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Pancreatic intraductal lesions with possible relationship with gastric type intraductal papillary mucinous neoplasm: pyloric gland‐type intraductal tubular adenoma and intraductal oncocytic papillary neoplasm

Sir: We read the recent article entitled ‘Intraductal tubular adenoma (pyloric gland-type) of the pancreas: a reappraisal and possible relationship with gastric-type intraductal papillary mucinous neoplasm’ by Chetty and Serra. It was of great interest for us because it sheds light on to the relationship between intraductal lesions of the pancreas. We would like to comment on two points. Firstly, the authors have suggested that pyloric gland-type intraductal tubular adenoma (ITA) of the pancreas could represent a form of gastric type of intraductal papillary mucinous neoplasm (IPMN), mainly based on the finding that ITA frequently coexists with epithelial lesions identical to gastric-type IPMN. We agree with this, but we would like to add some observations to support this notion. As we have already reported, gastric-type IPMN is frequently associated with findings that we call ‘pyloric gland-like structures’ and ‘low-grade pancreatic intraepithelial neoplasia (PanIN)-like complexes’. The former is observed at the base of the neoplastic epithelium giving a characteristic ‘two-storied’ appearance, and the latter is characterized by a collection of small ducts lined by tall columnar mucinous cells of low-grade atypia. Therefore, it is plausible that neoplastic epithelia of gastric-type IPMN would give rise to prominent pyloric gland-type proliferation. The mucin phenotype of the pyloric gland-like structures of gastric-type IPMN is also in accordance with that of pyloric gland-type ITA. Both express MUC6 as well as MUC5AC, although the authors did not perform MUC6 immunostaining. Besides, the ‘two-storied’ appearance and the mucin phenotype of gastric-type IPMN are also features of low-grade PanIN, which would be expected to exhibit both gastric-type IPMN and pyloric gland-type ITA. One controversial point is that the major location of low-grade PanIN and gastric-type IPMN is branch ducts, whereas that of pyloric gland-type ITA is the main pancreatic duct. The relationship between the extension of low-grade PanIN or gastric-type IPMN into the main pancreatic duct and the occurrence of pyloric gland-type ITA is speculative for the time being. The second point is a peripheral subject of the article, but has caught our attention. Case 2 presented in Figure 2 of the article by Chetty and Serra consists of cells with very eosinophilic cytoplasm and vesicular round nuclei, and in the left one-third of the figure the neoplastic glands seem to be arborizing rather than being simply tubular. These findings remind us of oncocytic-type IPMN or intraductal oncocytic papillary neoplasm, which is a controversial entity as regards whether it falls into a histological subtype of IPMN (oncocytic-type IPMN) or an entity distinct from IPMN. In Figure 4 of the article by Chetty and Serra, the authors touch on speculation that the oncocytictype IPMN is also related to gastric-type IPMN, although they do not raise this subject in the Discussion. We have examined several cases of pancreatic intraepithelial lesions with oncocytic features. These oncocytic lesions were usually associated with gastric-type IPMN-like lesions, had mucous cells admixed with oncocytic cells, and showed a gastric mucin phenotype, i.e. expression of MUC6 as well as MUC5AC. We consider that these observations indicate the close association between oncocytic lesions and gastric-type IPMN, and agree with the proposal for a consensus approach that the intraductal oncocytic lesions of the pancreas are regarded as a histological subtype of IPMN (oncocytic-type IPMN), and the authors’ speculation relating to Figure 4. Besides, some gastric-type IPMN lesions associated with oncocytic lesions were accompanied with pyloric glandlike structures and low-grade PanIN-like complexes, as observed in gastric-type IPMN associated with pyloric gland-type ITA. In this context, we wonder whether case 2 (Figure 2) of the article should be interpreted as oncocytic-type IPMN rather than pyloric gland-type ITA. Oncocytic-type IPMNs seem to have a unique molecular feature that they often lack mutations of the K-ras gene (our unpublished data). It is expected that further reappraisal investigations including molecular studies will be performed from the above mentioned standpoint of view.