Expression pattern of hypoxia-related genes in odontogenic cysts.

OBJECTIVE: The aim of the present study was to reveal the effects of hypoxia-associated signaling in odontogenic cysts. DESIGN: The expression levels of genes involved in the hypoxia-associated signaling pathway were determined by quantitative Polymerase Chain Reaction (PCR) method. RESULTS: As a result, it was found that phosphatase and tensin homolog (PTEN) expression was low (p = 0.037), and the expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (p = 0.0127), hypoxia inducible factor 1 alpha (HIF1A) (p < 0.001), and HIF1A antisense RNA 1 (HIF1A-AS1) (p = 0.0218) were higher in cyst tissue compared to normal tissue. HIF1A gene expression was found to be significantly altered according to the pathologic subtypes of odontogenic keratocyst, dentigerous cyst, and radicular cyst. CONCLUSIONS: Odontogenic cysts were found to have higher expression of HIF1A and HIF1A-AS1, which may be related to the increased hypoxia in these lesions. In addition, PI3K/Akt signaling may be stimulated by increased PIK3CA and decreased PTEN expression, which promote cell survival and support the mechanism of cyst formation.

EXPRESSION OF ALPHA-SMOOTH MUSCLE ACTIN IN ODONTOGENIC CYSTS AND TUMORS.

BACKGROUND: Odontogenic cysts and tumors exhibit different degrees of aggressiveness in their biological behavior. There has been evidence that the presence of myofibroblasts (MFs) at the invasion front promotes tumor invasion. Our study is based on the fact that MFs are important in the biological behavior of odontogenic cysts and tumors. AIM: To assess immunohistochemically expression of alpha-smooth muscle actin (α-SMA) of MFs in odontogenic cysts and tumors and correlate this expression to their biological behavior. MATERIALS AND METHODS: The archival tissues collected for 1.5 years were obtained from the Department of Oral Pathology & Microbiology, People's Dental Academy, Bhopal (India). A total of 40 cases consisting of 10 cases each of odontogenic keratocysts, radicular cysts, dentigerous cysts and ameloblastomas formed the study group. An immunohistochemical analysis of α-SMA expression and localization was carried out. RESULTS: Mean MF counts were the highest in odontogenic keratocysts which was followed by ameloblastomas, entigerous cysts and radicular cysts. Weak α-SMA-expression was found in 50% of cases, moderate in 22.5% of cases, and intense - in 10% cases. MFs were arranged in the spindle, focal, or network patterns in 35; 27.5 and 20% of cases, respectively. CONCLUSION: The analysis revealed that the MFs were distinctly heterogeneous in distribution and pattern of arrangement. This provided persuasive evidence that stroma of these lesions harbor MFs as reflected by α-SMA immunopositive cells.

Prevalence of Nonendodontic Diagnoses in Periapical Biopsies: A 6-year Institutional Experience.

INTRODUCTION: The purpose of this study was to identify nonendodontic periapical lesions (NPLs) mimicking endodontic pathosis, which are most frequently encountered by clinicians. METHODS: A retrospective study was conducted on biopsies obtained from 2015-2020 at Texas A&M College of Dentistry's oral pathology laboratory. The online database was screened for cases submitted as suspected endodontic pathology using specific key words. Histologic diagnoses were collected to determine the prevalence of NPLs that were originally thought to be of endodontic origin. The frequency and percentage of endodontic pathology and NPLs were documented. RESULTS: Among 6704 biopsies clinically diagnosed as endodontic lesions, 190 (2.8%) were histopathologically diagnosed as NPLs. The most frequent NPLs were odontogenic keratocytes' (n = 70, 36.8%), cemento-osseous dysplasia (n = 27, 14.2%), and dentigerous cysts (n = 22, 11.6%). Of all NPLs, 3.7% were malignant neoplasms, with the most common diagnosis being squamous cell carcinoma. Of 6514 endodontic histologic diagnoses, the prevalence of periapical granulomas and cysts was 60.2% (n = 3924) and 39.1% (n = 2549), respectively. CONCLUSIONS: Although most endodontic submissions are likely to be histologically diagnosed as periapical granulomas or cysts, the clinician should be aware that a small portion of these lesions may be nonendodontic in origin and possibly neoplastic in nature. Histopathologic evaluation of biopsied specimens is critical to achieve a proper diagnosis to ensure the appropriate management of patients.

Surgical and prosthodontics management of a perforating giant radicular cyst in anterior maxilla: A case report.

Radicular cyst is the most common type of odontogenic cyst associated with the apex of non-vital teeth. The lining of the radicular cyst usually arises from the epithelial rests of Malassez. These cyst usually persists even after the elimination of microbial load from the root canals. Surgical removal is deemed necessary for the management. For larger lesions extending to the facial or palatal cortical plates, additional regenerative procedures such as bone grafting along with collagen membrane are warranted. This case report describes the surgical and prosthetic management of a giant radicular cyst that was perforating the cortical plates in the anterior maxilla.

Evaluation of CT and MRI Imaging Results of Radicular Cysts, Odontogenic Keratocysts, and Dentigerous Cysts and their Contribution to the Differential Diagnosis.

AIM: This study aimed to evaluate the contribution of the MRI and CT results to the differential diagnosis of histopathologically different odontogenic cysts. BACKGROUND: Odontogenic cysts are commonly seen in the jaw bone and their surgical operations have an important place in the practice of maxillofacial surgery; treatment options for these cysts differ according to their histopathology. Differential results that can be obtained from the radiological evaluations of different cyst groups will allow the surgeon to plan a more accurate approach at the beginning of the operation. In this study, computed tomography (CT) and magnetic resonance imaging (MRI) results of different cyst groups were interpreted together with their histopathological diagnosis. METHODS: CT and MRI results of 17 patients aged between 19-61 were evaluated, whose histopathological diagnosis consisted of 3 radicular cysts (RC), a total of 9 odontogenic keratocysts (OKC) of which 4 were inflamed, and a total of 5 dentigerous cysts (DC) of which one of them was inflammatory. RESULTS: In the CT scan, all cysts showed lytic, a sclerotic surrounding, and showed MRI peripheral enhancement, whereas solid nodular enhancement was only observed in OKCs. Edema and/or air in the surrounding bone medulla was observed in the infected lesions. OKC was heterogeneous, whereas RC and DC were more homogeneous. Diffusion restriction was observed to be frequent in OKCs. The OKCs were ellipsoidal in appearance and were located parallel to the long axis of the bone, and their dimensions were observed to be larger than the other cysts. OKCs may be accompanied by unerupted teeth. Radicular cysts were located perpendicular to the long axis of the bone and were globular in appearance, and their dimensions were smaller and more homogeneous compared to the OKCs. Dentigerous cysts are also accompanied by an unerupted tooth, and their peripheral enhancement is minimal and homogeneous. However, dentigerous cysts can be dense in content and smaller in size, and ellipsoidal localization is more common than OKCs. CONCLUSION: In addition to classic panoramic radiography in the evaluation and differential diagnosis of maxillary and mandibular lesions, CT and MRI evaluations can provide helpful information to the surgeon and pathologist in making the diagnosis and may further help plan the operation.

Release of Matrix Metalloproteinases by Macrophages in Radicular Cysts and Residual Radicular Cysts.

INTRODUCTION: Radicular cysts (RCs) and residual radicular cysts (RRCs) are the sequelae of dental caries and that leads to proliferation of epithelial rests of Malassez in periapical tissues. OBJECTIVES: The aim was to evaluate the relationship between Langerhans cells, macrophages, matrix metalloproteinases (MMP-9, MMP-13), and tumor necrosis factor-alpha (TNF-α) in the capsule and lining epithelium of cystic lesions. MATERIALS AND METHODS: Twenty RCs and 20 RRCs were submitted to immunohistochemical analysis with anti-CD68, anti-CD1a, anti-MMP-9, anti-MMP-13, and anti-TNF-α antibodies. The Mann-Whitney test and the Spearman correlation test were used for analysis of the data (P<0.05). RESULTS: The immunoexpression of MMP-13 and CD68 was significantly higher in RCs when compared with RRCs (P=0.011 and 0.012, respectively). The presence of an intense inflammatory infiltrate was significantly correlated with the immunoexpression of CD68 in RCs (P=0.025). Expression of CD68 showed a significant positive correlation with MMP-13 (P=0.015). A moderate correlation was observed between MMP-9 and MMP-13 (P=0.010). TNF-α expression was more common in RCs (P=0.001). CD1a was more frequently expressed in atrophic epithelium (P=0.041) and was significantly correlated with TNF-α (P=0.014). CONCLUSION: Langerhans cells induce a greater release of TNF-α which, in turn, is responsible for the stimulation of M1 macrophages. Higher immunoexpression of MMP-13 and MMP-9 is observed in the early stages of RCs compared with RRCs. Therefore, the toxins of microorganisms present in highly inflamed RCs are the main factors triggering a proinflammatory immune response and greater cystic expansion in the early stages of these lesions.

Immunocolocalization of Interferon Regulatory Factory 5 with Tumor Necrosis Factor Receptor-associated Factor 6 and AKT2 in Human Apical Periodontitis.

INTRODUCTION: Interferon regulatory factor 5 (IRF5) is critical for the regulation of immune and inflammatory responses in health and diseases. However, the presence of IRF5 in human apical periodontitis remains unknown. This study aimed to explore the expression and colocalization of IRF5 with tumor necrosis factor receptor-associated factor 6 (TRAF6) and AKT2 in human apical periodontitis. METHODS: A total of 39 human periapical tissues, including healthy gingival tissues (n = 12), periapical granulomas (PGs, n = 13), and radicular cysts (RCs, n = 14), were used in this study. The inflammatory infiltrates of lesions were evaluated by hematoxylin-eosin staining. The expression of IRF5 was detected by immunohistochemistry. Double immunofluorescence assessment was performed to colocalize IRF5 with CD68, TRAF6, and AKT2, respectively. Data were analyzed using the Kruskal-Wallis test. RESULTS: Immunohistochemistry revealed significantly higher expressions of IRF5 in PGs and RCs than the healthy control group. IRF5-CD68 double-positive cells were more predominant in RCs and PGs than the healthy control group. Significant differences of the IRF5-TRAF6 and IRF5-AKT2 double-positive cells were detected in periapical lesions compared with the healthy control tissues. CONCLUSIONS: IRF5 was highly expressed in macrophages of human periapical tissues and was colocalized with TRAF6 or AKT2 in human periapical tissues. These findings may provide new clues for understanding the pathogenesis of periapical diseases.

Expression of epithelial growth factors and of apoptosis-regulating proteins, and presence of CD57+ cells in the development of inflammatory periapical lesions.

OBJECTIVE: The mechanisms that stimulate the proliferation of epithelial cells in inflammatory periapical lesions are not completely understood and the literature suggests that changes in the balance between apoptosis and immunity regulation appear to influence this process.To evaluate the expression of the epidermal growth factor (EGF), its receptor (EGFR) and of the keratinocyte growth factor (KGF), the presence of CD57+ cells, the epithelial cell proliferation index, and the expression of the Bcl-2 protein in inflammatory periapical lesions (IPL) at different stages of development. METHODOLOGY: Our sample was composed of 52 IPLs (22 periapical granulomas - PG - and 30 periapical cysts - PC), divided into three groups: PGs, small PCs, and large PCs. Specimens were processed for histopathologic and immunohistochemical analyses. Sections were evaluated according to the amount of positive staining for each antibody. RESULTS: We found no significant differences among the groups regarding Bcl-2 (p=0.328) and Ki-67 (p>0.05) expression or the presence of CD57+ cells (p=0.748). EGF (p=0.0001) and KGF (p=0.0001) expression was more frequent in PCs than in PGs, and CD57+ cells were more frequent in IPLs with intense inflammatory infiltrates (p=0.0001). We found no significant differences in KGF (p=0.423), Bcl-2 (p=0.943), and EGF (p=0.53) expression in relation to inflammatory infiltrates or to the type of PC epithelial lining, but observed greater KGF expression (p=0.0001) in initial PCs. EGFR expression was similar among the groups (p>0.05). CONCLUSION: More frequent EGF and KGF expression in PCs and the greater presence of CD57+ cells in lesions with intense inflammatory infiltrates suggest that these factors influence IPL development. The greater KGF expression in initial PCs suggests its importance for the initial stages of PC formation.

The differences in mitochondrial function, mitochondrial dynamics, and cell death between odontogenic cysts/tumors and normal dental follicles.

We aimed to compare mitochondrial function, mitochondrial dynamics, apoptosis, and necroptosis between odontogenic cysts/tumors, including radicular cysts, dentigerous cysts, ameloblastoma, vs. dental follicles as control. We demonstrated that mitochondrial dysregulation and imbalanced mitochondrial dynamics were observed in ameloblastoma. Apoptosis was increased in dentigerous cysts, and ameloblastoma, while necroptosis was suppressed in ameloblastoma. Necroptosis in radicular cysts was higher than that of control, suggesting that the inflammation-associated cell death occurred in radicular cysts. Our findings suggest ameloblastoma exhibited mitochondrial dysfunction, decreased mitochondrial fusion, and potential apoptosis. Therefore, alleviating mitochondrial dysregulation and apoptosis may be novel-targeted therapy for odontogenic cysts and tumors.

Langerhans Cells Correlate With Macrophages for Defense Mechanisms in the Atrophic Epithelium of Radicular Cysts.

Langerhans cells (LCs) play important roles in cell-mediated immune reactions, as well as in the pathogenesis of periapical lesions. The aim of this study is to evaluate the role of LCs in the proliferative epithelium of radicular cysts (RCs) and the release of the proinflammatory cytokine tumor necrosis factor α (TNF-α) associated with epithelial thickness. Thirty cases of RCs and 30 cases of residual RCs were randomly selected. Morphologic analysis was performed to evaluate the association between the inflammatory infiltrate, cystic epithelial thickness and lesion size, in addition to immunohistochemical assessment of CD1a, CD68, and TNF-α. The highest macrophage percentages and TNF-α scores were found in RCs (P=0.038 and 0.017, respectively). The largest number of LCs was observed in RCs (P=0.021), especially those exhibiting atrophic epithelium (P=0.05). In addition, LCs were positively correlated with the number of macrophages in both RCs and residual RCs (P=0.033 and 0.002, respectively). In contrast to LCs, the largest number of macrophages was detected in cases with an intense inflammatory infiltrate (P=0.022). In addition, the highest TNF-α scores were associated with an intense inflammatory infiltrate (P=0.024) when analyzed in the capsule of RCs (P=0.017). In conclusion, LCs participate in defense mechanisms and were present in all cases evaluated. Along with macrophages, these cells release proinflammatory cytokines such as TNF-α, which is responsible for inducing the continued proliferation of cystic epithelium.

Differentiated Immunohistochemical Expression of Osteoclastogenic Markers in Radicular Cyst, Odontogenic Keratocyst, and Ameloblastoma.

The aim of this study was to investigate the osteoclastogenesis process by means of immunohistochemical markers for receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), interleukin-6 (IL-6), and cathepsin K (CTSK) antigens in osteolytic lesions of maxillary bones. The sample consisted of 23 radicular cysts (RC), 25 odontogenic keratocysts (OKC), and 25 ameloblastomas (AM). RANKL was statistically higher in RC (49.6±15.2/53.7±18) and OKC (48.6±15.1/51.4±16.8) when compared with AM (37.2±12.5/36.4±13) in the epithelium and connective tissue. OPG was lower in OKC (34.8±18.5) only in connective tissue when compared with RC (44.5±11.2). The expression of RANKL was statistically higher than OPG in RC (epithelium and connective tissue) and OKC (connective tissue). For IL-6, a statistical difference was observed only in the connective tissue between groups, with higher expression in RC (48.2±15) and lower in OKC (22±11.9). The expression of IL-6 was correlated with the intensity of the inflammatory infiltrate. CTSK was statistically higher in AM (34±19) and OKC (29±13.8) compared with RC (19±10.5). According to the results of the present research the bone resorption in cysts and odontogenic tumors occurs through different mechanisms. The ostoclastogenic process in lesions with aggressive clinical behavior, as AM and OKC, seems to be associated with the expression of CTSK. In contrast, lesions with inflammatory etiology, as RC, the expression of IL-6 seems to have an important role in the bone resorption process. The highest expression of RANKL under the expression of OPG also seems to contribute to the growth mechanism of RC and OKC.

Comparative Metabolomics Reveals the Microenvironment of Common T-Helper Cells and Differential Immune Cells Linked to Unique Periapical Lesions.

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.

Residual cyst of the jaws: A clinico-pathologic study of this seemingly inconspicuous lesion.

OBJECTIVES: Residual cysts are relatively rare inflammatory cysts of the jaws. They are essentially radicular cysts without the presence of the offending dentition. These lesions have the ability to destroy bone within the jaws without any symptoms. Moreover, they can mimic more aggressive cysts and tumours on radiographs. The aim of this study was to describe the clinico-pathological features of residual cysts in order to discern them from other cystic lesions as well as analyse their management and recurrence patterns. MATERIALS AND METHODS: Sixty-four histopathologically confirmed residual cysts were analysed based on their clinical, radiological and histopathological features. Their management and follow-up were also noted. RESULTS: The majority of lesions presented in elderly (46.8%), edentulous patients (60.9%) and were most commonly found in the posterior regions of the mandible (51.6%). Clinico-pathological features that aided in their diagnosis included long-standing history with slow growing swelling and presence of well-defined, unilocular cystic lesion associated with previously extracted dentition. Enucleation was a successful method in the management of residual cysts with very low recurrence rate (1.6%). Two patients (3.1%) developed squamous cell carcinoma from the cyst lining. CONCLUSION: Residual cysts should be high on the list of differential diagnosis when elderly, edentulous patients present with cystic lesions in the jaws compared to dentate patients (P<0.01). All lesions should by biopsied and sent for histopathological examination along with radiological correlation as they have the potential to transform into primary intra-osseous squamous cell carcinoma with devastating consequences to the patient.

Dental Apical Inflammation Score (DAIS): Histopathological scoring for the evaluation of the apical inflammatory activity and local bone destruction.

OBJECTIVE: The purpose of this study was to evaluate 210 periapical lesions with a newly created Dental Apical Inflammation Score/DAIS with regard to their inflammatory cell infiltration, bone tissue, epithelium, bacteria and foreign material. STUDY DESIGN: Specimens were obtained from 51 different dental practices over a period of 11 months. These specimens were then sent in for histopathological routine diagnostics. RESULTS: The DAIS classified 81 cases of Type 1 (acute inflammation = low, chronic inflammation = low), 79 cases of Type 2 (acute inflammation = low, chronic inflammation = high), 46 cases of Type 3 (acute inflammation = high, chronic inflammation = low) and 4 cases of Type 4 (acute inflammation = high, chronic inflammation = high). Bone tissue was found in 141 cases, signs for bacterial osteitis in 49 cases, cyst epithelium in 40 cases and foreign material in 27 cases. In 210 cases, cyst epithelium was evident in 27.2 % of Type 1, 15.2 % of Type 2, 8.7 % of Type 3 and in 50 % of Type 4 (p = .019). The 141 cases containing bone tissue showed signs of bacterial osteitis in 16.1 % of Type 1, 29.8 % of Type 2, 77.8 % of Type 3 and in 100 % of Type 4 (p < .001). In 64 cases, Bacteria was evident in 30 % of Type 1, 25 % of Type 2, 55 % of Type 3 and in 100 % of Type 4 (p = .013). CONCLUSION: The DAIS could classify apical lesions with statistically significant differences. Bacterial osteitis in apical lesions was reported for the first time.

Myofibroblasts and increased angiogenesis contribute to periapical cystic injury containment and repair

BACKGROUND: Myofibroblasts (MF) and angiogenesis are important factors in the development and expansion of cystic lesions, where these cells secrete growth factors and proteases, stimulating angiogenesis, matrix deposition and cell migration, affecting the growth of these periapicopathies. The present study aimed to evaluate the immunohistochemical expression of CD34 and Alpha-SMA in radicular cysts (RC) and residual radicular cysts (RRC), with the purpose of contributing to a better understanding of the expansion and progression of these periapical lesions. MATERIAL AND METHODS: The present study os a descriptive, quantitative and comparative analysis of positive CD34 and Alpha-SMA immunohistochemical expressions in 30 RC and 30 RRC specimens. Alpha-SMA expression was evaluated in the fibrous capsule of the lesions, at 100x magnification below the epithelial lining. A total of 10 higher immunostaining fields were selected and subsequently, positive cells were quantified at 400x magnification, averaged per field. Regarding the angiogenic index, immuno-labeled microvessel counts for the anti-CD34 antibody were performed in 10 fields at 200x magnification. RESULTS: Statistically significant differences regarding Alpha-SMA immunostaining were observed (p = 0.035), as well as a correlation between Alpha-SMA versus CD34 (p = 0.004) in RRC. However, the angiogenic index obtained by immunostaining for CD34 indicated no statistical difference between lesions. Intense inflammatory infiltrates were predominant in RC, while mild and moderate degrees were more commonly observed in RRC (p < 0.001). Intense inflammatory infiltrates were also more often noted in larger RRC (p = 0.041). Inflammatory infiltrates showed no significant correlation with α-SMA and CD34 immunostaining. CONCLUSIONS: The results indicate that the significant correlation found between the presence of MF and the angiogenic index are related to the repair process in RRC

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Accuracy for diagnosis of periapical cystic lesions.

Clinical differentiation between cystic lesions of endodontic and non-endodontic origin is of importance because correct diagnosis may affect treatment decision making. Most radicular cysts are treated with conservative approaches and, therefore, are not surgically removed. The objective of this study was to determine the accuracy of clinical diagnosis of periapical lesions as compared to the histological findings, and to evaluate various associated factors. All biopsy specimens submitted for histological evaluation from 2002 to 2009 were assessed. Only cases of periapical lesions with complete patient data and clinical diagnosis were included. Sensitivity, specificity and accuracy of the clinical diagnosis were calculated and various patient-related factors were evaluated. Of the 4,908 cases, 183 met inclusion criteria. Histologically, there were 171 lesions of radicular cysts and 12 cases of non-endodontic cysts, including OKC and Incisive Canal Cyst. The diagnostic accuracy for clinical diagnosis for radicular cysts was 91.84% and 91.84% for non-endodontic cysts. There was a high accuracy of clinical differentiation between cystic lesions of endodontic and non-endodontic origin. However, some non-endodontic lesions may be incorrectly diagnosed clinically as lesions of endodontic origin. Histological evaluation may be necessary for the correct diagnosis. Further clinical studies are needed to evaluate clinical examination and histological diagnosis of periapical lesions.

Periapical Cyst and Odontogenic Remnants on Osseous Mandibulectomy Margins: Two Diagnostic Pitfalls.

In this article, we describe 2 high-stake diagnostic pitfalls that occurred in a single patient having undergone partial glossectomy and marginal mandibulectomy for invasive squamous cell carcinoma. Margins were grossly uninvolved. Histopathology showed a moderately differentiated squamous cell carcinoma. Microscopic evaluation of margins was challenging, as the inferior osseous margin submitted en face showed spongiotic epithelium with mixed chronic and acute inflammation, representing a periapical cyst after correlation with the gross examination. Another section of the osseous margin showed a small non-atypical epithelial nest, consistent with an odontogenic epithelial rest. We wish to raise awareness of these diagnostic pitfalls as a bone margin with such epithelial foci could be misinterpreted as positive, with serious therapeutic consequences.

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects.

The aim of this study was to evaluate macrophage M1 and M2 subpopulations in radicular cysts (RCs) and periapical granulomas (PGs) and relate them to clinical and morphological aspects. M1 macrophages were evaluated by the percentage of CD68 immunostaining associated with the inflammatory cytokine TNF-α, and M2 macrophages, by its specific CD163 antibody. The CD68+/CD163+ ratio was adopted to distinguish between the two macrophage subpopulations. Clinical, radiographic, symptomatology, treatment, and morphological parameters of lesions were collected and a significance level of p = 0.05 was adopted for statistical analysis. The results showed that the CD68+/CD163+ ratio was higher in the RCs (median = 1.22, p = 0.002), and the highest TNF-α immunostaining scores were found in RCs (p = 0.018); in PGs, the CD68+/CD163+ ratio was lower and associated with a greater CD163+ immunostaining (median = 1.02, p <0.001). The TNF-α in cyst epithelium had a score of 3 in 10 cases and predominance of M1 macrophages by CD68+/CD163+ (median = 2.23). In addition, CD68+ cells had higher percentage of immunostaining in smaller RCs (p = 0.034). Our findings suggest that increased CD68 immunostaining associated with TNF-α cytokine in RCs results in a greater differentiation of the M1 phenotype. The higher CD163 immunostaining in PGs results in greater differentiation of the M2 phenotype. Therefore, the inflammatory state promoted by M1 macrophages is related to growth and progression of RCs; on the other hand, the immunomodulatory state of M2 macrophages is related to maintenance of PGs.

Stromal Expression of CD10 by Immunohistochemistry in Odontogenic Keratocyst (OKC), Dentigerous and Radicular Cysts and Its Correlation with Local Recurrence and Aggressive Behaviour

Objective: To assess and compare the stromal expression of CD10 in OKC, dentigerous and radicular cysts. Materials and Methods: This comparative, cross sectional study was conducted at Armed Forces Institute of Pathology (AFIP), Rawalpindi, from Jan 2017 to Dec 2017. Total sixty cases comprising 20 of each OKC, Dentigerous and Radicular cysts were included in this study. Hematoxylin and eosin (H and E) sections were performed followed by immunohistochemical staining for CD10 antibody. Expression of CD10 was evaluated and compared. Results were analyzed by using SPSS version 20.0. Chi Square test was performed with P value < 0.05 was considered as significant. Results: A total of 60 cases, 20 of each OKC, dentigerous and radicular cysts were taken. In our study, 38 (63.3%) male and 22 (36.7%) female patients with the mean age of 32 ± 15 (mean ± SD) were included. Percentage of CD10 positive cells were highest in sub-epithelial stroma of OKC (95% cases) as compared to radicular and dentigerous cysts (60 and 70%) with highest number of cases showing intense staining in OKC 13(65%) as compared to other odontogenic cysts i-e 4(20%) and 2 (10%) respectively. There was a statistically significant association between odontogenic cysts and proportional score, intensity score and combined score of stromal CD10 expression (P=0.009, p=0.001 and p=0.000). Conclusion: In this study, we found that highest stromal CD10 expression in OKC as compared to dentigerous and radicular cyst, which might be due to aggressive behaviour and increased risk of recurrence in OKC. Expression of CD10 marker will further aid the clinician to plan appropriate surgical intervention and keep regular follow-ups to identify recurrences.