The intriguing role of IL33/ST2 axis signaling in oral diseases - A systematic review.

PURPOSE: Oral diseases act as a silent epidemic, and the pathogenetic role of interleukin-33/ suppression of tumorigenicity-2 axis (IL-33/ST2) remains unclear due to a lack of literature. This review has attempted to highlight the importance of this axis in oral diseases, which may be helpful in developing therapeutic modalities required to halt disease progression. MATERIALS AND METHODS: A thorough search was conducted using various databases. Original research articles that assessed both IL-33 and ST2 levels in oral diseases using different techniques were included in the review. The risk of bias for each study was analyzed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and Review Manager 5.4 was used to output the results. RESULTS: In the qualitative data synthesis we included 13 published articles. The most commonly used method was serum estimation, while methods with optimistic results were saliva, real-time quantitative polymerase chain reaction and immunohistochemistry. The predominant mechanism of action was nuclear factor kappa B signaling and type 2 immune response. However, salivary gland epithelial cell activation, activation of mast cells, type 1 immune response, and upregulated angiogenesis are crucial in mediating IL-33/ST2 signaling in oral diseases. CONCLUSIONS: Accumulating evidence demonstrates that the IL-33/ST2 axis is a fundamental pathogenetic mechanism of oral diseases of inflammatory, autoimmune, or neoplastic origin.

p53, Cytokeratin 19 Expression in Oral Squamous Cell Carcinoma and Correlation with Histopathologic Grading: An Immunohistochemical Study.

The purpose of this study was to examine the immunohistochemical expression of p53 and cytokeratin 19 (CK19) in normal oral mucosa (NOM) and oral squamous cell carcinoma (OSCC) and their association with histopathological differentiation grade. The secondary goal was to see if there was any correlation between p53 and CK19 expression in NOM and OSCC. A hospital-based retrospective analysis was conducted in which 40 NOM and 45 OSCC samples were acquired from archives and stained with mouse monoclonal antibodies p53 and CK19. For both the NOM and OSCC groups, the proportion of positively stained cells, staining intensity, and staining index were calculated. p53 immunoexpression revealed that 85% of positively stained cells in the NOM basal layer had a low staining index (mean ± SD 1.87 ± 0.34), whereas 66.7% of positively stained cells in the OSCC had a high staining index (mean ± SD 5.63 ± 3.02). When NOM and OSCC were compared, there was a statistically significant difference in staining intensity. However, despite a linear increase in the percentage of positive cells from well to poorly differentiated, the comparison between histopathological grades was non-significant. CK19 exhibited 18.5% positively stained cells in the NOM basal layer with a low staining index (mean ± SD 1.57 ± 0.53), whereas OSCC samples showed 4.44% immunopositivity with a high staining index. p53 is a marker of oral carcinogenesis independent of histological grade and CK19 expression. Further, CK19 is a marker of dysfunctional epithelial differentiation but lacks sensitivity and specificity; however, it demands further multicentric studies with a large sample size to draw definitive conclusions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04092-7.

Diagnostic Utility of Expression Pattern of S100/Mammaglobin/SOX10/DOG 1 Immunohistochemistry in Differentiation of Secretory and Acinic Cell Carcinoma: A Systematic Review and Meta-Analysis.

Secretory carcinoma (SC) is a relatively new disease entity, separate from acinic cell carcinoma (AciCC), which frequently displays ETV6-NTRK3 gene fusion. However, the differences between SC and AciCC remain ambiguous. Genetic diversity makes its diagnosis complicated. In this regard combined expression of immunohistochemistry markers S100/Mammaglobin/SOX10 and DOG1 is need of the hour as alternative methodology. The current systematic review was to investigate the diagnostic utility of combined immunohistochemical expression of S100/Mammaglobin/SOX10/DOG1 in distinction of SC from AciCC histologically. An electronic search of databases was carried out using MEDLINE by PubMed, Google scholar, Scopus and Web of science. Articles inclusive of SC and AciCC were assessed with S100/Mammaglobin/SOX10/DOG1 immunohistochemistry and their predominant expression pattern, predictive values, sensitivity and specificity were gathered. Fourteen eligible articles were analysed, which revealed predominant immunostaining pattern of S100 + /Mammaglobin + /SOX10 + /DOG1- by nearly all ETV6::NTRK3 fusion prevalent SCs alongside with other gene fusions like RET, MET and MAML3 with 98.4% sensitivity as well as 86.1% specificity. The evidence supports that S100/Mammaglobin/SOX10/DOG1 combined immunostaining can serve as a reliable diagnostic method to differentiate secretory from acinic cell carcinoma.

Acantholytic oral squamous cell carcinoma with clear cell change - a rare amalgamated variant.

Background: Acantholytic squamous cell carcinoma (ASCC) is an uncommon histological variation of oral squamous cell carcinoma (OSCC), accounting for fewer than 4% of all occurrences. The tumor shows a slight masculine predisposition, with the lower lip being the most commonly affected location. ASCC is reported to have a diverse biologic behavior, which explains its ability to metastasize to distant places and, thus, its poor prognosis. Similarly, clear cell change in OSCC is a rare occurrence with an unknown etiology that suggests its aggressive nature. Method and Results: Histopathology reveals central acantholytic cells with numerous duct-like features. The presence of distinct cytological atypia contributes to the diagnosis of SCC. Special stains and IHC aid in distinguishing tumor from other histopathologically similar entities. Conclusion: The case of a 29-year-old male presented here with an updated literature review highlights the need for histological study of the unique and seldom seen oral ASCC with clear cell change, which can be ignored because of similarities with other entities. Because recurrence rates are so high for ASCC, amalgamated clear cell change makes it critical for proper treatment initiation with a definite diagnosis. To the best of our knowledge, this is the first documented occurrence. Our experience with the present case suspected a more aggressive behavior due to a high Ki-67 index, anticipating a poorer prognosis in the oral cavity considering the patient's young age.

Demystifying Histologic Conundrum of Adenoid Ameloblastoma: Case Report with Literature Review.

Introduction: Odontogenic tumors encompass a heterogeneous group of lesions that range from hamartomatous lesions to malignancy. Considerable variation in histologic presentation can mislead their accurate diagnosis and categorization. Ameloblastoma is generally well understood and is easy to diagnose but there has been a constant change in the classification systems ever since Broca classified odontogenic tumors in the year 1867. Over the years, it has been modified by the World Health Organization with many additions and omissions. This dynamic change is based on the result and conclusions of molecular and genetic studies with the last modification in 2017. Case Report: We present two cases of females aged 32 and 60 years who reported with facial swellings, revealed the presence of distinct histopathological findings and were diagnosed as ameloblastoma with dentinoid or adenoid ameloblastoma. Literature search revealed dearth of distinct forms of ameloblastoma that show the formation of duct like structures and dentinoid. Conclusion: It is interesting to highlight such cases as the biological behavior is still unexplored due to paucity of relevant studies and follow up of patients. Understanding the pathogenesis and the histopathological characteristics of the newer entities will enable the prompt diagnosis, treatment plan and expanding the spectrum of the lesions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03534-6.

A Comparative Analysis of Effectiveness of Recombinant Interleukin-11 Versus Papaya Leaf Extract for Treatment of Thrombocytopenia: A Review.

Platelets or thrombocytes play an important role in thrombosis and maintaining hemostasis. Thrombocytes help in forming blood clots at the site of the wound. When the level of platelets decreases, uncontrolled bleeding occurs which can result in mortality. A decrease in the blood platelet level is known as thrombocytopenia which can be caused due to various reasons. A variety of treatment options are available for thrombocytopenia like platelet transfusion, splenectomy, platelet management with various types of corticosteroids, and recombinant interleukin-11 (rhIL-11). The use of rhIL-11 is approved by FDA for the treatment of thrombocytopenia. rhIL-11 is a recombinant cytokine that is administered to patients suffering from chemotherapy-induced thrombocytopenia as it enhances megakaryocytic proliferation which aids in platelet production. But this treatment has various side effects and is costly. Hence, there is a crucial need to identify cost-effective alternative strategies that present no side effects. The majority of the population in low-income countries requires a functional and cost-effective treatment for low thrombocyte count. Carica papaya is a tropical herbaceous plant that has been reported in recovering low platelet count during dengue virus infection. Even though multiple benefits of the Carica papaya leaf extract (CPLE) are popular, the active compound present in it, which mediates these benefits, remains to be identified. This review aims to highlight the different aspects of rhIL-11 and CPLE-induced platelet counts and their limitations and benefits in the treatment of thrombocytopenia. The literature related to the treatment of thrombocytopenia using rhIL-11 and CPLE from 1970 to 2022 was searched using PubMed and Google Scholar databases with the keywords Recombinant Interleukin-11, Papaya Leaf Extract, Thrombocytopenia, and Platelets.

Acantholytic oral squamous cell carcinoma with clear cell change - a rare amalgamated variant

ABSTRACT Background Acantholytic squamous cell carcinoma (ASCC) is an uncommon histological variation of oral squamous cell carcinoma (OSCC), accounting for fewer than 4% of all occurrences. The tumor shows a slight masculine predisposition, with the lower lip being the most commonly affected location. ASCC is reported to have a diverse biologic behavior, which explains its ability to metastasize to distant places and, thus, its poor prognosis. Similarly, clear cell change in OSCC is a rare occurrence with an unknown etiology that suggests its aggressive nature. Method and Results Histopathology reveals central acantholytic cells with numerous duct-like features. The presence of distinct cytological atypia contributes to the diagnosis of SCC. Special stains and IHC aid in distinguishing tumor from other histopathologically similar entities. Conclusion The case of a 29-year-old male presented here with an updated literature review highlights the need for histological study of the unique and seldom seen oral ASCC with clear cell change, which can be ignored because of similarities with other entities. Because recurrence rates are so high for ASCC, amalgamated clear cell change makes it critical for proper treatment initiation with a definite diagnosis. To the best of our knowledge, this is the first documented occurrence. Our experience with the present case suspected a more aggressive behavior due to a high Ki-67 index, anticipating a poorer prognosis in the oral cavity considering the patient's young age.

Cytotoxic Role of Chlorogenic Acid on Oral Squamous Cell Carcinoma Cell Line.

The aim of the present study was to determine the cytotoxic, anticancerous and antiproliferative activity of CGA on oral squamous cell carcinoma (OSCC) cell line (KB) and to evaluate expression level of p21 and p53 in these CGA treated OSCC cell line. Different concentrations of CGA varying from 500 to 2500 µM were tested on OSCC cell line. Trypan blue and MTT assay were performed to establish IC50. DNA fragmentation and expression level of p21 and p53 were evaluated with the help of RT-PCR. CGA exerted antiproliferative and cytotoxic effect on OSCC (KB) cell line. Statistically significant results were found regarding effect of different CGA concentrations on KB cell line with IC50 at 1800 µM. No DNA fragmentation was observed. p21 and p53 expression were down regulated after CGA treatment. CGA revealed neither apoptosis nor damage to the nucleus after DNA fragmentation. Antiproliferative role of CGA was hinted by down regulation of p53 and p21 probably through cell cycle arrest at G1-S phase. It was reaffirmed that CGA a natural chemo preventive agent could enhance the treatment modalities with minimal side effects.

Broder versus Bryne's histologic grading parameters on incision biopsy specimens: A comparative study with P53 and KI67 expression.

OBJECTIVE: Various histological grading of oral squamous cell carcinoma has been contributed to the literature at different periods, but the reliability of such grading systems is controversial. This study attempted to measure the efficacy of Bryne's parameters on the full thickness of incisional biopsies which are representative of the original lesion with the proven molecular malignancy markers P53 and Ki67. MATERIALS AND METHODS: One hundred incisional biopsy specimens of oral squamous cell carcinoma were obtained and histologically graded according to Broder's grading system. The same was graded using Bryne's parameters on full thickness of obtained incision sample. Immunohistochemistry was carried out for both p53 and Ki67. RESULTS: We found a high discrepancy in the grading of lesions with Broader as well as Bryne grading parameters within the same lesion. When compared with the molecular expression percentages of p53 and Ki67, highly significant correlation was found in Bryne's parameters (Pearson Chi-square, P value 0.000) in incisional biopsies than Broder's. CONCLUSION: The use of parameters by Bryne on invasive front of excision biopsies can provide significant grading on incisional biopsies which are more comparable to the molecular behavior of tumor given by the p53 and Ki67 expression.

A Rare Case of Ossifying Fibroma with Cystic Degeneration: Diagnostic Challenge with Literature Review.

Cystic degeneration can occur with various bone lesions. These non-epithelial lined cysts vary from aneurysmal bone cyst, solitary bone cyst or non specific cystic degeneration. In jaws, this association is not well documented. In literature only three cases have been reported as ossifying fibroma (OF) with cystic degeneration. This case appears to be the fourth case to highlight non specific cystic changes in OF. We report a case of OF in 23 year old female with asymptomatic swelling over the left side of face for the past 3 years involving the maxilla, maxillary sinus as well as nasal cavity. Histopathology revealed it to be OF complicated by non-specific cystic degeneration. OF of jaws is an odontogenic neoplasm arising from tooth bearing areas. It occurs more commonly in women in posterior mandible region. Microscopically it shows variable mixture of osteoid bone and basophilic acellular spherules while bony trabeculae frequently demonstrate both woven and lamellar patterns. Various pathogenesis have also been highlighted behind the cystic degeneration's in bony lesions. A review is also tabulated of OFs with cystic degenerations in the jaws reported in the past.