Inflammatory cells in the formation of tumor-related sarcoid reactions

Tumor-related sarcoid reactions were analyzed in 14 lymph nodes in comparison with sarcoidosis using immunohistochemical markers to lymphocytes (CD3, CD4, CD8, and CD20), myeloid-related protein (MRP) 8 and MRP14 (S100A8 and S100A9), angiotensin I-converting enzyme (CD143), and mature or immature dendritic cells (S100, HLA-DR, fascin, CD83, and CD1a). We found that solitary epithelioid cell granuloma (ECG) first occur between lymph sinus and T-zone and that multiple ECGs mainly occur within T-zone, whereas confluent types often occupy the whole lymph node except some residual lymphoid follicles. This pattern suggests a continuous spread and growth of ECGs in sarcoid reactions along T-zone, where antigen presentation mainly takes place. Irrespective of granuloma type, a constant invasion of freshly recruited MRP8+ and MRP14+ macrophages was observed. Similar to sarcoidosis, angiotensin I-converting enzyme expression was a constant finding in epithelioid and giant cells, suggesting a common inflammatory pathway. An increasing ratio of CD4+ to CD8+ T lymphocytes (r = 0.789, P = .001) and a decreasing number of S100+ and CD83+ dendritic cells (r = 0.787, P = .001) within ECGs correlated with granuloma growth, whereas CD1a+ immature dendritic cells were never observed inside ECGs. Our findings show that sarcoid reactions represent a T-cell-mediated immune response, leading to histological appearance and cell distribution similar to sarcoidosis and other granulomatous conditions, but the mechanism is different from dendritic cell-based tumor vaccination. Furthermore, mature dendritic cells occur inside ECGs especially of early sarcoid reactions but may not be required for the enlargement and further maintenance of ECGs, in contrast to CD4+ lymphocytes.