We appreciate Dr. Ide’s interest in our recent article and wish to respond to questions raised in his letter.

It is desirable to figure out any causative factors of salivary gland tumours for their preventive measure, though the aetiology of salivary gland tumours remains mostly unknown. Seeking possible pathogenetic pathways, we have so far been successful in demonstrating at least two etiological factors for salivary gland carcinomas. One was Epstein–Barr virus infection in lymphepithelial carcinoma . The other factor was radiation in Warthin tumour and mucoepidermoid carcinoma, which was confirmed in atomic bomb survivors of Hiroshima and Nagasaki . There were differences in the primary events between the two types of pathogenesis, in which it was possible to consider some inflammation-associated events. However, for salivary gland tumours other than the above-mentioned three types, no concrete causative factors have ever been proposed.

In our case report of adenoid cystic carcinoma (ACC) arising in the background of chronic sialadenitis, we have emphasized the possibility of inflammation as a pathogenetic background for ACC . This was the third case-report-based suggestion for such inflammatory aetiology for ACC, though sclerotic inflammation has been related to the other salivary gland tumours. In our case, we found very small ACC foci in a scar area of the submandibular gland, entire parts of which showed chronic inflammatory changes with multiple salivary stones. It was unknown which had been the primary event, sialolithiasis or sialadenitis in this case. The same situations may be considered for cholelithiasis vs . choelecystitis or pancreatolithiasis vs. pancreatitis. Histopathologically, however, the background of fibrohyaline granulation tissue was not a part of the stromal space of ACC. Since we have already and extensively characterized the stroma of ACC , we are able to distinguish the difference between the neoplastic stroma and the inflammatory stroma. Thus, it was reasonable for us to suggest the possibility of inflammatory background for this particular case of ACC. We did not intend to elaborate this idea to every case of ACC or to every case of sialadenitis or sialolithiasis. Instead, we considered our case was unusual and worthwhile to be documented.

Although the commentator suggested the difference between bile and saliva in their carcinogenic properties, it is too simplistic thinking. As long as bile and pancreatic juice or saliva flows out smoothly into the duodenum or into the oral cavity through ductal lumina with surface coats, they do not wrongly function. Once those fluids flow out into the subepithelial connective tissue space, they become irritative, as is already well known in mucous retention cysts . We have shown carcinomatous change in the lining epithelium of parotid lymphoepithelial cyst, which is also generated in the background of sialadenitis .

It is obvious that we have to be conscious that patients avoid too much radiation exposure, even if it is for medical purposes. We suggested in our report that careful examination might include the use of ultrasonography, CT, and MRI for patients with long-standing sialadenitis and anamneses of cancers. The reported patient had breast cancer as stated in the abstract. We do not recommend such extensive examination in every case of sialadenitis. It is important for surgeons to judge for themselves whether or not in-depth examinations are necessary for their patients. We have intentionally published this case report to the International Journal of Oral and Maxillofacial Surgery because we thought it our responsibility to caution clinicians about such a possibility of malignancy in the clinical manifestation of chronic sialadenitis with sialoliths. Recently, chronic inflammation has attracted more attention in carcinogenesis of various kinds of organs, and hence we are expected to be conscious about inflammation even for salivary tumourigenesis from the point of view of cancer prevention.