Diminution of Primary Cilia in the Stromal Cells at the Tumor-stromal Interface Correlates With an Aggressive Tumor Biology in the Urothelial Carcinoma of the Urinary Bladder.

BACKGROUND AND AIMS: Primary cilia (PC) are cellular organelles that regulate the cellular homeostasis. They are the seats of many oncogenic pathways and indirectly regulate the epithelial-mesenchymal transition (EMT) and extracellular matrix, both critical for the tumor microenvironment (TME). Though there are a few studies highlighting the alteration of PC in the tumor cells of various malignancies, none depict the PC in the stromal cells in the urothelial carcinoma of the urinary bladder (UC), the stromal cells being an essential component of TME. Therefore, we intend to evaluate the PC in the stromal cells at the tumor-stromal interface in UC. METHODS: Immunohistochemistry for acetylated-α-tubulin (for PC), Ki67, E-cadherin, and SNAI1 was performed in 141 cases of UC and 5 normal controls, and primary cilium: nucleus (C:N) ratio was counted in the stromal cells at the tumor-stromal interface. The C:N ratio was correlated with various clinical and histopathological parameters. RESULTS: The C:N ratio showed significant diminution from normal control (mean=0.75) to low-grade UC (mean=0.24) ( P =0.001) to high-grade UC (mean value=0.17) ( P =0.001). There was a significant diminution of the C:N ratio from the noninvasive to invasive UC ( P =0.025). The C:N ratio did not show any correlation with EMT although negatively correlated with the Ki67 index ( r =-0.32; P =0.001), and a higher ratio showed a trend with a higher recurrence-free survival ( P =0.07). CONCLUSIONS: The diminution of the PC in the stromal cells at the tumor-stromal interface is an early event and correlates with an aggressive tumor biology of UC.

Vocal Cord Nodule with Stromal Atypia: Case Report and Review of Literature.

Vocal cord nodule is a common reactive transformation of the laryngeal mucosa encountered routinely. Although benign, rare instances of stromal atypia have been demonstrated, which can often be confused with other spindle cell lesions. There is a dearth of literature explaining this peculiar transformation. Hence, the diagnosis of these lesions can be put-forth only after histopathological evaluation and appropriate immunohistochemical analysis. Herein, we report a case of a 55-year-old male who presented with vocal cord nodule with stromal atypia.

Expression of EZH2 and H3K27me3 predicts tumor biology of urothelial carcinoma.

Background: Enhancer of zeste homolog 2 (EZH2) is one of the major epigenetic modifiers involved in the transcriptional repression of target genes through trimethylation of H3K27 (lysine 27 residue of histone H3). Deregulated expression of both EZH2 and H3K27me3 has been implicated in the biological behavior and prognostic outcome of various malignancies. Aim: To assess the role of EZH2 and H3K27me3 in the carcinogenesis of urothelial carcinoma of urinary bladder. Materials and Methods: One hundred fifty consecutive urothelial carcinoma cases of urinary bladder (54.7% high-grade) were included in this study. Immunohistochemical analysis for EZH2 and H3K27me3 was performed on whole tissue sections. A multiplication score obtained by multiplying staining intensity and proportion of positively stained neoplastic cells was used for assessment. Results: EZH2 showed a significant correlation with the tumor grade and lamina propria invasion (p < 0.001). The cases with high EZH2 expression showed a significantly high proliferative index (Mean- 32.7%; p < 0.001). In contrast, negative and low expression of H3K27me3 was significantly more common in high-grade cases (p = 0.006). The expression of H3K27me3 was significantly associated with lamina propria (p = 0.01) and deep muscle invasion (p = 0.007). EZH2 showed a significantly higher expression in the high-grade invasive areas as compared to the high-grade non-invasive areas of the same tumor (p = 0.03). Conclusions: This study establishes an important role of the key epigenetic regulators EZH2 and H3K27me3 in the pathobiology of urothelial carcinomas. Strong expression of EZH2 and weak expression of H3K27me3 are associated with higher grade, proliferative index and invasive behavior.

Laryngeal Cellular Myxoma Presenting as Vocal Polyp.

Laryngeal myxoma is an uncommon benign mesenchymal neoplasm. It usually presents as a laryngeal polyp with a history of progressive hoarseness. Although benign, they have a propensity for recurrence if not excised properly. The diagnosis of laryngeal myxoma can only be rendered after histopathological evaluation. The laryngeal myxoma can be further classified as cellular myxoma and angiomyxoma, depending on the stromal cellularity and stromal vascularity, respectively. Herein, we report a case of a 66-year-old lady who presented with a cellular myxoma of the larynx. We believe that this is the second case of laryngeal cellular myxoma. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03291-y.

Expression of mismatch repair proteins in urothelial carcinoma of the urinary bladder.

Background: Urothelial carcinoma of the urinary bladder (UCUB) is a frequently diagnosed malignancy. Mismatch repair (MMR), a proofreading machinery of the DNA, prevents tumorigenesis. The role of MMR deficiency in UCUB in eastern Indian population is not known. Methods: Immunohistochemistry panel for MLH1, PMS2, MSH2, and MSH6 (MMR proteins) was performed on the biopsy specimens of UCUB (N=100). Results: MMR deficiency by immunohistochemistry was demonstrated in two cases (2%). One case showed deficiency of MSH2 and MSH6 and the other case showed the deficiency of all four mismatch proteins. Both cases showed high-grade invasive urothelial carcinoma by histomorphology. Conclusion: The prevalence of MMR deficiency by immunohistochemistry is 2% in eastern Indian population.