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The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.

Background Langerhans cell histiocytosis (LCH) rarely presents in the oral and maxillofacial region, and while isolated and small collections of Langerhans-type cells have been found in periapical cysts, there have been no reported cases of LCH arising in periapical cysts. Methods A 58-year-old female presented with isolated erythematous dry skin lesions and a radiolucent lesion of the anterior maxilla. Microscopic examination of the enucleation specimen revealed a periapical cyst with large collections of atypical cells with grooved folded nuclei with eosinophils consistent with LCH. Immunohistochemistry (IHC) was performed to confirm the diagnosis. BRAF mutation status was evaluated with the BRAF p. V600E antibody and the automated real-time PCR-based Idylla™ assay, capable of qualitative detection of 5 mutations in codon 600 of the BRAF gene. Results The LCH cells were positive for S100, CD1a, and Langerin (CD 207) and negative for BRAF p. V600E mutations. Ki-67 was 45%. Conclusion The association of LCH with a periapical cyst could be explained by the active surveillance and migration of neoplastic Langerhans-type cells in blood to the site of apical chronic inflammation, in a patient with LCH. Careful attention to morphologic features in conjunction with Langerin IHC, helps exclude other closely-related dendritic tumours. BRAF p. V600E testing, ideally with real-time PCR assays, can help identify patients who may benefit from BRAF inhibitor therapies. New generations of sequencing that cover a large panel of genetic alterations beyond the frequent BRAF p. V600E mutations (e.g. rare in-frame BRAF deletions), could provide valuable information about the extent, prognosis and treatment of LCH patients.

Periapical abscesses, radicular cysts, and periapical granulomas are the most frequently identified pathological lesions in the alveolar bone. While little is known about the initiation and progression of these conditions, the metabolic environment and the related immunological behaviors were examined for the first time to model the development of each pathological condition. Metabolites were extracted from each lesion and profiled using gas chromatography-mass spectrometry in comparison with healthy pulp tissue. The metabolites were clustered and linked to their related immune cell fractions. Clusters I and J in the periapical abscess upregulated the expression of MMP-9, IL-8, CYP4F3, and VEGF, while clusters L and M were related to lipophagy and apoptosis in radicular cyst, and cluster P in periapical granuloma, which contains L-(+)-lactic acid and ethylene glycol, was related to granuloma formation. Oleic acid, 17-octadecynoic acid, 1-nonadecene, and L-(+)-lactic acid were significantly the highest unique metabolites in healthy pulp tissue, periapical abscess, radicular cyst, and periapical granuloma, respectively. The correlated enriched metabolic pathways were identified, and the related active genes were predicted. Glutamatergic synapse (16–20),-hydroxyeicosatetraenoic acids, lipophagy, and retinoid X receptor coupled with vitamin D receptor were the most significantly enriched pathways in healthy control, abscess, cyst, and granuloma, respectively. Compared with the healthy control, significant upregulation in the gene expression of CYP4F3 , VEGF , IL-8 , TLR2 ( P  < 0.0001), and MMP-9 ( P  < 0.001) was found in the abscesses. While IL-12A was significantly upregulated in cysts ( P  < 0.01), IL-17A represents the highest significantly upregulated gene in granulomas ( P  < 0.0001). From the predicted active genes, CIBERSORT suggested the presence of natural killer cells, dendritic cells, pro-inflammatory M1 macrophages, and anti-inflammatory M2 macrophages in different proportions. In addition, the single nucleotide polymorphisms related to IL-10 , IL-12A , and IL-17D genes were shown to be associated with periapical lesions and other oral lesions. Collectively, the unique metabolism and related immune response shape up an environment that initiates and maintains the existence and progression of these oral lesions, suggesting an important role in diagnosis and effective targeted therapy.

Background Originating from odontogenic tissue, Odontogenic cysts are pathological cavities lined with epithelial cells and surrounded by fibrous connective tissue. This study investigated expression of CITED1 protein in different types of odontogenic cysts. Material and method 40 keratocysts, 40 radicular cysts, and 40 dentigerous cysts were excised and processed for routine paraffin wax embedding protocol. Macroscopic and panoramic radiographies images were used for diagnosis. Demographical properties and dental parameters were recorded. Cystic tissues were stained with hematoxylin-eosin dye and CITED1 antibody. Semi-quantitative analysis was performed for immune staining. The protein-protein interaction network, hub gene detection and KEGG analysis were conducted using Cytoscape software. Result Odontogenic keratocysts was imaged with 6–8 layered epithelial cells and fibrous cyst walls with inflammatory cells. Radicular cysts had stratified squamous epithelium with varying thickness, ciliated cells, and Rushton hyaline bodies. Dentigerous cysts presented hyperplastic non-keratinized epithelium, fibrous tissue, rete ridges, and inflammatory cells. CITED1 immunoexpression was highest in odontogenic keratocysts, followed by radicular cysts, and lowest in dentigerous cysts. Nuclear and cytoplasmic CITED1 expression was significantly elevated in odontogenic keratocysts compared to radicular and dentigerous cysts. The top five targets of CITED1 were identified, primarily showing enrichment in hormone and cancer related pathways. Conclusions Positive CITED1 expression in all three types of odontogenic cysts suggest a potential role for CITED1 in the pathogenesis of odontogenic cysts, particularly in keratocysts. Further investigations are needed to elucidate the exact mechanisms underlying the differential expression of CITED1 and its implications for the development and progression of odontogenic cysts.

Background Periapical lesions are common sequelae of endodontic infections, often presenting as chronic apical periodontitis. These lesions result from the microbial invasion of the root canal system, leading to inflammation and subsequent bone resorption. While conventional root canal therapy is the primary treatment modality, it occasionally fails to resolve periapical pathology. In such cases, surgical intervention becomes necessary. Case presentation This report presents the case of a 32-year-old female of Indian ethnicity with chief complaints of pain and pus discharge in the upper right front area in the past 2 months. Radiographic findings were evident, depicting periapical radiolucency. Upon debriding the lesion, it was observed to be creamish with irregular shape and size and, hence, it was sent for histopathological analysis. It was inferred to be a dental cyst associated with the right upper front region of the jaw. Conclusion This case report pinpoints the importance of considering the diagnosis of periapical lesions. It also adds to the point of treatment plan that can be followed as a multidisciplinary approach to challenging periapical lesions.

Aim The aim of the study was to evaluate the trabeculation increase of treated mandibular cysts. Material and method The study included 26 female and 33 male patients (age mean: 38,4 years) with cysts larger than 3 cm in the posterior region of the mandible who were admitted to the same center. Two groups in treatment technique: marsupialization ( n  = 29) and enucleation ( n  = 30). Four groups in cyst types: dentigerous cyst ( n  = 21), keratocyst ( n  = 19), radicular cyst ( n  = 15) and residual cyst ( n  = 4). Cyst size was divided into two categories: smaller than 5.5 cm ( n  = 31) and larger than 5.5 cm ( n  = 28). Panoramic radiographs (PR) of the patients were analyzed at the beginning, 6. month and 12. month. Result At the end of the treatment, there was no statistically significant difference in terms of Fractal Analysis (FA) between patients treated with marsupialization and enucleation, but considering that the cysts in the marsupialization group were larger in size, a faster increase in FA was observed in the marsupialization group. When the cysts were grouped according to their size, it was observed that healing tissues in cysts smaller than 5.5 cm reached normal FA values faster, while healing in the middle of cysts larger than 5.5 cm took more time. Conclusions FA is a reproducible and reliable method. In large cysts, marsupialization results in a faster recovery, but FA values at the end of treatment are similar to the enucleation group. Cysts larger than 5.5 cm show a more rapid increase in Fractal Dimension (FD). The centre of the cysts is the area that heals the latest. Studies with larger sample sizes are needed to evaluate the difference in healing between cyst types. Clinical trial number Clinical trial number: Not applicable

Background This retrospective cohort study primarily assessed three-dimensional changes in mandibular jaw cysts over time following decompression surgery. Secondary aims included evaluating factors potentially affecting the monthly reduction rates and assessing intra- and interexaminer reliability in the measurements. Methods Patients who underwent decompression therapy for mandibular cysts and histopathological diagnosis were included. Cone-beam computed tomography (CBCT) scans obtained before decompression surgery (baseline CBCT) and prior to enucleation surgery (follow-up CBCT) were analyzed using a specialized 3D software to measure cyst dimensions based on preview and final lesion outlines by two examiners. Patient demographics, cyst types, localization, and cortical bone perforation were recorded and evaluated for their influence on dimensional change rates. Results Forty patients (15 females and 25 males) with a median age of 47 years (range: 11 to 76 years) and treated with decompression of radicular ( n  = 10), dentigerous ( n  = 14), botryoid ( n  = 1), or odontogenic keratocysts ( n  = 15) were analyzed. The lesions were predominantly located in the posterior mandible ( n  = 32) and exhibited single ( n  = 14), multiple ( n  = 17), or no cortical bone perforations ( n  = 9). Mean lesion volumes decreased from baseline (3764 mm³) to follow-up (1413 mm³, p  < 0.0001), corresponding to an average monthly volumetric reduction rate of -5.2%, without significant differences between the cyst types. Female and younger patients showed higher reduction rates ( p  ≤ 0.04), whilst localization and cortical bone perforation did not significantly influence the dimensional changes. Both inter- and intraexaminer reliability of measurements were high (intraclass correlation coefficients > 95%). Conclusions Decompression surgery is an effective first-stage treatment to reduce the dimensions of large mandibular odontogenic cysts. Within a range of limited clinical relevance, patient-related factors such as sex and age may influence dimensional changes, whereas lesion-specific characteristics did not. Cyst measurements on CBCT were consistent across observers, indicating good reproducibility.

Inflammatory radicular cysts (IRCs) are chronic lesions that follow the development of periapical granulomas (PGs). IRCs result from multiple inflammatory reactions led initially by several pro-inflammatory interleukins and growth factors that provoke the proliferation of epithelial cells derived from epithelial cell rests of Malassez present in the granulomatous tissue, followed by cyst formation and growth processes. Multipletheories have been proposed to help explain the molecular process involved in the development of the IRC from a PG. However, although multiple studies have demonstrated the presence of epithelial cells in most PGs, it is still not fully understood why not all PGs turn into IRCs, even though both are stages of the same inflammatory phenomenon and receive the same antigenic stimulus. Histopathological examination is currently the diagnostic gold standard for differentiating IRCs from PGs. Although multiple studies have evaluated the accuracy of non-invasive or minimally invasive methods in assessing the histopathological nature of the AP before the intervention, these studies' results are still controversial. This narrative review addresses the biological insights into the complex molecular mechanisms of IRC formation and its histopathological features. In addition, the relevant inflammatory molecular mediators for IRC development and the accuracy of non-invasive or minimally invasive diagnostic approaches are summarised. (EEJ-2022-03-041)

Background Jaw cysts are a diverse group of intraosseous lesions commonly encountered in oral and maxillofacial pathologies. Several studies have addressed their distribution and clinicopathological features; however, further large-scale analyses using standardized classification systems may enhance cross-regional comparability and diagnostic consistency. We aimed to evaluate the demographic and anatomical characteristics of jaw cysts over an almost 50-year period. Methods We retrospectively reviewed 19,352 histologically confirmed jaw cysts diagnosed between 1975 and 2024. Each case was reclassified according to the 2022 WHO classifications for head and neck tumors. Patient age, sex, cyst type, and anatomical location data were collected and descriptively analyzed to identify trends across different cyst categories. Results Odontogenic cysts comprised the majority of cases. Radicular cysts were the most common, followed by dentigerous cysts and odontogenic keratocysts. Non-odontogenic cysts mainly consisted of surgical ciliated cysts and nasopalatine duct cysts. Bone cysts (simple bone cysts and aneurysmal bone cysts), which lack an epithelial lining and were therefore analyzed separately, were infrequent. A male predominance was observed overall, with sex- and age-related patterns differing according to cyst type. Mandibular involvement was more common than maxillary involvement, and several cysts showed specific anatomical predilections. These findings highlight distinct demographic and anatomical characteristics across cyst categories. Conclusions This large retrospective study provides a detailed epidemiological profile of jaw cysts. The findings revealed distinct patterns according to cyst type, age, sex, and anatomical site, providing a valuable reference for diagnostic refinement and future comparative studies of oral and maxillofacial pathology.

Background The destruction of tooth apical bone mainly comes from odontogenic apical cysts caused by pulp necrosis, chronic inflammation, or trauma. Some affected teeth can be cured by modern root canal treatment or non-surgical retreatment, but some affected teeth do not heal after treatment. Apical surgery should be considered when root canal therapy has failed, root canal retreatment through the crown channel is difficult, or true cysts are present. This article explores the use of microapical surgery to treat a periapical cyst caused by apical ramification, emphasizing a minimal surgical approach for this lesion. Case presentation A 47-year-old female (Han nationality) presented with a chief complaint of recurrent buccal mucosal fistula in their maxillary posterior teeth for 1 year. Clinical examination revealed a porcelain-fused-metal crown of the maxilla of the left second premolar (tooth 25) and buccal mucosa fistula. X-ray assessment showed a high-density shadow in the root canal and low-density transmission from the root apex to the middle third of distal root surface. Microscopic apical surgery was performed under local anesthesia. The apical ramification was exposed and a root apex of 3 mm was cut off. Then the apical foramen of buccal root canal, palatal root canal, and apical ramification were filled retrogradely with mineral trioxide aggregate, and finally sewn up. Follow-up X-ray at postoperative 12 months and 24 months showed that the bone density of the root apex and distal root surface was higher compared with the values measured immediately after operation. There were no clinical symptoms, and normal mucosa. Conclusion The patient presented with a recurrent buccal mucosal fistula in the maxillary left second premolar. Microscopic apical surgery was performed under local anesthesia. After minimally invasive surgery, apical resection, inverted preparation, and mineral trioxide aggregate treatment, at postoperative 24 months, the outcome was satisfactory, with recovered apical bone, normal mucosa, and no clinical symptoms. For periapical cysts, X-ray and cone-beam computed tomography images should be read carefully before the operation. The semicircular low-density transmission image around the apical sidewall indicates the apical ramification, and that root canal treatment or microapical surgery should be performed. The operating microscope enhances visibility and provides the surgeon with a better understanding of canal anatomy, a better surgical view, and the ability to undertake more complex but predictable apical resection techniques.