Approach to the investigation of lymphadenopathy and splenomegaly

Lymphadenopathy and splenomegaly, alone or in combination, are common presentations with a diverse range of causes. These can range from a normal physiological response to a simple, acute infection, to the first presentation of malignancy. As such, timely diagnostics is crucial. Understanding the function of these organs is a necessary step to forming a differential diagnosis. This article breaks down the roles of the lymph nodes and spleen within the immune system and common causes of lymphadenopathy and splenomegaly. It then provides a structure to history-taking and examination. An algorithm for a diagnostic approach is presented into which this information can be fed. It highlights important red flag symptoms and critical tests that should be performed to lead to timely diagnosis and treatment.