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Background  It is difficult to distinguish between multicentric Castleman’s disease (MCD) and IgG4-related lung disease (IgG4-LD), an IgG4-related disease (IgG4-RD) in the lung.    Methods  We focused on IL-6, which is elevated in MCD, to distinguish between MCD and IgG4-LD by RNAscope, a highly sensitive RNA in situ method. Six cases of MCD and four cases of IgG4-LD were selected.    Results  In all cases of MCD and IgG4-LD, 10 or more IgG4-positive cells were found in one high-power field. All MCD cases were inconsistent with the pathological IgG4-related comprehensive diagnostic criteria, but 2 of 6 cases had an IgG4/IgG ratio greater than 40%. In all IgG4-LD cases, histological features were consistent with the pathological IgG4-RD comprehensive diagnostic criteria.  IL-6  expression was observed in all MCD and IgG4-LD cases except for one IgG4-LD biopsy.  IL-6 -expressing cells were mainly identified in the stroma. Sites of  IL-6  expression were not characteristic and were sparse.  IL-6  expression tended to be higher in MCD compared with IgG4-LD. A positive correlation was found between the  IL-6  H-score and serum IL-6 level.    Conclusion  Differences in  IL-6  expression may help distinguish between MCD and IgG4-LD. In addition, the presence of high IL-6 levels may help elucidate the pathological mechanisms of IgG4-LD.

IL-6 expression helps distinguish Castleman’s disease from IgG4-related disease in the lung