Comparative manual and digital analysis of gonial angle in lateral cephalograms for gender determination.

Human skull has always been used for victim identification in forensic odontology. The gender-dimorphic bone of the skull is the mandible. The gonial angle has frequently been investigated for gender estimation with variable results and requires further exploration. We aim to compare the efficacy of gonial angle estimation by ancient methods of lateral cephalometric tracing compared with more recent digital analysis methods for gender estimation in the Indian population. Lateral cephalograms of 191 (96 M and 95F) cases above the age of 17 years were retrieved. Cephalometric analysis of gonial angle on radiographs was done using both manual cephalometric tracing method and digitally using Adobe Photoshop software. The results were subjected to statistical analysis for evaluation. The mean gonial angle was higher in females (125.05; 123.77 and 125.28) than in males (122.583; 121.715 and 122.008) using both manual and digital methods. On applying the logistical regression analysis (LRA), the digital method showed the highest gender estimation accuracy of 60.7% followed by Burstone's analysis (57.1%) and manual conventional analysis (56.5%). Burstone's analysis (57.9%) correctly identified increased females, whereas digital analysis (62.5%) and manual conventional analysis (59.4%) accurately recognised increased males. The present study showed a higher gender estimation accuracy using digital methods as compared to manual methods, but it still lacks the credibility to be used as a sole factor for predicting the gender of an individual. Hence, a cumulative factor must be taken into consideration for gender identification which would provide more promising results.

Localization of beta catenin across the domain of odontogenic lesions: A systematic review.

BACKGROUND: CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its translocation into cytoplasm and nucleus could trigger cell proliferation, inhibition of apoptosis, invasion and migration of the tumour cell. MATERIALS AND METHODS: Five electronic databases including MEDLINE by PubMed, Google scholar, Scopus, Trip, Cochrane library and EMBASE until 1 January 2023 without period restriction were thoroughly searched. Those articles that identified CTNNB1 mutation and beta catenin in odontogenic lesions were included for review. Risk of bias was analysed for each study using QUADAS 2 tool and Review Manager 5.3 was used to output its result. RESULTS: Thirty four published articles were included for data synthesis. A total of 1092 cases of odontogenic lesions were assessed for both CTNNB1 mutation and beta catenin expression. CTNNB1 mutation was observed in ameloblastoma, calcifying odontogenic cyst, calcifying cystic odontogenic tumour and all malignant odontogenic tumours. The beta catenin expression (nuclear and cytoplasmic) was maximum in odontogenic keratocyst and calcifying odontogenic cyst. The expression was variable in ameloblastomas, membranous in odontomas, calcifying cystic odontogenic tumour and nuclear in all malignant tumours. DISCUSSION AND CONCLUSION: High recurrence of odontogenic keratocyst and aggressiveness of solid ameloblastoma and malignant odontogenic tumours could be associated with the nuclear translocation of beta catenin. Disparity between CTNNB1 mutation and beta catenin expression within odontogenic lesions suggests alternate routes of beta catenin activation. The review results support the unique localisation of beta catenin as a helpful diagnostic factor in the pathogenesis of odontogenic lesions.

An exotic pathogenetic mechanism of angiogenesis in oral lichen planus-A systematic review.

OBJECTIVE: Angiogenesis plays a vital role at the molecular level in various inflammatory lesions, that lead to their chronicity. Oral lichen planus is an immune-mediated chronic inflammatory disorder. The angiogenetic role and exact mechanisms in oral lichen planus are still unclear due to a dearth of studies. Its clinical significance with angiogenesis also requires further elucidation necessitating a thorough review of the studies that have been conducted so far. The present review was designed to identify the dependence of oral lichen planus progression on angiogenesis which could aid in devising metronomic treatments required to halt the progression of this disease. MATERIALS AND METHODS: A thorough search was made using MEDLINE by PubMed, Scopus, Google scholar, Cochrane library, and EMBASE databases. Original research articles, that immunohistochemically evaluated angiogenesis in oral lichen planus were included for review. Risk of bias was analysed for each study using Modified Newcastle-Ottawa scale and Review Manager 5.4 was used to output its result. RESULTS: Twenty-nine published articles were included for data synthesis. The most commonly employed antibody was CD34, however, upregulated VEGF expression was the principal while ICAM-1, VCAM-1, and PECAM-1 were critical angiogenic factors to mediate angiogenesis in oral lichen planus. CONCLUSION: The current evidence supports that angiogenesis, a fundamental pathogenetic mechanism of oral lichen planus, leads to its persistence and chronicity. However, studies with a larger sample size, standard evaluation criteria, different subtypes, and adequate follow-up are warranted.

Immunohistochemical evaluation of cyclooxygenase-2 and mast cell density in periapical lesions.

AIM: Periapical granuloma (PG) and cyst (PC) are formed as a protective response consequent to pulpal infection leaching through the apical foramen and lateral canals. Various inflammatory mediators like mast cells and cyclooxygenase (COX)-2 are involved in this intricate process. This pilot study aimed to evaluate and compare the immunoexpression of tryptase and COX-2 in periapical granuloma and periapical cyst, and also correlate them with intensity of inflammatory infiltrate and thickness of cystic epithelial lining. METHODOLOGY: An observational and cross-sectional study was conducted on paraffin-embedded tissue sections of 50 PGs and 50 PCs submitted for morphological and immunohistochemical analysis using anti-tryptase and anti-COX-2 antibodies. The mean number of mast cells (total, granulated and degranulated), mean COX-2 expression and inflammatory score was calculated. The data obtained were analysed using Mann Whitney U, Student's T, Chi-square and Spearman correlation test (p < .05). RESULTS: The inflammatory score, total mast cells and COX-2 expression were similar in PGs and PCs (p = .352, .339 and .352) however, the degranulated mast cells were highly significant in PC while granulated mast cells were highly significant in PG respectively (p < .001 in both). Although a non-significant correlation existed between COX-2 and total mast cells in both groups but, total mast cells were significantly correlated with epithelial thickness in PC (p = .029). CONCLUSIONS: Mast cells and cyclooxygenase-2 proved to be independent inflammatory markers in periapical lesions. Further studies should be planned on mast cell and COX-2 inhibitors as treatment modalities of periapical lesions.

Primordial Odontogenic Tumor of Anterior Maxilla in a Young Male: A Case Report and an Updated Review of Literature.

Primordial odontogenic tumor (POT) is a recently designated benign mixed epithelial and mesenchymal odontogenic tumor and only sixteen cases have been reported worldwide till now. Here we report an another case of POT in a 14-year old boy who presented with an asymptomatic buccal enlargement in the right maxillary region for past 4-5 months. A well-defined, unilocular, radiolucent lesion with impacted teeth was observed radiographically. A detailed account of clinico-radiographical and histolological differential diagnoses along with an updated literature review has been presented.

Bucco-Parapharyngeal Occurrence of Pleomorphic Spindle Cell Lipoma-A Unique Entity: Case Report.

Lipomas are common benign neoplasms of oral region which occur scarcely in the parapharyngeal space (PPS). The diversity observed in its histologic presentation classified it into many subtypes among which Spindle Cell Lipoma (SCL) is a rare entity. SCL is an uncommon benign tumor of adipose tissue usually located superficially in the neck, back and shoulder region but its presentation in oral and pharyngeal spaces is very rare. Exhaustive literature search for oral and pharyngeal space pleomorphic SCL till date revealed 45 cases of oral SCL with a mean age distribution of 55 years. Only one reported case of parapharyngeal occurrence of pleomorphic SCL was found. A rare case of pleomorphic variant of SCL in PPS extending into the buccal space is being presented. This case could be the first to report the multiple presentation and the youngest age of occurrence of SCL in PPS.

Potential immmunohistochemical markers to characterize epithelial-mesenchymal transition in pleomorphic adenoma.

BACKGOUND: The histogenesis process of pleomorphic adenoma (PA) of salivary gland continues to remain a controversial subject. In this neoplasm, transition occurs from an epithelial or myoepithelial cell to a stromal element and is called an epithelial-mesenchymal transition (EMT) resulting in heterogeneity. The present research was aimed to study the morphological characteristics of varied components and epithelial-mesenchymal transitions in PA using histopathological and immunohistochemical (IHC) analysis. MATERIALS & METHODS: For this purpose 15 PAs cases were selected from the archives and from each case of PA and 5 cases of normal salivary gland, five additional sections were cut from each for immunohistochemical analysis using E- cadherin, vimentin and a-actin. The numbers of immunoreactive cells were semi- quantitatively measured and also determined the intensity of the immunostaining reaction. RESULT: Immunohistochemically, as the cells transitioned from the lumial cells to descrete/detached cells of ductal structures, the percentage of positive cells tends to decrease for E- cadherin and increases for vimentin and actin. Additionally, neoplastic cells towards the periphery of ducal-cystic structures or completely detached cells in the stroma showed intense to moderate positivity for vimentin and alpha smooth muscle actin (a-SMA). Chondroid/ hyalinized or myxoid stroma showed variable staining with these markers. CONCLUSION: Our study provides the evidence that epithelial-mesenchymal transition process represent the basic principle of the tisuse heterogeneity in pleomorphic adenomas.

A radiolucent lesion presenting calcification histopathologically: a classical case of CEOT.

OBJECTIVE: The calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic neoplasm that accounts for approximately 1% of all odontogenic tumors. Histologically, it shows sheets of polyhedral epithelial cells with deep eosinophilic cytoplasm and prominent nuclei. Globules of amyloid like material among tumor cells which undergoes calcification are evident. We present a case of CEOT which presented classical histopathologic picture but clinico- radiological it presented variably. Its non association with impacted tooth, no calcifications in the incisional material and finally on excision giving its classical picture of prominent intercellular bridges, hyperchromatic polyhedral cells and amyloid with calcifications made it an interesting case to report.

A mismatch of tumor grade and biologic behaviour in a rare case of Sclerosing Mucoepidermoid Carcinoma of Parotid - with review of literature.

OBJECTIVE: Although mucoepidermoid carcinoma is the most common primary malignancy of the salivary glands, the sclerosing morphologic variant of this tumor is extremely rare and only 26 cases have been reported till date in the english literature. This report describes a case involving a 35-year-old female with an intermediate-grade sclerosing mucoepidermoid carcinoma of parotid gland and we review the litreture. Immunohitochemical markers, Her-2/neu and MIB-1 evaluated to help predict the clinical outcome and to determine whether an association exists between the histologic grade and immunohistochemical findings. A PAS stain revealed cytic spaces filled with basophilic material. We found MIB-1 labeling indices of >50% and strong positivity for Her-2/neu suggesting poor prognosis. Our case did not show any correlation between MIB-1 index and tumor grade as shown in other case reports. This unusual but distinctive variant of mucoepidermoid carcinoma can be difficult to recognize and is frequently misdiagnosed as a benign lesion.

Entering the Double Digits-Ewing Sarcoma In Adult Maxilla.

OBJECTIVE: Ewing sarcoma is a rare malignant pediatric sarcoma of bone and soft tissues, which is more unusual in head and neck region. Although the exact histogenesis is still unknown, various cells have been proposed as cells of origin namely, endothelial, hematopoietic, fibroblastic, mesenchymal stem cells or neural derived mesenchymal stem cells. ES is more common in younger age group and among the gnathic bones, mandible is affected more than maxilla. This paper presents the first case of Ewing Sarcoma in the maxilla being reported in the adult age group from India and among the very few reported worldwide.

Immunohistochemical Comparison of Ki-67 and MCM-3 in Odontogenic Cysts: An Observational Study.

Odontogenic cysts are a diverse group of pathologic entities with different proliferation potential, leading to variations in their biological behavior. One of the most cited proliferation markers used in diagnostic histopathology is Ki-67. Another group of proteins recently investigated is minichromosome maintenance (MCM-3) and its expression has been evaluated in several odontogenic lesions but the results were controversial. Thus, the present study endeavored to compare the expression of MCM-3 and Ki-67 in odontogenic cysts. Furthermore, a pioneer attempt was made to evaluate the sensitivity of these markers to inflammation. A total of 101 cases (37 dentigerous cysts, 37 odontogenic keratocysts, and 27 radicular cysts) were included. Immunohistochemical expression of Ki-67 and MCM-3 were investigated using a labeling index (LI). In addition, they were scored for inflammation, followed by correlation with both markers. The data obtained were subjected to statistical analysis ( P <0.05). Overall, a higher LI of MCM-3 than Ki-67 was obtained in all study groups along with a positive correlation of Ki-67 LI with inflammation. Thus, MCM-3 proteins proved to be a more accurate means to determine the proliferation potential and were not sensitive to external stimuli like inflammation than conventional markers, such as Ki-67.

Keloid of Pinna Revealed a Chondroid Syringoma in Disguise.

Cutaneous mixed tumor or chondroid syringoma is a rare benign, skin appendageal tumor prevalent in areas of the head and neck. It represents the cutaneous counterpart of the pleomorphic adenoma of salivary glands. Its clinical presentation often misguides the clinician to underdiagnose it as a reactive lesion. We report the case of a 94-year-old male admitted for excision of cutaneous carcinoma concurrently with a chondroid syringoma of the pinna provisionally misdiagnosed as a keloid.

Association of Cellular Cannibalism with Immunohistochemical Expression of CD31, CD68 and BCL2 in Oral Squamous Cell Carcinoma: An Observational Study.

Objective: Cellular cannibalism (CC) is a prime metabolic event to determine the aggressive potential of oral squamous cell carcinoma (OSCC). However, the etiology and mechanism behind this degradation are still ambiguous. The aim of the study was to explore the etiopathogenetic mechanism behind CC, along with its association with degree of differentiation, angiogenic, phagocytic and antiapoptotic activity in OSCC. Design: Seventy-three tissue sections of various histological grades of OSCC were retrieved from departmental archives and scanned for cannibalistic cells. Immunohistochemical analysis using CD31, CD68, and BCL2 was performed. The data obtained were analyzed using Chi-square, Spearman's correlation test and multiple regression analysis (p < 0.05). Results: CCs were present significantly in various grades of OSCC (p < 0.00). Immunohistochemical analysis revealed a significant difference in CD68, BCL2 (p < 0.05 in both), and CD31 (p < 0.001) expression with CC. The internalized cells showed positivity for CD68 and negativity for BCL2. Regression analysis revealed that tumor grade, CD31 and BCL2 immunoreactivity were significant predictors of frequency of CC. Conclusion: The association of CC with degree of differentiation, CD31, CD68, and BCL2 expression could predict the biological behavior of OSCC and might serve as a promising histopathological parameter in future.

Histomorphological Evidence of Complex Cannibalism-An Uncharted Territory in Oral Squamous Cell Carcinoma.

Complex cannibalism (CxC) is an emerging new seeming entity in oral squamous cell carcinoma (OSCC) embody as a prime metabolic event in determining the aggressive potential. Owing to paucity in literature regarding it, the aim of the present study to deciphering the occurrence of CxC in OSCC. Further, the expression of cluster of differentiation 68 (CD68) was studied in tumor cells and correlated with CxC to ascertain the biological behaviour of OSCC. 30 Hematoxylin and Eosin stained sections of various grades of OSCC were scanned for CxC and correlated with clinicopathological parameters. Immunohistochemical analysis using CD68 was performed. While observing CxC in OSCC, statistically significant in age (p-0.048) and histological grades (p-0.004). CD68 expression in tumor cells was statistically significant in histopathological grades (p < 0.001) whereas on correlating with CxC (p - 0.171) was non-significant. The analogous rise in CxC and CD68 with increasing histopathological grades could aid in recognising CxC as a precise histopathological parameter to assess the aggressive biological potential in OSCC.

Diagnostic Utility of Expression Pattern of S100/Mammaglobin/SOX10/DOG 1 Immunohistochemistry in Differentiation of Secretory and Acinic Cell Carcinoma: A Systematic Review and Meta-Analysis.

Secretory carcinoma (SC) is a relatively new disease entity, separate from acinic cell carcinoma (AciCC), which frequently displays ETV6-NTRK3 gene fusion. However, the differences between SC and AciCC remain ambiguous. Genetic diversity makes its diagnosis complicated. In this regard combined expression of immunohistochemistry markers S100/Mammaglobin/SOX10 and DOG1 is need of the hour as alternative methodology. The current systematic review was to investigate the diagnostic utility of combined immunohistochemical expression of S100/Mammaglobin/SOX10/DOG1 in distinction of SC from AciCC histologically. An electronic search of databases was carried out using MEDLINE by PubMed, Google scholar, Scopus and Web of science. Articles inclusive of SC and AciCC were assessed with S100/Mammaglobin/SOX10/DOG1 immunohistochemistry and their predominant expression pattern, predictive values, sensitivity and specificity were gathered. Fourteen eligible articles were analysed, which revealed predominant immunostaining pattern of S100 + /Mammaglobin + /SOX10 + /DOG1- by nearly all ETV6::NTRK3 fusion prevalent SCs alongside with other gene fusions like RET, MET and MAML3 with 98.4% sensitivity as well as 86.1% specificity. The evidence supports that S100/Mammaglobin/SOX10/DOG1 combined immunostaining can serve as a reliable diagnostic method to differentiate secretory from acinic cell carcinoma.

Interobserver Reliability of Milan and Modified Milan System for Reporting Salivary Gland Cytopathology: An Institutional Experience.

Background: In 2018, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published, defining a diagnostic categorization scheme. However, this system of classification was criticized due to its suboptimal diagnostic accuracy and low interobserver reliability. For these reasons, the modified Milan system was recently proposed by a few authors claiming it to be more clinically reliable. The present study aimed to analyze the interobserver reliability of MSRSGC and modified MSRSGC. Methods: A total of 100 salivary gland fine-needle aspirations were reviewed over a 1-year period and classified by two independent observers according to MSRSGC and modified MSRSGC. Interobserver reproducibility was estimated using observed agreement and chance-corrected agreement (Cohen's kappa). Results: An overall chance corrected agreement of 0.37 (fair) was obtained for the original Milan system and 0.41 (moderate) for the modified one. In addition, subcategories of modified MSRSGC performed better than the MSRSGC in terms of interobserver reliability. Conclusion: The present study suggests that modified MSRSGC should be accepted worldwide as the clinical relevance of any categorization scheme requires diagnostic accuracy along with excellent interobserver reproducibility.

The intriguing role of IL33/ST2 axis signaling in oral diseases - A systematic review.

PURPOSE: Oral diseases act as a silent epidemic, and the pathogenetic role of interleukin-33/suppression of tumorigenicity-2 axis (IL-33/ST2) remains unclear due to a lack of literature. This review has attempted to highlight the importance of this axis in oral diseases, which may be helpful in developing therapeutic modalities required to halt disease progression. MATERIALS AND METHODS: A thorough search was conducted using various databases. Original research articles that assessed both IL-33 and ST2 levels in oral diseases using different techniques were included in the review. The risk of bias for each study was analyzed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and Review Manager 5.4 was used to output the results. RESULTS: In the qualitative data synthesis we included 13 published articles. The most commonly used method was serum estimation, while methods with optimistic results were saliva, real-time quantitative polymerase chain reaction and immunohistochemistry. The predominant mechanism of action was nuclear factor kappa B signaling and type 2 immune response. However, salivary gland epithelial cell activation, activation of mast cells, type 1 immune response, and upregulated angiogenesis are crucial in mediating IL-33/ST2 signaling in oral diseases. CONCLUSIONS: Accumulating evidence demonstrates that the IL-33/ST2 axis is a fundamental pathogenetic mechanism of oral diseases of inflammatory, autoimmune, or neoplastic origin.

Acantholytic oral squamous cell carcinoma with clear cell change - a rare amalgamated variant.

Background: Acantholytic squamous cell carcinoma (ASCC) is an uncommon histological variation of oral squamous cell carcinoma (OSCC), accounting for fewer than 4% of all occurrences. The tumor shows a slight masculine predisposition, with the lower lip being the most commonly affected location. ASCC is reported to have a diverse biologic behavior, which explains its ability to metastasize to distant places and, thus, its poor prognosis. Similarly, clear cell change in OSCC is a rare occurrence with an unknown etiology that suggests its aggressive nature. Method and Results: Histopathology reveals central acantholytic cells with numerous duct-like features. The presence of distinct cytological atypia contributes to the diagnosis of SCC. Special stains and IHC aid in distinguishing tumor from other histopathologically similar entities. Conclusion: The case of a 29-year-old male presented here with an updated literature review highlights the need for histological study of the unique and seldom seen oral ASCC with clear cell change, which can be ignored because of similarities with other entities. Because recurrence rates are so high for ASCC, amalgamated clear cell change makes it critical for proper treatment initiation with a definite diagnosis. To the best of our knowledge, this is the first documented occurrence. Our experience with the present case suspected a more aggressive behavior due to a high Ki-67 index, anticipating a poorer prognosis in the oral cavity considering the patient's young age.

Demystifying Histologic Conundrum of Adenoid Ameloblastoma: Case Report with Literature Review.

Introduction: Odontogenic tumors encompass a heterogeneous group of lesions that range from hamartomatous lesions to malignancy. Considerable variation in histologic presentation can mislead their accurate diagnosis and categorization. Ameloblastoma is generally well understood and is easy to diagnose but there has been a constant change in the classification systems ever since Broca classified odontogenic tumors in the year 1867. Over the years, it has been modified by the World Health Organization with many additions and omissions. This dynamic change is based on the result and conclusions of molecular and genetic studies with the last modification in 2017. Case Report: We present two cases of females aged 32 and 60 years who reported with facial swellings, revealed the presence of distinct histopathological findings and were diagnosed as ameloblastoma with dentinoid or adenoid ameloblastoma. Literature search revealed dearth of distinct forms of ameloblastoma that show the formation of duct like structures and dentinoid. Conclusion: It is interesting to highlight such cases as the biological behavior is still unexplored due to paucity of relevant studies and follow up of patients. Understanding the pathogenesis and the histopathological characteristics of the newer entities will enable the prompt diagnosis, treatment plan and expanding the spectrum of the lesions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03534-6.

Histopathological evaluation of minor salivary gland aberrations in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is one of the most established oral cancers in India, with high morbidity and mortality. The most common etiological agent associated with it is tobacco (in any form), which releases chemical carcinogens that affect not only the oral epithelial lining but also deep stromal structures such as minor salivary glands. They may cause changes in ductal or acinar part of gland depending on tumor grade, thus providing a fertile soil for tumor growth and recurrence. Aims and Objective: To observe the frequency of minor salivary gland changes associated with tobacco as well as to measure the length and depth of ductal involvement in routine tissue sections of OED and OSCC. Materials and Methods: A total of 94 hematoxylin and eosinstained archival slides which included cases of well, moderate, and poorly differentiated OSCC and oral epithelial dysplasia were histopathologically evaluated to observe changes in different components of minor salivary gland. Ductal hyperplasia, ductal metaplasia, mucous pooling within duct, acinar degeneration, pattern of malignant cell invasion (single/clusters), inflammatory infiltrate, eosinophilic cuffing around the gland, and glandular/vascular involvement were evaluated in each slide and correlated with different grades of OSCC. Results: Ductal hyperplasia, inflammatory cell infiltrate, mucous pooling, and pattern of malignant cell infiltration came out to be statistically significant with the highest percentage of changes being observed in poorly differentiated squamous cell carcinoma > moderately differentiated squamous cell carcinoma> well differentiated squamous cell carcinoma>oral epithelial dysplasia. Further, the results of this study suggest that extension of dysplasia or squamous cell carcinoma from overlying oral epithelium along salivary gland ducts is an uncommon finding. Conclusion: Hence, histopathological interpretation for OED and OSCC should also include changes related to associated minor salivary gland tissue as detection and eradication of the putative precursors are the best way of decreasing the overall morbidity caused by tumors.