ORIGINAL ARTICLE Inflammatory histopathogenesis of nasopalatine duct cyst: a clinicopathological study of 41 cases M Tsuneki 1,2 , S Maruyama 3 , M Yamazaki 1 , T Abé 1,3 , HA Adeola 1 , J Cheng 1 , H Nishiyama 4 , T Hayashi 4 , T Kobayashi 5 , R Takagi 5 , A Funayama 6 , C Saito 6 , T Saku 1,3 1 Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata; 2 Fellow, the Japan Society for the Promotion of Science, Tokyo; 3 Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata; 4 Division of Oral and Maxillofacial Radiology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata; 5 Division of Oral and Maxillofacial Surgery, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata; 6 Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan OBJECTIVE: The aim of this study is to characterize immunohistochemical profiles of lining epithelia of nas- opalatine duct cyst (NPC) as well as to correlate those findings with their clinicopathological features to under- stand the histopathogenesis of NPC. MATERIALS AND METHODS: Forty-one surgical speci- mens from NPC were examined for clinical profiles and expression of keratin-7, 13, MUC-1, and P63 by immu- nohistochemistry, compared to radicular cyst (RC) and maxillary sinusitis. RESULTS: Nasopalatine duct cyst was clinically character- ized by male predominant occurrence: 44% of the cases involved tooth roots, and 70% with inflammatory back- grounds. Lining epithelia of NPCs without daughter cysts were immunohistochemically distinguished into three layers: a keratin 7-positive (+) ciliated cell layer in the surface, a ker- atin-13+ middle layer, and a MUC-1+/P63+ lower half, indi- cating that they were not respiratory epithelia, and the same layering pattern was observed in RC. However, those immu- nolocalization patterns of the main cyst lining with daughter cyst were exactly the same as those of daughter cyst linings as well as duct epithelia of mucous glands. CONCLUSIONS: Two possible histopathogeneses of NPC were clarified: one was inflammatory cyst like RC and the other was salivary duct cyst-like mucocele. Oral Diseases (2013) 19, 415--424 Keywords: nasopalatine duct cyst; inflammatory cyst; im- munohistochemistry; mucous retention cyst; radicular cyst Introduction Nasopalatine duct cyst (NPC), also known as incisive canal cyst, was first reported by Meyer in 1914 (Meyer, 1914). Since then, several reports have characterized its clinico- pathological features (Abrams et al, 1963; Allard et al, 1981; Escoda Francolí et al, 2008; Killy et al, 1977; Nelson and Linfesty, 2010; Shear and Speight, 2007; Swanson et al, 1991; Vasconcelos et al, 1999; White and Pharoa, 2000), and NPC has basically been regarded as a non-odon- togenic developmental jaw cyst arising from epithelial rem- nants of the nasopalatine duct (Kramer et al, 1992; Shear and Speight, 2007). However, some inflammatory back- grounds including bacterial infection have been suggested for the histopathogenesis of NPC (Abrams et al, 1963; Shear and Speight, 2007), although there has been insuffi- cient evidence to support such an inflammation-based caus- ative hypothesis. Histopathological diagnosis of jaw cysts is not always easy when epithelial linings of the cyst wall are modified by inflammation. However, their differential diagnosis is important because such neoplastic lesions as cystic amelo- blastoma or keratocystic odontogenic tumor are included in jaw cysts. To resolve this challenging issue, we have introduced several combinations of immunohistochemistry for epithelial linings to routine diagnostic services, because hematoxylin and eosin-stained sections did not work in the differential diagnoses of inflamed cystic jaw lesions (Saku et al, 1991; Murata et al, 2000; Ida-Yonemochi et al, 2002, 2011; Yamazaki et al, 2004; Tsuneki et al, 2008a,b, 2010). Our diagnostic criteria for cystic jaw lesion with immunohistochemical aids cover the five most common cystic lesions: cystic ameloblastoma, keratocystic odontogenic tumors, dentigerous cyst, lateral periodontal cyst, and radicular cyst (RC) (Saku et al, 1991; Tsuneki et al, 2008b; Tsuneki et al, 2010). However, NPC has not been included as an object for the differential diagnosis, Correspondence: Takashi Saku, DDS, PhD, Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata Univer- sity Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho- dori, Chuo-ku, Niigata 951-8514, Japan. Tel: (+81) 25 227 2832, Fax: (+81) 25 227 0805, E-mail: tsaku@dent.niigata-u.ac.jp Received 18 February 2012; revised 6 August 2012; accepted 3 September 2012 Oral Diseases (2013) 19, 415--424 doi:10.1111/odi.12022 © 2012 John Wiley & Sons A/S All rights reserved www.wiley.com