Exploring miR-155-5p and miR-1246 as Diagnostic and Prognostic Markers in Oral Squamous cell carcinoma.

INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC) is one of the leading cancers worldwide, significantly impacting developing nations. This study aimed to explore the diagnostic and prognostic potential of miR-155-5p and miR-1246 in OSCC in the Indian population, as their comparative roles in this context remain unexplored. MATERIAL AND METHODS: The present cross-sectional study comprised 50 histopathologically confirmed OSCC cases, with adjacent normal mucosa as controls. MiRNA expression was assessed via qRT-PCR and correlated with clinicopathological factors. MiRwalk and miRTargetlink were used for miRNA:mRNA interaction prediction, and gprofiler was employed to analyze validated targets for functional insights. RESULTS: The expression analysis showed a significant upregulation of miR-155-5p and miR-1246 in OSCC tissues compared to adjacent controls. Receiver operating curve analysis revealed that miR-1246 exhibited excellent diagnostic accuracy (AUC = 0.94) compared to miR-155-5p (AUC = 0.69). Higher miRNA levels were associated with age and extracapsular extension while overexpression of miR-1246 was correlated significantly with increased tumor size, tumor grade, TNM staging, and depth of invasion. The analysis for target prediction unveiled a set of validated targets, among which were WNT5A, TP53INP1, STAT3, CTNNB1, PRKAR1A, and NFIB. CONCLUSION: miR-155-5p and miR-1246 may be used as potential prognostic biomarkers in OSCC, with miR-1246 demonstrating superior diagnostic accuracy.

Dentinogenic Ghost Cell Tumor associated with Odontoma: A unique Histopathological Entity and its Surgical Management.

We report a rare case of dentinogenic ghost cell tumor (DGCT) associated with complex composite odontoma in a 17 years male affecting the posterior segment of the mandible. On radiographic examination, there was a well-defined multilocular radiolucency surrounding the radio opaque mass with respect to 44, 45 and 46. Histopathologically it showed ameloblastomatous proliferation with dentin like areas and ghost cells. It was associated with tooth like structures consisting of dentin, cementum and pulp like areas. DGCT with odontoma is extremely rare with only two cases being reported in literature till date. The management with its rare occurrence is discussed here.

A novel approach for extracting DNA from formalin-fixed paraffin-embedded tissue using microwave.

BACKGROUND: Formalin-fixed paraffin-embedded (FFPE) tissue is the gold standard procedure for tissue preservation. However, the extraction of DNA is a cumbersome procedure as the extracted DNA is fragmented because of the cross-linking effect of formalin. Hence, the aim of the present study is to extract DNA from FFPE tissues using different techniques with a specific objective of comparing the extracted DNA, both quantitatively and qualitatively. METHOD: Ten samples of FFPE tissues were retrieved from the archives of the Department of Oral Pathology. Total genomic DNA was extracted by different methods which included QIAamp DNA FFPE Tissue Kit, Norgen DNA FFPE Tissue Kit, phenol-chloroform method, mineral oil-based extraction, M/10 NaOH solution method, and microwave method. A 280-base pair sequence was selected for evaluation of downstream amplification. RESULTS: The statistical analysis was performed using unpaired student's t-test to compare the DNA yields and quality obtained by microwave methods with other methods using SPSS software. Total genomic DNA retrieved by the microwave method was superior to other methods both qualitatively and quantitatively. CONCLUSION: DNA extraction from FFPE tissues is an onerous task as irreversible bonds form between the nucleic acid during fixation which are difficult to break during DNA retrieval. Hence, the microwave method provides good total genomic DNA which gives better downstream results when compared with other methods.

Assessment of Interleukin-18 gene polymorphism and serum levels in oral lichen planus in an Indian population.

BACKGROUND: Oral lichen planus (OLP) is a chronic, inflammatory disease with uncertain etiology. The aim of this study was to assess Interleukin-18 (IL-18) gene polymorphism and serum levels in OLP cases of Indian origin and to compare them with a control population of similar background. METHODS: The assessment of single-nucleotide polymorphisms (SNPs) of IL-18 gene at promoter regions -137(G/C) and -607(C/A) was done in 70 OLP cases and 70 healthy controls using sequence-specific primer-polymerase chain reaction (SSP-PCR). In a subset of this cohort, comprising of 41 OLP cases and 41 controls, serum IL-18 levels were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean serum levels of IL-18 among OLP cases were significantly higher when compared to controls. Genotypic and allelic frequencies of IL-18 at position -137(G/C) showed that GG genotype and allele G was significantly higher in OLP cases, whereas, GC genotype and C allele was high in the control group. Polymorphism of IL-18 at position -607(C/A) showed no significant differences. CONCLUSIONS: Gene polymorphism at -137GG genotype and allele G seems to be associated with genetic susceptibility to OLP whereas -137GC and allele C may have a protective role against its development. However, our study lacks clear statistical correlation, the differences observed could be caused by sampling problems and the results could not be fully representative of Indian patients with OLP. Further studies are warranted to explore the role of IL-18 genetic polymorphisms in OLP development.

Correlation of Cyfra 21-1 levels in saliva and serum with CK19 mRNA expression in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for 90 % of malignant lesions of oral cavity. The study assessed the potential of Cyfra 21-1 as a tumor marker in OSCC. The study included 50 patients of OSCC to evaluate levels of Cyfra 21-1 in serum and saliva by electrochemiluminescent immunoassay (ECLIA) and CK19 messenger RNA (mRNA) expression in tissue by florescent quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) along with healthy individuals as control. The salivary and serum Cyfra 21-1 levels in patients of OSCC were significantly higher compared to controls (p value < 0.01). There was a 2.75-fold increase in CK19 mRNA expression in OSCC cases compared to controls. A significant positive correlation was found between serum and salivary Cyfra 21-1, serum Cyfra 21-1, and CK19 mRNA expression and between salivary Cyfra 21-1 and CK19 mRNA expression. Among these, correlation between serum and salivary Cyfra 21-1 was highly significant. Salivary and serum Cyfra 21-1 showed significantly elevated levels in grade II OSCC compared to grade I histopathologically. Elevated levels of salivary Cyfra 21-1 were associated with recurrence in OSCC patients. Reverse operating curve constructed using 3 ng/ml as a cutoff for serum Cyfra 21-1 revealed the sensitivity and specificity to be 88 and 78.2 %, respectively. Using a cutoff value of 8.5 ng/ml for salivary Cyfra 21-1, the sensitivity was found to be 93.8 % and specificity 84.3 %. We advocate salivary Cyfra 21-1 as a better diagnostic marker over serum Cyfra 21-1 as well as a potential marker in the prognosis of OSCC.

Cementoblastoma Solely Involving Maxillary Primary Teeth--A Rare Presentation.

Cementoblastoma is a rare benign neoplasm of odontogenic ectomesenchyme origin, involving the roots of any tooth, which occurs predominantly in second and third decade of life. Very few cases of cementoblastoma associated with a primary tooth or having a maxillary presentation have been reported in the past. Here, a rare case of a ten year old boy who presented to the department with a swelling in maxillary posterior region since one month is being discussed. The radiographic presentation was mimicking an odontoma. The final diagnosis was cementoblastoma. We have advocated the use of polarized microscopy to support the histopathological diagnosis with respect to its cemental origin. Cementoblastoma should be considered in the differential diagnosis of radio-opaque lesions in the transitional dentition.

Treatment of Oral Mucosal Lesions by Scalpel Excision and Platelet-Rich Fibrin Membrane Grafting: A Review of 26 Sites.

PURPOSE: One of the preferred treatment options for oral mucosal lesions (eg, leukoplakia and lichen planus) is excision, with or without the use of a coverage agent. Platelet-rich fibrin (PRF) membranes are popular fibrin scaffolds with entrapped platelets that release various growth factors and cytokines to support and enhance wound healing. The aim of the present report was to describe the technique, postoperative wound care, and clinical results of PRF membrane grafting after excision of superficial potentially malignant oral lesions. MATERIALS AND METHODS: Autologous PRF membrane was fabricated and grafted over 26 wounds created by excision of small, superficial, potentially malignant lesions of oral mucosa (or fiberotomy in cases of oral submucous fibrosis) and assessed clinically at 7, 15, 30, and 60 days. RESULTS: Healing was satisfactory in all cases, with minimal and manageable complication at 1 site. CONCLUSION: The results of the present study suggest that PRF membrane is a successful coverage agent that aids in the healing of superficial oral mucosal wounds. Additional comparative studies are required to establish its efficacy compared with that of other agents.

Vestibular Schwannoma in a paediatric case-A rare entity.

Neurilemmoma, also known as Schwannoma, is a benign, slow-growing, encapsulated neoplasm that arises from Schwann cells of the peripheral nerve sheath. Although it is extremely rare, it affects the head and neck region in roughly 25-45% of all cases. Intraorally, the tongue is the most common site and is rarely involves vestibular mucosa. Here, we report a rare case of Schwannoma of vestibular mucosa in a 13-year-old girl and contribute a review to the current literature. Clinically, based on age, site, and appearance, a diagnosis of a benign tumour such as lipoma, fibroma, neurofibroma, and benign lesions of salivary glands was made. An excisional biopsy showed solely Antoni type A tissue with central acellular eosinophilic Verocay bodies surrounded by spindle-shaped neurilemma cells arranged compactly with wavy, twisted nuclei arranged in a palisaded manner. The patient was recurrence-free after 6 months. Hence, this case is of interest due to its rarity in terms of age, site, and histopathology (Antoni type A neurilemmoma) for a presumed initial diagnosis. Here, we also hypothesize regarding the type of growth pattern in the earlier diagnosed cases.

Juvenile trabecular ossifying fibroma associated with central giant cell granuloma and aneurysmal bone cyst like changes - A triple hybrid tumour? Or a pathologic sequelae?

Hybrid tumours encompass lesions containing two or more pathologic entities. The pathogenesis of these lesions is barely understood and described. Juvenile trabecular ossifying fibroma (JTOF) is a benign but locally aggressive fibro-osseous neoplasm commonly affecting the maxilla of the adolescent age group. Hybrid lesions of JTOF have been reported along with central giant cell granuloma (CGCG), aneurysmal bone cyst (ABC) and traumatic bone cyst, respectively. However, the co-occurrence of JTOF with CGCG and ABC in a single patient has not yet been reported in the literature, hence, making ours the first case report of this kind. Theories describing the pathogenesis of this rare phenomenon have also been proposed and elaborated.

Expression and analysis of CX3CL1 chemokine and CD57+ lymphocytes in oral squamous cell carcinoma and their correlation with clinicopathologic features.

INTRODUCTION: CX3CL1 exhibits chemoattraction for T-cells, monocytes, and CD57+ natural killer cells mediating antitumor immunity. The role of CX3CL1 has been studied in tumors of the breast, lung, colon, pancreas, prostate, etc. The current study was undertaken to understand the importance of CX3CL1 and its correlation with CD57+ cells in oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Seventy-five primary OSCC were staged and histopathologically graded, followed by immunohistochemistry for CX3CL1 and CD57. Mann-Whitney U-test, Kruskal-Wallis test, Post hoc Bonferroni test, and Pearson's correlation coefficient were applied. RESULTS: CX3CL1 assessment within the tumor cells was high in 62.66% of cases, and the CD57 Labeling Index (LI) varied over a wide range of 8.2-111.6. A statistically significant reduction in expression of both CX3CL1 and CD57 was observed with an increase in histologic grade (p = 0.021 and 0.038, respectively). DISCUSSION: It is concluded that CX3CL1 and CD57 may be important players in the immune surveillance of OSCC. Further studies with detailed follow-up for the overall survival of patients will help in studying the diagnostic, prognostic, and therapeutic roles of CX3CL1 in OSCC.

Angioleiomyomatous Hamartoma of Incisive Papilla in an Adolescent.

Hamartomas, a focal excess of normal tissue usually presenting as isolated masses, are rarely found in the head and neck region. The purpose of this report is to discuss a rare case of an intra-oral angioleiomyomatous hamartoma in a 14-year-old male who presented with a congenital nodule over the anterior palatal mucosa. The confirmatory diagnosis was done based on histopathology and immunohistochemistry using various markers. A brief review of the literature and clinical differential diagnoses are discussed, along with the clinical significance of hamartomas associated with syndromes. Hence, the identification of such hamartomas may lead to early diagnosis of associated syndromes in pediatric patients.

Mandibular primary intraosseous carcinoma arising from long-standing odontogenic keratocyst.

Primary intraosseous carcinoma (PIOC) of the jaw is a rare neoplasm arising from the lining epithelium of odontogenic cysts or de novo from odontogenic epithelial rests that has no communication with the surrounding mucosa of the upper aerodigestive tract. We present a case of PIOC ex-odontogenic keratocyst (PIOC ex-OKC) in a 35-year-old male. Histopathologic examination revealed a cystic lesion with a fibrous capsule lined by corrugated parakeratinized stratified squamous epithelium resting on a basal cell layer composed of columnar cells exhibiting palisaded hyperchromatic nuclei, features consistent with OKC. Surgical treatment consisted of bilateral crestal and crevicular incision, a reflection of the flap, breaking of all OKC locules, creation of a continuous cavity, and fitting of a decompression mold around the mandibular teeth. This case highlights the importance of knowing the features of PIOC and considering PIOC in the differential diagnosis of malignant tumors of odontogenic epithelium for timely surgical treatment.

Adenomatoid odontogenic tumor: A histopathologic profile of 43 cases with evidence supporting a mixed odontogenic origin.

BACKGROUND: Adenomatoid Odontogenic Tumor (AOT) accounts for 3% of all odontogenic tumors. It has been classified by WHO as an odontogenic tumor of purely epithelial origin. The current study attempts to establish the origin of the tumor along with detailed histopathological and clinicoradiographic analysis of 43 cases of AOT. MATERIAL AND METHODS: Forty-three cases were reviewed from the departmental archives for demographic data, radiographic features and histological features. Further, histopathological slides were stained with Picrosirius Red (PSR) and observed under polarised light. RESULTS: A majority of the cases were seen in the anterior jaws (76.7%), and were less than 3 cms (76.7%) in greatest dimension. Equal number of cases were of follicular and extra-follicular location while one was peripheral. Predominantly solid histological pattern was noted in 53.5%. Varied sub-patterns were observed with most cases exhibiting solid nodules and strands of tumor cells. Few cases showed melanin pigmentation. Over a third of cases (37.2%) showed dentigerous cyst like areas and one case each showed features of ossifying fibroma and focal cemento-osseous dysplasia. Tumor droplets, hyaline rings within duct-like structures, dentinoid material and osteodentin showed reddish yellow birefringence when observed under polarised microscopy post PSR staining. CONCLUSION: This study highlights the diverse histopathological variation of AOT with evidence to reclassify it as a mixed odontogenic tumor based on the polarising microscopic findings with PSR staining.

Upregulation of miRNA-196a and miRNA-196b correlates with Bryne's prognostic score in oral squamous cell carcinoma.

BACKGROUND: microRNA(miRNA)-196a and miRNA-196b expression has been found to be dysregulated and involved in tumorigenesis and tumor progression in array of cancers through different targets. The role of these miRNAs together in clinical application is not always consistent and, its prognostic value in oral squamous cell carcinoma (OSCC) is still elusive. This study was performed to investigate the correlation of these miRNAs expression with histological grades of OSCC according to Bryne's histological grading system, to predict prognosis and to evaluate their relationship with clinico-pathological data. METHODS: Real-time quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) was done to evaluate the expression levels of miRNA-196a and miRNA-196b in 75 pairs of OSCC tissue matched with adjacent normal mucosa, used as a control. RESULTS: miRNA-196a and 196b expression in OSCC was significantly higher than that in corresponding adjacent normal tissues (p > 0.001). Also, a significant differential correlation was found in between the expression levels of these two miRNAs (Pearson correlation test r = 0.676, p-value<0.0001). The increased expression of these miRNAs was more frequently observed in OSCC tissues with advanced clinical and pathological TNM stages (IVa and IVb, pIVb respectively, p-value<0.0001). Significant correlation was found between miRNA-196a upregulation and moderate prognostic score (p-value<0.0001) in comparison with good and poor prognostic score of histological grades of OSCC. Sensitivity and specificity for miRNA-196a were 95 % and 85 %, respectively (AUC = 1, 95 % CI = 0.617-0.850; p 0.001), while for miRNA-196b were 94 % and 86 %, respectively (AUC = 0.808, 95 % CI = 0.701-0.916; p0.0001). CONCLUSIONS: These findings suggest that the increased expression of miRNA-196a and 196b may play an important role in tumor progression in OSCC. miRNA-196a might be a useful marker for predicting the clinical outcome of OSCC, especially for advanced stages. In conclusion, our data demonstrate for the first time that these miRNAs may serve as a potent prognostic marker for tumor progression. We further highlight miRNA-196a and miRNA-196b as a promising predictor of prognostic assessment in OSCC.

Metastatic Sarcomatoid Renal Cell Carcinoma: A Journey From the Kidney to the Gingiva.

Oral metastatic lesions are very rare and are often diagnosed at a later stage, complicating treatment. Renal cell carcinoma (RCC) is the third most frequent neoplasm to metastasize to the oral cavity, following breast and lung cancers. These metastatic lesions are usually asynchronous and develop after the initial diagnosis, affecting the overall survival rate. This report describes a known case of RCC with a growth in the mandibular gingiva. Multiple pulmonary and femoral metastases appeared five years after the initial renal lesion. The gingival growth was excised and referred for histopathological examination, which revealed a pleomorphic sarcomatoid cellular morphology. Immunohistochemistry with an array of markers led to the diagnosis of sarcomatoid RCC, a rare high-grade tumor. This case underscores the importance of detailed history-taking, interpretation of clinical findings, and emphasis on histopathological examination to arrive at a conclusive diagnosis.

Telangiectatic osteosarcoma of the mandible-A rare case report and an insight into differential diagnosis.

Telangiectatic osteosarcoma (TOS) is a rare variant of osteosarcoma that typically affects young individuals and long bones. The case under discussion was seen in the mandible of a 57-year-old female and had rapidly grown in size within a week. Microscopically, the tumour was characterised by large vascular cavities surrounded by anaplastic cells. Thin lacy tumour osteoid was observed at various foci. Abundant multinucleated osteoclastic giant cells along with areas of necrosis were also noted. The tumour cells were positive for SATB2, while negative for Cytokeratin AE1/3, CD 34. Ki-67 positivity was observed in more than 50% of tumour cells. A diagnosis of high grade telangiectatic osteosarcoma was thus made.

Clinicopathologic and radiologic correlation of ossifying fibroma and juvenile ossifying fibroma--an institutional study of 22 cases.

To analyze the clinical, radiographic, and histopathologic features of ossifying fibroma (OF) and juvenile OF (JOF), an archival study of 17 cases of OF and 5 cases of JOF reported over a period of 4.5 years was undertaken to analyze the aforementioned features. Age incidence of OF varied from 8 to 53 years, and JOF was seen in a comparatively younger age of 8 to 28 years. Both tumors were almost equally distributed between men and women. Thirteen cases of OF were found to occur in posterior mandible, whereas JOF was predominant in the anterior maxilla. Radiographically, OF varied from completely radiolucent (n = 7), mixed (n = 5), to completely radiopaque (n = 5), whereas JOF was predominantly radiolucent. Microscopically, stroma in OF varied from fibrous to highly cellular with overlap between various types of calcification. Juvenile OF showed highly cellular stroma and 2 distinct patterns of mineralization-psammomatoid and trabecular with osteoid seams. The origin of OF and JOF seems to be distinct from each other with OF arising from periodontal ligament and JOF arising from precursor myxoid tissue of paranasal sinuses.

Cysticercosis: Unearthing the worm.

Cysticercosis, a helminthic disease caused by T. Solium, is a major health concern in developing and underdeveloped nations of the world. If left untreated, it may lead to severe neurological and ophthalmic complications. The diagnosis of oral cysticercosis depends on the identification of the larva in the biopsied tissue. However, an accurate diagnosis can be challenging, if the larva is dead because of which it cannot be identified. In such a scenario, step by step approach to unearth the worm is discussed here.

Potential role of mast cells and eosinophils in establishing the clinical severity of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) can be broadly classified clinically as an erosive (e) and non-erosive (ne) form. Mast cells (MCs) are granules containing cells that play an important role in the etiopathogenesis of OLP and have bidirectional interaction with eosinophil. In the present study, MCs and eosinophil densities were studied to find out if they could aid in the clinical severity of eOLP and neOLP. METHODS: The study group included 20 cases of eOLP and 30 cases of neOLP. All the sections were stained with special stains, toluidine blue (TB) for MCs and Congo red (CR) for eosinophils. Histopathological analysis was done by using Nikon NIS Elements Version 5.30 software (Nikon, Tokyo, Japan) by applying 100×100 µm grids to standardize the field of evaluation. Three subepithelial zones were demarcated as follows: 1) zone I was up to a subepithelial depth of 100 µm from the basement membrane; 2) zone II was beneath zone I from 100 µm to 200 µm; and 3) zone III was beneath zone II from 200 µm to 300 µm. In each of these zones, five high power fields with high cellular density were chosen to count MCs and eosinophils. RESULTS: The results of the study showed a significant increase in the number of MCs (intact and degranulated) in zone II and III compared to zone I in both eOLP and neOLP. Eosinophil density was significantly higher in zone II of both eOLP and neOLP when compared to zone I and III. We also observed a significantly higher number of both MCs and eosinophils in eOLP compared to neOLP. This difference was most prominent between zone II of eOLP and neOLP. No significant difference between granulated and degranulated MCs was found between the three zones. CONCLUSIONS: Increased MC and eosinophil densities, as well as their interactions in eOLP, suggest that they play a significant role in etiopathogenesis and in establishing the clinical severity of the disease.

"Is it time for personalised medicine for Ameloblastoma?": A hypothesis.

Ameloblastoma is a benign odontogenic tumor that is locally destructive. The most common treatment option is surgery, which often results in disfigurement of the face. BRAFV600E is the common gene mutation associated with its pathogenesis. Therefore, this paper hypothesizes the use of targeted drug therapy against this mutated gene.