Date Published: October 11, 2017
Publisher: The American Society of Tropical Medicine and Hygiene
Author(s): Daniela E. Kirwan, Cesar Ugarte-Gil, Robert H. Gilman, Syed M. Hasan Rizvi, Gustavo Cerrillo, Jaime Cok, Eduardo Ticona, José Luis Cabrera, Eduardo D. Matos, Carlton A. Evans, David A. J. Moore, Jon S. Friedland.
The differential diagnosis for lymphadenopathy is wide and clinical presentations overlap, making obtaining an accurate diagnosis challenging. We sought to characterize the clinical and radiological characteristics, histological findings, and diagnoses for a cohort of patients with lymphadenopathy of unknown etiology. 121 Peruvian adults with lymphadenopathy underwent lymph node biopsy for microbiological and histopathological evaluation. Mean patient age was 41 years (Interquartile Range 26–52), 56% were males, and 39% were HIV positive. Patients reported fever (31%), weight loss (23%), and headache (22%); HIV infection was associated with fever (P < 0.05) and gastrointestinal symptoms (P < 0.05). Abnormalities were reported in 40% of chest X-rays (N = 101). Physicians suspected TB in 92 patients (76%), lymphoma in 19 patients (16%), and other malignancy in seven patients (5.8%). Histological diagnoses (N = 117) included tuberculosis (34%), hyperplasia (27%), lymphoma (13%), and nonlymphoma malignancy (14%). Hyperplasia was more common (P < 0.001) and lymphoma less common (P = 0.005) among HIV-positive than HIV-negative patients. There was a trend toward reduced frequency of caseous necrosis in samples from HIV-positive than HIV-negative TB patients (67 versus 93%, P = 0.055). The spectrum of diagnoses was broad, and clinical and radiological features correlated poorly with diagnosis. On the basis of clinical features, physicians over-diagnosed TB, and under-diagnosed malignancy. Although this may not be inappropriate in resource-limited settings where TB is the most frequent easily treatable cause of lymphadenopathy, diagnostic delays can be detrimental to patients with malignancy. It is important that patients with lymphadenopathy undergo a full diagnostic work-up including sampling for histological evaluation to obtain an accurate diagnosis.
The differential diagnosis for lymphadenopathy is wide and includes infectious, immunological and metabolic disorders, and primary or secondary neoplasms.1,2 In the developed world, common infectious causes predominate including upper respiratory tract infections, Epstein–Barr Virus, and cytomegalovirus, whereas in resource-poor settings other infections such as tuberculosis (TB), toxoplasmosis, HIV seroconversion, leishmaniasis, and fungal infections may be important causes.3 Malignant causes such as lymphoma and leukemia are less frequent but correct and prompt diagnosis has prognostic and therapeutic implications. Rarer disorders such as systemic lupus erythematosus and storage diseases are also causes of lymphadenopathy. HIV-infected patients are particularly susceptible to developing hematological malignancies and to acquiring bacterial, fungal, parasitic, and viral infections.
Patients were prospectively recruited over a 14-month period from the infectious diseases, head and neck surgery, and general medical and surgical departments of three public hospitals in Lima, Peru: the Hospital Nacional Dos De Mayo, Hospital Nacional Daniel Alcides Carrión, and Hospital Nacional Arzobispo Loayza. Lymphadenopathy was defined as enlargement of one or more lymph nodes. All adult patients with lymphadenopathy of unknown cause and in whom diagnostic lymph node tissue sampling was indicated were eligible for the study. This was carried out as part of a prospective evaluation for the accuracy of the Microscopic-Observation Drug-Susceptibility assay (MODS)5 for the diagnosis of lymph node TB, reported elsewhere.6 Ethical approval was obtained from the Institutional Ethics Committee of the Universidad Peruana Cayetano Heredia, Asociación Benéfica PRISMA, and each study site’s local ethics committee. Written informed consent was obtained from all patients. Demographic and clinical data were collected from patients using a standardized form. Before the biopsy, the patients’ physician was asked to predict the most likely diagnosis based on available clinical information. Tissue sampling procedures and clinical management were undertaken by the hospital clinical staff with no input from the study team. Where HIV status was not known, an HIV test was offered.
One hundred and thirty-two patients agreed to participate in the study and underwent biopsy. Paraffin blocks were retrieved for full histopathological evaluation for 121/132 (92%) patients. The 11/132 (8.3%) for whom this had not been possible were excluded from all analyses. There was no significant difference in age, sex, frequency of HIV positivity, or rate of previous TB between patients who were included in and those who were excluded from analysis.
This study defined the clinical and histopathological characteristics of a prospective cohort of Peruvian patients with lymphadenopathy. The spectrum of conditions causing lymphadenopathy was broad and comprised a mixture of infective, malignant, and benign causes similar to findings from case series in Peru8 and resource-limited settings elsewhere.9–14 Clinical characteristics were not specific in attaining a diagnosis. TB was given as the most likely diagnosis in the majority of the patients (76%), whereas in fact hyperplasia, lymphoma, and other malignancy each also contributed a significant burden of disease. These findings highlight the importance of tissue sampling for histological evaluation as part of a thorough diagnostic workup.