Figure shows low and high power images of node involved by LCH. The near-exclusive sinusoidal involvement with focal paracortical spilling is typical, recapitulating the normal functional histoanatomical migration pattern of Langerhans cells from extranodal resident tissues to nodal sinuses. Higher power shows the typical grooved and folded nuclear cytomorphology of the lesional cells with a generous sprinking of eosinophils.

Immunostains depicting S-100, CD1a and Langerin, all of which are positive in LCH lesions cells with near exclusive sinusoidal localization. S-100 is also known to stain interdigitating dendritic cells and Rosai Dorfman histiocytes, while CD1a is more specific to Langerhans cells. Hence, the combination of S-100 (sensitive), Langerin (specific), and CD1a (specific) offer better sensitivity and specificity to a Langerhans cells phenotype.

Notably, the sinus component of LCH expresses high CD1a and Langerin while the paracortical component of the LCH cells often lose both antigens with acquisition of HLA Class II antigens recapitulating the functional transition of Langerhans from antigen capture cells to antigen presenting cells (requiring HLA class II expression) within the nodal microenvironment.