Cervical lymphadenopathy is one of the most common clinical findings in children and encompasses a broad spectrum of reactive, infectious, inflammatory, and neoplastic disorders [1]. Although most enlarged cervical lymph nodes in pediatric patients are benign, persistent, progressive, or clinically suspicious lymphadenopathy may indicate significant underlying pathology, including lymphoma or metastatic malignancy [2,3]. Distinguishing benign from malignant lymph node lesions is therefore essential for appropriate clinical management, while avoiding unnecessary invasive procedures in children [4].

Fine-needle aspiration cytology (FNAC) is a minimally invasive, rapid, and cost-effective technique for evaluating lymph node lesions [5]. However, variability in cytological terminology and interpretation can create difficulties in communicating the level of diagnostic certainty and risk of malignancy [6]. To address this issue, the Sydney System provides a standardized five-tier reporting framework for lymph node cytology, comprising L1 (inadequate), L2 (benign), L3 (atypical), L4 (suspicious of malignancy), and L5 (malignant) [7]. Standardized categorization may improve diagnostic communication, facilitate risk stratification, and assist clinicians in determining the need for further tissue sampling or surgical intervention [8].

Histopathological examination remains the definitive diagnostic reference for many surgically excised cervical lymph node lesions, particularly when lymphoma, metastatic disease, or an unusual inflammatory disorder is suspected [9]. Correlating Sydney System cytological categories with histopathological findings is therefore important for determining the reliability of cytological risk stratification in pediatric patients [10]. However, evidence specifically evaluating the performance and histopathological correlation of the Sydney System in pediatric cervical lymph node lesions remains limited, particularly in patients undergoing surgical biopsy or excision.

Therefore, the present study aimed to evaluate the risk stratification of pediatric cervical lymph node lesions using the Sydney System and to determine its correlation with histopathological diagnosis in surgically managed patients.

This hospital-based observational diagnostic study was conducted among pediatric patients presenting with cervical lymph node lesions who underwent surgical excision or biopsy followed by histopathological examination. A total of 45 consecutive patients were included in the study. Patients aged ≤18 years with clinically evident cervical lymphadenopathy for whom fine-needle aspiration cytology (FNAC) and subsequent histopathological evaluation were available were eligible for inclusion. Patients with inadequate clinical records, unavailable cytological smears, or specimens unsuitable for definitive histopathological assessment were excluded. The study was conducted in accordance with the principles of the Declaration of Helsinki, and approval was obtained from the Institutional Ethics Committee before commencement of the study. Written informed consent from parents or legal guardians, with assent from children when appropriate, was obtained before participation. Clinical details including age, sex, presenting symptoms, duration of lymph node enlargement, nodal distribution, laterality, and relevant clinical findings were recorded using a structured data collection proforma. FNAC of the cervical lymph node was performed using standard aseptic techniques, and aspirated material was processed for cytological examination. Smears were prepared and appropriately stained using routine cytological staining methods and examined by an experienced pathologist. Cytological findings were categorized according to the Sydney System for reporting lymph node cytopathology into L1 (inadequate/non-diagnostic), L2 (benign), L3 (atypical), L4 (suspicious of malignancy), and L5 (malignant). The cytological category was assigned based on the overall morphological features and, where appropriate, relevant ancillary findings. All patients subsequently underwent surgical excision or biopsy of the involved cervical lymph node as clinically indicated. The resected specimens were fixed in 10% neutral buffered formalin, routinely processed, sectioned, and stained with hematoxylin and eosin for histopathological evaluation. Histopathological examination was considered the reference standard. Final diagnoses were recorded and grouped into benign and malignant categories for diagnostic-performance analysis. Benign lesions included reactive lymphoid hyperplasia, tuberculous lymphadenitis, suppurative lymphadenitis, and Kikuchi-Fujimoto disease, whereas malignant lesions included Hodgkin lymphoma, non-Hodgkin lymphoma, and metastatic malignancy. The histopathological diagnosis was compared with the corresponding Sydney System cytological category for each patient. Data were entered into Microsoft Excel and analyzed using appropriate statistical software. Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages. The association between Sydney System categories and histopathological diagnosis was assessed using the Chi-square test or Fisher's exact test, as appropriate. For assessment of diagnostic performance, L4 (suspicious of malignancy) and L5 (malignant) were considered positive cytological results for malignancy, while L1–L3 were considered negative. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated using histopathology as the reference standard. Agreement between cytological categorization and histopathological diagnosis was assessed using Cohen's kappa coefficient. A two-sided p-value <0.05 was considered statistically significant.

The study included 45 pediatric patients with cervical lymph node lesions, of whom 25 (55.6%) were males and 20 (44.4%) were females. The mean age of the participants was 9.1 ± 3.8 years, with the largest proportion belonging to the 5–10-year age group (21, 46.7%), followed by 11–15 years (16, 35.6%) and <5 years (8, 17.8%). (Table 1)

Table 1. Demographic Characteristics of Study Participants (N = 45)

Neck swelling was present in all 45 (100.0%) patients, while fever was reported in 19 (42.2%) and pain/tenderness in 15 (33.3%). Most patients had a duration of swelling of 1–3 months (20, 44.4%). Cervical level III–IV was the most frequently involved nodal region (21, 46.7%), and unilateral lymphadenopathy was observed in 32 (71.1%) patients. (Table 2)

Table 2. Clinical Characteristics and Distribution of Cervical Lymph Node Lesions (N = 45)

According to the Sydney System, the majority of lesions were categorized as L2 (benign), comprising 27 (60.0%) cases. L5 (malignant) accounted for 9 (20.0%) cases, while 4 (8.9%) were classified as L4 (suspicious of malignancy), 3 (6.7%) as L3 (atypical), and 2 (4.4%) as L1 (inadequate/non-diagnostic). (Table 3)

Table 3. Distribution of Cases According to the Sydney System

Histopathological examination showed reactive lymphoid hyperplasia as the most common diagnosis, observed in 16 (35.6%) cases, followed by tuberculous lymphadenitis in 10 (22.2%) and suppurative lymphadenitis in 5 (11.1%). Kikuchi-Fujimoto disease was identified in 4 (8.9%) cases, while Hodgkin lymphoma, non-Hodgkin lymphoma, and metastatic malignancy accounted for 5 (11.1%), 3 (6.7%), and 2 (4.4%) cases, respectively. (Table 4)

Table 4. Histopathological Diagnosis of Cervical Lymph Node Lesions

On comparison with histopathology, benign lesions predominated among L1 and L2 categories, with 2 (100.0%) L1 and 26 (96.3%) L2 cases showing benign histopathology. Malignancy was increasingly represented in higher Sydney categories, with malignant histopathology identified in 1 (33.3%) L3, 2 (50.0%) L4, and 6 (66.7%) L5 cases. The association between Sydney System category and histopathological diagnosis was statistically significant (χ² = 17.82, p < 0.001). (Table 5)

Table 5. Correlation Between Sydney System Category and Histopathological Diagnosis

When L4 and L5 categories were considered positive for malignancy, the Sydney System demonstrated a sensitivity of 61.5% and specificity of 93.8%. The positive predictive value was 80.0%, negative predictive value was 85.7%, and overall diagnostic accuracy was 84.4%, indicating good discriminatory performance for identifying malignant cervical lymph node lesions. (Table 6)

Table 6. Diagnostic Performance of the Sydney System for Detection of Malignancy

The agreement between the Sydney System and histopathological diagnosis was 84.4%, with a Cohen's kappa value of 0.62, indicating substantial agreement. The observed agreement was statistically significant (p < 0.001), supporting a meaningful concordance between cytological risk stratification using the Sydney System and the definitive histopathological diagnosis. (Table 7)

Table 7. Agreement Between Sydney System and Histopathology

In the present study of 45 pediatric patients with cervical lymph node lesions, benign cytological findings predominated, with 60.0% of cases classified as L2, whereas 20.0% were categorized as L5 and 8.9% as L4. Histopathology demonstrated reactive lymphoid hyperplasia as the most frequent diagnosis (35.6%), followed by tuberculous lymphadenitis (22.2%) and suppurative lymphadenitis (11.1%). This pattern is broadly consistent with the pediatric experience reported by Sable et al., who found that L2 was the predominant Sydney category, accounting for 85.8% of 803 pediatric lymph node FNAC cases, while L1, L3, L4, and L5 accounted for 4.35%, 0.49%, 2.7%, and 6.6%, respectively [11]. The higher proportion of atypical, suspicious, and malignant categories in the present series may be related to the study population being restricted to surgically managed patients with available histopathological confirmation, whereas the study by Sable et al. included a broader pediatric FNAC population [11]. A significant association was observed between the Sydney System categories and histopathological diagnosis in the present study (χ² = 17.82, p < 0.001), with malignant histopathology becoming progressively more frequent toward the higher-risk categories. Malignancy was identified in 3.7% of L2 cases, 33.3% of L3 cases, 50.0% of L4 cases, and 66.7% of L5 cases. This progressive increase supports the fundamental risk-stratification concept of the Sydney System, which was specifically developed to provide standardized categories with increasing concern for malignancy and clearer communication between cytopathologists and clinicians [12]. In the large study by Ahuja and Malviya involving 1205 lymph node aspirates, the risk of malignancy increased markedly from 1.5% in L2 to 37.5% in L3, 96.9% in L4, and 98.2% in L5 [13]. Similarly, a large real-world study of 1458 lymph node FNACs reported progressively increasing malignancy risk across the diagnostic categories, with particularly high risk in suspicious and malignant categories [14]. Differences in the absolute malignancy rates between these studies and the present series are likely attributable to differences in patient selection, age distribution, prevalence of malignancy, and the proportion of cases undergoing histopathological verification. When L4 and L5 were considered positive for malignancy, the present study demonstrated a sensitivity of 61.5%, specificity of 93.8%, positive predictive value of 80.0%, negative predictive value of 85.7%, and diagnostic accuracy of 84.4%. The relatively high specificity indicates that higher-risk Sydney categories were strongly associated with malignant histopathology, although the lower sensitivity suggests that a proportion of malignant lesions may remain in lower or indeterminate categories. These findings are directionally consistent with the pediatric study by Sable et al., which reported sensitivity, specificity, PPV, NPV, and accuracy of 72.34%, 98.48%, 97.14%, 83.33%, and 87.61%, respectively [11]. However, diagnostic performance in the present study was lower than that reported in several predominantly adult series. Das et al. reported high diagnostic performance using the Sydney System, while a study by Ahuja and Malviya demonstrated that diagnostic accuracy depended on the threshold used to define a positive result, with the highest accuracy obtained when suspicious and malignant categories were considered positive [13,15]. These differences emphasize that the performance of the Sydney System is influenced by the clinical population and by the choice of cutoff category for malignancy. The present study also demonstrated substantial agreement between cytological risk stratification and histopathological diagnosis, with an observed agreement of 84.4% and Cohen's kappa of 0.62 (p < 0.001). This supports the practical value of standardized Sydney categorization in pediatric cervical lymph node lesions, particularly in distinguishing lesions with a low likelihood of malignancy from those requiring definitive tissue evaluation. Sable et al. similarly demonstrated the usefulness of FNAC in heterogeneous pediatric lymphadenopathies, supporting its role as an initial diagnostic approach while recognizing that selected cases, particularly suspected lymphomas, may require histopathological and ancillary investigations [11]. More broadly, a recent meta-analysis of studies evaluating the Sydney System noted substantial heterogeneity in risk estimates and diagnostic performance because of differences in study populations, verification methods, ultrasound use, operators, and definitions of a positive result [16]. The relatively small sample size and restriction of the present study to surgically managed patients may therefore explain some of the differences from larger published series, but the observed substantial cytology–histopathology agreement supports the applicability of the Sydney framework in this selected pediatric population. A major strength of the present study is the direct correlation of Sydney System cytological categories with histopathological findings, allowing assessment of its diagnostic performance and agreement with the definitive reference standard in pediatric cervical lymph node lesions. The use of standardized five-tier Sydney System classification, assessment of diagnostic parameters, and inclusion of surgically confirmed cases further strengthens the analysis. However, the study is limited by its relatively small sample size of 45 patients and single-center design, which may limit the generalizability of the findings. Selection of only surgically managed patients may also introduce selection bias and may overrepresent clinically suspicious lesions. In addition, the small number of malignant and indeterminate cases limits the precision of diagnostic-performance estimates, and the study did not evaluate interobserver variability or the potential contribution of ancillary investigations such as immunohistochemistry and microbiological testing.

The Sydney System provides a useful standardized framework for risk stratification of pediatric cervical lymph node lesions and demonstrates substantial correlation with histopathological diagnosis. In the present study, higher Sydney categories were associated with an increasing likelihood of malignancy, while the system showed high specificity, good negative predictive value, and satisfactory overall diagnostic accuracy. These findings support the use of Sydney System-based cytological reporting as an effective initial approach for categorizing pediatric cervical lymph node lesions and identifying patients who require definitive histopathological evaluation.

Acknowledgement: None

Funding: None

Conflict of Interest: None