebensburger Jeffrey D. 
Published: October 2019

Abstract
Background: Lymphadenopathy is a common pediatric problem that pediatricians and general practitioners face in their clinic. Although typically found in the setting of an infection and benign in nature, referrals to a Pediatric Hematologist/Oncologist are sometimes made to evaluate for hematologic malignancy. The associated health care costs and potential psychological impact on family members as a result of making a referral to a hematology/oncology specialist warrants consideration. To better understand the outcomes of patients with lymphadenopathy and provide evidence based recommendations for need for referral, we have conducted a retrospective chart review to assess clinical features as risk markers for malignancy among patients referred for lymphadenopathy.
Methods: We conducted a retrospective chart review of 1,164 patients referred to the Division of Pediatric Hematology Oncology at Children's of Alabama over a four year period (2013-2016). The diagnosis and demographics were recorded for every patient. Location of lymphadenopathy (cervical, supraclavicular, axillary, abdominal, inguinal, and mediastinal) and size of lymph nodes on exam and imaging were recorded. Symptomatology (fever, night sweats, weight loss, fatigue, bone pain, shortness of breath, and bleeding symptoms) and laboratory findings, such as white blood cell (WBC), Hemoglobin, Platelet count, lactate dehydrogenase (LDH), uric acid, and erythrocyte sedimentation rate (ESR) were recorded. Descriptive statistics, Student's t-test, and Wilcoxon signed-rank test were conducted using JMP® 12. Sensitivity and specificity were calculated using a conventional two-by-two table (2x2).
Results: Among 1,164 patients that were referred to Pediatric Hematology Oncology, sixty nine (5.9%) were referred for lymphadenopathy. Sixty one (88.5%) out of sixty nine patients presented to our clinic for evaluation. Thirteen patients (21%) were diagnosed with malignancy (11 lymphoma, 2 leukemia). While all patients in this cohort were referred for concern of enlarged lymph nodes (lymphadenopathy) by their primary physician, we assessed the sensitivity and specificity of utilizing a cut-off of ≥ 2cm assessed by physical exam or imaging to define a population with "abnormal lymphadenopathy". In total 32 patients met this criteria for abnormal lymphadenopathy. All 13 patients who ultimately were diagnosed with a malignancy by biopsy met this size criteria for abnormal lymphadenopathy in at least one location (sensitivity 100%). Nineteen of 42 patients without malignancy were noted to have abnormal lymphadenopathy in at least one location (specificity 55%). The mean age of patients with lymphadenopathy was 9.49 years. Older patients were more likely to have a diagnosis of malignancy (13.61 years vs. 8.38 years, p=0.0034). Mean months of lymphadenopathy was 8.2 months. No statistical difference was noted between months of lymphadenopathy present and diagnosis of malignancy (p=0.56). Patients with malignancy had a significantly higher WBC (43.5 10*3/ µL vs. 27.6 10*3/ µL, z = 2.84, p=0.0044) than patients without malignancy. No statistical differences were noted for patients with and without malignancy for hemoglobin (p=0.9), platelet count (p=0.7), LDH (p=0.2), uric acid (p=0.5), or ESR (p=0.7). None of the symptomatology parameters demonstrated a sensitivity greater than 60%.
Conclusion: Lymphadenopathy is a common pediatric problem in the outpatient setting that may require referral to a Pediatric Hematologist/Oncologist to evaluate for malignancy. Our data suggests that lymphadenopathy≥2cm in at least one location either by physical exam or imaging is highly sensitive for malignancy. Thus, pediatricians and general practitioners should consider continued monitoring and conservative management of patients with lymphadenopathy <2cm. Our data also supports that in the context of lymphadenopathy, evaluation of blood cell counts is important and an elevated WBC should prompt greater concern for malignancy. By taking this approach, referrals may be reduced resulting in fewer costs and avoidance of psychological stressors among family members.

Disclosures
Lebensburger: American Society of Hematology, Scholar Award: Research Funding; NHLBI: Research Funding.