Histopathology of parotid gland before and after treatment with rituximab in primary Sjögren's syndrome. Comparison of parotid biopsy specimens obtained from a primary Sjögren's syndrome (pSS) patient before rituximab therapy (A1 to A4) and 12 weeks after therapy (B1 to AB4). (A1) Before treatment, double staining illustrates intense inflammation (arrows) with highly proliferating, large germinal center-like structures (GS; red nuclear staining for Ki-67), fully developed lymphoepithelial lesions (LEL; brown staining for cytokeratin 14 (CK14)), and reduced glandular parenchyma (PAR). (B1) After treatment, inflammation was reduced (arrows), with the absence of GS and the presence of regular striated ducts (SD) devoid of lymphoepithelial lesions. (A2) Before treatment, there was a dominance of B lymphocytes with GS (CD20) in comparison with T lymphocytes (CD3) (A3). (B2) After treatment, the lymphoid infiltrate overall was reduced, with a slight dominance of T lymphocytes (CD3) (B3) compared with B lymphocytes(CD20). (A4) Higher-magnification view showing fully developed lymphoepithelial lesions with many intraepithelial lymphocytes and increased basal cell proliferation (arrows), in contrast to the SD after therapy with CK14-positive basal cells (B4) (arrows) with regular differentiation into luminal ductal cells devoid of intraepithelial lymphocytes (arrowheads). Original magnification: A1 and B1, ×120; A2 and B2, ×100; A3 and B3, ×60; A4 and B4, ×200. Reprinted with permission from .