Lymphoproliferative Disorders Mimicked by Tuberculosis: A Retrospective Study on Lateral Flow Urine Lipoarabinomannan (LF-ULAM) Limitations

TL;DR

This study shows that a TB test commonly used in HIV patients can incorrectly suggest TB when the real issue is a lymphoproliferative disorder, stressing the need for biopsies to avoid misdiagnosis.

Contribution

The study highlights the limitations of LF-ULAM in diagnosing TB in HIV patients and emphasizes the importance of histopathology for accurate diagnosis of lymphadenopathy.

Findings

69% of HIV patients with positive LF-ULAM tests were later diagnosed with lymphoproliferative disorders.

53% of patients had confirmed mycobacterial disease through histology, culture, or NAAT.

Empiric TB treatment without histological confirmation can delay cancer care and worsen outcomes.

Abstract

Introduction

The human immunodeficiency virus (HIV) remains South Africa's (SA) largest epidemic. Furthermore, tuberculosis (TB) continues to be the leading cause of death in SA. People living with HIV/AIDS (PLHA) are at increased risk of both TB and lymphoproliferative disorders (LPD). PLHA commonly manifest lymphadenopathy as part of their disease spectrum, with extra-pulmonary TB being the most common cause. Local guidelines recommend lateral flow urine lipoarabinomannan (LF-ULAM) assay testing for all PLHA admitted to the hospital. The LF-ULAM assay is therefore widely used in SA. The LF-ULAM assay does not provide definitive confirmation of the cause of lymphadenopathy. In resource-limited settings, TB can impetuously be attributed as the sole cause of lymphadenopathy in many PLHA with positive LF-ULAM assays. Misdiagnosis of LPD as TB can lead to catastrophic patient outcomes. Therefore, initial correct diagnosis is of utmost importance.

Aims and objectives

The aims and objectives of this study are to identify the etiology of lymphadenopathy in PLHA with positive LF-ULAM assays and to highlight the need for a high index of suspicion of LPD in PLHA with lymphadenopathy.

Materials and methods

A retrospective census study was carried out at a tertiary hospital in a rural province of SA. A total of 13 PLHA with lymphadenopathy, diagnosed with disseminated TB by LF-ULAM assay, were identified for this study. Eligible participants were identified using medical records from the medical wards. All PLHA included had generalized lymphadenopathy diagnosed by clinical palpation. Histopathologists were unblinded to LF-ULAM results. The results of TB investigations, excisional lymph node biopsies, and trephine biopsies from these patients were analyzed to confirm the etiology of their lymphadenopathy.

Results

A total of 13 PLHA were included in this study. All patients were initiated on anti-tuberculous treatment (ATT) following LF-ULAM assay positivity. The majority of cases (n = 9/13; 69%) in this small cohort had histological confirmation of an LPD. More than half of the cases (n = 7/13; 53%) were confirmed to have mycobacterial disease by means of either histology, culture, or TB nucleic acid amplification test (NAAT).

Conclusion

Histological confirmation of the etiology of lymphadenopathy is crucial in PLHA to differentiate between LPD and TB. Empiric TB treatment without appropriate confirmation of TB can lead to worse patient outcomes and significantly delay oncological care for PLHA. We recommend expanding biopsy access in resource-limited settings to prevent diagnostic delays and improve patient outcomes.