Turkish Journal of Pathology最新文献

Objective: The Papanicolaou (PAP) smear remains the cornerstone of early detection and prevention in cervical cancer screening, Today, liquid-based cytology (LBC) techniques are more widely used for this purpose. ThinPrep is one of the most effective of these methods. In this study, we aimed to investigate the contributions of the cell block method when using ThinPrep liquid-based cervical samples.

Material and methods: We retrospectively reviewed a total of 453 cases in which we applied cell block to assist in correct diagnosis in terms of four criteria we determined from ThinPrep LBC samples accepted to our department between 2020 and 2023. We investigated the benefits of cell block according to the four criteria we defined in these cases; these criteria were adequacy, determination of cellular origin based on atrophy, and correct diagnosis of squamous cell lesions and glandular cell lesions. Cell blocks were re-evaluated by 3 experienced pathologists, and the results were analyzed.

Results: The cell block method contributed significantly to the adequacy in 97 of the 136 samples. It contributed to understanding the cellular origin and correct diagnosis of atrophic background in 113 of the 165 samples. It also contributed to the correct diagnosis of squamous cell lesions in 26 of the 107 samples and glandular cell lesions in 40 of the 45 samples. Overall, it was detected to be useful in 272 out of 453 cases.

Conclusion: The cell-block method represents powerful contributions for each parameter, especially if it is used selectively, particularly in evaluating glandular cell lesions and atrophic background. Additionally, it facilitates ancillary testing in the field of cervical cancer screening and management.

Objective: Loss of mismatch repair (MMR) protein expression, assessed via immunohistochemistry (IHC), and microsatellite instability (MSI) status, determined through molecular methods, are two tumor-agnostic predictive biomarkers for immunotherapy eligibility. However, there remains no consensus on the preferred testing method, nor on the type and extent of molecular testing required for optimal patient selection. This study investigates the correlation between MMR protein loss detected by IHC and MSI status identified through next-generation sequencing (NGS) to evaluate the concordance and potential complementary roles of these methods.

Material and methods: A total of 139 tumor samples were analyzed for MSI using NGS. The cohort included colorectal carcinoma (n=51), pancreatic ductal adenocarcinoma (n=22), cholangiocarcinoma (n=9), non-small cell lung carcinoma (n=6), adenoid cystic carcinoma (n=6), gastric adenocarcinoma (n=6), high-grade serous ovarian carcinoma (n=5), and 34 other tumor types. IHC was performed to assess MLH1, MSH2, MSH6, and PMS2 protein expression. The correlation between MSI status and MMR protein loss was evaluated.

Results: Twelve tumors (8.6%) were classified as MSI-High (microsatellite instable). Among them, ten exhibited MMR protein loss, whereas two MSI-High tumors (a mucinous adenocarcinoma of omental origin and a mucinous colon adenocarcinoma) retained MMR protein expression. No MMR-deficient tumors were identified as MSI-Low (microsatellite stable/MSS).

Conclusion: A strong correlation exists between IHC-based MMR loss and NGS-based MSI detection. IHC remains widely used due to its accessibility and cost-effectiveness, whereas NGS offers higher accuracy and broader genomic insights. With its ability to detect multiple alterations simultaneously, NGS is particularly valuable when tissue is scarce. Combining both methods can improve diagnostic accuracy and guide optimal immunotherapy selection.

Objective: Oral squamous cell carcinoma is the most common head and neck malignancy reported worldwide. Tumor budding represents a histopathological feature characterized by the presence of isolated single/small clusters of cancer cells dispersed within the stroma at the invasive tumor front. Its prognostic significance has not been studied much in lip and oral squamous cell carcinomas in India. The aim of this study was to investigate the prognostic role of tumor budding in a large single-center retrospective cohort of 333 patients with oral squamous cell carcinoma at a tertiary cancer center in North Kerala, India.

Material and methods: The primary resection slides of 333 patients with oral squamous cell carcinoma from 2018 to 2020 were retrieved from the pathology archives and were evaluated by two independent pathologists for tumor budding and other histopathological parameters. The survival data were collected from the patient files.

Results: We found a significant association between tumor budding and other known histopathological prognosticators using Chi-square analysis. Univariate logistic analysis showed tumor budding, depth of invasion ( > 10 mm), worst pattern of invasion 5, and perineural invasion were significantly associated with locoregional recurrence/distant metastasis. Multivariate logistic regression analysis identified tumor budding as an independent prognostic marker for locoregional recurrence/distant metastasis. Univariate cox proportionality analysis showed that tumor budding, depth of invasion ( > 10 mm), worst pattern of invasion 5, pathological T4 stage, and perineural invasion were associated with decreased overall survival and poor disease-free survival in patients with oral squamous cell carcinoma. Multivariate cox proportionality analysis showed tumor budding as the only independent predictor for decreased overall survival and poor disease-free survival.

Conclusion: Based on this study, we can conclude that tumor budding is a simple and a reliable independent prognosticator that facilitates personalized management in patients with oral squamous cell carcinoma.

Objective: Preeclampsia is a pregnancy-specific disorder characterized by impaired maternal-fetal immune tolerance. The maternal immune system plays a crucial role in maintaining pregnancy, and its dysfunction is believed to contribute to preeclampsia. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1), may play a key role in this process. This study evaluated PD-L1 expression in the placentae of patients with pre-eclampsia (PE) and eclampsia (EC). We also compared PD-L1 expression with histomorphological features and fetal outcomes.

Material and methods: A prospective case-control study was conducted, including fifty pre-eclampsia cases, twenty-five eclampsia cases, and twenty-five normal pregnancy controls. Detailed clinicopathological data, histomorphological features of the placenta, and fetal outcomes were collected. PD-L1 expression was assessed using immunohistochemistry, with a semi-quantitative scoring system. The relationship between PD-L1 expression, histopathological scores, and fetal outcomes was also evaluated.

Results: In this study, a lower expression of PD-L1 was observed in pre-eclampsia and eclampsia as compared to a normal pregnancy. Adverse fetal outcomes were associated with lower PD-L1 expression and with reduced placental weight and high histopathological scores ( > 5).

Conclusion: Lower PD-L1 expression was observed in pre-eclampsia and eclampsia compared to normal pregnancies. Reduced PD-L1 expression correlated with histomorphological changes in the placenta and adverse fetal outcomes.

Objective: A growing body of evidence suggests a correlation between endothelial cell dysfunction and cancer, as well as facioscapulohumeral dystrophy, both of which are DUX4-related diseases. However, the endogenous expression of DUX4 within endothelial cells (ECs) remains unexplored. This study aims to investigate DUX4 expression in ECs and examine the presence of DUX4-counteracting proteins named PAX3 and PAX7.

Material and methods: This is a cell study in which human umbilical vein endothelial cells (HUVECs) were selected as an in vitro representative of the EC population. The presence of the DUX4, PAX3 and PAX7 proteins in the HUVECs was examined using immunofluorescence staining. The mRNA levels of these proteins were investigated using qPCR with specific primers for each transcript.

Results: It was observed that 51% of HUVECs expressed the DUX4 protein whereas only a small number of cells were stained with PAX3/PAX7 antibody. At the mRNA level, HUVECs exhibited expression of DUX4, PAX3 and PAX7. The mRNA levels of PAX3 and DUX4 were lower compared to PAX7 mRNA.

Conclusion: The high rate of DUX4 protein expression observed in HUVECs is the first positive data and suggests a potential role for DUX4 protein in endothelial cells. Further analyses including the functional analyses of DUX4, PAX3 and PAX7 in ECs could improve our understanding of a vascular pathogenesis in DUX4-related diseases, particularly in the contexts of cancer and facioscapulohumeral dystrophy.

Objective: Lung cancer, the second most common type of cancer, is the leading cause of cancer-related mortality, with non-small-cell lung carcinoma (NSCLC) being the most prevalent subtype. The presence of EGFR mutations in NSCLC influences tumor behavior and treatment response. The prevalence of EGFR mutation in Iranian patients is limited. This study investigated the frequency of EGFR mutation and its association with PD-L1, ALK, and ROS1 expression in patients with NSCLC from Northwest Iran.

Material and methods: A retrospective analysis was conducted on 647 cases of NSCLC from April 2018 to August 2024 at Imam Reza Hospital in Tabriz, Iran. Histologic diagnoses were confirmed, and patient data were collected. EGFR mutation testing targeted exons 18-21 using Sanger sequencing and Real-Time PCR. ALK and ROS1 rearrangements were assessed using fluorescence in situ hybridization (FISH), while PD-L1 expression was evaluated through immunohistochemistry (IHC). The statistical analysis was performed using SPSS version 27.0.

Results: The cohort comprised 430 males and 217 females, with a median age of 62 years (IQR: 54-70). EGFR mutations were identified in 171 (26.4%) cases, more frequently in females (33.6% vs. 22.8%; p = 0.003). The most common mutation was exon 19 deletion (56.7%), followed by L858R (21.6%). No significant association was found between EGFR mutations and ALK (p = 0.126) or PD-L1 expressions ( p = 0.29). ROS1 mutations were not detected.

Conclusion: This study confirmed the mutual exclusivity of EGFR and ALK mutations and found no significant association with PD-L1. Comprehensive EGFR testing remains crucial to guide targeted therapies. Broader studies are needed to include diverse populations and additional clinical factors to improve personalized treatment.

Objective: We aimed to investigate the association between CMV immunohistochemistry positivity and clinical, endoscopic, histologic, and tissue CMV PCR findings in ileocolonoscopic biopsies of inflammatory bowel disease patients, and to assess the diagnostic value of CMV immunohistochemistry as a reflex test during routine histopathologic evaluation.

Material and methods: We conducted a retrospective analysis of 191 patients (136 ulcerative colitis, 55 Crohn`s disease) between 2018 and 2021. We analyzed clinical data, endoscopic Mayo scores, histologic activity (Simplified Geboes Score), cytopathic changes, CMV immunohistochemistry and tissue CMV PCR results.

Results: CMV immunohistochemistry was positive in 32.4% of cases, significantly associated with ulcerative colitis (p=0.003), symptomatic presentation (p=0.001), extensive colonic involvement (p < 0.001), high histologic activity scores (p < 0.001), and ulceration (p < 0.001). Notably, 74.2% of CMV immunohistochemistry-positive cases had no preliminary clinical suspicion of CMV infection. Viral cytopathic changes were identified in only 30.6% of immunopositive cases on hematoxylin-eosin staining. CMV immunohistochemistry showed a significant correlation with tissue PCR (p < 0.001), although some discordant cases occurred. The PCR-positive group had significantly higher immunopositive cell counts compared to the PCR-negative group (p < 0.001). The number of biopsy fragments did not affect CMV detection by immunohistochemistry.

Conclusion: While evaluating endoscopic biopsies of patients with inflammatory bowel disease, CMV immunohistochemistry assessment as a reflex test may be considered by the pathologist-even in the absence of identifiable viral cytopathic effects with hematoxylin-eosin- particularly when severe histologic inflammation is present. Although the clinical significance of CMV immunohistochemistry could not be fully determined in this study, this approach may increase the likelihood of detecting CMV infection and, in the appropriate clinical context, could contribute to timely diagnosis and management.

Carcinoma cuniculatum (CC) is a rare and distinct clinicopathological variant of well-differentiated squamous cell carcinoma. It is a rare and slow-growing tumor with a peculiar infiltrative growth pattern resembling rabbit burrows (cuniculi). It usually occurs over the plantar aspect of the foot but can also occur at other sites like the oral cavity and genitals. The pathogenesis is unknown, with various hypotheses of trauma as proposed by different authors. It is essential to be aware of this entity as it commonly mimics benign and other low-grade squamous cell carcinoma (SCC). Diagnosis of CC can be challenging and requires repeated histological evaluation and clinical correlation. Herein, we present a case report of CC of the plantar and dorsal aspect of the foot in a 60-year-old male with a history of multiple chronic non-healing ulcers, which was clinically suspected as eumycetoma and remained inconclusive on numerous biopsies.

Objective: Cytological examination of pleural effusion is minimally invasive and low risk but faces challenges due to the lack of architectural features, low cell counts, and overlapping characteristics among reactive mesothelial cells (RMCs), carcinoma cells, and malignant epithelioid mesothelioma (MPM) cells. The aim of this was study to detect the diagnostic accuracy of the expression of HEG1 and Claudin-4 in distinguishing malignant mesothelioma from lung adenocarcinoma in pleural effusion.

Material and methods: The present study was carried out on 84 cases of pleural effusion. Sixty-four representative cell blocks of the studied malignant cases and twenty control cases were stained with HEG1 and Claudin-4 immunostaining, and the results were recorded.

Results: Positive membranous HEG1 immunoexpression was found in 95% of RMCs in benign effusions. Also, positive membranous HEG1 immunoexpression was found in 96% of cases of MPM, and only 2.6% of lung adenocarcinoma cases. There was a statistically significant difference between benign effusion with RMCs and lung adenocarcinoma immunoreactivity. There was a highly statistically significant difference between HEG1 immunoexpression in MPM and lung adenocarcinoma. On the other hand, all cases of benign effusions and all MPM cases had negative Claudin-4 immunoexpression while positive membranous Claudin-4 immunoexpression was found in 94.9% of lung adenocarcinoma cases. There was a statistically significant difference in immunoexpression of Claudin-4 between benign effusion and lung adenocarcinoma. There was a statistically significant difference in the immunoexpression of Claudin-4 between MPM and lung adenocarcinoma.

Conclusion: HEG1 and Claudin-4 IHC staining is extremely valuable in the differential diagnosis between reactive or malignant mesothelial cells and adenocarcinoma in pleural effusion.

Objective: This study aimed to identify the expression profile and prognostic significance of inflammation-associated lncRNAs in chronic viral hepatitis (CVH) and CVH-associated hepatocellular carcinoma (CVH-HCC).

Material and methods: In the first step, lncRNA expression analysis was performed by real-time polymerase chain reaction (RT-PCR) using an array panel of 84 inflammation-associated lncRNAs in 48 formalin-fixed paraffin-embedded (FFPE) tissue samples (12 CVH-HCC, 12 peritumoral cirrhotic parenchyma, 12 nontumoral cirrhotic CVH parenchyma, 12 normal liver samples). In the second step, 7 lncRNAs (DLEU2, HOTAIR, LINC00635, LINC00662, RP11-549J18.1, SNHG16 and XIST) were chosen for RT-PCR assay testing in 72 samples (24 CVH-HCC, 24 peritumoral cirrhotic parenchyma, 24 nontumoral cirrhotic CVH parenchyma samples).

Results: Fifty-six inflammation-associated lncRNAs were significantly up-regulated in the peritumoral cirrhotic parenchyma compared to the normal liver. Expression of 71 lncRNAs was significantly higher in peritumoral cirrhotic parenchyma compared to cirrhotic CVH parenchyma. DLEU2 and SNHG16 were up-regulated both in the tumor and peritumoral cirrhotic parenchyma compared to cirrhotic CVH parenchyma. Expression of LINC00662 was significantly higher in CVH-HCC than in cirrhotic CVH parenchyma. Expression of XIST was also increased in both tumor and peritumoral parenchyma samples, albeit without statistical significance. No significant association was found between lncRNA expressions and survival.

Conclusion: Inflammation-associated lncRNAs DLEU2, SNHG16, LINC00662, and XIST are candidate diagnostic biomarkers in CVH-HCC. More evidence is needed to prove their utility as prognostic markers.