GPR34 activation by paracrine stimulation potentially bridges LELs to the genesis of salivary gland MALT lymphoma. (A) Left: western blot analysis shows PLA1 expression in a salivary gland biopsy specimen, with pancreatic tissue as a positive control. Middle: Immunohistochemistry shows PLA1 expression in the ductal but not acinar epithelium of adjacent normal salivary glands and those involved in LELs in a case of salivary gland MALT lymphoma. Right: Immunocytochemistry for cleaved caspase 3 shows prominent apoptotic activities in LELs in a salivary gland MALT lymphoma. (B) Histology of salivary gland MALT lymphoma. An early lesion shows emergence of neoplastic B cells surrounding the LELs, with some of the neoplastic B cells invading the epithelial gland, as indicated by the immunoglobulin K (IgΚ) light chain restriction. An advanced lesion displays diffuse lymphoid infiltration and prominent LELs with malignant B cells expanding around the LELs. (Images are courtesy of Peter G. Isaacson.) (C) GPR34 activation by paracrine stimulation: PLA1 released by duct epithelial cells of LELs can hydrolyze PS exposed on apoptotic cells, generating LysoPS and hence stimulating malignant B cells via GPR34.