The main causes of morbidity with the illness are systemic infection from impaired immune response and organ dysfunction from histiocyte deposition throughout the body.

The most common sites of extranodal disease in Rosai's registry were skin, nasal cavity/paranasal sinuses, soft tissue, eyelid/orbit, bone, salivary glands, central nervous system, and heart.

For instance, accumulation in closed spaces such as the cranium can lead to poor outcomes compared to growth in the dermis of an extremity where surgical excision is possible.

Microscopic examination of stained specimens will show histiocytes with lymphocytes and possibly other types of cells trapped within them, a phenomenon known as emperipolesis.

[1] In 2002, authors from Sapienza University of Rome stated on the basis of a comprehensive literature review that "clinical observation without treatment is advisable when possible".

[1] In 1965, Pierre-Paul Louis Lucien Destombes had described, in French, four patients having "adenitis with lipid excess" which is recognized as the original description of the condition.