Is mediastinal fine needle aspiration cytology required or redundant? A single institution-based correlation study with core needle biopsy.

INTRODUCTION: Fine Needle Aspiration cytology (FNAC) and core needle biopsy (CNB) are rapid, minimally invasive and useful techniques to evaluate mediastinal lesions. OBJECTIVES: To compare cytopathology with histopathology of mediastinal lesions and analyse reasons for discordance. MATERIAL & METHODS: Retrospective analysis was done in a tertiary care centre in North West India over a period of seven and half years from 1stJuly 2016 to 31st December 2023. Only those patients who had undergone FNAC and trucut biopsy of mediastinal masses were included. The cytopathology and histopathology slides were studied to analyse causes of discordance. Sensitivity, specificity, positive and negative predictive values of FNAC were calculated keeping histopathology as gold standard. RESULTS: Out of 57 cases analysed, eight cases were non diagnostic on cytology. Cytology could effectively classify a lesion as non neoplastic (7) or neoplastic (42). For further subtyping, histopathology and Immunohistochemistry (IHC) were required. Out of 27 cases of cytological - histopathological discordance, 8 cases had sampling error, 15 cases had limited concordance where FNAC could predict possibility of tumor and 4 cases were discordant where subtyping of malignancy varied on CNB. Sensitivity of FNAC to predict definite diagnosis was 90.2 %, specificity was 50 %, positive predictive value of FNAC to give a definite diagnosis was 93.9 %, negative predictive value was 37.5 %. CONCLUSION: Evaluation of mediastinal masses requires combination of cytology, histopathology and ancillary techniques like IHC. FNAC and CNB are complementary modalities and both are essential for rapid, accurate and comprehensive diagnosis.

Biased eviction of variant histone H3 nucleosomes triggers biofilm growth in Candida albicans.

IMPORTANCE: Candida albicans lives as a commensal in most healthy humans but can cause superficial skin infections to life-threatening systemic infections. C. albicans also forms biofilms on biotic and abiotic surfaces. Biofilm cells are difficult to treat and highly resistant to antifungals. A specific set of genes is differentially regulated in biofilm cells as compared to free-floating planktonic cells of C. albicans. In this study, we addressed how a variant histone H3VCTG, a previously identified negative regulator of biofilm formation, modulates gene expression changes. By providing compelling evidence, we show that biased eviction of H3VCTG nucleosomes at the promoters of biofilm-relevant genes facilitates the accessibility of both transcription activators and repressors to modulate gene expression. Our study is a comprehensive investigation of genome-wide nucleosome occupancy in both planktonic and biofilm states, which reveals transition to an open chromatin landscape during biofilm mode of growth in C. albicans, a medically relevant pathogen.

Negative regulation of biofilm development by the CUG-Ser1 clade-specific histone H3 variant is dependent on the canonical histone chaperone CAF-1 complex in Candida albicans.

The CUG-Ser1 clade-specific histone H3 variant (H3VCTG ) has been reported to be a negative regulator of planktonic to biofilm growth transition in Candida albicans. The preferential binding of H3VCTG at the biofilm gene promoters makes chromatin repressive for the biofilm mode of growth. The two evolutionarily conserved chaperone complexes involved in incorporating histone H3 are CAF-1 and HIRA. In this study, we sought to identify the chaperone complex(es) involved in loading H3VCTG . We demonstrate that C. albicans cells lacking either Cac1 or Cac2 subunit of the CAF-1 chaperone complex, exhibit a hyper-filamentation phenotype on solid surfaces and form more robust biofilms than wild-type cells, thereby mimicking the phenotype of the H3VCTG null mutant. None of the subunits of the HIRA chaperone complex shows any significant difference in biofilm growth as compared to the wild type. The occupancy of H3VCTG is found to be significantly reduced at the promoters of biofilm genes in the absence of CAF-1 subunits. Hence, we provide evidence that CAF-1, a chaperone known to load canonical histone H3 in mammalian cells, is involved in chaperoning of variant histone H3VCTG at the biofilm gene promoters in C. albicans. Our findings also illustrate the acquisition of an unconventional role of the CAF-1 chaperone complex in morphogenesis in C. albicans.