Granulation tissue with a poorly formed granuloma to the left of centre. Within this area there is a multinucleate giant cell of the Langhans type. The patient had a healing mycobacterial infection of the skin (M. ulcerans infection).
Although traditionally their presence was associated with tuberculosis, they are not specific for tuberculosis or even for mycobacterial disease. In fact, they are found in nearly every form of granulomatous disease, regardless of etiology.
Recently, a research paper has shown that when activated CD4+ T cells and monocytes are in close contact, the interaction of CD40-CD40L between these two cells and the followed IFN-γ secretion by the T cells, causes the up regulation and secretion of DC-STAMP (Dendritic cell-specific transmembrane protein) by the monocytes which results in LGC formation
^Sakai H, Okafuji I, Nishikomori R, et al. (January 2012). "The CD40-CD40L axis and IFN-γ play critical roles in Langhans giant cell formation". Int. Immunol.24 (1): 5–15. doi:10.1093/intimm/dxr088. PMID22058328.