From sadness to stiffness: the spleen's progress.

The spleen is a lymphoid organ that has been poorly studied compared to other solid organs, probably because it has been considered a useless and unnecessary part of the body. For many centuries it has been considered a mysterious organ with uncertain functions. The first descriptions of the spleen date back to ancient ages. The spleen has been considered as a reservoir of liquids, strictly linked to stomach digestion, and in different cultures, it has been linked to melancholy and sadness due to the accumulation of black bile (humoral doctrine). A detailed anatomic description was first made by Vesalius during the Renaissance, and further implemented with the description of its microscopic structure by Marcello Malpighi in the seventeenth century. The first case reports regarding spleen functions and pathology regarded common causes of splenomegaly, such as malaria infection, and traumatic rupture. At the beginning of the last century, the pivotal concepts of hypo- and hypersplenism were introduced, along with the cumulating evidence of the relation between spleen removal and increased susceptibility to infections and thromboembolism. The study of hyposplenic states, which occur much more commonly than originally thought in many immune-mediated disorders, has rapidly increased after the validation of a simple method for assessing spleen function, namely pitted red cell count. In recent years, spleen morphology, in particular spleen stiffness, has been proposed as a marker of portal hypertension. In this paper, we retrace the fundamental steps of the discovery of the functions of the spleen.