Evaluation of micrometastasis and isolated tumor cells in node-negative early-stage oral tongue squamous cell carcinoma: a cross-sectional study in tertiary-level hospitals in eastern India.

OBJECTIVE: The present study aimed to investigate the incidence of micrometastasis (MMs) and isolated tumor cells (ITCs) in node-negative early-stage oral tongue squamous cell carcinoma (T1-T2 N0). The secondary objective was to correlate the incidence with the clinicopathologic parameters of age, sex, depth of invasion, pattern of invasion, host lymphocytic response, and size and grade of primary tumor. STUDY DESIGN: Micrometastasis and ITCs in cervical nodes of 30 patients with early-stage oral tongue squamous cell carcinoma were detected and compared using 3 methods: routine hematoxylin and eosin staining, serial-sectioning at intervals of 150 microns employing hematoxylin and eosin, and serial sectioning pan-cytokeratin immunostaining. Associations with clinicopathological variables were analyzed. RESULTS: Metastatic tumor cells were detected in the cervical nodes of 2 patients using serial sectioning and immunohistochemistry, resulting in upstaging of 6.6% of all cases. Level I and II lymph nodes were primarily involved. CONCLUSIONS: Early-stage oral tongue squamous cell carcinoma has a significant potential for MMs that frequently go undetected in routine histopathologic examination. However, laborious and technique-sensitive, serial sectioning in combination with pan-cytokeratin staining (AE1/AE3) may aid in detecting MMs and ITCs in patients with early-stage OTSCC.

Comparative immunohistochemical analysis of WT-1, Syndecan and Snail in Ameloblastoma and odontogenic keratocyst: A retrospective study.

Background: The purpose of this experimental study was to evaluate and compare the degree of expression of Wilm's Tumor Gene-1 (WT-1), Syndecan (CD 138) and Snail in Ameloblastoma and odontogenic keratocyst (OKC) and to analyse their potential role in pathogenesis. Methods and Material: Immunohistochemical analysis was performed to evaluate WT-1, Syndecan and Snail expression in Ameloblastoma (n = 20) and OKC (n = 20). Topographical immunoexpression pattern of Ameloblast-like cells, Stellate Reticulum-like cells in Ameloblastoma and basal layer as well as suprabasal layer of cells of OKC were also compared. The results obtained were subjected to ANOVA test and Tukey HSD test through SPSS software 20.0 for Microsoft Windows. Results: WT-1 and Snail overexpression was seen in both Ameloblastoma and OKCs. Syndecan, responsible for maintaining normal cellular morphology, cell-cell adhesion and differentiation was significantly downregulated in both the lesions. The Ameloblasts-like cells and the basal cells showed significantly higher immunopositivity for WT-1 and Syndecan as compared to that of basal cells. An inverse relation was noted for Snail protein. The ANOVA test predicted a statistically significant difference of expression across the lesions with a P value <0.0001 for Syndecan and Snail. Conclusions: The under-expression of epithelial membrane protein Syndecan-1 and upregulation of EMT transcription factor Snail can promote local invasion and is indicative of poor prognosis of these lesions. The overexpression of WT-1 results in tumorigenesis, proliferation and localized aggressiveness of Ameloblastoma and intrabony growth of OKC. Further investigation on the biologic behaviour of OKC is still recommended to arrive at more specific conclusions regarding its nature.

The Study of Expression of Hypoxia-Inducible Factor-1 Alpha (HIF-1 Alpha) and Hypoxia-Inducible Factor-2 Alpha (HIF-2 Alpha) in Oral Squamous Cell Carcinoma: An Immunohistochemical Study.

CONTEXT: Oral cancer is the major cause of mortality and morbidity worldwide. There are many factors that influence the tumor microenvironment that promotes tumorigenesis. Hypoxia is one of the factors that affects the process of angiogenesis by inducing proangiogenic factors to maintain the blood supply which in turn enhances the aggressiveness of the tumor and prognosis of solid tumors such as oral squamous cell carcinoma. AIM AND OBJECTIVE: The aim of the study was to compare the expression of hypoxia-inducible factor 1α (HIF-1α) and hypoxia-inducible factor 2α (HIF-2α) in various histological grades of oral squamous cell carcinoma immunohistochemically. METHODOLOGY: Immunohistochemical evaluation of HIF-1α and HIF-2α was done in 90 samples of oral squamous cell carcinoma which were graded histologically into 30 samples each of well, moderately and poorly differentiated squamous cell carcinoma. Statistical evaluation: Statistical analysis was done to study the prognostic significance of the biomarkers. RESULTS: All the cases showed positivity for expression of HIF-1α and HIF-2α. The number of positive staining in both markers reduced as the tumor severity increased from well to poorly differentiated. The expression of MIL of HIF-2α was higher than HIF 1α and HIF 2α expression was mostly seen in cytoplasmic in well-differentiated and nuclear in both moderately and poorly differentiated OSCC suggestive that HIF-2α is a more specific marker to hypoxia. CONCLUSION: Hypoxia is an essential factor that triggers other angiogenic switch and inflammatory factors which facilitates the process of tumorigenesis. This is also important for predicting the treatment outcome and prognosis of the patients. HIF-2α is a more sensitive marker that appears to be correlated and could perhaps serve as a good surrogate marker of hypoxia.

Is Epithelial-Mesenchymal Transition a New Roadway in the Pathogenesis of Oral Submucous Fibrosis: A Comprehensive Review.

Epithelial-mesenchymal transition (EMT) collectively refers to a series of episodes that reshape polarized, intact epithelial cells into discrete motile cells that can conquer the extracellular matrix (ECM). It performs a pivotal role in embryonic development, wound healing, and tissue repair. Surprisingly, the exact mechanism can also lead to the onset of malignancy and organ fibrosis contributing to scar formation and loss of function. transforming growth factor signaling, WNT signaling, Notch signaling, Hedgehog signaling, and receptor tyrosine kinase signaling, as well as non-transcriptional changes in response to extracellular cues, such as growth factors and cytokines, hypoxia, and contact with the surrounding ECM, are responsible for the initiation of EMT. Although the pathogenesis of oral submucous fibrosis (OSMF) is multifactorial, compelling evidence suggests that it results from collagen deregulation. EMT is one of the spotlight events in the pathogenesis of OSMF, with myofibroblasts and keratinocytes being the victim cells. EMT is an essential step in both physiological and pathological events. The importance of EMT in the malignant development of OSMF and the inflammatory reaction preceding fibrosis implies a new upcoming area of research. This review aims to focus on the EMT events that function as a double-edged sword between wound healing and fibrosis and further discuss the mechanisms along with the molecular pathways that direct changes in gene expression essential for the same in the oral cavity. As OSMF involves a risk of malignant transformation, understanding the cellular and molecular events will open more avenues for therapeutic breakthroughs targeting EMT.

A Case Report of Carcinosarcoma of the Tongue Mimicking a Fibroma: An Enigmatic Lesion With a Diagnostic Dilemma.

Carcinosarcoma of the tongue is a rare biphasic tumor composed of squamous cell carcinoma (SCC), either in situ and/or in invasive form, and a mesenchymal component but of epithelial origin. It is important to diagnose this variant because of its aggressive nature and tendency to metastasize early. The present report describes the case of a carcinosarcoma of the tongue in a 48-year-old male with a short history of 30 days, the clinical feature of which resembles that of an irritational fibroma. The diagnosis often represents a clinicopathological challenge where the study with immunohistochemical technique (IHC) is key to the histopathological diagnosis. We here present a case report of this rare tumor, with an unusual presentation, to contribute in part to better understanding and awareness of this rare malignancy.

A rare presentation of benign fibrous histiocytoma in the maxilla.

Fibrous histiocytoma is a soft-tissue tumor that may present as a fibrous mass anywhere in the human body. The involvement of the oral cavity is rare. We here report a case of benign fibrous histiocytoma localized in the maxilla. A 25-year-old male presented with a slowly increasing large painless mass over the left side of the upper jaw for 5 months. The swelling was of gradual onset, slowly progressive and was not associated with pain, tenderness, or discharge. The radiographic appearance showed a multilocular mixed radiodense, radiolucent lesion in the left posterior maxilla. The histopathological report showed connective tissue component having streaming fascicles of spindle-shaped cells showing a storiform pattern. Many areas showed foamy histiocytes along with few multinucleated giant cells. The cells were appearing benign without any appearance of atypia. The tumor cells were positive for CD-68 and vimentin and negative for CD-34 and S100. The lesion was excised under general anesthesia.