Diagnostic accuracy of pan-TRK immunohistochemistry in differentiating secretory carcinoma from acinic cell carcinoma of salivary gland-A systematic review.

BACKGROUND: Secretory carcinoma (SC) is a well-established salivary gland malignancy that has earned its popularity for its unique clinicopathological behavior. Although it is an indolent malignancy, few of them have been reported with high grade transformation making it mandatory to differentiate it from its prime histological mimicker, acinic cell carcinoma (AciCC). Recently, many studies have been directed toward validating the sensitivity and specificity of pan-TRK IHC for confirming ETV6::NTRK3 gene fusion in SCs involving salivary gland. AIM: The aim of the present systematic review was to establish the diagnostic utility of pan-TRK immunostaining in histological differentiation of SC from AciCC. MATERIAL AND METHODS: An electronic search was carried out using MEDLINE by PubMed, Scopus, Google scholar, Trip, Cochrane library and EMBASE databases. Articles in which SC assessed with pan-TRK immunohistochemical expressions were included for systematic review and their staining pattern (cytoplasmic, nuclear and/or combined), sensitivity, specificity, positive as well as negative predictive were gathered. Risk of bias was analyzed for each study using QUADAS-2 tool. RESULTS: Thirteen eligible articles were included for the quantitative analysis, which revealed positive immunostaining of pan-TRK by nearly all the ETV6::NTRK3 fusion prevalent SCs alongside negative expression in almost all the cases of AciCC with 100% of sensitivity as well as specificity. CONCLUSION: The evidence from the included studies supports that pan-TRK immunostaining could be used as a reliable preliminary screening tool for discerning SC from AciCC. PROSPERO No: CRD42022308913.

Morphometric analysis of papillary synovial metaplasia-like changes in oral mucoceles.

BACKGROUND: Oral mucoceles (OMs) are common cystic lesions seen mainly on the lower lip in young males. Histologically, OMs show variegated features such as clear cell changes, myxoglobulosis, calcifications, and papillary synovial metaplasia (PSM)-like changes. The aim of the present paper is to morphometrically analyze PSM-like changes seen in OMs. METHODOLOGY: Seventy-two cases of histologically proven OMs were retrospectively retrieved and divided into two groups: group I without PSM-like changes and group II with PSM-like changes. The internal area was measured using Image J software. SPSS version 26 was used to analyze the data. RESULTS: There were 50 cases in group I (mean age 19.23 years) and 22 cases in group II (mean age 30.25 years). The lower lip was the most commonly affected site for both groups. The mean age in group II was significantly higher than group I. In contrast, the mean internal area was significantly higher in group I. CONCLUSION: We speculate that PSM-like changes in OMs represent an incomplete repair phenomenon. Knowledge of such an innocuous process is essential for differentiation from malignant histopathological mimickers.

Apoptolysis: a less understood concept in the pathogenesis of Pemphigus Vulgaris.

Pemphigus Vulgaris (PV) is a severe autoimmune disease characterized by supra-basal blisters in the skin and mucous membranes of a wide range of mammals, including humans. It not only affects the skin but also has severe oral manifestations. It has been stated that auto-antibodies are produced, for unknown reasons, which are directed against desmogleins present on the epithelium and thus leads to acantholysis and intraepithelial blistering. But the exact mechanism is still not completely understood. Here we would like to shed light on a new pathologic mechanism i.e., apoptolysis, which emphasizes that apoptotic enzymes contribute to acantholysis development both in terms of molecular events and chronologic sequence. A possible role of apoptolysis has been discussed in purview of PV.

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.

Expression of p16INK4a in oropharyngeal squamous cell carcinoma from a tertiary cancer centre of South India: A preliminary study.

Background & objectives: Human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma (OPSCC) are found to be strongly associated with each other with an increase in incidence has been noted globally over the years. A literature search for data depicting the role of HPV in oropharyngeal carcinoma in South India, however, has resulted in little information, thus, the present study was aimed to assess a possible association between the two among OPSCC patients from a tertiary care cancer centre in South India. Methods: One hundred and fourty three OPSCC cases were included in the study and analyzed for age, gender, marital status, habits, clinical TNM staging, site, laterality, symptoms, histological type (keratinizing and non-keratinizing), primary treatment and follow up period. All the cases were subjected to p16INK4a immunostaining. Statistical analysis was done using SPSS software. Results: Of the 143 cases 12 were found to be p16 positive with no significant difference between the study variables among p16 positive and negative cases. Base of the tongue was the most commonly involved site for the p16 positive cases. The p16 positive cases presented at an elderly age, early stage and were mainly the keratinizing type. Interpretation & conclusions: The p16 positive OPSCC cases constituted a small proportion in the present study and behaved similar to p16 negative cases. Usage of tobacco and alcohol appear to be the susceptible factors even in p16 positive cases. More studies from other States would be helpful to determine if HPV-related SCC in the Indian subcontinent behave differently or similarly to cases from Western countries.

Gingival Carcinoma Cuniculatum: A Case Series of Seven Cases with Emphasis on Immunohistochemical and Histochemical Features.

Oral carcinoma cuniculatum (CC) is a rare distinct variant of oral squamous cell carcinoma (OSCC) displaying unique clinical and histopathological features. CC is a locally aggressive malignancy with lower metastatic potential and has a tendency to invade the underlying bone yielding nonspecific clinical presentation resembling fungal/bacterial infections or osteomyelitis. Seven rare cases of gingival CC are reported with special emphasis on immunohistochemistry and special stains. Clinical and demographic profile were analysed and all cases were subjected to Ki-67 and p53 immunostaining and Ayoub-Shklar histochemical staining. For comparison, age and gender matched seven cases of conventional OSCC with bony involvement were recruited. IBM SPSS statistics software version 26 (IBM Analytics, Armonk, New York, U.S.) was used to analyse the data. All cases of CC lacked p53 expression in contrast to OSCC and demonstrated intermediate to high proliferation index in stroma also. The keratin staining and cytokeratin profile in OSCC and CC were also found to be statistically different. CC is a rare well differentiated variant of OSCC with different pathways involved in the pathogenesis. Local aggressive and invasive nature could be the result of unique interaction between epithelium and stromal elements. Oral health care provider must be familiar with this uncommon variant of OSCC.

Plausible mechanisms in malignisation of non-habit related chronic nonhealing traumatic ulcers of oral cavity.

ABSTRACT: Chronic nonhealing ulcers of the oral mucosa and lateral tongue, in particular, can transform into invasive oral squamous cell carcinoma (OSCC). Sometimes these ulcers do not heal even after the removal of the etiological agent that actually initiated these lesions, something similar to what happens in "neoplasia." Numerous factors have been postulated in the literature; however, the exact mechanism remains unclear. We hereby would suggest few plausible factors that could be considered for future studies to shed light on some untapped territories in the pathogenesis of OSCC arising from chronic nonhealing traumatic ulcers in purview of chromoanagenesis and the concepts of "quantum entanglement and coherence."

Optimizing Ideal Thickness of Sections for Epidermis in Intra-Operative Frozen Sections.

AIM AND OBJECTIVES: To estimate and evaluate the optimal thickness of tissue section for skin and dermal appendages intra-operatively and to compare the morphology and architecture of the epidermis and its appendages at 7 and 10 microns. METHODOLOGY: After obtaining clearance from the institutional human ethical committee, 101 skin margins were prospectively analyzed using a two-step embedding technique. After multiple trials and errors, 7- and 10-micron thicknesses were selected for the present study. Artefacts, staining characteristics, cellular morphology, cellular outline, and nuclear outline were assessed and scored as unacceptable or acceptable. The data were entered in a Microsoft Excel spreadsheet and analyzed using SPSS software. RESULTS: There was a statistically significant difference between the sections obtained at 7 microns and 10 microns (p-value: <0.001), the latter were better in all the parameters analyzed. However, no difference was noted in the characteristics of the dermal appendages (p-value: >0.05). CONCLUSION: While mucosal margins can be obtained at the usual 5-7 microns, the same thickness is not optimal for skin margins intra-operatively. Frozen sections for the skin margins may be set at 10 microns, to save time, minimize artefacts, and for better readability.

Clinicopathological comparison of periapical cyst and periapical granuloma in a cohort of Tamil population.

Aim: The aim of this study was to present and analyze detailed clinicopathological data of periapical cysts (PCs) and periapical granuloma (PG) in a cohort of 135 cases from the South Indian Population. Methodology: The present study included 135 cases of PC and PG out of 2696 biopsies submitted over 3 years. The clinicodemographic data which included age, gender, location, radiographic appearance, and treatment were collected along with the histopathological examination of the biopsied specimen. Data were entered in a Microsoft Excel spreadsheet, 2021, and analyzed using SPSS software ver. 26. Results: There were 71 cases of PG and 64 cases of PC. The mean age of occurrence in PG was slightly lower than cases in PC. Irrespective of the group, there was a clear male preponderance, and maxillary permanent central incisors were most commonly affected. However, no significant difference was noted. Radiographically, PC significantly showed more well-defined corticated radiolucent lesions compared to PG where most cases were ill-defined (69.01%). Histologically, all cases showed classic features for diagnosis with additional histological characteristics which may aid in diagnosis. Conclusion: PG was more common than PC. There was a predilection for the male gender in both lesions. The actual incidence of these lesions would be actually high, as some cases are lost to private practitioners, and not all the lesions are submitted for histopathological examination.

Immunohistochemical Expression of CK14 and Bcl-2 in Odontogenic Keratocyst and Its Variants.

Odontogenic keratocysts (OKCs) are aggressive cystic jaw lesions with a high epithelial turnover rate and increased propensity for recurrence. Sometimes, the characteristic histopathological features of OKCs are either completely lost or seen focally due to previous marsupialization or inflammation. This research aimed to determine whether specific patterns of CK14 and Bcl-2 staining could assist in diagnosing OKCs with altered epithelial features and provide clues in elucidating their aggressive nature. CK14 expression was restricted to basal and suprabasal layers near satellite cysts and in areas showing subepithelial split. The entire epithelial lining showed CK14 expression in areas of inflammation and after marsupialization. The typical basal/suprabasal staining of Bcl-2 was lost in areas of inflammation and intensity is decreased in OKCs after marsupialization. These new findings could offer a hint into the biological nature and pathogenesis of OKCs. Because of its therapeutic consequences and high recurrence rate, proper recognition and diagnosis are essential for treatment planning.

Literature Review, Case Presentation and Management of Non-ossifying Fibroma of Right Angle of Mandible: More Than just a Cortical Defect!

Non-ossifying fibroma (NOF) of jaw bones are rare. While NOF is the most common benign bone tumor of long bones with pathognomonic radiological features and bear a tendency for self-regression, gnathic NOF appears to be comparatively larger in size and behave more aggressively. A 16 years old female patient reported with painless swelling of the right side of the face of 4 months duration. Radiographic analysis showed a unilocular radiolucent lesion of right angle of the mandible with ill-defined margins, cortical perforation and thinning of inferior border. The lesion was provisionally diagnosed as odontogenic keratocyst/unicystic ameloblastoma and incisional biopsy was performed. The histopathological features and immunohistochemical characteristics favored a diagnosis of NOF. The lesion was excised and reconstructed. The excised specimen confirmed the diagnosis. There are no signs of recurrence at 18 months follow-up. NOF should be considered in the differential diagnosis of uni-/multilocular radiolucencies of jaws particularly the posterior mandible.

Helicobacter pylori positive oral squamous cell carcinoma demonstrate higher pathological tumor staging and poorer overall survival.

BACKGROUND: Helicobacter pylori (H pylori), a bacterium characterized by its spiral shape and gram-negative nature, impacts approximately half of the global population, showing a greater prevalence in developing nations. There are various factors that contribute to the pathogenicity of H pylori in the gastric mucosa, leading to gastric ulcer, gastritis and gastric cancers. The relationship between H pylori and gastric cancers has been well documented. The association between Oral Squamous Cell Carcinoma (OSCC) and H pylori still remains a grey field. The study aimed to evaluate the presence of H pylori in OSCC. MATERIALS AND METHODS: The study consisted of 46 case samples and 21 controls. The case samples comprised of histopathologically confirmed cases of OSCC obtained from patients undergoing wide local excision. Fresh tissue samples were collected during cryosection and stored in eppendorf tubes. The control samples were collected from the gingiva and buccal mucosa of apparently healthy patients with no history of habits, undergoing procedures such as gingivectomy and impaction. All the cases and controls were subjected to immunohistochemistry for Helicobacter pylori antibody. The cases demonstrating Helicobacter pylori in immunohistochemistry further underwent additional Real-Time- Polymerase Chain Reaction (RT-PCR) and culture methodology for subsequent confirmation. RESULTS: 15/46 cases (32.6 %) showed positive immunohistochemical expression of H pylori in OSCC, while all the twenty-one controls were negative (p value 0.001). Out of the 15 cases tested using culture methodology, a total of 7 cases, representing 46.7 % of the sample, were positive for the presence of H pylori (p- value 0.003). Similar statistically significant results were also obtained for 16S rRNA gene with RT- PCR. Furthermore, H pylori positive cases were frequently found in higher pathological tumor staging. A significant increase in overall survival rate was evident among the H pylori negative cases. CONCLUSION: Helicobacter pylori was significantly expressed in OSCC tissues when compared to healthy tissues. Immunohistochemical analysis of the presence of H pylori in FFPE OSCC samples yielded more positive results when compared to culture and PCR methodology. We opine that in OSCC, H pylori may have a role in the faster progression of the disease, rather than merely a 'chance spectator'.

Comparison of Broder's and Bryne's Grading System for Oral Squamous Cell Carcinoma With Lymph Node Metastases and Prognosis: A Scoping Review.

Oral squamous cell carcinoma (OSCC) has the highest mortality rate of any type of head and neck squamous cell carcinoma. For many eons, the clinical TNM (tumor size, nodal metastasis, and distant metastasis) classification and histological grading of malignancies have been used to predict clinical behavior, confusing it with prognosis and overall survival. This review aimed to systematically identify and evaluate the prognostic value of Broder's and Bryne's grading system for OSCC. Electronic resources such as PubMed, Cochrane Database of Systematic Reviews, Google Scholar, Scopus, and direct web searches were used to conduct a thorough search. The titles were examined to identify relevant papers, which were then reviewed for inclusion by reading the abstract. To incorporate studies published outside of the electronic database, the bibliography of all recognized papers was scanned. This review examined all research that investigated the prognostic value of Broder's and Bryne's grading systems in OSCC. The electronic database search identified 221 articles. After reading full articles, based on the titles and abstracts and after removing duplicates, six articles were screened. Finally, six articles were selected based on their ability to meet the inclusion criteria and answer the research question. All studies analyzed the competence of this histological grading system in predicting the prognosis of OSCC patients. Four studies evaluated lymph node metastasis and two studies analyzed the histological grading of OSCC. While evaluating the histological grade, we recommend the application of Bryne's (1992) system for grading OSCC. The standardization of a single, effective method would make it easier to compare results from various studies. This grading system yields better interobserver agreement and bears a prognostic value which may help in devising a treatment strategy for better patient outcomes.

Estimation of Tooth Dimensions and Golden Divine Ratio in Extracted Human Permanent Maxillary and Mandibular Canines in a Cohort of Tamil Ethnicity.

Background Teeth serve many functions, and aesthetics is one of the most important aspects served by teeth, perceived by the limbic system of the human brain. The golden divine ratio is the unique proportion often correlated with beauty. The present study was devised to estimate the dimension of human permanent canines and approximation to the golden divine ratio. Materials and methods The present study included 47 extracted human permanent canines retrieved from the tooth repository of our institute's Department of Oral Biology. Using digital vernier calipers (Themisto TH-M61 digital vernier caliper, 0-150mm/ 6 inch, JIPVI Ecommerce Pvt. Ltd, India, 2022), the following measurements were taken: Mesio-distal and labiolingual dimensions of the crown, crown length, root length, root to crown ratio (R/C) and the tooth to root ratio (T/R). The data were analyzed using Statistical Package for Social Sciences (SPSS) software version 26. Results All the dimensions' mean and standard deviations were calculated for both maxillary and mandibular canines. While the means of mesio-distal and labiolingual dimensions of the crown approximated the values reported in the literature, there was some variation in crown and root lengths. The mean crown lengths of the upper and lower canines were 10.34mm and 9.76mm, respectively, while the root lengths were 16.52 and 15.54mm, respectively. The R/C of both sets and the T/R of the upper canine only followed the golden ratio. T/R of the lower canine was slightly higher (1.64) Conclusion Although the number of included teeth was less, owing to the fact that canines are rarely extracted, our results provided new values of canines for updation in a unique population. More studies are required for comparative anthropological data updates.

Osteogenic and Biomedical Prospects of Hafnium and Its Compounds: A Scoping Review.

The direct engagement of hafnium (Hf) in biological processes or its critical function in living things is not well understood as of now. Unlike key elements like oxygen, carbon, hydrogen, and nitrogen, which are necessary for life, Hf is not known to have any biological activities or functions. It is essential to acknowledge that scientific research is ongoing and that new findings may have been made. This systematic review aimed to aggregate and analyze the studies that discuss biomedical applications of Hf metal. This systematic review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The following search strategy was used: two independent researchers conducted electronic searches in databases including PubMed, Embase, Cochrane Database of Systematic Reviews, and Google Scholar. The search was conducted up to August 2023 using the Medical Subject Headings (MeSH) terms "transition elements," "hafnium," and "biomedical research." Boolean operators "AND" and "OR" were used to refine the search. Electronic databases, along with hand searches, identified a total of 38 studies. The various database searches resulted in a total of 38 studies, of which 12 were excluded as duplicates, and five were unavailable for full-text data. The remaining 21 full-text articles were then assessed for their eligibility based on the inclusion and exclusion criteria, and finally, a total of 12 studies were included in the present systematic review. Among the 12 chosen studies, six were on cancer-related targeted radiotherapy or chemoradiotherapy, five were on bone or apatite-forming capabilities, and one was on the treatment of inflammatory bowel disease. The common outcome measures included cell proliferation, osteoblast formation, radiotherapy intensification, and immunotherapy. This review outlines an overall picture of the biomedical uses of Hf metal, a transition element, as a potent biomaterial. In conclusion, this transition element, Hf, has some promising scope in the fields of biomedicine, with a special focus in terms of cancer radiotherapy and osteogenic capabilities.

Photobiomodulation Therapy in the Management of Oral Lichen Planus: A Systematic Review and Meta-Analysis.

Photobiomodulation therapy (PBMT) is a non-invasive and the latest form of therapy used in the treatment of non oncological diseases as well as cancers of various types and locations. The aim of this study was to systematically review and assess the efficacy of PBMT in managing oral lichen planus (OLP) compared to the interventions. A systematic review and meta-analysis were implemented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search using PubMed, Scopus, and Cochrane was conducted to retrieve relevant studies published until June 2023. The outcomes evaluated included the reduction in pain score and clinical severity scores (Prospero No CRD42023428626). A total of eight studies were identified for qualitative synthesis. The pooled analysis incorporating six studies revealed that there are no significant differences for both mean pain score (mean difference [MD] = 0.21, 95% confidence interval [CI] = -0.51, 0.93) as well as clinical score (MD = -0.08, 95% CI = -0.4, 0.25) between PBMT and comparison groups. Subgroup analysis based on corticosteroids as controls showed that there was no significant difference in mean reduction in pain score between PBMT and topical steroids (MD = 0.38, 95% CI = -0.54, 1.31). PBMT is as effective as other interventions in the treatment of OLP, though not superior, and can be a promising alternative treatment for cases resistant to steroids or when steroids are contraindicated. Further studies are recommended to standardize the optimal settings for the treatment of OLP.

Correlation between Vascularity and Advancing Histological Grades of Oral Submucous Fibrosis with a Plausible Role in Malignisation: Systematic review of a persisting matter of conflict.

Objectives: This study aimed to quantify the vascularity in histological grades of oral submucous fibrosis (OSMF) and to determine if there is any connection between vasculogenesis and malignisation. Recent studies show no significant change in vascularity as the stage advances as opposed to the conventional concept. Methods: A comprehensive database search until December 2022 was conducted for published articles on vascularity in OSMF following preferred reporting items for systematic reviews and meta-analyses guidelines. Results: A total of 98 articles were screened of which 13 were included for systematic evaluation. The study included 607 cases, with a definite predilection for the male gender. Of the 13 studies, 11 evaluated mean vascular density. In more than half of the studies, the vascularity decreased as the stage advanced. Similar results were obtained for endothelial cells/µm2, mean vascular area percentage and mean vascular area. Conclusion: The present review supports the prevailing concept that vascularity decreases with the advancement of the OSMF stage. This denies the systemic absorption of carcinogens into the circulation with resultant longer exposure of compromised epithelium and malignisation.

Necroptosis in human cancers with special emphasis on oral squamous cell carcinoma.

Necroptosis is a type of caspase independent 'programmed or regulated' necrotic cell death that has a morphological resemblance to necrosis and mechanistic analogy to apoptosis. This type of cell death requires RIPK1, RIPK3, MLKL, death receptors, toll like receptors, interferons, and various other proteins. Necroptosis is implicated in plethora of diseases like rheumatoid arthritis, Alzheimer's disease, Crohn's disease, and head and neck cancers including oral squamous cell carcinoma. Oral carcinomas show dysregulation or mutation of necroptotic proteins, mediate antitumoral immunity, activate immune response and control tumor progression. Necroptosis is known to play a dual role (pro tumorigenic and anti-tumorigenic) in cancer progression and targeting this pathway could be an effective approach in cancer therapy. Necroptosis based chemotherapy has been proposed in malignancies, highlighting the importance of necroptotic pathway to overcome apoptosis resistance and serve as a "fail-safe" pathway to modulate cancer initiation, progression, and metastasis. However, there is dearth of information regarding the use of necroptotic cell death mechanism in the treatment of oral squamous cell carcinoma. In this review, we summarise molecular mechanism of necroptosis, and its protumorigenic and antitumorigenic role in cancers to shed light on the possible therapeutic significance of necroptosis in oral squamous cell carcinoma.

Vasculogenic mimicry.

Vasculogenic mimicry (VM) refers to the ability of malignant cells to form microvascular channels, having nature of blood vessels but are not endothelium lined. These channels contain blood cells & plasma and provide sufficient nutrient supply to the cancerous cells to meet their metabolic demands. VM can be seen in various tumors and is associated with their malignant phenotype, high tumor grade, invasion, metastasis and poor clinical outcome. In this paper, we made an attempt to explain the mechanism, visualisation and prognostic significance of vasculogenic mimicry.