Histological characterizations of periapical inflammatory lesions and foreign bodies in severe periapical infections

Apical periodontitis (AP), or a periapical lesion (PL), is an inflammatory disease affecting the tooth apex and periradicular tissues, primarily triggered by host defenses responding to microorganisms such as bacteria. AP is categorized as either a periapical granuloma (PG), a radicular cyst (RC) or an abscess based on the histology of the lesion. Apart from a bacterial irritation, a trauma or foreign body (FBs) can also induce AP. The prevalence of FBs in PLs varies, ranging from 8% to 31%. The etiology of RC formation remains unclear and certain characteristics of PLs, including an oral pulse granuloma (OPG) and Rushton body (RB), have provoked controversy related to their origin. Bacterial lipopolysaccharide (LPS) is well-established as an initiator of host defenses in AP, and microorganisms like Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) have been cultured from root canals and apical regions. Furthermore, Pg can induce dysbiosis, impair innate host defenses, and promote an inflammatory response in periodontitis and AP, while Fn has been detected during the acute phase of AP. This dissertation aims to explore inflammatory PLs, their characteristics, FBs, and bacteria as well as their byproducts present in samples obtained from Helsinki University Hospital (HUH). The presence of cellulose was investigated in OPG, while LPS immunopositivity was examined in RBs exclusive to odontogenic inflammatory cysts. All available samples of PGs and RCs were meticulously reevaluated, and histopathological data, including the inflammatory state and fibrosis, were systematically tabulated. The radiological detectability of FBs was assessed, and the presence of periodontopathogens Pg and Fn was visualized in PLs. Pathological data for the studies were derived from university hospital records. The biotinylated cellulose-binding domain (CBM) of β-1,4-glycanase (EXG:CBM) was employed to visualize the cellulose fibers in tissue slides of PG in study I. In study IV, the immunoexpression of the Gingipain R1 antibody and rabbit anti-Fn antibody were used to visualize the presence of Pg and Fn in PLs, followed by statistical analyses of the co-occurrence of these periodontopathogens in lesions. Study II utilized an anti-LPS antibody to examine the presence of LPS in PLs and RBs. Studies III and IV conducted statistical analyses to compare the imaging detectability of FBs and their association with the state of inflammation, and to assess the association between fibrosis and the degree of inflammation. The findings revealed the presence of cellulose in OPG in the form of hyaline rings, while LPS is present in RBs within the epithelial lining of odontogenic cysts and the calcification foci. Fibrosis is evident in lesions with low-grade inflammation. Pg and Fn appear to coexist in PLs, with a higher incidence in RCs compared with PGs. FBs are detectable in 53.5% of lesions with imaging, yet they do not exhibit a statistically significant association with the state of inflammation. This study sheds light on the relatively high occurrence of fibrotic lesions with minimal inflammation: up to one-fifth of PLs are fibrotic and present with none-tomild degrees of inflammation. LPS might serve as an etiological factor for cyst formation and Pg and Fn might be associated with the development of cysts by provoking more severe inflammation. OPG results from cellulose penetrating the periradicular space during endodontic treatment or when consuming fiber-rich foods. Further studies on the relationship between severe marginal periodontitis and the formation of AP are needed.