An evidence based immunohistochemical panel for diagnosing oral lymphoma along with a case series.

Oral lymphomas are rare and present a diagnostic challenge. Immunophenotyping is essential to decipher their biology and identify therapeutic targets. Histopathology can prove to be diagnostically difficult to type these lesions, and hence, immunohistochemistry (IHC) proves useful in deciphering their biology. Here, we present an evidence-based approach using a novel immunohistochemical marker panel to diagnose oral lymphomas by discussing four unique cases.

Lipoblastoma of the lip.

ABSTRACT: Lipoblastomas are benign tumors arising from embryonic white fatty cells that continue to proliferate and develop during the postnatal period. It commonly affects children 3 years of age or younger, with the neck being the most frequent site in the head and neck region. Only 10% of cases are seen at 10 years or above. The etiopathogenesis of lipoblastomas is linked to polysomy and rearrangement of chromosome 8q11-13 with or without the involvement of the pleomorphic adenoma gene 1 (PLAG1) gene. Here, we report one of the first cases of lipoblastoma of lip in a 10-year-old boy with atypical immunohistochemical features and the need for thorough clinical and histopathological evaluation of cases with atypical findings. The novel pathogenetic mechanism of lipoblastoma from the cluster of differentiation 34-positive (CD34+) stem cells has also been discussed.

Oral Epithelial Dysplasia in Tobacco Non-habitués: A Case Report and Review of Literature.

Oral potentially malignant disorders (OPMDs) encompass a diverse group of clinical lesions, which, on histopathological evaluation, may reveal features of hyperplasia, oral epithelial dysplasia (OED), or even early invasive squamous cell carcinoma. OEDs are often perceived to be associated with a deleterious habit such as tobacco chewing. It has emerged that OEDs may occur even in the absence of a tobacco habit and could be attributed to factors such as trauma, chronic inflammation, and inherent genetic aberrations. Authors have reported a preponderance of such lesions in young females, particularly at sites distinct from those noted in habitués. Additionally, the probability of malignant transformation of OED has been reported to be higher in non-habitués as compared to habitués when lesions are left unaddressed. There remains a paucity of data regarding the exact molecular basis, behavior, and response to treatment of OED among tobacco non-habitués. In view of the increasing number of oral lesions demonstrating epithelial dysplasia in the absence of exposure to significant risk factors, we highlight the scenario with a case. A 39-year-old female, non-habitué, presented with a non-scrapable, white lesion on the maxillary buccal gingiva. Incisional biopsy revealed features of moderate epithelial dysplasia that, on further evaluation of the excisional specimen, confirmed features of severe epithelial dysplasia. Genotyping for human papillomavirus (HPV) was carried out to assess the presence of high-risk HPV strains (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), which are usually associated with OED and/or oral squamous cell carcinomas (OSCCs) in non-habitués. A comprehensive review of various tissue and molecular factors, which play a key role in the pathophysiology of non-habit-associated OED has been illustrated in this report. While the etiological focus of OPMDs is often directed toward deleterious habits and exposure to carcinogens, it is essential to be vigilant for this entity even among non-habitués. A meticulous screening of the oral cavity, for all patients, shall facilitate the prevention and early diagnosis of OED, particularly in individuals not exposed to habit-forming risk factors.

Detection and evaluation of the presence of the BRAF V600E mutation in ameloblastomas in an Indian population.

Introduction: Ameloblastoma is a benign epithelial odontogenic neoplasm that constitutes approximately 1% of all oral tumors and about 9 to 11% of all odontogenic tumors. They are slow-growing, locally invasive, and demonstrate a potential for metastasis and malignant transformation. The molecular pathogenesis of ameloblastoma is attributed to aberrant activity of the signal transduction pathways relating to developmental stages of odontogenesis including the mitogen-activated protein kinase (MAPK) pathway. The BRAF V600E mutation was identified as the most frequently mutated gene in this neoplasm. Studies have shown that use of BRAF inhibitors in patients diagnosed with ameloblastomas led to a significant reduction in tumor volume. Aims: To detect the expression of BRAF V600E mutation in ameloblastomas in an Indian population using immunohistochemistry. To compare the difference in the occurrence of the BRAF V600E mutation between mandibular and maxillary cases. Materials and Methods: Thirty-three formalin-fixed paraffin-embedded tissues of histopathologically proven cases of ameloblastoma were assessed for the BRAF V600E mutation by immunohistochemistry using the BRAF V600E monoclonal antibody. Patient data such as age, sex, anatomical site, recurrence were documented. Statistical Analysis: The statistical analysis was performed using the Pearson Chi-square test and Student's t-test. Results: The present study revealed a high expression of the BRAFV600E mutation in mandibular cases of ameloblastoma among Indians irrespective of the age, sex, site, recurrence or histological pattern. Conclusions: The identification of this driver mutation opens the possibility of an adjuvant therapeutic modality to reduce the significant facial disfigurement and morbidity following surgical management.

Elastin remodeling: Does it play a role in priming the malignant phenotype of oral mucosa?

Background: The extracellular matrix (ECM) is a dynamic tissue that provides nutrition and support to overlying epithelium. During tumorigenesis, the tumor microenvironment (TME) dysregulates the ECM. This is reflected by morphological changes seen in collagen and elastic fibers and is thought to facilitate metastasis. Aim: To study the degradation of elastic fibers in different grades of oral squamous cell carcinoma (OSCC) and in oral epithelial dysplasia (OED) using histochemistry and to correlate it to the TNM stage of OSCC. Materials and Methods: Tumor cores from 38 cases of OSCC (well-differentiated[15], moderately differentiated[14], and poorly differentiated[9]) and 15 incisional biopsies of OED were analyzed. Hematoxylin-eosin and Verhoeff's-Van Gieson (VVG) stains were used. The stained sections were assessed for morphological changes in elastic fibers. Statistical Analysis: Data were analyzed using Statistical Package for Social Sciences (SPSS) version 22 software. Fisher's exact, Kruskal-Wallis, one-way ANOVA, and Turkey post hoc tests were used to establish significance (P ≤ 0.05). Spearman's correlation test was used to correlate elastin fiber degradation with TNM stage of OSCC. Results: All grades of OSCC showed absence of elastic fibers around the tumor islands. Elastic fiber degradation (fragmented and clumped type fibers) increased proportionately with the grade and TNM stage of OSCC. In OED, A significant reduction in the amount of elastic fibers with increasing grade was noted. Conclusion: A positive correlation was noted between elastin degradation and grade and stage of OSCC. Therefore, it may be implicated in tumor progression of OSCC.

Tagging the pre-metastatic node in oral cancer: A cross-sectional study.

INTRODUCTION: Lymph node involvement is the first indication of spread of oral squamous cell carcinoma (OSCC) and it is also a most significant prognostic factor. Lymph nodes show various tumor-induced histological changes preceding actual metastasis, viz. increased vascularity, follicular hyperplasia and desmoplasia which leads to pre-metastatic niche formation. This pre-metastatic niche primarily provides a favorable microenvironment to for the survival and subsequent growth of cancer cells within the lymph node. AIM: A retrospective study to evaluate carcinoma-induced changes in lymph nodes harvested from radical neck dissection in OSCC patients. OBJECTIVES: 1) To evaluate cancer-induced histological changes in positive and negative lymph nodes in OSCC patients. 2) To look for common histopathological changes in both pre-metastatic and metastatic lymph nodes. MATERIALS AND METHODS: Forty lymph nodes harvested from seven OSCC patients were sectioned and stained (Hematoxylin-Eosin) for documentation of histologically evident morphological and functional alterations. The Chi-square test was applied between the non-metastatic and metastatic lymph nodes findings and a statistically significant difference was seen. RESULTS: Sections from 28 negative nodes showed changes associated with pre-metastatic niche conditioning whereas, 12 sections exhibit frank metastases. CONCLUSION: The modified immunological responses and remodeling of the vasculature are the most common histologic tumor-induced pre-metastatic changes. This study reviewed and categorized these histological changes that point to pre-metastatic niche conditioning of lymph nodes.

Pemphigus vulgaris in an elderly woman diagnosed with subacute thyroiditis: A case report.

Epitope spreading phenomenon explaining the molecular link between subacute thyroiditis (SAT) and pemphigus vulgaris.

Oro-facial-digital syndrome type I: a case report with novel features.

Oro-facial-digital syndrome is a group of rare heterogeneous hereditary disorders characterized by abnormalities of the oral cavity, face and digits, along with varying degrees of mental retardation. Currently, Oro-facial-digital syndrome has been classified into 14 types and two additional unclassified variants have been proposed. Amongst the various variants described, Oro-facial-digital syndrome type I is the most common. We report an interesting subclinical sporadic case of Oro-facial-digital syndrome type I in a 21-year-old female patient. Interestingly, our patient presented with a few novel hitherto unreported clinical findings like midline pits in the philtrum area and a hamartomatous proliferation of tissue in the anterior maxillary alveolar gingival region. This case report highlights the importance of prudent histopathological-clinical correlation, which can direct the flow of clinical investigations leading to the detection and diagnosis of unsuspected conditions as learned in this case. We would also like to emphasize that comprehensive examination of new born for structural abnormalities of the orofacial region is crucial to early diagnosis of syndromes and subsequent referral for further evaluation and management.

Tumor-associated macrophages: Harbingers of aggressiveness in oral squamous cell carcinoma.

BACKGROUND: The significance of the tumor microenvironment (TME) as a modulator of tumor behavior was acknowledged by Hanahan and Weinberg in 2011 as the emerging hallmarks and enabling characteristics of the hallmarks of cancer. Subsequently, the role of inflammation, in conferring aggressiveness to a tumor, was regarded as a fundamental process in the evolution of the TME. Tumor-associated macrophages (TAMs) are distinctly polarized inflammatory cells and key shapers of a protumorigenic microenvironment. AIMS: The aim of the study was to evaluate the distribution of TAMs and the expression of CD-163 as a marker to evince tumor aggressiveness, in oral squamous cell carcinoma (OSCC). SETTINGS AND DESIGN: A retrospective institutional study was approved by the institutional ethics committee, and random sampling was carried out. Cases fulfilling the inclusion criteria were subjected to S(site), T(tumor), N( node), M( metastasis), P(pathology) STNMP staging along with immunohistochemical evaluation of CD-163. METHODS: Samples for this study included 58 archival cases of OSCC. Demographic details were recorded, and the STNMP stage ascertained, following which, each case was reevaluated histopathologically for the invasive front. Cases with sufficient stroma and demonstrating the invasive front were further subjected to immunohistochemical evaluation of CD-163 for TAMs. The density of CD-163-positive cells was assessed by three pathologists, independently, in a double-blinded evaluation using Image-J©. STATISTICAL ANALYSIS: Descriptive data were evaluated and analyzed statistically using Spearman's/Pearson's correlation tests based on the distribution of data. RESULTS: The density of TAMs was noted to be directly proportional to the STNMP stage. In addition, a strong positive, statistically significant correlation was noted between the density of TAMs and tumor size, nodal status and STNMP stage. CONCLUSION: The crucial role of the tumor microenvironment must be considered when evaluating OSCC. TAMs prove to be a reliable marker for assessing tumor aggressiveness and could aid in improved prognostication of OSCC, while also being potential targets for therapy.

Keyes Triad in Type 2 Diabetes Mellitus: A Microbiological Study.

BACKGROUND: With the increasing prevalence of type 2 diabetes mellitus (DM), there is a need to assess if the elevated salivary glucose levels provide an environment conducive to the growth of cariogenic microorganisms specifically Streptocooccus mutans and Lactobacillus acidophilus. MATERIALS AND METHODS: Forty-five patients were divided into three groups consisting of patients with type 2 DM with caries, patients with type 2 DM without caries and age-matched healthy nondiabetic individuals (control). Saliva samples were subjected to semiautomatic salivary glucose estimation by the glucose oxidase-peroxidase method, using the Tulip glucose estimation kit. Swabs were immediately inoculated onto Mitis Salivarius Bacitracin agar and Man Rogosa Sharpe agar. RESULTS: In Group A, statistically significant positive correlation was found between S. mutans and salivary glucose (r = 0.858) as well as L. acidophilus and salivary glucose (r = 0.853). In Group B, a statistically significant positive correlation was found only between S. mutans and salivary glucose (r = 0.705) and not between L. acidophilus and salivary glucose (r = 0.387). The control group did not show a statistically significant correlation. CONCLUSION: It is established that salivary glucose levels reflect the diabetic state of an individual. The salivary glucose level predicted a 1.7 times higher caries susceptibility in a diabetic, as shown by results in this study. Salivary glucose causes an increase in the cariogenic load in diabetic patients, thus warranting a modification of the Keyes triad.

Oro-facial-digital syndrome type I: a case report with novel features

Oro-facial-digital syndrome is a group of rare heterogeneous hereditary disorders characterized by abnormalities of the oral cavity, face and digits, along with varying degrees of mental retardation. Currently, Oro-facial-digital syndrome has been classified into 14 types and two additional unclassified variants have been proposed. Amongst the various variants described, Oro-facial-digital syndrome type I is the most common. We report an interesting subclinical sporadic case of Oro-facial-digital syndrome type I in a 21-year-old female patient. Interestingly, our patient presented with a few novel hitherto unreported clinical findings like midline pits in the philtrum area and a hamartomatous proliferation of tissue in the anterior maxillary alveolar gingival region. This case report highlights the importance of prudent histopathological-clinical correlation, which can direct the flow of clinical investigations leading to the detection and diagnosis of unsuspected conditions as learned in this case. We would also like to emphasize that comprehensive examination of new born for structural abnormalities of the orofacial region is crucial to early diagnosis of syndromes and subsequent referral for further evaluation and management.

The Stromal Dictators in a Concomitant Case of Oral Submucous Fibrosis - Oral Squamous Cell Carcinoma.

Oral submucous fibrosis (OSMF) is a potentially malignant disorder, characterized by alteration in the connective tissue stroma. Its association with oral squamous cell carcinoma (OSCC) has been recognized and conferred a special status as a distinct disease entity with improved prognosis as compared to conventional squamous cell carcinoma. Such cases of concomitant presentation of OSMF and OSCC have not yet been defined, leading to ambiguity regarding the evaluation. The concomitant occurrence of OSMF-OSCC is associated with histopathological features, unlike OSMF, yet similar to an aggressive presentation of OSCC. An indepth evaluation of the connective tissue, along with other tumor characteristics such as tissue hypoxia, inflammatory cell population, neoangiogenesis, and stromal cells fortify the possibility of these cases of concomitance being as aggressive, if not more, as compared to conventional OSCC. Thus, recognizing such cases along with the evaluation of probable prognostic indicators is necessary to improve the current understanding of tumorigenesis and progression in concomitant cases of OSMF-OSCC.

Assessing the prognostic significance of MUC4ß in mucoepidermoid carcinoma of the salivary glands: An immunohistochemical study.

OBJECTIVES: - Routine histopathological grading for salivary gland mucoepidermoid carcinoma (MEC) have failed to prognosticate these tumors, resulting in poor post-surgical outcomes. In developing countries, the lack of technologically advanced infrastructure curtails, efficient treatment modalities. This study aimed at determining if MUC4ß can characterize salivary gland MEC and serve as a practical and inexpensive method to prognosticate salivary gland MEC. MATERIALS AND METHODS: - Fifteen cases of archived paraffin embedded tissue blocks of mucoepidermoid carcinomas were reassessed for histopathological grading using Healey's system, modified by Batsakis and Luna and immunohistochemically evaluated for expression of MUC4ß. Statistical analysis (Kappa statistics and Spearman's rho correlation coefficient) was performed to assess inter-observer reproducibility and to correlate the expression of MUC4ß with the histopathological grade of the tumor. RESULTS: MUC4ß expression is related to tumor differentiation in an inverse relationship. Two cases of high grade MEC were the exception to this rule. CONCLUSION: Our study revealed that MUC4ß alone cannot serve as a reliable prognostic marker due to its divergent tumor suppressor and oncogenic pathway. The role of MUC4ß needs further evaluation and research so as to potentiate therapeutics depending upon its context dependent function, as a cancer marker or an oncogenic factor.

Clinico-pathological correlations of odontogenic tumors: Some critical observations based on a 20 year institutional study and a comprehensive review of literature.

CONTEXT: Odontogenic tumors (OTs) represent a rare subset of pathologies of the oral and maxillofacial region. The classification of OTs has undergone several changes over the years due to a lack of uniform international identification criteria. The histomorphological similarity and the many variations in behavioral patterns elaborated by these lesions warrant research. AIMS: Using the update from the fourth edition of the World Health Organisation Classification of Head and Neck Tumors (2017), this dental institution carried out an epidemiological study on OTs in the state of Goa (India) and compared the data obtained with similar studies on OTs done within India. MATERIALS AND METHODS: The clinical and pathological data of OTs from August 1996 to December 2016 was retrieved from the oral and maxillofacial pathology department archives, belonging to the lone dental college and hospital in the state of Goa, India. Demographic data such as frequency, age, gender, and site along with pathological subtype was analysed. STATISTICAL ANALYSIS USED: Descriptive analysis (i.e. frequency of age, gender, and location), Chi-Square Test and Fischer Exact test. RESULTS: The relative frequency of OTs was 2.61% of all oral biopsied specimens. The most common OT encountered was ameloblastoma (57.9%). The posterior aspect of the mandible was the most favored site (77.2%). The frequency of OTs decreased after the fourth decade. An overall marginal male predilection (55%) was seen. CONCLUSIONS: This study contributes to the establishment of a comprehensive loco-regional epidemiological database on OTs in India, aiding research on their aetio-pathogenesis and diagnosis.

Detection of Type VII collagen in odontogenic keratocyst: An immunohistochemical study.

BACKGROUND: Separation of the epithelial lining from the underlying connective tissue wall has been a frequently observed and unique feature in odontogenic keratocysts (OKC), but not in other odontogenic cysts nor neoplasms. No study on OKC has been reported evaluating the role of type VII Collagen, the anchoring fibrils, which function in stabilising the epithelial structure. The purpose of this study was to assess the role of type VII collagen in the fragility of the epithelium leading to a high recurrence rate in OKCs. MATERIAL AND METHODS: Immunohistochemical staining with Abcam® Monoclonal Mouse Anti-Collagen VII Antibody [LH7.2] (used at a dilution of 1:200) on 30 tissues of OKC. The chi-square test was applied to confirm the statistical significance between the control and test groups. The frequencies of the pattern of distribution for the staining characteristics of collagen VII were calculated in the OKC samples. RESULTS: Out of the 30 OKC samples 22 (73.3%) showed negative staining for type VII Collagen. Among the infected cases, 7 showed a positive basement membrane staining and one of the non-infected OKC showed positive basement membrane staining. However, none of the syndrome associated or recurrent OKCs showed any evidence of type VII collagen reactivity. CONCLUSIONS: Considering the distribution of type VII collagen in OKCs it can be concluded that type VII collagen expression is altered in OKCs, leading to destabilisation of the epithelium connective tissue interface thus rendering the epithelium-connective tissue interface fragile. Key words:Type VII Collagen, Odontogenic Keratocyst, Basal Lamina, Immunohistochemistry.

Bilateral Nonsyndromic Dentigerous Cyst in a 10-Year-Old Child: A Case Report and Literature Review.

Dentigerous cysts are the most common developmental cysts of the jaws, accounting for approximately 20% of all jaw cysts. These cysts are usually unilateral, surrounding the crowns of impacted mandibular third molars. Bilateral dentigerous cysts have been associated with syndromes such as cleidocranial dysplasia and Maroteaux-Lamy syndrome. Nonsyndromic bilateral dentigerous cysts are extremely rare, particularly in the mixed dentition. Seventeen such cases have been reported till date. This article reports the eighteenth case of bilateral dentigerous cysts involving permanent maxillary canines in a 10-year-old boy.

Human oral dirofilariasis.

Zoonotic filarial infections particularly dirofilariasis have been reported worldwide. The route of transmission to human beings is vector-borne through mosquitoes. Increased mosquito activity subsequent to global warming has influenced the transmission of dirofilarial infection in many geographic regions, including Asia. Dirofilariasis presents as mucocutaneous and pulmonary infections. Dirofilarial infections rarely manifest in the oral and perioral region and can pose to be a diagnostic challenge to clinicians. We report the first case of oral dirofilariasis in Goa, India.

Rare presentation of cementoblastoma associated with the deciduous maxillary second molar.

Cementoblastoma is a benign odontogenic neoplasm accounting for less than 0.69%-8% of all odontogenic tumours and is characterised by the presence of sheets of cementum-like tissue demonstrating large number of reversal lines. It shows an unlimited growth potential and a recurrence rate as high as 37.1%. It most commonly affects the permanent mandibular molars. This paper presents the third reported case of cementoblastoma affecting the deciduous maxillary posterior dentition. A 12-year-old male patient reported to the Department of Oral and Maxillofacial Pathology with a chief complaint of pain and swelling in relation to the deciduous maxillary left second molar.

Solitary Intra-Osseous Myofibroma of the Jaw: A Case Report and Review of Literature.

Myofibroma is a rare benign spindle cell neoplasm in children that usually affects both soft tissue and bone in the head and neck region. Approximately one third of these cases are seen within jaw bones as solitary lesions. Solitary intra-osseous myofibroma of the jaw bone shares its clinical, radiographic and histological features with other spindle cell tumors. The rarity of this lesion can make diagnosis difficult for clinicians and pathologists. We report a case of a solitary intra-osseous myofibroma in the mandible of a nine-year-old child.

Small cell neuroendocrine carcinoma of the paranasal sinus with intraoral involvement: Report of a rare case and review of the literature.

The diffuse neuroendocrine system continues to be an enigmatic topic of study in pathology due to its controversial embryologic origins, biology and a variety of tumors engendered. Originally thought to be localized to the classic neuroendocrine organs (pituitary, thyroid, pancreas and adrenal medulla), the neuroendocrine cells are now known to be distributed in every organ system of the body. A number of human diseases have been linked to aberrations in the functioning of the neuroendocrine cells. Neoplasms of the neuroendocrine system can thus occur in myriad primary sites and range in behavior from benign to lethal. Small cell neuroendocrine carcinoma (SNEC) is a high-grade neuroendocrine tumor, rarely presenting in the sinonasal region. This article reports a case of a 68-year-old male patient with primary paranasal SNEC showing intraoral involvement. The diagnosis is based on a thorough clinical, histopathological and immunohistochemical workup to differentiate it from the other small round blue cell tumors.