Bladder cancer is the ninth leading cause of death worldwide and 14th leading cause of death in Pakistan. The objective of this study was to determine the frequency of urothelial carcinoma in various age groups, its gender distribution, and grades. A total of 131 cases of urothelial carcinoma, received at Department of Pathology, Peshawar Medical College, Peshawar, between January 2017 to December 2022, were included in the study; of them 107 (81.6%) were males while 24 (18.3%) were females with a mean age of 62±13 years. The most common histological subtype was papillary urothelial carcinoma in 117(89.3%) cases, followed by Squamous and Glandular in 5(3.8%) cases. Majority of the urothelial carcinoma with high grade showed a statistically significant relation with muscle invasion 38 (50.66%). Males were four times more likely to have urothelial carcinoma while older age groups were more likely to have high grade urothelial carcinoma.

Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients\' immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.

Thyroid carcinoma of follicular cell origin exists on a histopathologic and clinical spectrum. The authors focus on the category of tumors that fall between the very favorable well-differentiated thyroid carcinomas and the very unfavorable anaplastic thyroid carcinomas. These intermediately aggressive tumors include poorly differentiated thyroid carcinoma and the newly defined differentiated high-grade thyroid carcinoma. Both diagnoses require certain histopathologic requirements be met in order to accurately identify these tumors post-operatively. Management remains primarily surgical though adjunctive treatments such as molecular targeted therapies (eg, tyrosine kinase inhibitors) and differentiation therapy (to restore tumor response to radioactive iodine) are also becoming available.

BACKGROUND: This study aimed to evaluate the T2W hypointense ring and T2-FLAIR mismatch signs in gliomas and use these signs to construct prediction models for glioma grading and isocitrate dehydrogenase (IDH) mutation status.
METHODS: Two independent radiologists retrospectively evaluated 207 glioma patients to assess the presence of T2W hypointense ring and T2-FLAIR mismatch signs. The inter-rater reliability was calculated using the Cohen\'s kappa statistic. Two logistic regression models were constructed to differentiate glioma grade and predict IDH genotype noninvasively, respectively. Receiver operating characteristic (ROC) analysis was used to evaluate the developed models.
RESULTS: Of the 207 patients enrolled (119 males and 88 females, mean age 51.6 ± 14.8 years), 45 cases were low-grade gliomas (LGGs), 162 were high-grade gliomas (HGGs), 55 patients had IDH mutations, and 116 were IDH wild-type. The number of T2W hypointense ring signs was higher in HGGs compared to LGGs (p < 0.001) and higher in the IDH wild-type group than in the IDH mutant group (p < 0.001). There were also significant differences in T2-FLAIR mismatch signs between HGGs and LGGs, as well as between IDH mutant and wild-type groups (p < 0.001). Two predictive models incorporating T2W hypointense ring, absence of T2-FLAIR mismatch, and age were constructed. The area under the ROC curve (AUROC) was 0.940 for predicting HGGs (95% CI = 0.907-0.972) and 0.830 for differentiating IDH wild-type (95% CI = 0.757-0.904).
CONCLUSIONS: The combination of T2W hypointense ring, absence of T2-FLAIR mismatch, and age demonstrate good predictive capability for HGGs and IDH wild-type. These findings suggest that MRI can be used noninvasively to predict glioma grading and IDH mutation status, which may have important implications for patient management and treatment planning.

The prognostic significance of unconventional histology (UH) subtypes including intraductal carcinoma of the prostate (IDC-P), ductal adenocarcinoma, and cribriform pattern has been investigated for prostate cancer (PCa). However, little is known about magnetic resonance imaging (MRI) features and the oncological impact of tumor localization in localized PCa with UH. Clinical data of 211 patients with acinar adenocarcinoma (conventional histology [CH]) and 82 patients with UH who underwent robotic-assisted radical prostatectomy (RARP) were reviewed. Patients with UH are more likely to be older and have higher Gleason grade group, higher Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score, and larger tumor volume (TV) than those with CH. Multivariate analysis identified the presence of UH as an independent prognostic factor for progression-free survival (PFS) (hazard ration (HR) 2.41, 95% confidence interval (CI) 0.22-0.79, P = 0.0073). No significant difference in PFS was seen regarding tumor localization (transition zone [TZ] or peripheral zone [PZ]) in patients with UH (P = 0.8949), whereas PZ cancer showed shorter PFS in patients with CH (P = 0.0174). PCa with UH was associated with higher progression than PCa with CH among resection margin (RM)-negative cases (P < 0.0001). Further, increased PI-RADS v2.1 score did not correlate with larger TV in UH (P = 0.991), whereas a significant difference in TV was observed in CH (P < 0.0001). The prognostic significance of UH tumor was independent of tumor localization, and shorter PFS was observed even in RM-negative cases, indicating an aggressive subtype with micro-metastatic potential. Furthermore, UH tumors are more likely to harbor a large TV despite PI-RADS v2.1 score ≤ 3. These findings will help optimal perioperative management for PCa with UH.

OBJECTIVE: Gastric cancer and its precancerous lesions represent a significant public health concern. A subset of gastric cancers exhibits mutations in the TP53 gene, often accompanying distinctive morphologic alterations. This study aimed to assess the diagnostic efficacy of p53 immunostaining in real-world clinical settings.
METHODS: A retrospective analysis was conducted on 50 cases of gastric tumors and tumor-like lesions, wherein p53 immunostaining played a pivotal diagnostic role. The staining pattern of p53 was examined in conjunction with clinicopathologic parameters.
RESULTS: Mutant p53 staining pattern demonstrated a significant association with high-grade nuclear atypia (p<0.001), high-grade dysplasia, and tubular adenocarcinoma (p<0.001), as well as microsatellite instability status (p=0.034). Furthermore, the diagnostic utility of p53 immunostaining was evident in scenarios where: 1) biopsy specimens contained few tumor cells, 2) pathologic evaluation of resection margins was limited by cauterization artifacts, and 3) distinction between low-grade and high-grade gastric dysplasia was challenging.
CONCLUSIONS: P53 immunostaining can be helpful for the diagnosis of gastric tumor and tumor-like lesions, and accurate pathologic margin evaluation, particularly in lesions demonstrating intestinal-type differentiation and some degree of nuclear atypia.

OBJECTIVE: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST.
METHODS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed.
RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4).
CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

Poor differentiation is strongly associated with poor outcomes in cutaneous squamous cell carcinoma (CSCC). In addition, the National Comprehensive Cancer Network (NCCN) guidelines designate poorly differentiated tumors as \"very high risk\". Despite its clear prognostic implications, there is no standardized grading system for CSCC differentiation in common use today. CSCC differentiation is graded inconsistently by both dermatopathologists and Mohs surgeons, and reliability studies have demonstrated suboptimal inter- and intra-rater reliability in both of these groups. The absence of a standardized and reliable grading system has impeded the use of differentiation in CSCC staging, despite its apparent correlation with disease outcomes. We performed a comprehensive review of the literature summarizing historical CSCC differentiation grading systems, as well as grading systems in non-cutaneous head and neck SCC as a point of reference. Relevant articles were identified by searching Embase and PubMed, as well as by reviewing reference lists for additional articles and histology textbook excerpts. CSCC grading systems that were identified and summarized include the historical Broders system, the World Health Organization system, the College of American Pathologists\' system, and a system described by a 2023 Delphi consensus panel of dermatopathologists.

OBJECTIVE: Perioperative chemotherapy combined with surgical resection represent the gold standard in the treatment of locally advanced gastric cancer. The Mandard tumor regression score (TRG) is widely used to evaluate pathological response to neoadjuvant treatment. The aim of this study was to assess the prognostic value of TRG in terms of overall survival (OS) and disease-free (DFS).
METHODS: Retrospective analysis of all consecutive patients who underwent oncological gastrectomy after neoadjuvant chemotherapy from January 2007 to December 2019 for gastric adenocarcinoma was performed. Based on their TRG status they were categorized into two groups: good responders (TRG 1-2) and poor responders (TRG 3-5). Subsequent multivariable analyses were conducted.
RESULTS: Seventy-four patients were included, whereby 15 (20.3%) were TRG 1-2. Neoadjuvant regimens for TRG 1-2 vs. TRG 3-5 were similar: MAGIC (53% vs. 39%), FLOT (40% vs. 36%), FOLFOX (7% vs. 15%, p = 0.462). Histologic types according to Lauren classification for TRG 1-2 vs. TRG 3-5 were: 13% vs. 29% intestinal, 53% vs. 44% diffuse and 34% vs. 27% indeterminate (p = 0.326). TRG 1-2 group exhibited significantly less advanced ypT (46% vs. 10%, p = 0.001) and ypN stages (66% vs. 37%, p = 0.008), alongside a diminished recurrence rate (20% vs. 42%, p = 0.111). The 3-year DFS was significantly better in this group (81% vs. 47%, p = 0.041) whereas the disparity in three-year OS (92% vs. 55%, p = 0.054) did not attain statistical significance.
CONCLUSIONS: TRG 1-2 was associated with less advanced ypT and ypN stage and better DFS compared to TRG 3-5 patients, without a significant impact on OS.

This study describes a novel method for grading pathological sections of gliomas. Our own integrated hyperspectral imaging system was employed to characterize 270 bands of cancerous tissue samples from microarray slides of gliomas. These samples were then classified according to the guidelines developed by the World Health Organization, which define the subtypes and grades of diffuse gliomas. We explored a hyperspectral feature extraction model called SMLMER-ResNet using microscopic hyperspectral images of brain gliomas of different malignancy grades. The model combines the channel attention mechanism and multi-scale image features to automatically learn the pathological organization of gliomas and obtain hierarchical feature representations, effectively removing the interference of redundant information. It also completes multi-modal, multi-scale spatial-spectral feature extraction to improve the automatic classification of glioma subtypes. The proposed classification method demonstrated high average classification accuracy (>97.3%) and a Kappa coefficient (0.954), indicating its effectiveness in improving the automatic classification of hyperspectral gliomas. The method is readily applicable in a wide range of clinical settings, offering valuable assistance in alleviating the workload of clinical pathologists. Furthermore, the study contributes to the development of more personalized and refined treatment plans, as well as subsequent follow-up and treatment adjustment, by providing physicians with insights into the underlying pathological organization of gliomas.