Abstract
Lymphadenopathy (LN) is a cancer symptom in children; however, most cases are benign. This study aimed to identify risk factors for malignant LN. Differences in LN cases referred to general or pediatric outpatient clinics. All children older than 4 years with LN who were referred to our General Pediatrics or Pediatric Oncology Clinics from 2018 to 2022 were evaluated according to clinical presentation, including complete blood count (CBC), viral serology, bone marrow aspiration, biopsy, and imaging. Of 874 children aged 4-16 years (median 7 years), 56% were boys. LN associated with acute bacterial infections was excluded (n= 412). Among children referred to the General Pediatrics Clinic (n=213), 1.9% of cases were malignant compared with 16% of cases referred to the Pediatric Oncology Clinic (n=249), including acute leukemia (n=24) and lymphoma (n=11) cases. Among malignant cases, 40% were secondary to non-Hodgkin lymphoma (n=4) and cases eventually identified as non-malignant included non-common variable immune deficiency (CVID) hemophagocytic lymphohistiocytosis (n=4), collagen-related lymphoproliferation (n=5), CVID (n=2), and autoimmune lymphoproliferation (n=4). Among those referred to the General Pediatrics Clinic, EBV and CMV were identified in 56% and 22% of cases, respectively, with a male prevalence. No differences in the frequencies of fever, sore throat, bad breath, or respiratory symptomatology were identified between malignant and benign cases. Splenomegaly was more frequently observed in malignant cases, but the difference between groups was not significant. A leukemia diagnosis (defined as associated fever >2 weeks, purpura, bone aches) was more likely (odds ratio 4.5) for generalized LN, characterized as non-regressive, firm, and non-tender, than for non-infectious LN (odds ratio 3.2). The delay in diagnosis ranged from 4 to 47 days (median 19 days). Bone marrow was assessed in 59 cases. The most commonly reported investigations were CBC (100%), EBV or CMV IgM (66%), erythrocyte sedimentation rate (50%), and imaging (local ultrasound in 80%, chest or abdomen CT in 25%, and CT-guided biopsy in 10%). EBV was the most common viral infection. Leukemia was rare in our cohort, and alarming signs included persistent fever >2 weeks, non-regressive bone aches, and splenomegaly.
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