Presence of tuft cells expressing haematopoietic prostaglandin D synthase in intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasm (IPMN) is the second most common pancreatic tumour and a common precursor lesion of invasive carcinoma. Tuft cells are chemosensory epithelial cells present in the gastrointestinal and respiratory tracts that serve roles in response to infection and tissue repair. In addition, tuft cells have pivotal roles in the carcinogenesis of pancreatic ductal adenocarcinoma (PDAC), especially in tumour suppression, by producing prostaglandin (PG)D2; however, their role in IPMN remains unclear. The present study aimed to evaluate the presence of tuft cells producing PGD2 in human IPMN. Consecutive patients with IPMN who underwent surgical resection were retrospectively enrolled. Dual immunohistochemical staining for POU domain class 2 transcription factor 3 (POU2F3), as a specific tuft cell marker, and haematopoietic PGD synthase (H-PGDS), as a useful marker for PGD2 production, were performed. The present study included 21 patients with IPMN (11 women and 10 men; median age, 74 years). A total of 11, two and eight patients had IPMN with low-grade dysplasia, high-grade dysplasia and associated invasive carcinoma, respectively. POU2F3-positive tuft cells were noted in IPMN, and 20.0% of POU2F3-positive cells in IPMN without invasive carcinoma and the non-invasive regions of IPMN-associated invasive carcinoma expressed H-PGDS. Moreover, POU2F3-positive tuft cells and the ratio of H-PGDS expression in POU2F3-positive tuft cells were significantly lower in the invasive regions than in the non-invasive regions of IPMN-associated invasive carcinoma. These results indicated that POU2F3-positive tuft cells have possible roles in the tumourigenesis of IPMN, as well as in the carcinogenesis of PDAC, because tuft cells present in non-invasive IPMN may serve tumour-suppressive roles via production of PGD2 and they were absent in the invasive carcinoma component. Notably, further analyses are required to clarify the role and importance of POU2F3-positive tuft cells in IPMN, which will lead to a better understanding of the pathogenesis of this tumour.