Alarming Signs: Pediatric Lymphadenopathy Is Not Always Benign

Context Assessment of lymphadenopathy (LN) in children represents a diagnostic challenge because of the extensive differential diagnoses, including reactive and malignant conditions. Objective The present study was carried out to identify different etiologies of LN in children and assess parameters commonly associated with malignancy, with an emphasis on the role of the diagnostic workup. Design Four hundred fifty-three patients aged 2–16 years (median 6 years); 58% were males. Study duration was 2 years (2018–2020). They were sorted into neoplastic and non-neoplastic groups. Acute bacterial-related LNs were excluded (n=236), and 217 were enrolled. Of those referred to general pediatrics clinic (n=117), only 1.9% were malignant. Of those referred to pediatric oncology clinic (n=110, 20%) the following diagnosis were reported: leukemia (n=8), lymphoma (n=6), HLH (n=2), collagen (n=3), COVID-19 (n=1), and ALPS (n=2). Results Viral infection was the most common; 60% had EBV, and 20% had CMV infection. In only 56 patients, biopsy, whether fine-needle aspiration cytology, core-needle, or excision biopsy, was essential to reach the diagnosis. Affected children were most commonly younger than 8 years. Males were more affected. No difference was found in frequencies of the following symptoms: high temperature, sore throat, dyspnea, and respiratory symptomatology between examined children in both conditions, with differences in gastrointestinal symptoms, eyelid swelling, skin rash, and fatigue. Differences were not proven in the frequency of LN and hepato-splenomegaly between both groups. Odds ratio (4.5) for risk of leukemia (associated fever >1 week, purpura, bone aches, LNs). Generalized, non-regressive, firm, and non-tender were more at risk for non-infection (odds ratio 3.2). Delay in diagnosis was 4–42 days (median 18 days). Most reported investigations were CBC (100%), EB, CMV IgM (66%), ESR (50%), imaging (local ultrasound 80%, one-third repeated at 2 weeks), CT chest or abdomen in 25% (half were unnecessary or non-conclusive), and 10% were CT-guided. Conclusion EBV infection was the most common viral infection; leukemia was rare. Alarming signs were bone aches with non-regressive course of the disease. Malignancy should be suspected in the following conditions: generalized multiple LN, LN size >2 cm, blast cells in blood film, and elevated LDH level. In such cases, LN biopsy is recommended.