Search

Aim: To evaluate M1 and M2 macrophage polarization in radicular cysts and periapical granulomas through an immunohistochemical analysis and the correlation between macrophage polarization and histopathological diagnosis, clinical characteristics and lesion volume using cone‐beam computed tomography. Methodology: Periapical biopsies diagnosed as radicular cysts (n = 52) and periapical granulomas (n = 51) were analysed by immunohistochemical method. Teeth with periapical lesion with no history of root canal treatment (primary lesion) and lesions persistent to root canal treatment (persistent lesions) were included. Pathological diagnosis, patients' age, gender and clinical characteristics were obtained from treatment records. A cone‐beam computed tomographic periapical volume index (CBCTPAVI) score was assigned to each periapical lesion based on the volume of the lesion. Immuno‐expressions of CD68 and CD163 were quantified. The CD68/CD163 ratio was adopted to represent M1 or M2 macrophage polarization. Mann–Whitney U test was used to determine the different CD68/CD163 ratio between groups of radicular cyst and periapical granuloma. Spearman's correlation test was performed to assess the correlation between the CD68/CD163 ratio and lesion volume and CBCTPAVI score. Results: Radicular cysts and periapical granulomas had CD68/CD163 median of 2.05 (IQR = 1.33) and 1.26 (IQR = 0.81), respectively. A significantly higher CD68/CD163 ratio was observed in radicular cysts (p <.001). In contrast, periapical granulomas had significantly lower median of CD68/CD163 ratio. Larger lesions had a higher median of CD68/CD163 ratio, while smaller lesions had lower median of CD68/CD163 ratio (p =.007, rs =.262). CD68/CD163 ratio was significantly correlated with the CBCTPAVI score in the overall periapical lesions (p =.002, rs =.306). The higher CD68/CD163 ratio in larger lesions indicated a higher degree of M1 polarization compared to smaller lesions. Regarding the pathological diagnosis, there was a significant positive correlation between CBCTPAVI score and CD68/CD163 ratio in periapical granulomas (p <.001, rs =.453), whereas the negative correlation was observed for radicular cysts (p <.001, rs = −.471). Conclusions: Periapical granulomas are characterized by a M2‐dominant macrophage polarization, while radicular cysts have significantly higher M1 macrophages. The higher degree of M1 macrophage polarization was significantly correlated with larger volume and higher CBCTPAVI scores of overall periapical lesion and periapical granuloma. [ABSTRACT FROM AUTHOR]

A 10‐year‐old male neutered Bichon Frise presented for assessment of right unilateral exophthalmos. The ophthalmological assessment revealed signs of retrobulbar disease. Computed tomography of the head showed a cavitary, well‐defined, fluid‐filled structure, which displayed a strong peripheral rim of contrast enhancement, and was centred around the tooth roots of the right maxillary first and second molar teeth (109 and 110). Focused ultrasound‐guided fluid sampling and fine needle aspirates were obtained for diagnostic purposes. After discussing the case with a veterinary dentist, extraction of the 109 and 110 and debridement of the cyst were performed. Histopathology supported the suspicion of a radicular cyst. Radicular cysts, despite being benign lesions, need to be included as a possible differential in cases with exophthalmos due to their potential retrobulbar mass effect. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Materials and Methods Results Conclusions The epidemiology of cysts and odontogenic tumors is important for differential diagnosis and treatment strategies. We aimed to describe the epidemiological features of cysts and odontogenic tumors in the Chilean population using the current WHO classification.We reviewed 22,914 biopsy requests received between January 1984 and September 2023 at the oral pathology department, School of Dentistry, Universidad Mayor, Santiago, Chile. Patients diagnosed with cysts of the jaws and odontogenic tumors were selected and information regarding age, sex, and location was recorded.4226 (18.4%) were cysts, and 551 (2.4%) were odontogenic tumors, ranging from 2 to 97 years old. Males represented 54.4% and females 45.7% of the total sample. The most prevalent cysts were radicular cysts (58.6%), dentigerous cysts (17.9%), and odontogenic keratocysts (13.3%). The most prevalent odontogenic tumors were odontomas (40.1%) and conventional ameloblastoma (17.6%).Our study was the first retrospective analysis to determine the epidemiological features of both cysts and odontogenic tumors together, based on the 2022 WHO classification. This is relevant as it offers a potential basis for comprehensive comparisons of the epidemiological features of these entities, which could contribute to an accurate differential diagnosis, therefore, leading to more effective therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: Intraosseous lipomas (IL) are rare benign neoplasms of bone which very rarely occur in the facial bones such as the mandible. Of the documented cases, many are often asymptomatic and consequently, are an incidental finding discovered by the practitioner. Case Report: The following case report recounts a 22‐year‐old patient referred for extraction of a carious molar at an Oral and Maxillofacial unit with an incidental finding of pathology involving the contralateral lower left wisdom tooth (LL8) on radiographic examination. Further investigations showed associated external root resorption of the lower left wisdom tooth and a provisional diagnosis of a radicular cyst was made. The case was managed by extracting the associated tooth and enucleating the lesion. During the procedure, fatty tissue was curetted at the apex instead of the expected cystic content. Subsequent histopathology confirmed the diagnosis of an IL. Conclusion: To the authors' knowledge, this is only the second documented case of an IL associated with tooth resorption. Findings from this case further our knowledge of the relatively uncommon pathology of intraosseous lipomas in the mandible and highlight the need for histopathological documentation and reporting of apical lesions. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the indication of the endodontic treatment for vital intact teeth with the root apex involved in large radicular cystic lesions of endodontic origin. Methodology: This prospective cohort study enrolled healthy participants with radicular cysts of endodontic origin and with the root apex of vital intact teeth involved in the bone defect, as determined by cone beam computed tomography (CBCT). Thirty‐two sound vital teeth were analysed by thermal (TPT) and electric pulp tests (EPT) before surgery (T0) and 1 week (T1), 2 weeks (T2), 3 months (T3) and 6 months (T4) post‐surgery. Student's t‐test (p <.05) was used to compare the EPT values at baseline and T4. anova (p <.05) was used to analyse the EPT variations for all maxillary and mandibular teeth. McNemar test (p <.05) was used to compare the results according to variation in EPT values gathering by variation, no variation and no response. Results: At T1, 75 and 65.7% of teeth responded positively whilst 25 and 34.3% did not respond to EPT and TPT, respectively. The variation of the EPT values between T0 and T1 was observed for 50.0% of teeth, whilst no variation was noticed in 25.0% of teeth. At T4, 90.6 and 87.5% of teeth responded positively whilst 9.4 and 12.5% did not respond to EPT and TPT, respectively. At T4, variation of the EPT values between T0 and T4 was observed for 28.1%, whilst no variation was noticed in 62.5% of teeth. There were no statistical differences in EPT results between T0 and T4 (p >.05), but significant differences were observed for EPT values between T1 and T4 (p <.05), and between mandibular and maxillary teeth. The pulp sensibility of maxillary teeth worsened after surgery, before reverting progressively to T0 values, whilst no statistically significant differences were observed for mandibular teeth at the different time points. Conclusions: These data support the inconsistence of the prophylactic endodontic treatment in healthy vital teeth with apex involvement in large cystic lesions of endodontic origin. Post‐surgery follow‐up with TPT and EPT is recommended to assess pulp status. [ABSTRACT FROM AUTHOR]

Introduction. A postsurgical ciliated cyst (PSCC) is an epithelial cyst that usually develops in the maxilla, although in rare cases, it can affect the mandible or other facial bones. The typical age of diagnosis is 40-50 years, with no gender prevalence, and the mean cyst development occurs approximately 10-15 years following a surgical or traumatic event. Some epithelial respiratory cells can be trapped into the bone tissue during maxillary surgical procedures or maxillary fractures. The pathogenetic mechanism can be attributed to an inflammatory process that stimulates epithelial proliferation, leading to cyst expansion caused by osmotic pressure difference. Methods. This study presents case series involving three surgical ciliated cysts located in the left maxilla, affecting two female patients (aged 49 and 55 years) and one male patient (aged 39 years). In all three cases, symptoms such as pain or swelling were mild and not consistently present. Two cases showed cyst development 10 and 15 years after implant placement, while one case was not associated with any surgical or traumatic event. CT scan identified well-defined unilocular lesions in the maxillary bone in each patient. Results. Histopathological examination of the surgical specimens confirmed the suspected diagnosis of a PSCC of maxilla. The cystic walls consisted of fibrous connective tissue with chronic inflammatory infiltrate, lined exclusively by a thin layer of ciliated pseudostratified columnar epithelium. In the third patient, it was not possible to rule out an unusual radicular cyst. Conclusions. Although PSCCs are not commonly encountered in daily practice, clinicians should consider this possibility including it in the differential diagnosis of odontogenic jaw cysts and benign jaw tumors, particularly in patients who have undergone previous surgeries in the maxillary area. [ABSTRACT FROM AUTHOR]

Background Methods and Results Conclusions Key points Dens invaginatus (DI), an unusual developmental anomaly is a challenge for the operating dentist with regard to its diagnosis and treatment. This case report presents the successful management of a Type‐3b DI in a permanent maxillary lateral incisor associated with a large radicular cyst and communicating apico‐marginal defect (Von Arx type IIb).A 19‐year‐old female patient reported pain and palatal swelling. During the clinical examination, tooth #12 exhibited tenderness to percussion, and presented a deep periodontal pocket depth (PPD) of 12 mm, along with grade I mobility. Radiographic examination revealed a large peri‐radicular radiolucency with atypical tooth morphology. Cone beam computed tomography clarified the complicated root canal anatomy to be Type‐3b DI associated with an apico‐marginal defect. The case was managed successfully by non‐surgical endodontic therapy followed by surgical intervention utilizing a guided bone regenerative (GBR) approach. Eighteen‐month follow‐up showed an asymptomatic and functional tooth with a significant reduction in pocket depth. The periapical radiographs showed continued healing of the osseous defect.The successful healing outcome of a challenging case, characterized by a complex DI morphology, a large peri‐radicular lesion, a through‐and‐through defect, and a combined endodontic‐periodontal apico‐marginal defect was achieved through accurate diagnosis, treatment planning, and execution using contemporary endodontic and periodontal treatment techniques. The application of GBR techniques during the surgical phase of treatment may have contributed to the improved regenerative healing outcome in this case, which was initially considered prognostically questionable.Why is this case new information? Type‐3b DI exhibits a complex root canal structure, each case displaying unique characteristics, necessitating a case‐specific treatment plan. In this case report the Type‐3b DI morphology was associated with a large peri‐radicular, through and through defect and combined endodontic periodontal apico‐marginal defect. The treatment approach involved incorporating guided bone regenerative (GBR) principles during the surgical phase. This case report contributes to the existing evidence on the diagnosis and successful management of Type‐3b DI with a concurrent apico‐marginal defect. What are the keys to successful management of this case? The successful management of a prognostically challenging case was achieved through a closely integrated multidisciplinary coordination between the endodontist and periodontist. Utilization of contemporary techniques and tools contributed to the successful management The use of three‐dimensional radiological examination through cone beam computed tomography enabled a precise preoperative assessment, facilitating the formulation of a treatment plan for managing both the Type‐3b DI morphology and the associated peri‐radicular lesion. Employing GBR techniques in peri‐radicular surgery may have assisted in the healing of through‐and‐through periapical defects with concurrent apico‐marginal defects (Von Arx type IIb). What are the primary limitations to the success of this case? A complex root canal anatomy associated with Type‐3b DI morphology A large peri‐radicular through and through defect with concurrent apico‐marginal defect. Difficulty in weekly and long‐term follow‐up of the patient. [ABSTRACT FROM AUTHOR]

Aim: Cyst formation of the jaws is frequently accompanied by the proliferation of odontogenic epithelial cells located in the periodontal ligament (PDL), which consists of heterozygous cells and includes the most fibroblasts. The lining epithelium of radicular cyst, an odontogenic cyst of inflammatory origin, is derived from the proliferation of the remnants of the Hertwig epithelial root sheath (odontogenic epithelial cell rests of Malassez; ERMs) in the PDL. ERMs are maintained at a lower proliferative state under physiological conditions, but the regulatory mechanisms underlying the inflammation‐dependent enhanced‐proliferative capabilities of ERMs are not fully understood. The aim of this study was to evaluate the effects of cytokine pathway association between TGF‐β signalling and IL‐1β signalling on the regulation of odontogenic epithelial cell proliferation using radicular cyst pathological specimens and odontogenic epithelial cell lines. Methodology: Immunofluorescence analyses were performed to clarify the expression levels of Smad2/3 and Ki‐67 in ERMs of 8‐week‐old mouse molar specimens. In radicular cyst (n = 52) and dentigerous cysts (n = 6) specimens from human patients, the expression of p65 (a main subunit of NF‐κB), Smad2/3 and Ki‐67 were investigated using immunohistochemical analyses. Odontogenic epithelial cells and PDL fibroblastic cells were co‐cultured with or without an inhibitor or siRNAs. Odontogenic epithelial cells were cultured with or without TGF‐β1 and IL‐1β. The proliferative capabilities and Smad2 phosphorylation levels of odontogenic epithelial cells were examined. Results: Immunohistochemically, Smad2/3‐positivity was increased, and p65‐positivity and Ki‐67‐positivity were decreased both in ERMs and in the epithelial cells in dentigerous cysts, a non‐inflammatory developmental cyst. In contrast, p65‐positive cells, along with the expression of Ki‐67, were increased and Smad2/3‐positive cells were decreased in the lining epithelia of radicular cysts. Co‐culture experiments with odontogenic epithelial cells and PDL fibroblastic cells revealed that PDL cells‐derived TGF‐β1/2 and their downstream signalling suppressed odontogenic epithelial cell proliferation. Moreover, TGF‐β1 stimulation induced Smad2 phosphorylation and suppressed odontogenic epithelial cell proliferation, while IL‐1β stimulation reversed these phenotypes through p65 transactivation. Conclusions: These results suggest that IL‐1β‐p65 signalling promotes odontogenic epithelial cell proliferation through suppressing TGF‐β‐Smad2 signalling, which would be involved in the pathogenesis of radicular cysts. [ABSTRACT FROM AUTHOR]

Aim: As a key DNA sensor, cyclic GMP–AMP synthase (cGAS) has emerged as a major mediator of innate immunity and inflammation. Human apical periodontitis has yet to be studied for the presence of cGAS. This investigation was conducted to determine if cGAS is involved in the pathological process of human apical periodontitis. Methodology: Sixty four human periapical lesions, comprising 20 periapical granulomas and 44 radicular cysts, were employed in this investigation. Healthy gingiva (n = 6), dental pulp (n = 3), and apical papilla (n = 3) were used as control samples. The expression of cGAS in the periapical tissues was discovered using immunohistochemical staining. mRNA‐Sequencing and qRT‐PCR were utilized to determine the differentially expressed genes (DEGs) associated with DNA‐sensing signalling in periapical lesions compared to the healthy control. Immunofluorescence labelling was used to identify the co‐expression of cGAS, interleukin‐1β, and interleukin‐18. Results: A significantly greater expression level of cGAS was discovered in the periapical lesions, with no significant difference between radicular cysts and periapical granulomas. mRNA‐Sequencing analysis and qRT‐PCR identified differentially expressed mRNA, such as cGAS and its downstream DEGs, between periapical lesions and healthy control tissues. Immunofluorescence labelling further revealed that cGAS, interleukin‐1, and interleukin‐18 were co‐localized. Conclusions: These observations imply that along with the synthesis of interleukin‐1 and interleukin‐18, cGAS may be involved in the aetiology of apical periodontitis. [ABSTRACT FROM AUTHOR]

Aim: To describe the radicular dentine thickness in mandibular first premolars presenting C‐shaped root canals, to identify the canal walls with less thickness as potential danger zones. In addition, to describe the internal and external anatomical characteristics of these teeth and associate them with the dentine thickness. Methodology: A total of 70 mandibular first premolars presenting C‐shaped root canals were examined. Their internal morphology was analysed using Vertucci's and Fan's criteria, and their external morphology was analysed using the ASUDAS score. Besides, the dentine thickness around the root canals was two/three‐dimensionally determined at five root planes and quantified in the distal and the mesial aspects. Results: According to Fan's, ASUDAS, and Vertucci's classifications, the most common canal configurations were category C3, grade 3, and type V, respectively. In Vertucci's type III anatomy, the mesial root wall of the lingual canal showed significantly less dentine thickness than the distal wall in the middle plane (p =.031). Similarly, in Vertucci's type V anatomy, significantly less dentine thickness was observed in the mesial root wall of the buccal and lingual canals in the middle plane (p <.001) and the buccal canal in the middle‐apical plane (p =.014) than the distal root wall of these canals. In teeth with ASUDAS grade 3 and 4 scores, significantly less dentine thickness was observed in the mesial in comparison with the distal root wall of these canals. These differences were demonstrated in the middle and middle‐apical planes (p <.001) of grade 3 teeth and the middle‐apical plane (p <.001) of grade 4 teeth. In these root planes, the Ver1‐AS3 and VerV‐AS3 combinations presented a 4‐times greater risk of presenting walls with a critical dentine thickness of 0.6 mm (odds ratio [OR] = 4, p =.025) than the combinations Ver1‐AS2, VerV‐AS2, VerV‐AS4, and VerIII‐AS3. Conclusions: The root canal system configuration of mandibular first premolars with C‐shaped canals showed a wide range of anatomical variations. The lowest dentine thickness was located in the mesial wall of the canals in the middle and apical root thirds of Vertucci's type III and V anatomies and in teeth with deep radicular grooves scored as ASUDAS grades 3 and 4. In the middle and middle‐apical planes, the presence of the combinations Ver1‐AS3 and VerV‐AS3 showed a high risk of presenting a critical dentine thickness of 0.6 mm. Therefore, these root canal walls with less dentine thickness represent potential instrumentation danger zones in mandibular first premolars with C‐shaped canals. [ABSTRACT FROM AUTHOR]

A cutaneous sinus tract of dental origin may easily be misdiagnosed and incorrectly treated. This paper reported a case of a 20‐year‐old male patient referred for a productive cutaneous sinus tract misdiagnosed by medical doctors for more than 4 years. The clinical and radiographic examinations confirmed the odontogenic origin related to a mandibular first right molar presenting an infected radicular cyst. Surgical treatment was performed leading to a significant healing of the sinus tract. [ABSTRACT FROM AUTHOR]

Blessed Egidio was a revered Catholic friar who lived in Basilicata (southern Italy) between the 15th and 16th centuries A.D. His natural mummy is preserved in the Mother Church of Laurenzana, the village where he lived. During the recent restoration and conservation of the relic, palaeopathological analysis was carried out. This revealed osteolytic lesions that affected the maxillary bones, as two injuries that were different in morphology and size that distinctly afflicted the right and left maxillae. The macroscopic and radiographic appearance of the lesion on the right maxilla and its proximity to the right premolar tooth that showed periapical granuloma suggest a diagnosis of an inflammatory odontogenic cyst (radicular cyst). The second lesion, of the left maxilla, was non‐specific and might have been the consequence of an inflammatory process. Odontogenic cysts are common in modern human populations but have been poorly described to date in ancient populations. The case of Blessed Egidio represents a new and rare case diagnosed in the field of palaeopathology. [ABSTRACT FROM AUTHOR]

Residual radicular cysts also called residual cysts, are inflammatory odontogenic cysts of the tooth-bearing areas of the jaws. Some authors believe that they are not distinct entities, but represent previously undetected or persistent radicular cysts. Though they are slow-growing and are usually found incidentally, they have the potential to reach massive sizes, displace adjacent structures and transform into benign and malignant tumours. In comparison to other odontogenic cysts, there is a paucity of literature regarding residual cysts. This article comprehensively reviews the literature available on the etiopathogenesis, presentation, microscopic and biochemical features, management and prognosis of residual cysts along with a report of a large residual cyst in the maxilla, displacing the maxillary sinus. The cyst presented 10 years after extraction of the offending teeth and was filled with brownish-red semisolid content, which is uncommon. The lesion was enucleated and no postoperative complications were observed. [ABSTRACT FROM AUTHOR]

Aim: To characterize plasma cell subsets in chronic periapical lesions affecting permanent and primary teeth. Methodology: Only chronic periapical lesions without root canal treatment were selected. Twenty‐one radicular cysts and 7 periapical granulomas affecting permanent teeth and 19 radicular cysts and 4 periapical granulomas affecting primary teeth were assessed for immunoglobulin (Ig) light chain (kappa and lambda), Ig heavy chain (IgG, IgG4, IgA, IgM and IgD) and plasma cell immunohistochemical markers (MUM1/IRF4, EMA and CD138). The data acquired were analysed by Student's t test, Mann–Whitney U, Friedman test followed by Dunn's multiple comparison test and Spearman's rank correlation. Results: All cases were polyclonal (having similar kappa/lambda light chain ratios). IgG was most abundant compared to other Ig heavy chains (all, P < 0.001); like Ig light chains, but unlike IgA, there was greater expression of IgG in the primary compared to the permanent dentition, for both radicular cysts (P < 0.001) and periapical granulomas (P = 0.53). Notably, IgG4 expression was greater in the permanent than the primary dentition, for both radicular cyst (P < 0.05) and periapical granuloma (P = 0.65). IgM and IgD expression was scarce and variable, whereas plasma cell populations were detected efficiently through EMA, CD138 and MUM1/IRF4 markers, the latter being more sensitive in both dentitions. Conclusions: There were slight variations in the Ig light and heavy chain profiles in chronic periapical lesions when comparing the permanent and primary dentitions. The ability of IgG4+ plasma cell infiltration to modulate inflammatory responses in chronic periapical lesions arising from permanent as opposed to primary teeth should be considered in future studies. [ABSTRACT FROM AUTHOR]

Objective: Cysts of the mouth and jaws are common, and their management is an essential component of oral surgery. Patients may present with symptoms though more frequently they are asymptomatic and are referred as a result of incidental finding by a dentist. This retrospective study reviews the clinical presentation, radiologic features, management and outcomes of jaw cysts treated by a single oral surgeon between 2005 and 2018. Methods: Medical records were reviewed for data on diagnosis, pathology, treatment modalities and follow‐up outcomes among the patients. The principal emphasis is to report the outcome of odontogenic keratocytes managed conservatively in relation to recent World Health Organization classification. Results: Records of 214 patients having a true cystic jaw lesion were reviewed. The most common cystic lesions were radicular cyst (38%) followed by dentigerous cysts (36%) and odontogenic keratocyst (OKC) (10%). Fifty‐six percent (56 of 214) of all cystic lesions were asymptomatic on presentation and were identified by imaging. All patients underwent surgical intervention, including biopsy, enucleation and/or curettage as indicated. Cases were treated principally by enucleation. None of 214 cases showed any recurrence. Marsupialisation was the treatment for seven cases of eruption cyst and two cases of dentigerous cyst associated with erupting teeth in children. Conclusions: Jaw cysts are not unusual, many of these cysts are asymptomatic and are identified incidentally on orthopantomography. Radicular cyst was the most common followed by dentigerous cyst and OKC. All the patients were treated successfully with surgical intervention and none showed any recurrence. [ABSTRACT FROM AUTHOR]

The genetic base for soybean cultivars is narrow compared to most other crop species. Twenty‐seven wild perennial Glycine species comprise the tertiary gene pool to soybean that may contain many genes of economic importance for soybean improvement. We evaluated 16 accessions of G. argyrea, G. clandestina, G. dolichocarpa, and G. tomentella for resistance to Heterodera glycines (HG), also known as the soybean cyst nematode, and to multiple isolates of Phakopsora pachyrhizi, the causal fungus of soybean rust. All 16 accessions were classified as resistant to H. glycines HG Type 2.5.7, based on number of cysts per root mass with plant introductions (PIs) 483227, 509501, 563892, and 573064 (all G. tomentella) void of any cysts indicating no reproduction by this pest. All 16 accessions had an immune reaction to one isolate of P. pachyrhizi. Regardless of isolate, no sporulating uredinia were observed on G. argyrea (PI 505151) and G. tomentella (PIs 483227, 509501, and 573064). These results demonstrate that some accessions within the perennial Glycine species harbour resistance to both H. glycines and P. pachyrhizi and would be good candidates for wide hybridization programs seeking to transfer potentially unique multiple resistance genes into soybean. [ABSTRACT FROM AUTHOR]

The article describes a rare case of radicular cyst associated with deciduous right upper molars in a 5 y.o. male patient. The cyst developed asymptomatically in the maxillary sinus, thus causing considerable displacement of both premolar germs. Due to the severity of surgery, the patient was treated under general anesthesia in a one-day surgery system with use of the enucleation method. The extent of the lesion results in necessity of removal of the second premolar germ. Early diagnosis of the lesion would have resulted in a more conservative treatment plan. The purpose of this article is to lay emphasis on the pedodontist's role in early diagnosis of such lesions. [ABSTRACT FROM AUTHOR]

An untreated root canal infection usually stimulates the development of a radicular cyst. Nonsurgical root canal procedures and periapical surgery followed by placement of bone substitute will promote the healing process of the bony defect. [ABSTRACT FROM AUTHOR]

This article reports a case of a large osteolytic lesion in the mandible, mostly associated with the apices of the premolars, and suspected as having a non‐endodontic origin because the 2 premolars responded positively to the cold sensibility test. The distal border of the lesion reached the mesial root of the first molar, which also had a small lesion in its distal aspect. Cone‐beam computed tomography revealed that the large lesion communicated with the small molar lesion. Because the large lesion was suspected as having a non‐endodontic origin, surgery was scheduled for enucleation and biopsy. The molar was root canal‐retreated, and the 2 premolars treated. Histologic analysis of the premolar pulps showed vitality but advanced degenerative changes. The lesion was histologically diagnosed as an inflammatory periradicular cyst, which originated in the first molar and had an atypical growth to the premolar area. Follow‐up revealed that the affected area healed uneventfully. [ABSTRACT FROM AUTHOR]

Aim: To analyze the heterogeneity of fibroblasts isolated from the fibrous capsules of radicular cysts and explore the effects of fibroblast subsets on bone destruction. Methodology: Radicular cysts were divided into groups according to varying perilesional sclerosis identified by radiograph. Colony‐forming units (CFUs) were isolated from the fibrous capsules of cysts, by which Trap + MNCs were induced, and the expression of osteoclastogenesis‐related genes was compared among groups by real‐time PCR. The variances in gene profiles of CFUs were identified by principal component analysis, and then, CFUs were divided into subsets using cluster analysis. The induction of Trap + MNCs and related gene expression was compared among subsets, and osteoclastogenic induction was blocked by IST‐9 or bevacizumab. The fibroblast subsets in cysts were investigated by retrospective immunostaining with IST‐9, VEGF‐A, and CD34. A fibroblast subset that underwent gene editing by CRISPR/Cas was injected into the site of bone defects in animal models, and the in vivo effects on osteoclastogenesis were investigated. Results: The fibroblast CFUs isolated from radicular cysts with perilesional unsclerotized cysts induced more Trap + MNCs than those with perilesional sclerotic cysts (p <.05). Most fibroblast CFUs from unsclerotized cysts belonged to Cluster 2, which induced more Trap + MNCs (p <.05) and highly expressed genes facilitating osteoclastogenesis; these results were different from those of Cluster 1 (p <.05), in which most CFUs were isolated from perilesional sclerotic cysts or controls (p <.05). The high expression of EDA + FN and VEGF‐A was investigated in both the fibroblasts of Cluster 2 and the fibrous capsules of unsclerotized cysts (p <.05), and the number of Trap + MNCs induced by Cluster 2 was decreased by treatment with IST‐9 and bevacizumab (p <.05). Consistently, EDA exon exclusion significantly decreased the osteoclastogenic induction of fibroblasts from Cluster 2 in vivo (p <.05). Conclusion: The fibrous capsules of radicular cysts contain heterogeneous fibroblasts that can form subsets exhibiting different effects on osteoclastogenesis. The subset, which depending on the autocrine effects of EDA + FN on VEGF‐A, mainly contributes to the osteoclastogenesis and bone destruction of radicular cysts. The regulation of the proportion of subsets is a possible strategy for artificially interfering with osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Aim: To quantify M1 and M2 macrophages in radicular cysts of permanent (n = 14 cases) and primary teeth (n = 15 cases). Methodology: All patients who attended the School of Dentistry Ribeirão Preto, University of São Paulo with primary teeth or permanent molars that were scheduled for extraction and fulfilled the inclusion criteria: absence of pain; presence/absence of fistulae; extensive coronal destruction due to caries lesions without possibility of restoration; pulp necrosis; radiographically visible apical periodontitis; and no previous treatment, were selected. The radicular cysts were removed and subsequently submitted to histopathologic analysis in order to classify the type of inflammatory infiltrate. In addition, CD68 (M1+, M2+) and CD163 (M1−, M2+) markers were quantified through an immunohistochemistry analysis. The data acquired were submitted to a Mann–Whitney test, with a 5% significance level. Results: The patients had a mean age of 38.6 years and 5.9 years for cysts associated with permanent and primary teeth, respectively. In the histopathological analysis, no significant difference (P = 0.87) was found between radicular cysts in primary and permanent teeth regarding the intensity of the chronic inflammatory infiltrate. A significantly greater prevalence of M2 macrophages (P < 0.05) was observed in the lesions of both permanent and primary teeth, even though both M1 and M2 macrophages were detected. No significant difference (P > 0.05) was found for M1 and M2 macrophages associated with the cysts of primary and permanent teeth. Conclusion: M1 and M2 macrophages were present in radicular cysts associated with primary and permanent teeth, with a greater quantity of M2 cells. The immunophenotypic quantification of M1 and M2 macrophage polarization in radicular cysts associated with primary and permanent teeth were similar. [ABSTRACT FROM AUTHOR]

Aim: To analyse the effects of the alternatively spliced fibronectin (FN) gene and its isoforms on osteoclastogenesis in radicular cysts. Methodology: Specimens of radicular cysts were collected surgically from 22 patients whose radiolucent periapical areas were measured on digital panoramic radiographs before surgery. The associations between the radiolucent areas and FN isoforms, vascular endothelial growth factor (VEGF) expression or micro‐vessel density, as well as the relationships amongst them, were analysed by immunohistochemical staining using the antibodies IST‐9, BC‐1, P1F11, VEGF and CD34. Fibroblasts isolated from those specimens were used to induce Trap + MNCs, and the effects of induction were assessed by blocking FN containing extra domain A (EDA + FN), COX‐2 or VEGF in vitro. The effects of EDA exon knockout using CRISPR/Cas system were also assessed. Quantitative PCR was used to analyse relative expression of FN isoforms and osteoclastogenic genes. Data were analysed using linear regression, Spearman's rank correlation analysis, chi‐square test and Student's t‐test; P < 0.05 was considered significant. Results: Micro‐vessel density and EDA + FN staining were positively associated with the size of radiolucent periapical areas (mm2; P < 0.05), consistent with a positive association between Trap + MNCs and VEGF expression in fibroblasts (P < 0.05). Blocking the interaction between EDA + FN and fibroblasts inhibited Trap + MNC formation. In addition, EDA exon knockout decreased VEGF expression and inhibited Trap + MNC formation to the extent of blocking VEGF by bevacizumab, but osteoclastogenic induction was restored by recombinant VEGF. Using retrospective clinicopathological data, VEGF staining was shown to be positively associated with EDA + FN staining, micro‐vessel density and the size of radiolucent areas (P < 0.05). Conclusion: In fibrous capsules of radicular cysts, the alternatively spliced isoform EDA + FN generated by fibroblasts stimulated VEGF expression via an autocrine effect and then facilitated osteoclastogenesis. Both blockage of VEGF and EDA exon knockout could be used to inhibit bone destruction. [ABSTRACT FROM AUTHOR]

In rare cases, pancreatic enzymes can enter the bloodstream and cause fat necrosis in the bone and tissue leading to a disorder called pancreatitis, panniculitis, and polyarthritis syndrome. Clinicians should have this syndrome in mind when treating patients with pancreatitis. [ABSTRACT FROM AUTHOR]

A radicular variant of dens invaginatus (DI) is a rare form of dens invaginatus which develops in the root of the tooth after the crown development is completed. This report involves successful management of a case with guided tissue regeneration and describes the cone beam computed tomography (CBCT) characteristics of true radicular DI. A 20‐year‐old woman reported with recurrent swelling and pus discharge associated with her maxillary left central incisor (#21). Cone beam computed tomography (CBCT) of the region revealed #21 had an invagination in the mesial aspect of the coronal third of the root with a para radicular low‐density region perforating both the cortices. A diagnosis of true radicular variant of DI was made by exclusion. The case was managed with Biodentine®, platelet‐rich fibrin and freeze‐dried demineralised bone graft. A 2‐year review showed that the tooth was functional with normal periodontal parameters and normal response to electric pulp sensibility test. [ABSTRACT FROM AUTHOR]

Distinguishing squamous odontogenic tumor-like proliferations (SOTLPs) is important in odontogenic cysts to avoid misinterpretation such as a squamous odontogenic tumor, well-differentiated squamous cell carcinoma, and acanthomatous type of ameloblastoma. This study is aimed at reporting 4 cases of these clinicopathological proliferations in order to shed more light on the importance of distinguishing them from other similar types. 150 odontogenic cysts were studied in which four cases (2.66%) with SOTLPs were identified including 2 radicular cysts, 1 dentigerous cyst, and 1 odontogenic keratocyst. These proliferations were observed in the cysts' wall particularly adjacent to the epithelial lining. All cysts had inflammation while 3 cases showed budding from the epithelial cyst lining. The findings suggested that lining of odontogenic cysts could be a source of SOTLPs, and inflammation probably played an effective role in their development. Its incidence was 2.66% in the present study. Although SOTLPs are not frequent in odontogenic cysts, their identification is important to prevent wrong histopathologic interpretation and treatment. [ABSTRACT FROM AUTHOR]

Aim: To describe an in vitro experimental model of cystic structure formation to conduct research on radicular cyst development. Methodology: To form spheroid structures, various numbers (1 × 104, 5 × 104 or 1 × 105) of epithelial cells (HaCaT and Cal27) were seeded in 96‐well plates previously coated with 1.5% low‐melting agarose. After 24 h, the spheroids were collected, embedded in 3D collagen matrix and transferred to 24‐well plates previously coated with polymerized collagen and kept for up to 21 days. Images of spheroids were captured at each time‐point (1, 5, 9, 15 and 21 days), and samples underwent histological and confocal microscopy analyses. Spheroid area, perimeter and cell dispersion were measured. One‐way Anova was used for statistical analysis. Results: Both epithelial cell lines were able to generate regular and circular spheroids after 24 h of incubation regardless of cell density. Spheroid structures in the collagen matrix were uniform in most samples until day 15, when several spots that appeared to be new cultures were seen. Spheroids from HaCaT were significantly more stable than those from Cal27 (P < 0.05). Starting on the third day, the examination of histological sections revealed a cavity with epithelial lining morphology, similar to a pathological radicular cyst. Conclusions: This study describes an experimental model of cystogenesis in vitro that may be used to test theories and investigates the effects of different growth factors during cyst development and maintenance. [ABSTRACT FROM AUTHOR]

Apoptosis (a programmed cell death mechanism) within the radicular cyst epithelium has still not been correlated with any clinical factor. This study aimed to investigate the effect of calcium hydroxide on apoptosis, via the detection of caspase‐9. Thirty radicular cysts collected during apicoectomies and stored in paraffin were retrospectively retrieved. Conservative endodontic treatments had been carried out either without (group (a) n = 14), or with calcium hydroxide application (group (b), n = 16) before obturation. All cysts were immunohistochemically stained for caspase‐9 to record apoptosis of the epithelium. Statistical analysis followed. The frequency of caspase‐9 immunoreactivity in the cystic epithelium in the two groups was 42.86% and 93.75% of cysts respectively. This difference was statistically significant (P = 0.04 < 0.05). In cysts larger than (or equal to) 10 mm, caspase‐9 was more frequently expressed. It was found calcium hydroxide appears to enhance the expression of caspase‐9, especially in large lesions. [ABSTRACT FROM AUTHOR]

Epidermoid splenic cysts are rare lesions in the spleen. These cysts are characterized by a stratified squamous epithelial lining, internal septations, and calcification. Congenital in origin, epidermoid splenic cysts are postulated to arise from misfolding and mesothelial cell incorporation into the splenic parenchyma. This report presents a unique case of an 18-year-old woman with an epidermoid splenic cyst in a congenital wandering spleen. Computed tomography and transabdominal ultrasound imaging along with immunochemistry staining confirmed the diagnosis. To the authors' knowledge, this is the first reported case of an epidermoid cyst in a wandering spleen. [ABSTRACT FROM AUTHOR]

This case report discusses the management of a large radicular cyst using current periapical surgery techniques associated with the use of modified guided tissue regeneration (GTR) techniques. The cyst involved several anterior teeth and measured 40 mm in its widest dimension, involving both cortical plates, and extending into the floor of the nose. The surgical endodontics techniques used here included the use of enhanced magnification, minimal root resection, ultrasonic root‐end preparation and retrograde obturation with a bioceramic root repair material. The large bone defect was reconstructed with the use of a mixture of autogenous bone harvested from the mandibular ramus, Bio‐oss® and platelet‐rich fibrin (PRF), covered with a thin PRF membrane acting as a modified GTR. The combination of these techniques ensured successful clinical, radiographic and tomographic outcomes after 4 years of follow‐up. [ABSTRACT FROM AUTHOR]

Background. A radicular cyst is the most common odontogenic cyst of inflammatory origin. Radiographically, it commonly demonstrates clear unilocular radiolucency; radicular cysts with multilocular radiolucency are quite rare. Case Presentation. A 64-year-old Japanese man who presented with a bilocular radiolucent lesion in his left mandible was referred by a dental clinic to our oral and maxillofacial surgery department. He had no particular subjective symptoms. Orthopantomography and computed tomography (CT) revealed an 18 mm×15 mm lesion with well-defined bilocular radiolucency in the left mandible expanding from the distal side of a canine tooth to the bottom of the 2nd premolar. The lesion included the roots of the 1st and 2nd premolars. The root of the 2nd premolar showed knife-edge resorption. Although the 1st premolar was nonvital, the 2nd premolar was a vital tooth. As differential diagnoses, a radicular cyst, ameloblastoma, odontogenic keratocyst, pseudocyst, and others might be considered. We performed a total resection of the bilocular lesion and diagnosed the lesion as a radicular cyst with tooth structure components inside. The tooth structure components represented lamellar structures of cementum; they were located only in the proximal part (under the 1st premolar) of the lesion. The distal part of the lesion presented distinctive inflammation without tooth structure components. Conclusion. We encountered a rare case of a bilocular radicular cyst with tooth structure components inside. [ABSTRACT FROM AUTHOR]

Aim: To investigate the expression of TP63 in apical periodontitis (AP) tissues and the association of single nucleotide polymorphisms (SNPs) in the TP63 gene with AP using a case‐control dataset. Methodology: Expression of TP63 in human AP lesions (apical abscess, radicular cyst, periapical granuloma) was evaluated using immunohistochemistry. A case‐control association study was performed to assess the association of TP63 polymorphisms in individuals having AP with or without associated pain. Cases were defined as subjects with deep caries and AP (n = 151) and subjects with symptomatic apical periodontitis or acute apical abscess (n = 124). Subjects without AP (n = 169) and asymptomatic (n = 196) were used as controls, respectively. Saliva samples were collected as source of genomic DNA. Twelve SNPs in the TP63 gene were selected for genotyping using Taqman chemistry in real‐time PCR. Data analysis was performed using PLINK software. The Bonferroni method was applied to correct for multiple testing; α ≤ 0.004 indicates significant differences between groups. Results: TP63 expression was evident in apical abscesses and radicular cysts, while weaker expression was observed in periapical granulomas. Positive expression was observed in mononuclear cells in the granulation tissues of all AP lesions. Regarding the presence of AP, a trend for allelic association was observed for rs16864812 and rs9810322 (P = 0.04) and rs9810322 genotypes were also nominally associated with AP under a dominant model (P = 0.04). When considering the presence of periapical pain, a trend for allelic and genotypic association was observed for rs10155037 (P = 0.03). Haplotypes were also associated with AP and periapical pain (P ≤ 0.05). Conclusions: Apical periodontitis is a complex multifactorial condition and it is likely that multiple genes and environmental effects may influence its susceptibility, progression or both. TP63 variants may play a role in AP pathogenesis and susceptibility, individually or interactively with other genes. Additional studies in other populations and functional studies are needed to improve understanding of the role of TP63 in AP. [ABSTRACT FROM AUTHOR]

Summary: An 11‐year‐old Thoroughbred broodmare was diagnosed with extensive radicular cysts that affected the left horizontal mandibular ramus. A left mandibular swelling was present clinically, and mandibular lesions appearing cystic in nature were identified with successive radiographic and ultrasonographic examinations. Surgical enucleation of the cysts was performed under a standing sedation protocol and the excised cystic structures submitted for histopathological analysis. Histological examination of the cystic structures confirmed a diagnosis of multiple radicular cysts. [ABSTRACT FROM AUTHOR]

The present communication describes the endodontic retreatment of a rare four-rooted maxillary second molar. A 25-year-old patient was referred to our dental practice requesting an apicoectomy because of continuous and permanent pain reaction six months after the first endodontic treatment. The sent radiograph demonstrated three filled root canals (one mesial, two distal) and four radiographically superimposing roots (two mesial, two distal). Due to the diagnosed chronic apical periodontitis and based on the visible untreated root canal, we decided to endodontically re-treat the quadrangular tooth against the referred apicoectomy. In the first session, only the previously untreated mesiopalatal root canal was mechanically prepared and filled with a corticosteroid- and tetracycline-containing paste. After two symptom-free weeks, the gutta-percha was removed from the other canals and calcium hydroxide was applied. Another two weeks later, the four root canals, whose orifices were "irregular quadrilateral" shaped on the pulp chamber floor representing Versiani Type A, were obturated. After the verification of this rare anatomy by cone beam computed tomography, the tooth was classified as Christie's radicular type II. One characteristic of this type is parallel running buccal and palatal roots, which caused a radiographic superimposition and probably led to the endodontic mistreatment in the first case. [ABSTRACT FROM AUTHOR]

Objective: To investigate the alternative spliced isoforms of Fibronectin (FN) in the stroma of radicular cysts and analyze the associations between these isoforms and the osteoclastogenic effects of fibroblasts. Methods and materials: The specimens of radicular cysts were stained with immunohistochemistry, and the associations between each FN isoform and clinical parameters were assessed. The fibroblasts isolated from cysts or jaw bone were cultured to induce the Trap + MNCs. In the conditioned medium, the Fibronectin containing extra domain A (EDA + FN) was neutralized by antibody IST‐9, and the EDA exon of fibroblasts was knockout by CRISPR/Cas system, for assessing the osteoclastogenic effects. The mRNA level of FN isoforms and the osteoclastogenesis‐related genes were analyzed by quantitive PCR. Results: EDA + FN staining was positively associated with the size of the lesions (p < 0.05). In contrast with the controls, the ratio of EDA + FN/total FN in the fibroblasts from radicular cysts was significantly higher (p < 0.05), and positively associate with Trap + MNCs counting, it was consistent with increased expression of COX‐2, IL‐6, IL‐17, and the RANKL/OPG (p < 0.05). The Trap + MNCs counting and osteoclastogenesis‐related genes were decreased by IST‐9 blocking and EDA exon knockout in fibroblasts, but the blockage of the interaction between EDA + FN and pre‐osteoclasts exhibited little effects on Trap + MNCs formation. Conclusion: The microenvironment of the fibrous capsule of radicular cysts facilitates the splicing of EDA exon, it endues EDA + FN with autocrine effects on fibroblast itself, and it increases the expression of osteoclastogenesis‐related genes, by which the osteoclastogenesis in radicular cysts could be initiated. [ABSTRACT FROM AUTHOR]

Odontogenic cysts are usually treated by enucleation (cystectomy). Limited cysts (less than 5 cm) are usually managed by primary excision (total cystectomy), whereas larger ones (exceeding 5 cm) are often decompressed or marsupialized. Because it consists only of opening a much smaller surgical window, decompression is regarded as a more conservative method of treatment: this method associates the creation of an opening (window) into the cystic cavity with the suturing of a decompressing device (plastic tube or stent) at the periphery of the cyst. Apart from releasing intraluminal pressure in the pathological cavity, this procedure helps the lesion to progressively decrease in volume "with a gradual increase in bone apposition" and preserves pulp vitality and periodontal integrity of the adjacent teeth. We are reporting a case of a mandibular radicular cyst that was treated by decompression, followed by enucleation, bone reconstruction, and restoration with two osseointegrated dental implants. The cystic cavity progressively decreased in volume and increased in bone density. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To investigate the diagnostic reliability and accuracy of magnetic resonance imaging (MRI) to differentiate periapical lesions of endodontic origin and to compare the results with histopathological information. Methodology: The radiolucent periapical jaw lesions of 34 patients, which were surgically enucleated, were investigated by two radiologists using MRI, based on the same six criteria, to categorize the lesions as granulomas, radicular cysts or others. After apicoectomies, two oral pathologists (blinded to the radiologist's diagnoses) analysed all specimens by referring to seven specific parameters and diagnosed the specimens as granulomas, radicular cysts or other conditions. The inter‐rater agreements between the radiologists and pathologists in terms of MRI and histological diagnoses, respectively, along with the discriminant power of the adopted criteria and the accuracy of the MRI assessments compared with the histopathological results, were calculated. Cohen's kappa test was adopted to examine inter‐rater agreement between the two radiologists and two pathologists. Guttman's lambda coefficient (λ6) was used to evaluate the internal consistency of the items used for the differential diagnosis by radiologists. The accuracy resulted from a receiver operator characteristic (ROC) analysis. Results: A strong inter‐rater reliability was observed between the two radiologists (k‐statistic = 0.86, P = 0.0001) and the two pathologists (k‐statistic = 0.88, P = 0.0001). The internal consistency of the diagnostic items was 0.605 for cysts and 0.771 for granulomas. The accuracy (true positives plus true negatives) of the radiologists was greater than that of the pathologists based on analysis (area under the curve = 0.87 and 0.91, respectively). Conclusions: The reliability and accuracy of MRI were high and comparable to histopathological reliability, highlighting the usefulness of this noninvasive technique as a pre‐treatment diagnostic method for periapical endodontic lesions. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To achieve a better understanding of a calcified extraradicular deposit on the apical root surfaces of a mandibular first molar associated with a radicular cyst and a sinus tract. A multimodular approach was applied using a combination of multiple investigation methods. Summary: This case report presents a mandibular first molar with a calcified extraradicular deposit on the apical root surfaces of both roots. An apical periodontitis lesion was present and a sinus tract served as the only communication with the oral cavity. Diagnosis and treatment planning were based on clinical, radiographic (two‐ and three‐dimensional) and ultrasound examination. The tooth was further analysed after extraction using microscopic imaging, nano‐computed tomography (nano‐CT), hard‐ and soft tissue histology and electron probe microanalysis. This multimodular approach revealed the calculus‐like appearance and mineral composition of the extraradicular deposit. Multiple hypotheses about its aetiology are discussed. Key learning points: Calcified extraradicular deposits can develop on the apical root surfaces of teeth with apical periodontitis in association with a radicular cyst and sinus tract. A sinus tract can serve as the only communication between the apical lesion and the oral cavity whilst no periodontal defects are present. The interplay of intra‐oral radiography, high resolution CBCT, nano‐CT, hard tissue histology and EPMA can reveal the calculus‐like appearance and composition of the extraradicular deposit. Calcified extraradicular deposits appear hyperechoic on ultrasound imaging and can lead to the occurrence of twinkling artefacts due to their rough mineralized surface. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To determine the expressions of hypoxia‐related [hypoxia‐inducible transcription factors (HIF)‐1α, BCL2/adenovirus E1B 19 kDa protein‐interacting protein 3 (BNIP3) and phospho‐adenosine monophosphate activated protein kinase (pAMPK)] and autophagy‐related [microtubule‐associated protein 1 light chain 3 (LC3), beclin‐1 (BECN‐1), autophagy‐related gene (Atg)5–12, and p62] proteins in human inflammatory periapical lesions. Methodology: Fifteen samples of radicular cysts (RCs) and 21 periapical granulomas (PGs), combined with 17 healthy dental pulp tissues, were examined. Enzyme‐linked immunosorbent assay (ELISA) was used to detect interleukin (IL)‐1β cytokine; immunohistochemical (IHC) and Western blot (WB) analyses were employed to examine autophagy‐related and hypoxia‐related proteins. Transmission electron microscopy (TEM) was used to explore the ultrastructural morphology of autophagy in periapical lesions. Nonparametric Kruskal–Wallis tests and Mann–Whitney U‐tests were used for statistical analyses. Results: ELISA revealed a significantly higher (P < 0.001) IL‐1β expression in periapical lesions than in normal pulp tissue. Immunoscores of IHC expressions of pAMPK, HIF‐1α, BNIP3, BECN‐1 and Atg5–12 proteins in periapical lesions were significantly higher (P < 0.001) (except BECN‐1) than those in normal pulp tissue. The results of IHC studies were largely compatible with those of WB analyses, where significantly higher (P < 0.05) expressions of hypoxia‐related and autophagy‐related proteins (except BECN‐1, p62 and LC3II in WB analyses) in periapical lesions were noted as compared to normal pulp tissue. Upon TEM, ultrastructural double‐membrane autophagosomes and autolysosomes were observed in PGs and RCs. Conclusions: Autophagy associated with hypoxia may play a potential causative role in the development and maintenance of inflamed periapical lesions. [ABSTRACT FROM AUTHOR]

Aim To evaluate the immunoexpression of tryptase, MMP-9 and MMP-13 in periapical lesions, correlating them with the type of lesion, intensity of the inflammatory infiltrate and thickness of the epithelial lining. Methodology Twenty periapical granulomas ( PGs), twenty radicular cysts ( RCs) and twenty residual radicular cysts ( RRCs) were submitted to immunohistochemical analysis using antitryptase, anti- MMP-9 and anti- MMP-13 antibodies. Immunoexpression of MMP-9 and MMP-13 was quantitatively evaluated both in the connective tissue of all lesions and in the epithelial lining of RCs and RRCs. Tryptase-positive mast cells were counted only in the connective tissue. The data were analysed using Kruskal-Wallis and Fisher's exact tests, as well as Spearman's correlation test ( P < 0.05). Results In comparison with RCs and RRCs, PGs exhibited higher immunoexpression of tryptase, MMP-9 and MMP-13 ( P = 0.002, P = < 0.001 and P < 0.001, respectively). In comparison with lesions with inflammatory infiltrates grades I and II, lesions with inflammatory infiltrate grade III had higher median percentages of MMP-13-positive cells ( P = 0.003) and a tendency for higher expression of MMP-9 ( P = 0.059). No significant difference was observed between the expression of the studied markers and epithelial thickness ( P > 0.05). There were positive correlations between the number of tryptase-positive mast cells and the immunoexpression of MMP-9, as well as between the immunoexpression of MMP-9 and MMP-13. Conclusion A larger number of tryptase-positive mast cells and greater enzymatic activity of MMP-9 and MMP-13 were found in PGs compared to RCs and RRCs. These findings are a characteristic of the dynamics of periapical diseases. [ABSTRACT FROM AUTHOR]

Background: The number of studies investigating the immunohistochemical characteristics of glandular odontogenic cysts (GOCs) is limited, due to its rarity. TGF-beta has been suggested to induce podoplanin expression in some lesions. We aimed to evaluate and compare podoplanin and TGF-beta expression in GOC and other odontogenic cystic lesions.Methods: A total of 43 samples including five GOCs, 10 dentigerous cysts (DCs), eight unicystic ameloblastoma (UAs), and 20 radicular cysts (RCs) were selected and subjected to immunohistochemical staining using monoclonal antibodies against podoplanin and TGF-beta. Kruskal-Wallis test and Mann-Whitney U-test were used for statistical analysis along with Bonferroni for adjusting P-values (P < 0.05).Results: Podoplanin immunoreactivity was observed in 80%, 70%, and 100% of DCs, RCs, and UAs, respectively, while none of the GOCs were positive for this marker (P = 0.004). Significant differences were only found in the GOC specimens. TGF-beta positivity occurred in the capsule and epithelium of all GOCs and DCs, while RCs and UAs demonstrated different expression percentages in the capsular and epithelial tissues. Epithelial TGF-beta showed significant differences among the studied lesions (P = 0.007) with the main difference found between DCs with RCs and DCs with UAs.Conclusions: Lack of podoplanin expression might be involved in the characteristic histologic and behavioral features of GOC, which seems to be unrelated to TGF-beta expression. [ABSTRACT FROM AUTHOR]

Background: Unicystic ameloblastoma, an odontogenic neoplasm, presents clinical and radiographic similarities with dentigerous and radicular cysts, non-neoplastic lesions. It is not always possible to reach a final diagnosis with the incisional biopsy, leading to inappropriate treatment. The BRAFV600E activating mutation has been reported in a high proportion of ameloblastomas. The purpose of the study was to assess the utility of the detection of the BRAFV600E mutation in the differential diagnosis of unicystic ameloblastoma with dentigerous and radicular cysts.Methods: Twenty-six archival samples were included, comprising eight unicystic ameloblastomas (UAs), nine dentigerous and nine radicular cysts. The mutation was assessed in all samples by anti-BRAFV600E (clone VE1) immunohistochemistry (IHC) and by TaqMan mutation detection qPCR assay. Sanger sequencing was further carried out when samples showed conflicting results in the IHC and qPCR.Results: Although all UAs (8/8) showed positive uniform BRAFV600E staining along the epithelial lining length, the mutation was not confirmed by qPCR and Sanger sequencing in three samples. Positive staining for the BRAFV600E protein was observed in one dentigerous cyst, but it was not confirmed by the molecular methods. Furthermore, 2/9 dentigerous cysts and 2/9 radicular cysts showed non-specific immunostaining of the epithelium or plasma cells. None of the dentigerous or radicular cysts cases presented the BRAFV600E mutation in the qPCR assay.Conclusions: The BRAFV600E antibody (clone VE1) IHC may show non-specific staining, but molecular assays may be useful for the diagnosis of unicystic ameloblastoma, in conjunction with clinical, radiological and histopathological features. [ABSTRACT FROM AUTHOR]

Aim To evaluate the relationship between mononuclear inflammatory infiltrate and the expression of a proliferative immunomarker (Ki-67) as well as to evaluate basement membrane and extracellular matrix proteins (laminin and collagen type IV) in radicular cysts and dentigerous cysts ( DC). Methodology Immunohistochemical analyses were performed in heavily inflamed radicular cysts ( HIRC), slightly inflamed radicular cysts ( SIRC) and DC ( n = 20) using Ki-67 (Dako®, 1 : 50), anticollagen type IV ( DBS®, 1 : 40) and antilaminin ( DBS®, 1 : 20). The data were analysed using anova/Tukey's test (Ki-67) and Kruskal-Wallis/Dunn's test (collagen type IV and laminin) ( P < 0.05). Results The immunoexpression of Ki-67 was significantly greater in the SIRC group compared with the HIRC and DC ( P = 0.0040). Likewise, the immunoexpression of collagen type IV in the basement membrane of the SIRC group was significantly more continuous ( P = 0.0475) than in the HIRC group. DC had significantly less collagen type IV in extracellular matrix immunoexpression than HIRC and SIRC ( P = 0.0246). Laminin was absent in the basement membrane in the SIRC and DC groups, and the extracellular matrix of the HIRC was weak and punctate. Conclusion The presence of inflammatory factors in the radicular cyst wall modified the expression of proliferation factors in the epithelial lining and the expression of collagen type IV and laminin in the basement membrane, but did not modify extracellular matrix behaviour in radicular cysts. [ABSTRACT FROM AUTHOR]

Background: Interleukin-33 (IL-33) is a recently identified cytokine belonging to the IL-1 family and ligand for the IL-1 receptor-related protein ST2. IL-33/ST2 signaling plays a critical role in allergy, autoimmunity, and chronic inflammatory disorders, but its role in the pathogenesis of periapical lesions is unknown. We aimed to investigate the expression patterns of IL-33 and ST2 in human periapical lesions. Methods: Periapical lesions (n = 36) and healthy periapical tissues (n = 10) were evaluated by immunohistochemistry using antibodies specific for human IL-33 and ST2. Lesion samples were further analyzed by double immunofluorescence to assess IL-33/ST2 co-expression. Results: The numbers of IL-33- and ST2-positive fibroblasts were significantly higher in periapical lesions compared to healthy periapical tissues (both P < 0.05), while the numbers of IL-33- and ST2-positive endothelial cells were similar (both P > 0.05). There were no significant differences in the numbers of IL-33- and ST2-positive fibroblasts and endothelial cells between periapical granulomas and radicular cysts (all P > 0.05). Similarly, numbers of ST2-positive mononuclear cells did not differ between periapical granulomas and radicular cysts (P > 0.05). The majority of epithelial cells in radicular cysts were IL-33 positive, while the small proportion of epithelial cells was ST2 positive. Double immunofluorescence analysis revealed IL-33/ST2 co-expression in fibroblasts and endothelial cells. Conclusions: IL-33 and ST2 are expressed in periapical granulomas and radicular cysts. Increased numbers of IL-33- and ST2-positive fibroblasts in periapical lesions when compared to healthy periapical tissues suggest that IL-33/ST2 signaling may be involved in periapical inflammation and tissue fibrosis. [ABSTRACT FROM AUTHOR]

Aim To record the incidence of lesions that were not the sequelae of pulpal necrosis (non- SPN) amongst 1521 biopsies of periapical lesions submitted with a clinical diagnosis of a sequelae of pulpal necrosis ( SPN). Methodology A retrospective study of 1521 biopsy request forms of specimens submitted for histopathological examination with a clinical diagnosis 'periapical inflammation', 'periapical abscess', 'periapical granuloma' or 'periapical cyst' during an arbitrarily selected 14-year period was undertaken. Gender and age of the patient, site and maximum diameter of the lesion, symptoms, inclusion of the final diagnosis in the differential diagnosis and specialty of the clinician submitting the biopsy material were recorded in each case. The final diagnosis for each case was extracted from the pathology report, and two groups were formed, SPN and non- SPN lesions. Differences between the respective features of SPN and non- SPN cases were analysed with Yate's chi-square test and t-test (significance level P < 0.05) Results In 52 of the 1521 cases examined (3.42%), the histological diagnosis was not consistent with a SPN. In most non- SPN cases, the histopathological diagnosis was not included in the differential diagnosis. The keratocystic odontogenic tumour [odontogenic keratocyst ( OKC)] was the most frequent non- SPN lesion (34.62%). Other, yet less frequent, non- SPN lesions included glandular odontogenic cysts, lateral periodontal cysts, central ossifying fibromas as well as malignancies (metastatic carcinomas and Langerhans cell histiocytosis). Conclusions Non- SPN lesions appeared in the periapical region mimicking a SPN, although rarely. Most of them were developmental cysts, in particular OKCs, but odontogenic tumours, such as ameloblastoma, or malignant lesions were also diagnosed. Histological examination of tissue harvested from periapical lesions should be performed, in particular when those lesions are large. [ABSTRACT FROM AUTHOR]

Maxillary cysts, including the cysts lined by respiratory epithelium, can present a diagnostic challenge. We report an unusual case of a maxillary cyst on an endodontically treated tooth #16, in which the cavity was totally lined by a respiratory epithelium. The patient, a 35-year-old male, presented with a generalized chronic periodontitis and complained of a pain in the tooth #16 region. A periodontal pocket extending to the root apices with pus coming out from the gingival was found. A combined endodontic periodontal was observed on a panoramic radiography. CBCT-scan revealed a well-circumscribed radiolucent lesion at the apices of the distobuccal root of the 16. A communication with the right maxillary sinus cavity and a maxillary and ethmoidal sinusitis were also observed. The lesion was removed and histological examination revealed a cyst lined exclusively by respiratory epithelium. Ciliated and rare mucous cells were also observed. The diagnosis could evoke a surgical ciliated cyst mimicking the radicular cyst but the patient has no previous history of trauma or surgery in the maxillofacial region. It could also be an unusual radicular cyst in which the stratified squamous epithelium was destroyed by inflammation and replaced by a respiratory epithelium of the maxillary sinus. [ABSTRACT FROM AUTHOR]

Aim To evaluate the influence of sodium hypochlorite associated with EDTA and etidronate on apical root transportation. Methodology Forty-five roots of human mandibular molars with curvatures of 15-25° were embedded in acrylic resin to allow standardized angulation of the initial and final radiographs. The pre-instrumentation radiographs of the mesiobuccal canal of each root were taken using a radiograph digital sensor with a size 15 K-file in the canal. The canals were prepared with the ProTaper Universal system (Dentsply Maillefer, Ballaigues, Switzerland), using one of the following irrigation regimens during the instrumentation ( n = 15): G1 - irrigation with 20 mL of saline solution (control); G2 - alternating irrigation with 2.5% hypochlorite solution (NaOCl) (15 mL); and 17% ethylenediaminetetraacetic acid (EDTA) (5 mL). During instrumentation, the canal was filled with NaOCl and then between each exchange of instrument filled with EDTA for 1 min, and G3 - irrigation with 20 mL of 5% NaOCl and 18% etidronate solution (HEBP) mixed in equal parts. The postinstrumentation radiographs were made with a F3 instrument in the canal. The images were magnified and superposed with Adobe Photoshop software (Adobe Systems, Mountain View, CA, USA). Apical transportation was determined with AutoCAD 2012 software (Autodesk Inc., San Rafael, CA, USA) by measuring the distance in millimetres between the tips of the instruments. The results were subjected to the nonparametric statistical Kruskal-Wallis test (α < 0.05). Results The median transportation and interquartile range values were 0.00 ± 0.05 for G1, 0.08 ± 0.23 for G2 and 0.13 ± 0.14 for G3. Comparison between groups showed that apical transportation in G3 was significantly greater than in G1 ( P < 0.05). Conclusion The use of Na OCl associated with etidronate increased apical transportation in the canals of extracted teeth. [ABSTRACT FROM AUTHOR]

Aim To investigate whether the apoptotic cascade is activated through the extrinsic pathway in epithelial lining and connective tissue of radicular cysts. Methodology Fifteen radicular cysts were fixed in formalin, embedded in paraffin wax and processed for immunohistochemistry to evaluate the expression of polyclonal antibodies against Tumour necrosis factor-related apoptosis-inducing ligand ( TRAIL), DR5 and caspase-3. Immunocomplexes were treated with the secondary antibodies and finally detected using the avidin-biotin-peroxidase complex. Immunoreactivity was visualized by development with 3,3′-diaminobenzidine. Data were analysed using the Mann-Whitney U-test; P < 0.05 was considered significant. Results The three antibodies were detected in connective tissue fibroblasts of all radicular cysts; TRAIL and DR5 immunoexpression was significantly greater ( P < 0.05) compared with that of caspase-3. The three antibodies were also expressed in almost all epithelial layers and in endothelial cells of newly formed vessels. Conclusion The involvement of apoptosis in the pathogenesis of radicular cysts, demonstrated by the immunoexpression patterns of TRAIL, DR5 and caspase-3 in lining epithelium and connective tissue, may explain their bland clinical aggressiveness and slow, benign evolution. [ABSTRACT FROM AUTHOR]

Aim To investigate the effect of medicaments used in endodontic regeneration on root fracture resistance and microhardness of radicular dentine. Methodology The root canals of mandibular premolars ( n = 180) were instrumented and randomized into three treatment groups and an untreated control group. Each treatment group received either triple antibiotic paste ( TAP), double antibiotic paste ( DAP) or calcium hydroxide paste [Ca( OH)2] intracanal medicament. Teeth were kept in saline for 1 week, 1 month or 3 months. After each time-point, 15 teeth were randomly selected from each group and two root cylinders were obtained from each tooth. One cylinder was subjected to a fracture resistance test, and the other cylinder was used for a microhardness test. Two-way anova and Tukey's pairwise comparisons were used for statistical analysis. Results For the microhardness test, the two-way interaction between group and time was significant ( P < 0.001). The intracanal application of TAP and DAP caused significant and continuous decrease in root dentine microhardness after one ( P < 0.05) and 3 months ( P < 0.001), respectively. The three-month intracanal application of Ca( OH)2 significantly increased the microhardness of root dentine ( P < 0.05). The time factor had a significant effect on fracture resistance ( P < 0.001). The three intracanal medicaments caused significant decreases in fracture resistance ranging between 19% and 30% after 3-month application compared to 1-week application. Conclusion In this laboratory study, the 3-month application of triple antibiotic paste, double antibiotic paste or calcium hydroxide paste medicaments significantly reduced the root fracture resistance of extracted teeth compared to a 1-week application. [ABSTRACT FROM AUTHOR]

Background Radicular ( RC) and dentigerous cysts ( DC) can show a range from little to quite extensive primary/secondary inflammation and it is possible that the variation seen in the fibrous capsule of these cysts might reflect differences in the osteolytic activity. Moreover, the presence of hemorrhagic areas in the fibrous capsule of DC could also contribute to the increase in osteolytic activity. The aim of this study was to compare immunohistochemical expression of nuclear factor κappaB ( RANK), RANK ligand ( RANKL), and osteoprotegerin ( OPG), vascular endothelial growth factor ( VEGF) and angiogenic index in RC and DC. Methods These proteins were evaluated in 20 RC and DC by immunohistochemistry. Angiogenic index was determined by microvessel count ( MVC) using anti-von Willebrand factor antibody. Results RANK and RANKL were higher in DC than RC in fibrous capsule. RC showed higher expression of VEGF in the epithelium and capsule. DC exhibited higher MVC than RC. Conclusions Ours results suggest that RANK and RANKL play an important role in bone resorption in DC and the hemorrhagic areas in the capsule of DC could be explained by increased vessel′s number. The higher VEGF expression in RC might be related to nature of these lesions, where the inflammatory process contributes significantly to these findings. [ABSTRACT FROM AUTHOR]

Objective The aim of this study is to characterize immunohistochemical profiles of lining epithelia of nasopalatine duct cyst ( NPC) as well as to correlate those findings with their clinicopathological features to understand the histopathogenesis of NPC. Materials and methods Forty-one surgical specimens from NPC were examined for clinical profiles and expression of keratin-7, 13, MUC-1, and P63 by immunohistochemistry, compared to radicular cyst ( RC) and maxillary sinusitis. Results Nasopalatine duct cyst was clinically characterized by male predominant occurrence: 44% of the cases involved tooth roots, and 70% with inflammatory backgrounds. Lining epithelia of NPCs without daughter cysts were immunohistochemically distinguished into three layers: a keratin 7-positive (+) ciliated cell layer in the surface, a keratin-13+ middle layer, and a MUC-1+/P63+ lower half, indicating that they were not respiratory epithelia, and the same layering pattern was observed in RC. However, those immunolocalization 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. [ABSTRACT FROM AUTHOR]