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Gall bladder cancer (GBC) is common among the socioeconomically deprived populations of certain geographical regions. Aflatoxin is a genotoxic hepatocarcinogen, which is recognized to have a role in the pathogenesis of hepatocellular carcinoma. However, the role of aflatoxin in the pathogenesis of GBC is largely unknown. We determined serum AFB1‐Lys albumin adduct (AAA) levels as a marker of aflatoxin exposure in the patients with GBC and compared to those without GBC. The relationship of AAA levels to cytogenetic (TP53mutation&HER2/neu amplification) and radiological characteristics of the tumor was assessed. We included GBC cases (n = 51) and non‐GBC controls (n = 100). Mean serum AAA levels were higher in the GBC group (n = 51) than those without GBC (n = 100) (26.1 ± 12.2 vs. 13.1 ± 11.9 ng/mL; p <.001). HER2/neu expression was associated with higher AAA levels compared to those with equivocal or negative expression (43.9 ± 3 vs. 28.6 ± 10 vs. 19.3 ± 7 ng/mL; p <.001). Older age (age >50 years) (odds ratio [OR] = 3.2 [CI: 1.3–8.2]; p =.013), positive Helicobacter pylori serology (OR = 5.1 [CI: 1.4–17.8]; p =.012), presence of GS (OR = 5 [CI: 1.5–16.9]; p =.009) and detectable AAA levels (OR = 6.8 [CI: 1.3–35.7]; p =.024) were independent risk factors for the presence of the GBC among all study subjects. Among patients harboring GS, older age (age >50 years) (OR = 4.5 [CI: 1.3–14.9]; p =.015), female gender (OR = 3.8 [CI: 1.2–12.5]; p =.027), presence of multiple GS (OR = 21.9 [CI: 4.8–100.4]; p <.001) and high serum AAA levels (OR = 5.3 [CI: 1.6–17.3]; p =.006) were independent risk factors for the presence of the GBC. Elderly age >50 years (OR = 2.6 [CI: 1.3–5.2]; p =.010) and frequent peanut consumption (OR = 2.3 [CI: 1.1–4.9]; p =.030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the leading causes of mortality amongst women in developing countries, and resistance to therapy is the main reason for treatment failure. Recent advances suggest that cancer stem cells (CSCs) are critically involved in regulating the chemo-resistant behavior of cervical cancer cells. In our study, cells with the CSC phenotype were isolated, and we examined the expression levels of stem cell markers and genes associated with epithelial--mesenchymal transition (EMT) using different assays. However, the cells with the CSC phenotype could not be cultured for further cytotoxicity studies, so we established a model of CSC in cervical cancer cells. We performed siRNA-mediated knockdown of E-cadherin in these cells, and studied them for EMT-associated stem-cell-like properties. We also performed dose-dependent cell viability assays using clinically relevant drugs such as cisplatin, cyclopamine, and GANT58 to analyze the drug resistant behavior of these cancer cells. We found that knockdown of E-cadherin induces EMT in cervical cancer cells, imparting stem-cell like characteristics along with enhanced tumorsphere formation, cell migration, invasiveness, and drug resistance. This is the first study to establish a CSC model in cervical cancer cells by knockdown of E-cadherin, which can be used to develop anti-cancer therapies. Key words: cervical cancer, cancer stem cells, E-cadherin, epithelial--mesenchymal transition (EMT). Le cancer du col de l'utérus est l'une des principales causes de mortalité chez les femmes des pays en développement et la résistance aux traitements est la principale raison de son échec thérapeutique. Des avancées récentes suggèrent que les cellules souches cancéreuses (CSC) sont impliquées de manière importante dans la régulation du comportement chimiorésistant des cellules du cancer du col de l'utérus. Dans cette étude, les cellules du phénotype CSC ont été isolées et l'expression d'un marqueur de cellules souches et d'un gène associé à la transition épithélio-mésenchymateuse (TEM) a été confirmée par différents tests. Cependant, ces cellules de phénotype CSC ne peuvent pas être cultivées pour des études de cytotoxicité supplémentaires. Les auteurs ont donc essayé d'établir un modèle de CSC de cellules du cancer du col de l'utérus. Ils ont procédé à l'élimination de la E-cadhérine dans ces cellules à l'aide d'un ARNsi et étudié chez elle les propriétés associées à la TEM de type cellules souches. Ils ont également réalisé un test de viabilité cellulaire dépendant de la dose en utilisant des médicaments cliniquement pertinents tels que le cisplatine, la cyclopamine et le GANT58 pour analyser la résistance aux médicaments de ces cellules cancéreuses. Ils ont constaté que le knockdown de la E-cadhérine induit la TEM dans les cellules cancéreuses du col de l'utérus, ce qui leur confère des caractéristiques semblables à celles des cellules souches et accroît la formation de microsphères tumorales, la migration, la capacité d'invasion et la résistance aux médicaments. Il s'agit de la première étude à établir un modèle de CSC de cellules cancéreuses du col de l'utérus par le knockdown de E-cadhérine qui peut être utilisé pour le développement de thérapies anticancéreuses. [Traduit par la Rédaction] Mots-clés : cancer du col de l'utérus, cellules souches cancéreuses, E-cadhérine, la transition épithélio-mésenchymateuse (TEM)., Introduction Cervical cancer (CC) is one of the leading causes of cancer-related deaths in women, especially in developing countries (Brisson et al. 2020). Routine screening and treatment of precancerous lesions [...]

Objective: Atypia of undetermined significance (AUS) is an indeterminate category which presents a significant challenge for pathologists and clinicians. The management options are dependent on the rate of malignancy for a given populace. Material and Methods: This is a retrospective analysis of 61 cases of the AUS Bethesda category III with grouping into neoplastic and non-neoplastic according to the histopathology data and clinical follow-up. Detailed cytomorphological features were analyzed and image morphometry was done using image J software. Student's t -test was used. Results: Out of the total 61 cases, 35 were neoplastic cases of AUS (histopathology proven), and 26 were non-neoplastic (on follow-up) cases. The risk of neoplasia and risk of malignancy observed were 57.4% and 47.5%, respectively. Neoplastic cases displayed prominent intranuclear inclusions (54%) and pseudopapillary clusters (20%). Majority of non-neoplastic cases revealed fine chromatin (96%) and pale chromatin (4%) while among neoplastic cases, 14% showed pale chromatin. Neoplastic cases showed moderate to marked nuclear pleomorphism (20%) compared to non-neoplastic cases which were monomorphic to mildly pleomorphic. None of the non-neoplastic cases exhibited frequent nuclear overlapping, nuclear grooving, or nucleoli which emphasizes the need for scrutiny of smears for these features. On image morphometry, cases with malignant outcome had larger nuclear area, perimeter, diameter, and nuclear density which were statistically significant. Conclusion: The study illustrates the importance of identifying subtle cytomorphological features and usefulness of image morphometry as an adjunctive objective tool in AUS cases. This helps in making an accurate cytological diagnosis which guides the treating clinician regarding surgical management or need for clinical follow-up. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of a specific type of kidney cancer called Wilms tumor with rhabdomyoblastic differentiation. The patient, a 7-year-old boy, had a large renal mass and underwent fine-needle aspiration cytology (FNAC) to diagnose the tumor. The FNAC smears showed a tumor composed of stromal cells with rhabdomyoblastic differentiation. The patient received chemotherapy and surgery, and the tumor was successfully removed. The article also explores different variants of Wilms tumor, including fetal rhabdomyomatous nephroblastoma (FRN) and stromal predominant Wilms tumors. It emphasizes the importance of FNAC and cell-block immunohistochemistry in diagnosing and understanding these rare variants of Wilms tumor. [Extracted from the article]

This article discusses a case study of a rare type of ovarian tumor called Sertoli-Leydig cell tumor (SLCT). SLCTs are composed of Sertoli and Leydig cells and make up less than 0.5% of all ovarian tumors. The article describes the cytomorphologic features of an SLCT found in an uncommon metastatic site in a young female. The study highlights the importance of accurate cytologic diagnosis and clinical correlation in determining the prognosis and appropriate treatment for SLCTs. [Extracted from the article]

Introduction: Urinary cytology (UrCy) is highly sensitive to diagnosing high-grade urothelial carcinoma (HGUC) but cannot predict muscularis propria invasion. Further, the atypical urothelial cell category (AUC) may have variable outcomes. Image morphometry (IM) may be a valuable adjunct technique in this setting. Hence, we evaluated IM in the AUC and HGUC categories to improve the diagnostic performance. Materials and Methods: The following six nuclear parameters were evaluated by IM on 3150 cells: nucleo-cytoplasmic (N:C) ratio, nuclear area, diameter, perimeter, standard deviation of the nuclear area (SDNA; pleomorphism) and integrated density (ID; nuclear chromasia), using the ImageJ software, in three cohorts based on the histopathology outcome: 20 cases of AUC – benign non-neoplastic outcome (AUC-B); 22 cases of HGUC Muscle invasive (HGUC-MI) and 21 cases of HGUC non-muscle invasive (HGUC-MF). Results: A retrospective analysis of urine cytology. The patient's ages ranged from 36 to 85 years, with a mean age of 60.6. The male-to-female ratio was 5.4:1. A total of 20 cases of AUC-B and 43 cases of HGUC were selected for IM analysis. HGUC cases had higher nuclear parameters than AUC-B, and HGUC-MI had higher SDNA, ID, diameter, and area than HGUC-MF. SDNA and ID predict muscularis propria invasion in HGUC. Conclusions: Image morphometry successfully differentiates HGUC cases from benign non-neoplastic ones and might help to identify muscularis propria invasion in HGUC using a combination of nuclear parameters. [ABSTRACT FROM AUTHOR]

Introduction: Whole-genome sequencing of diffuse large B-cell lymphoma (DLBCL) has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness. Material and Methods: A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and 8 cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse. Results: A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion: The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction. [ABSTRACT FROM AUTHOR]

Purpose: Isolating circulating tumour cells (CTCs) from the blood is challenging due to their low abundance and heterogeneity. Limitations of conventional CTC detection methods highlight the need for improved strategies to detect and isolate CTCs. Currently, the Food and Drug Administration (FDA)-approved CellSearch™ and other RUO techniques are not available in India. Therefore, we wanted to develop a flexible CTC detection/isolation technique that addresses the limitation(s) of currently available techniques and is suitable for various downstream applications. Methods: We developed a novel, efficient, user-friendly CTC isolation strategy combining density gradient centrifugation and immuno-magnetic hematogenous cell depletion with fluorescence-activated cell sorting (FACS)- based positive selection using multiple CTC-specific cell-surface markers. For FACS, a stringent gating strategy was optimised to exclude debris and doublets by side scatter/forward scatter (SSC/FSC) discriminator, remove dead cells by 4',6-diamidino-2-phenylindole (DAPI) staining, and eliminate non-specific fluorescence using a "dump" channel. APC-labelled anti-CD45mAB was used to gate remaining hematogenous cells, while multiple epithelial markers (EpCAM, EGFR, and Pan-Cytokeratin) and an epithelial-mesenchymal transition (EMT) marker (Vimentin) labelled with fluorescein isothiocyanate (FITC) were used to sort cancer cells. The technique was initially developed by spiking Cal 27 cancer cells into the blood of healthy donors and then validated in 95 biopsy-proven oral squamous cell carcinoma (OSCC) patients. CTCs isolated from patients were reconfirmed by Giemsa staining, immuno-staining, and whole transcriptome amplification (WTA), followed by qRT-PCR. In vitro culture and RNA sequencing (RNA-Seq) were also performed to confirm their suitability for various downstream applications. Results: The mean detection efficiency for the Cal 27 tongue cancer cells spiked in the whole blood of healthy donors was 32.82% ± 12.71%. While ~75% of our patients (71/95) had detectable CTCs, the CTC positivity was independent of the TNM staging. The isolated potential cancer cells from OSCC patients were heterogeneous in size. They expressed different CTC-specific markers in various combinations as identified by qRT-PCR after WTA in different patients. Isolated CTCs were also found to be suitable for downstream applications like short-term CTC culture and RNA-Seq. Conclusion: We developed a sensitive, specific, flexible, and affordable CTC detection/isolation technique, which is scalable to larger patient cohorts, provides a snapshot of CTC heterogeneity, isolates live CTCs ready for downstream molecular analysis, and, most importantly, is suitable for developing countries. [ABSTRACT FROM AUTHOR]