Abstract
BACKGROUND: There are three common and significant causes of lymphadenopathy (LAP) in tuberculosis-and-HIV-endemic settings - tuberculosis, lymphoma, and metastatic solid organ cancers. Overlapping clinical symptoms of these diseases necessitates diagnostic procedural investigation. Fine needle aspiration (FNA) with Xpert TB/RIF Ultra has good sensitivity for tuberculosis diagnosis, while FNA cytology can detect solid cancer lymph node metastasis, although with lower sensitivity. Critically, lymphoma cannot be reliably detected or classified using FNA. Lymphoma diagnosis often is made after repeat testing and eventual surgical excision biopsy (SEB), contributing to treatment delays, inappropriate empiric anti-tuberculosis therapy, and increased strain on already limited healthcare resources. METHODS: This study presents a comparative provider-perspective cost analysis of three diagnostic procedures: FNA, SEB and core-needle biopsy (CNB). Costs were evaluated for individual procedures and within investigative pathways for unexplained LAP. Data were collected at Groote Schuur Hospital, a tertiary academic hospital in South Africa, during 2018 and 2025. Costing was conducted using a mixed-methods approach combining bottom-up ingredients-based costing with top-down allocation of overheads. Capital costs were annualised, and all costs were adjusted to 2025 values in United States dollars. RESULTS: Histological diagnosis and tuberculosis testing using CNB were less costly (US$ 145) than either SEB (US$ 244), or FNA cytology and tuberculosis testing (US$ 179). Total investigative costs increased substantially when repeat FNAs were required while awaiting access to SEB (US$ 518). CNB demonstrated high diagnostic accuracy and obviated the need for further procedures in most cases, improving diagnostic efficiency and offering significant potential for cost savings. Sensitivity analyses suggested further reductions in CNB costs are possible through task-shifting to junior clinicians and through the use of reusable biopsy equipment. CONCLUSION: The CNB-centred diagnostic approach to lymphadenopathy provides lower-cost, timeous, and accurate diagnosis of the three most significant causes of LAP in tuberculosis- and HIV-endemic settings. This approach enables early initiation of appropriate treatment, reduces unnecessary procedures, and optimises the use of limited healthcare resources. These findings support the integration of CNB into national diagnostic algorithms and highlight the value of investments in training and equipment to enable its decentralised implementation.