Non-neoplastic lymph node pathology in infectious diseases: histopathological findings and clinical correlates

Infectious lymphadenopathies can be diagnostically challenging since reactive and inflammatory patterns can morphologically mimic lymphoma. This review discusses key morphological findings in lymph nodes associated with the major groups of infectious organisms and presents a diagnostic workflow that can be implemented in daily practice. Evaluation for lymphadenitis first requires obtaining clinical history, including exposure history to potential pathogens. Proper specimen triage is crucial in diagnostic workups across infectious lymphadenopathies. This includes allocating fresh tissue for culture and nucleic acid amplification tests in addition to formalin-fixed, paraffin-embedded tissue for histomorphology and special stains. Histopathologic evaluation of lymph nodes is then based on a two-step model: (1) assessment of whether nodal architecture is preserved or effaced, and (2) identifying the dominant compartmental response, i.e. – follicular, paracortical (interfollicular), sinus, mixed/diffuse pattern or tissue-destructive necrosis/granulomata. This approach can minimize diagnostic pitfalls and allows diagnostic consistency across adult and pediatric cohorts.