Multinucleated giant cells of bladder mucosa are modified telocytes: Diagnostic and immunohistochemistry algorithm and relation to PD-L1 expression score

BACKGROUND: Multinucleated giant cells (MGCs) in bladder carcinomas are poorly studied. AIM: To describe the function, morphogenesis, and origin of mononuclear and MGCs in urothelial carcinoma (UC) of the bladder in Bulgarian and French patients. METHODS: Urothelial bladder carcinomas (n = 104) from 2016-2020 were analyzed retrospectively using immunohistochemical (IHC) and histochemical stain examination. Giant cells in the bladder stroma were found in 35.6% of cases, more often in high-grades. RESULTS: We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers (vimentin, smooth muscle actin, Desmin, and CD34) and the macrophage marker CD68. Furthermore, IHC studies revealed the following profile of these cells: Positive for p16; negative for epithelial (CK AE1/AE3 and GATA-3), vascular (CD31), neural (PS100 and C-KIT), cambial, blastic (CD34-blasts and C-KIT), and immune markers (IG G, immunoglobulin G4, and PD-L1); no proliferative activity, possess no specific immune function, and cannot be used to calculate the Combined Positive Score scale. CONCLUSION: In conclusion, the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant, although nonspecific, histological marker for chronic bladder damage, reflecting the chronic irritation or inflammation. Likewise, according to the morphological and IHC of the mono- and multinucleated giant cells in the bladder, they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.