A Clinicopathological Study of OSMF to Evaluate the Response After Treatment with Intralesional Steroid Versus Intralesional Steroid Plus Hyaluronidase.

Oral submucous fibrosis (OSMF) is a chronic debilitating and a well-recognized potentially malignant condition of the oral cavity, sometimes involving oropharynx associated with trismus and burning sensation. Apart from medical management and counselling, local injection of hyaluronidase mixed with triamcinolone acetonide has been used at our centre for the last 20 years with satisfactory clinical results and without any significant side effects. The problem with the treatment was that the doses and duration of treatment has not been standardized. Therefore, in this study, authors aim to evaluate and compare the efficacy of Triamcinolone alone versus Triamcinolone acetonide plus Hyaluronidase at weekly interval and improvement in Clinical and Histopathological staging of disease after 6 weeks of treatment. This study was conducted in Department of Otorhinolaryngology & Head Neck Surgery, with a total sample of 80 participants divided into two Groups, group A received Inj. Triamcinolone acetonide and group B received Inj. Triamcinolone Acetonide and Hyaluronidase 1500 IU at weekly interval. Pre-treatment and post-treatment clinical and histopathological profile of the patients were recorded and analyzed using SPSS 16 software. According to pre-treatment status, the proportion of clinical grades I, II and III were found in proportion 12.5%, 18.8% and 15.0% respectively. No significant difference was found in proportion of various grades between the groups (p = 0.388). At post treatment, the grading was reduced with changed proportion of grades I, II and III cases as 33.8%, 41.3% and 7.5% respectively. There was no significant difference in proportion of various grades between the groups (p = 0.681). Further, the intragroup comparison showed significant improvement Pre to post in group A (p = 0.002), Group B (p < 0.001) and overall, as well (p < 0.001). The inj. Triamcinolone acetonide and Inj. Hyaluronidase showed a better improvement on post treatment histopathological grading although the difference between the two groups was not significant statistically.

Application of the Milan System for Reporting Salivary Gland Lesions and Its Cytohistological Correlation for Risk Stratification: A Single-Institution Experience.

INTRODUCTION:  Salivary gland tumors are known to have a heterogeneous profile with variable clinical presentation and a wide variety of histological subgroups of prognostic significance. Immunocytochemical markers that aid in the diagnosis and characterization of the cell type of origin are critical for this heterogeneous group of malignancies. AIMS AND OBJECTIVES: To study the application of The 'Milan System' for Reporting Salivary Gland Cytology and the diagnostic utility of a panel of immunocytochemical markers in the diagnosis of salivary gland neoplasms and their cytohistological correlation for their risk stratification. MATERIALS AND METHODS: This was a prospective study carried out in which a total of 60 patients were enrolled in the study. Fine-needle aspiration cytology (FNAC) smears and cell blocks were prepared with standard techniques and staining procedures. Immunocytochemistry (ICC) was performed on cell block sections by immunoperoxidase procedure. Immunocytochemical (ICC) stains were used for the differentiation of the lesions in cell blocks. Histopathology was also studied if the patient underwent excision of salivary gland lesions. DISCUSSION AND RESULTS: Almost 60 cases were studied under FNAC and cell block evaluation, as well as ICC, among those five (8.33%) samples were inadequate, eight (13.3%) were non-neoplastic, 27 (45%) were benign, one (1.7%) was neoplasm with uncertain malignancy potential, one (1.7%) was suspected of malignancy, and 19 (31.7%) were malignant. The histopathological diagnosis was confirmed in 47 cases. Of these, 24 (51.1%) were benign and 23 (48.9%) were malignant. The malignancy rate for Milan Categories I, II, III, IVa, IVb, V, and VI was 0%, 0%, 100%, 24%, 50%, 80%, and 84.6%, respectively. The study showed that malignancy risk stratification could be further improved by using cell block with immunocytochemistry as a complementary diagnostic modality. CONCLUSIONS: The present study was carried out to assess the usefulness of the Milan system to report salivary gland cytology results. Thus, the findings of the present study show that the Milan system is helpful in stratifying the risk of malignancy in salivary gland tumors.

BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer.

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George's Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (≥3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of "BRCAness" in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP-ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

Immunohistochemical appraisal of epithelial mesenchymal transition type III in gall bladder cancer.

Background: Epithelial-mesenchymal transition (EMT) is the heart of invasion. EMT associated with cancer progression and metastasis is known as type III EMT. Beta-catenin, E-cadherin, and MMP9 markers of EMT are routinely employed for diagnostic purposes. Aims: We employed these markers to study EMT by immunohistochemistry (IHC) in gall bladder cancer (GBC) with respect to depth of tumor invasion, clinical outcome, and disease-free survival. Settings and Design: This was a prospective case-control study. Material and Methods: Seventy gall bladders were included (50 GBC and 20 CC). After detailed histology, immunoexpression was studied in terms of percentage and strength of expression. Statistics Analysis Used: Expression was compared between CC and GBC by Student t test and analysis of variance. Kaplan-Meier was used for survival analysis, and the extent of agreement ("Kappa") was calculated. Results and Conclusions: The age of incidence of GBC was 49.40 (+11.6) years with female predominance (F:M = 4:1). In 88% (44/50) of GBC, the fundus was involved. Moderately differentiated adenocarcinoma was most frequent [54%; 27/50]. Significant downregulation of E-cadherin (P = 0.022) and beta-catenin (P < 0.001) and upregulation in MMP9 (P < 0.001) were seen in GBC with respect to CC with significant association among them. MMP9 expression was significantly associated with higher tumor stage but with chemotherapeutic response. Our results display that epithelial-mesenchymal transition type III plays a role in GBC invasion. MMP9 overexpression and loss of membranous beta-catenin may be considered a marker for poor clinical outcomes and advanced disease.

Expression of aldehyde dehydrogenase 1A1 in oral squamous cell carcinoma and its correlation with clinicopathological parameters.

Background: Aldehyde dehydrogenase 1A1 (ALDH1A1) is a key aldehyde dehydrogenase (ALDH) isozyme, related to the cancer stem cells which are responsible for initiating tumor growth, progression, and recurrence. High expression of ALDH1A1 has been reported in several tumor types in humans and its expression is associated with poor prognosis. The aim of this study was to assess the expression of the ALDH1A1 in oral squamous cell carcinoma (SCC) and its correlation with various clinicopathological parameters. Materials and Methods: ALDH1A1 expression was analyzed by using immunohistochemistry on paraffin blocks of 112 cases of primary oral SCC and their corresponding 68 lymph nodes with metastatic deposits. ALDH1A1 expression was also correlated with various clinicopathological parameters. Statistical analysis was done with statistical analysis software, the Statistical Package for the Social Sciences version 21.0. Results: High ALDH1A1 expression was observed in 31.2% of cases of primary oral SCC as compared to 73.5% in lymph node metastasis. A statistically significant difference (P = 0.04) was observed in high TNM stages (68.6%) of the tumor as compared to low TNM stages (31.4%). However, histopathological grades of tumor showed nonsignificant correlation with ALDH1A1 expression (P = 0.093). 40.2% of patients were expired at the end of the study, and the rate of mortality was significantly higher (P = 0.01) in patients with high ALDH1A1 expression as compared to low expression (60.0% vs. 31.2%). Conclusion: High ALDH1A1 expression was associated with higher TNM tumor stage and high nodal stage. It was also associated with high mortality rate which validates it as a marker of invasiveness and poor prognosis in oral SCC.

Tuberculous parotitis: A series of eight cases and review of literature.

Although tuberculosis is a common health problem in developing countries such as India, tuberculous parotitis (tubercular involvement of parotid gland) is rarely encountered. Because of very low incidence and nonspecific symptoms, it is often misdiagnosed as parotid neoplasm. Ultrasonographic and computed tomographic findings are also noncontributory for this entity. Hence, to increase awareness about this rare entity, here, we report a series of eight cases of tuberculous parotitis which were diagnosed on fine-needle aspiration cytology (FNAC) and successfully treated with antitubercular drugs. Majority of our cases (five cases) presented as asymptomatic unilateral swelling or acute tender painful swelling (two cases) in the parotid region. FNAC smears showed caseous necrosis, epithelioid granulomas along with variable amount of mixed inflammatory exudates, and few benign ductal or acinar cell clusters. One case had unilateral recurrent swelling in the preauricular region with fistula. Superficial parotidectomy was done and histological examination revealed the diagnosis of tubercular parotitis. Following diagnosis, all patients were kept on antitubercular treatment and responded well to treatment with no evidence of recurrence on 9-month regular follow-up.