Tumour Microenvironment as a Potential Immune Therapeutic Target for Tongue Cancer Management.

Immunotherapy is a promising approach in the management of human cancers and has been proven to provide a durable response in many cancers. It is helpful as an adjuvant therapy for cancers and at present is considered as a fourth pillar supporting surgery, chemotherapy and radiotherapy. In the treatment of oral cancer, immunotherapy is approved in late-stage diseases where surgical resection cannot be carried out or fails, leading to recurrences and metastasis. Evidences suggest that when given as a first-line treatment, it can elicit an immune response that shrinks tumours, which could provide long-term benefit for patients. But unlike the traditional approach which follows the uniform protocol for all oral cancer patients, effective immunotherapy requires a more site-specific personalized approach. The aim of this paper is to review the various immune evasive mechanisms adopted by tumour cells and their relevance as potential targets for immunotherapy in oral tongue squamous cell carcinoma.

Premetastatic Niche: A Novel Area for Research in Metastasis with a Potential as Therapeutic Targeting in Oral Cancer.

Premetastatic niche (PMN) concept, introduced by David Lyden and colleagues, is an area that can support cancer cells to nurture in it, but the area itself being bereft of cancerous cells. It provides a microenvironment that is congenial for tumor invasion, endurance, and or proliferation of malignant cells to develop into metastasis. These are noncancerous variations in a tumor-free organ and are the most primitive indications of metastasis. These may have a potential to serve as a diagnostic aid, prognostic biomarkers, and therapeutic target. Nevertheless, there is still no clear elucidation on diverse trails of tumor metastasis via lymphatic or hematogenous route, especially in relationship with the PMN. In this review, contemporary knowledge associated with nodal premetastatic niche formation with forthcoming directions on translational and clinical research is deliberated.

Primordial odontogenic tumour: Report of a novel entity - The third case from India.

Primordial odontogenic tumour (POT) is a newly described benign mixed odontogenic neoplasm that has been included in the World Health Organization classification 2017. Only 19 cases that conform to the clinico-pathologic criteria for diagnosis have been reported worldwide. We present the 20th case of POT reported worldwide and is only the third case to be reported from India. The need for considering POT as a possible diagnosis in lesions affecting posterior mandible in patients below 10 years, the need for clinicians and pathologists to be aware of this entity and the need to draw more specific conclusions on the diagnostic criteria of POT make it necessary to report every single case of this entity from different parts of the world. Along with the case report in a 3-year-old child patient, we also present here a summary of the cases reported till date and the review of literature.

Melanotic Neuroectodermal Tumour of Infancy.

Melanotic neuroectodermal tumour of infancy (MNTI) is a locally aggressive neoplasm of neural crest origin. It is primarily a paediatric tumour, and 95% of the cases occur in children below 1 year. The tumour mainly affects the head and neck region. It shows a predilection for the craniofacial sites and the most common site affected is anterior maxilla. Microscopically, it is characterized by a biphasic population of neuroblastic cells and pigmented epithelial cells. Although generally considered as a benign tumour, it can invade the adjacent muscle and bone, causing destruction of the involved site. The rapidity in growth and the aggressive clinical behaviour of the tumour can be deceptive and hence lack of familiarity with the clinical characteristics of the tumour may often lead to an erroneous diagnosis of malignancy. The treatment of choice for MNTI is excision, and it is usually curative. Extensive surgery in a child may interfere with the normal growth and development of the facial structures and reconstruction can be very challenging in infants. Hence, early diagnosis is critical for the effective management. Clinical findings, histopathological features, and differential diagnosis of a classic case of melanotic neuroectodermal tumour of infancy are discussed.

Minichromosome maintenance protein 5 - a promising prognostic marker of oral epithelial dysplasias and oral squamous cell carcinomas.

Background: Early diagnosis is the single most effective means of reducing the mortality rate of oral cancer. Aim: This study was undertaken to assess the expression of minichromosome maintenance protein 5 (MCM5) in oral epithelial dysplasias and oral squamous cell carcinomas (OSCCs) and to evaluate their possible role as a biomarker for early diagnosis and prognosis of OSCC. Design: A retrospective cross-sectional study. Materials and Methods: The study was conducted to assess the expression of MCM5 immunohistochemically in the tissue samples of oral epithelial dysplasias (n = 27) and OSCCs (n = 30) diagnosed between 2014 and 2019. Statistical Analysis: The difference in the mean nuclear labelling index (LI) between the groups and the subgroups was analysed statistically using the Kruskal-Wallis test and the post hoc test, and the Dunn-Bonferroni multiple comparison analysis was conducted for pairwise comparison between the four main groups and the subgroups. The association between mean MCM5 LI and clinicopathological parameters was analysed using Spearman's rank correlation coefficient. Results: A progressive increase in the nuclear expression of MCM5 protein (P-value <0.001) was noticed from normal oral mucosa through oral epithelial hyperplasia and oral epithelial dysplasia to OSCC. A significant correlation was also observed between the mean nuclear MCM5 LI of OSCC and TNM staging (R2 = 0.268, P = 0.029). Conclusion: Our findings suggest that MCM5 may be of great value in assessing the malignant potential of dysplastic lesions and may serve as biomarker of utility in the early diagnosis and prognosis of OSCC.

Nonspecific Cystic Degeneration in Craniofacial Fibrous Dysplasia: A Rare Finding.

Fibrous dysplasia (FD) is a developmental pathology of the bones in which normal bone is replaced by fibrous tissue and immature bone. It can affect single bone (monostotic) or multiple bones (polyostotic), sporadically or in association with McCune-Albright syndrome, Jaffe-Lichtenstein syndrome, or Mazabraud syndrome. When multiple bones in the craniofacial region are affected, the term "craniofacial FD" is used. Nonspecific cystic degeneration occurring in FD of the jaws has rarely been reported in the literature. Here, we present a 52-year-old male patient who reported with a longstanding gradual expansion of the mandible unilaterally. Investigations revealed the presence of mixed radiolucent radioopaque appearance in the mandible and dense sclerotic multiple craniofacial bones. In addition, a lytic lesion in the mandible was appreciated. Histopathological examination of the mandible confirmed the diagnosis of FD with nonspecific cystic degeneration.

A Rare Case of Intra-Oral Dirofilariasis Manifesting on The Buccal Mucosa.

Dirofilariasis is a rare zoonotic disease endemic in tropical and sub-tropic countries, including India. Caused by the nematode of the genus Dirofilaria, the disease usually affects canines which form the primary hosts. Humans rarely get infected through the bite of potential mosquito vectors. Manifestations in humans have been reported to affect the orbital region, and intra-oral involvement is rarely reported. Our case was a 5-year-old boy who presented with a slow-growing diffuse swelling on the buccal mucosa. Dirofilariasis was diagnosed when the excised specimen was subject for histopathologic evaluation, yielding the identification of the Dirofilaria worm with the typical morphologic characteristics in the tissue sections. An extremely rare occurrence intra-orally, dirofilariasis can manifest as subcutaneous nodules. Pathologists have an important role in the final diagnosis of the disease through identifying the adult worm in the tissue sections of the biopsy specimen. Dental practitioners must be aware of such an entity as rarely this can be encountered in routine dental practice.

Congenital granular cell epulis: a rare paediatric tumour of newborn.

Congenital granular cell epulis is a congenital growth rarely found on the gingiva of neonates. These remarkably large tumours present in an infant's mouth may impede with feeding, respiration or adequate mouth closure. Recognition of this entity and prompt treatment are essential for preventing any difficulties for the neonate. This is a case report of a 35-day-old female neonate who presented with a single exophytic lesion in the maxillary alveolar ridge. The differential diagnosis, management regimens and complications of this condition are reviewed. The lesion was excised under intravenous sedation and subjected to histopathological analysis. Based on the microscopic findings, the diagnosis of congenital granular cell epulis was confirmed. Clinicians including paediatricians, sonographers, dentists and surgical pathologists should be able to timely recognise and intervene such tumours as they may be potentially harmful to the infant.

Spindle cell haemangioma - Report of a rare entity.

Spindle cell haemangioma is a rare benign vascular neoplasm. Its occurrence in the oral cavity is uncommon and may be mistaken for other common oral lesions such as mucoceles or fibromas. Microscopically, it has features which are similar to those of other vascular neoplasms and may be a cause for potential mis-diagnosis. In this article, we report a case in the lower lip of a young male patient.

Immunohistochemical analysis of cathepsin-D in benign and malignant salivary gland neoplasms. Evaluation of its role as a prognostic indicator.

Background: Salivary gland tumors are histologically the most heterogeneous group of tumors. Traditional diagnostics and grading of these tumors often fail to provide any insight into patient's clinical course. Cathepsin-D is a lysosomal acid protease secreted in increased levels in several malignancies. However, its role in salivary gland tumors has not been studied extensively. The present study aims to assess the expression of cathepsin-D in malignant and benign salivary gland tumors and to compare its expression in these tumors. Materials and Methods: A total of 40 salivary gland tumors which included 10 cases each of adenoid cystic carcinoma, mucoepidermoid carcinoma, pleomorphic adenoma and Warthin's tumor were evaluated immunohistochemically for cathepsin-D expression. Intergroup comparison of cathepsin-D expression was done between the benign and malignant groups using the Mann-Whitney U-test. Intragroup comparison was also done using Kruskal-Wallis test. Results: A statistically significant difference in the expression of cathepsin-D was observed between the benign and malignant groups. The malignant group showed a considerably higher cathepsin-D expression (mean value 6.284 ± 4.377) when compared to the benign group (mean value 2.281 ± 2.459). The differences in the immunopositivity between the malignant and benign groups were found to be highly significant (P = 0.004). Conclusions: Increased expression of cathepsin-D is observed in the malignant salivary gland neoplasms. This may prove to be a useful marker for the aggressive biologic behavior as well as invasive potential of salivary gland neoplasms.

Canalicular adenoma: palatal presentation of an uncommon lesion.

Canalicular adenoma is a unique, rare, benign salivary gland neoplasm whose reported prevalence varies in different studies. According to literature, this neoplasm has a marked predilection to occur in the upper lip of elderly women. Histological features are usually distinctive and diagnostic. This neoplasm has good prognosis after conservative surgical management but the propensity of multifocal nature and recurrence of this lesion mandates regular follow-up. This case report illustrates the case of a canalicular adenoma in the palate in a 71-year-old male patient. Here, we discuss the differential diagnosis with a brief review of literature.

Oral myofibroma presenting as an aggressive gingival lesion.

Myofibromas are benign neoplasms of myofibroblastic origin and rarely encountered in the oral cavity. Myofibroma may frequently grow rapidly leading to suspicion of malignancy. This may lead to a tendency for aggressive management. The histopathology of this tumour has similarity with other spindle cell tumours and often requires immunohistochemical staining for diagnosis. Here, we present a case of myofibroma in a 15-year-old female patient who reported with an aggressive gingival swelling and discuss the various histopathological differential diagnosis.

Mucoepidermoid carcinoma of retromolar area: an incidental finding.

Salivary gland tumours can arise in any location in the oral cavity but are rather rare in the retromolar region. The majority of the salivary neoplasms arising here are malignant in nature. Mucoepidermoid carcinoma is more commonly seen in the palate. Tumours arising in the retromolar region tend to show symptoms late in onset and may be greater in extent than evident clinically. Imaging studies will help in understanding the full extent of these lesions. We report a case of mucoepidermoid carcinoma arising in a young female patient who reported for orthodontic correction. In the course of examination, a palpable swelling was identified in the right retromolar area, which was eventually diagnosed as intermediate-grade mucoepidermoid carcinoma. Wide resection with adjuvant radiotherapy was the treatment given for the patient.

Carcinoma Cuniculatum of Mandible Masquerading as Odontogenic Keratocyst: Challenges in the Histopathological Diagnosis.

Carcinoma cuniculatum is a locally aggressive, low-grade variant of squamous cell carcinoma. Though primarily a tumour of the skin, it has also been found to be arising from various mucosal surfaces including oral mucosa. When it occurs in the mandible it starts as a mucosal lesion which progressively invades the jaw and destroys the underlying bone, often presenting as a cystic lesion. With only around 30 cases reported in the mandible, this entity remains an elusive one for the pathologist and all except a few cases reported so far, had been misdiagnosed initially. The delay in the diagnosis is a major concern as it results in further progression of the disease with extensive involvement of bone and associated soft tissue structures. The aim of this article is to discuss the histopathological challenges faced in arriving at the diagnosis of a case of carcinoma cuniculatum involving the mandible. Owing to its overlapping clinico-pathological characteristics with odontogenic keratocyst the lesion has been misdiagnosed initially resulting in inadequate management, leading to multiple recurrences and unexpected complications. As a few cases like the present one had been erroneously diagnosed as odontogenic keratocyst previously, it becomes important to identify the varied clinical presentation and unique histopathological characteristic of carcinoma cuniculatum of mandible to help us in recognizing this often-missed entity at an earlier stage, so that it can be managed effectively.

Histopathologic evaluation of oral lichen planus and oral lichenoid reaction: A comparative analysis based on basement membrane thickness and the distribution of mast cells.

Background: Lichen planus is a chronic mucocutaneous disease of unknown etiology with well-established clinical and microscopic features. Oral lichenoid reactions are a family of lesions triggered by contact with specific agents such as metallic restorative materials, resins and drugs. Oral lichenoid reactions share clinical and histological features of oral lichen planus (OLP) but has varied management options. Hence, the discrimination between these two lesions is a major challenge for clinicians as well as pathologists. Aim: Histopathologic categorization of OLP and oral lichenoid reaction by comparing the thickness of basement membrane and the distribution of mast cells using special stains. Materials and Methods: The test group consists of formalin-fixed paraffin-embedded blocks of OLP (n = 15), and oral lichenoid reactions (n = 15) obtained from the archives of the Department of Oral Pathology, Amrita School of Dentistry. Three serial sections of 4 µm thickness were cut from each block. The sections were stained with H & E, periodic acid-Schiff (PAS) and toluidine blue, respectively. Results: A significant increase in the maximum basement membrane thickness (BMT) was noticed in OLP when compared to oral lichenoid reaction. A definite increase was also noticed in the number of mast cells in OLP and oral lichenoid reaction when compared to normal oral mucosa. There was a statistically significant increase in the number of degranulated mast cells in the deeper connective tissue in oral lichenoid reaction when compared to OLP. Conclusion: OLP and oral lichenoid reactions are two different entities showing similar clinical and microscopic presentation. The histochemical analysis of basement membrane and mast cells in these lesions might provide a more authentic method for differentiating these two lesions and might be of utmost value in deciding the treatment options.

Primary Intraosseous Adenoid Cystic Carcinoma with Widespread Skeletal Metastases Showing Features of High-Grade Transformation.

Malignant salivary gland carcinomas arising primarily within the jaw bones are extremely rare. The most common salivary malignancy in these locations is mucoepidermoid carcinoma followed by adenoid cystic carcinoma and adenocarcinoma. The clinical picture and imaging studies of these malignancies may be confused with odontogenic lesions which are more common in this location. Adenoid cystic carcinomas have a prolonged clinical course, tendency for perineural invasion and distant metastasis and multiple recurrences. The diagnosis of these tumors requires thorough histopathologic examination. Immunohistochemical studies may be required in cases showing solid growth pattern. High-grade transformation, earlier termed as dedifferentiation, has been observed in several salivary gland carcinomas including adenoid cystic carcinoma. These transformed tumors are reported to have an extremely poor prognosis. Here, we report a case of primary intraosseous adenoid cystic carcinoma with extensive skeletal metastases which showed a negative staining with p63 and positive staining with CD117. The tumor had a predominant solid growth pattern with areas indicative of high-grade transformation. A negative p63 staining may indicate an incomplete or focal loss of abluminal layer and this is one of the criteria for high-grade transformation in adenoid cystic carcinoma.

Unusual presentation of lipoma on the tongue.

Lipomas are benign soft tissue neoplasm which rarely occur in the oral cavity. Of the total reported cases of lipoma, only about 15% to 20% of cases have occurred in the head and neck region and the tongue is an even rarer site with only about 4% of the reported cases occurring in that region. They are slow growing and usually asymptomatic in nature. When it grows to a large size, it can hinder the physiological processes that are associated with the area. This case report describes the diagnostic features of tongue lipoma with a brief review of literature.

Expression of CK 19 as a biomarker in early detection of oral squamous cell carcinoma.

BACKGROUND: Increased mortality in oral squamous cell carcinoma (OSCC) had been attributed to delay in diagnosis. Lack of a specific marker to assess the malignant potential of premalignant lesions is thought to be one of the reasons for late detection. Expression of Cytokeratin 19, which is widely used as an odontogenic epithelial marker had been reported in OSCC. Downregulation of CK 19 expression plays an important role in terminal differentiation of superficial squamous cell and increased expression in various epithelial malignancies has been suggested to be an indicator of malignant change. AIMS AND OBJECTIVES: To assess the role of CK19 as a potential marker in predicting malignant transformation in oral precancerous lesions and as a prognostic marker in OSCC. MATERIALS AND METHODS: Study population consisted of ten samples each of normal oral mucosa, epithelial hyperplasia, varying grades of both oral epithelial dysplasias and OSCC. The tissue sections were subjected to immunohistochemical staining for the marker cytokeratin 19. RESULTS: An increased expression of CK19 was noted in oral epithelial hyperplasia, severe dysplasia and in superficial epithelium at the invading front in OSCC. In mild and moderate dysplasias, CK19 expression was lower than the normal mucosa. In oral squamous cell carcinoma, the expression of CK19 was restricted to either a few islands or a few cells within the islands, resulting in a lesser expression than the normal epithelium. The malignant epithelial islands in the superficial connective tissue stroma were showing greater expression than the deeper islands. The epithelial cells associated with formation of keratin pearls were found to be showing more expression than those with infrequent keratin pearls. CONCLUSION: The study suggests that malignant transformation of epithelium can be predicted based on the increased expression of CK19. But it should be done with caution as a similar increased expression may also be noticed in presence of inflammation.

Prevalence of odontogenic cysts and its associated factors in South Indian population.

BACKGROUND: Odontogenic cysts (OCs) constitute a major part of oral pathological lesions, but little is known about their distribution patterns in various populations. AIMS: The aim was to determine the prevalence and factors associated with the cases of histopathologically diagnosed OCs that report to our institution and to analyze the factors associated with the presence of OCs and to study the biologic behavior of different types of cysts. MATERIALS AND METHODS: A cross-sectional study was performed on 596 oral and maxillofacial specimens during 2013-2017. Out of these, the cases which were histopathologically proven as OCs were separated and data were collected and analyzed regarding the age, gender, primary symptom, site, radiographic feature, histopathologic diagnosis, treatment given, recurrences and associated conditions if any. RESULTS: Of the 596 cases included in the study, 67 (11.2%) had a histopathological diagnosis of OCs. 41 cases were inflammatory cysts and 26 developmental cysts. 28 cases (41.8%) were reported as periapical cysts, 10 cases (14.9%) were odontogenic keratocysts (OKCs), 9 cases (13.4%) were dentigerous cysts, 8 cases (11.9%) were inflamed cyst wall, 5 cases (7.5%) each of residual cyst and developmental OCs and one case (1.5%) each of orthokeratinized OC and calcifying OC. CONCLUSION: This study showed that the prevalence of OCs was similar to other reported studies. Periapical cysts were the most common cysts reported, followed by OKCs showing that the latter were more frequent than dentigerous cysts.

An immunohistochemical evaluation of podoplanin expression in oral leukoplakia and oral squamous cell carcinoma to explore its potential to be used as a predictor for malignant transformation.

BACKGROUND: Oral leukoplakia (OL) is a potentially malignant disorder with increased risk for the development of oral squamous cell carcinoma (OSCC). Many cases of OSCC arise from the malignant transformation of preexisting OL. However, the risk of progression into OSCC and the possible prediction of malignant potential of OL remain inconclusive. Recent studies have shown that podoplanin, a mucin-like transmembrane glycoprotein specifically expressed in lymphatic endothelial cells, is expressed in various neoplasms including OSCC, indicating its possible biologic role in tumor cells. In this study, an evaluation of podoplanin expression in OL and OSCC has been carried out to assess its potential role as a biomarker to predict the possibility of malignant transformation in OL cases. AIMS AND OBJECTIVES: To assess the usefulness of podoplanin as a potential biomarker for predicting the risk of malignant transformation in OL, by comparing its immunohistochemical expression in OL and OSCC. MATERIALS AND METHODS: Archival paraffin-embedded blocks of 25 OL cases with varying grades of dysplasia and 30 OSCC cases showing its varying grades were selected. Sections were subjected to immunohistochemical staining for podoplanin and compared with the control group for evaluation of results in the three groups. RESULTS: A statistically significant increase in podoplanin expression was observed from normal mucosa through OL to OSCC. In the OL cases, the podoplanin staining score progressively increased from mild dysplasia to carcinoma in situ, whereas in OSCC, well-differentiated group showed the maximum expression of podoplanin. CONCLUSION: The progressive increase in podoplanin expression through the increasing grades of dysplasia in OL is suggestive of an increased risk for malignant transformation with increased expression of podoplanin in OL cases. A high podoplanin expression in the well-differentiated OSCC may indicate a vital role for podoplanin in the early stages of tumorigenesis.