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Medicina
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Towards Improved Cancer Diagnosis: New Developments in Histopathology
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Towards Improved Cancer Diagnosis: New Developments in Histopathology

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 1655

Special Issue Editors

Prof. Dr. Ovidiu Simion Cotoi

E-Mail Website
Guest Editor
Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Targu Mures, Romania
Interests: pathology; dermatopathology; lung pathology
Special Issues, Collections and Topics in MDPI journals
Dr. Iuliu Gabriel Cocuz

E-Mail Website
Guest Editor Assistant
Pathophysiology Department, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540139 Targu Mures, Romania
Interests: pathology; dermatopathology; digital pathology; molecular pathology

Special Issue Information

Dear Colleagues,

Histopathology has long been a cornerstone in the field of cancer diagnosis, offering critical insights into the cellular and tissue-level changes associated with malignancy. Over the decades, advancements in microscopy, immunohistochemistry, and molecular techniques have revolutionized our understanding of cancer pathology, enabling more accurate diagnoses and prognostications. Dermatopathology, lung pathology, and digital pathology have further refined diagnostic precision, bridging traditional methods with innovative, technology-driven approaches.

This Special Issue in Medicina seeks to explore the evolving landscape of histopathology in cancer diagnosis, with a focus on integrating classical approaches with cutting-edge methodologies. By addressing both foundational and novel aspects of pathology, we aim to provide a platform for the dissemination of research that enhances diagnostic accuracy, informs therapeutic strategies, and improves patient outcomes.

The issue will highlight state-of-the-art research in histopathology, molecular pathology, digital pathology, and artificial intelligence applications in histopathology. Topics such as novel biomarkers, machine learning algorithms for image analysis, and advancements in immunohistochemical techniques will be emphasized, showcasing their transformative impact on cancer diagnostics and personalized medicine.

We invite original research articles, systematic reviews, and reviews that advance knowledge in pathology, dermatopathology, digital pathology, and molecular pathology. Interdisciplinary studies that integrate pathology with genomics, bioinformatics, and computational tools are also welcome.

Prof. Dr. Ovidiu Simion Cotoi
Guest Editor

Dr. Iuliu Gabriel Cocuz
Guest Editor Assistant

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • histopathology
  • cancer diagnosis
  • digital pathology
  • molecular pathology
  • dermatopathology

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Published Papers (4 papers)

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Research

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12 pages, 1841 KiB  
Article
Correlations Between Immunophenotypic Markers and Clinical Progression in Romanian Patients Diagnosed with Diffuse Large B-Cell Lymphoma
by Georgian Halcu, Anca Evsei-Seceleanu, Dana-Antonia Tapoi, Mihai Cerbu, Cristian Barta and Mihail Constantin Ceausu
Medicina 2025, 61(6), 948; https://doi.org/10.3390/medicina61060948 - 22 May 2025
Viewed by 162
Abstract
Diffuse large B-cell lymphoma is a prevalent subtype of adult non-Hodgkin lymphoma; noted for its biological and clinical variability. Background and Objectives: This study seeks to assess the expression and prognostic implications of Ki-67, MYC, and BCL2 utilising immunohistochemistry on a cohort [...] Read more.
Diffuse large B-cell lymphoma is a prevalent subtype of adult non-Hodgkin lymphoma; noted for its biological and clinical variability. Background and Objectives: This study seeks to assess the expression and prognostic implications of Ki-67, MYC, and BCL2 utilising immunohistochemistry on a cohort of Romanian patients diagnosed with DLBCL while also addressing the limitations imposed by the absence of fluorescence in situ hybridisation testing in resource-constrained settings. Materials and Methods: A single-centre, retrospective study involved 66 cases of formalin-fixed, paraffin-embedded tissue specimens obtained from patients with this lymphoma. Results: The median age at diagnosis was 61.81 years, with most individuals being 60 years or older; 59.1% of the patients were male. Our study identified that 65.2% of the cases belonged to the non-GCB subtype (ABC). MYC-positive expression was observed in 5 out of 66 cases (7.6%), and BCL2 protein expression exhibited a trend toward statistical significance, indicating a lower overall survival for BCL-2-positive patients. The expression of Ki-67 demonstrated a significant correlation with variations in overall survival (OS) (p < 0.001). Patients with low Ki-67 expression had an average survival duration of 76.39 months, contrasting with individuals exhibiting high Ki-67 expression, with a mean survival of 38.98 months. In conclusion, MYC, BCL2, and Ki-67 may be valuable prognostic indicator biomarkers. Conclusions: The prognostic significance of each biomarker varies based on the established cut-off point value. Future research should examine the relationship between protein biomarkers, morphological characteristics, and clinical outcomes in Romanian patients diagnosed with DLBCL, aiming to elucidate clinical ramifications and foster effective management. Full article
(This article belongs to the Special Issue Towards Improved Cancer Diagnosis: New Developments in Histopathology)
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12 pages, 3256 KiB  
Article
Prognostic Impact of Klintrup–Mäkinen (KM) Score in Gastric Cancer and Its Association with Pathological Parameters
by Andreea-Raluca Cozac-Szőke, Georgian-Nicolae Radu, Anca Negovan, Dan Alexandru Cozac, Sabin Turdean, Andreea-Cătălina Tinca, Emőke-Andrea Szász, Iuliu-Gabriel Cocuz, Adrian-Horațiu Sabău, Raluca Niculescu, Diana Maria Chiorean, Alexandru Nicușor Tomuț and Ovidiu Simion Cotoi
Medicina 2025, 61(4), 715; https://doi.org/10.3390/medicina61040715 - 13 Apr 2025
Viewed by 377
Abstract
Background and Objectives: Gastric cancer (GC) remains a significant global health challenge with a poor prognosis. This study aimed to evaluate the association between Klintrup–Mäkinen (KM) inflammatory infiltrate grading and clinicopathological features in gastric cancer patients, investigating its potential as a prognostic marker. [...] Read more.
Background and Objectives: Gastric cancer (GC) remains a significant global health challenge with a poor prognosis. This study aimed to evaluate the association between Klintrup–Mäkinen (KM) inflammatory infiltrate grading and clinicopathological features in gastric cancer patients, investigating its potential as a prognostic marker. Material and Methods: This retrospective study analyzed 133 gastric adenocarcinoma patients diagnosed between 2020 and 2021 at County Clinical Hospital in Târgu Mureș, Romania. Patients were divided into two groups based on KM grades: low (grades 0–1, n = 62) and high (grades 2–3, n = 71). Clinicopathological characteristics and survival outcomes were compared between the groups. Results: Demographic characteristics were similar between the groups. Patients with low KM grades demonstrated significantly more aggressive tumor features, including a higher prevalence of Borrmann classification types III-IV (75.8% vs. 54.9%, p = 0.01), poorly differentiated histology (74.1% vs. 33.8%, p < 0.0001), advanced T stage (93.5% vs. 80.2%, p = 0.04), and lymph node involvement (87% vs. 60.5%, p = 0.0008). This group also exhibited higher rates of lymphatic invasion (79% vs. 50.7%, p = 0.001), venous invasion (51.6% vs. 30.9%, p = 0.02), perineural invasion (50% vs. 22.5%, p = 0.001), and positive surgical margins (32.2% vs. 15.4%, p = 0.02). Survival analysis revealed a hazard ratio of 1.642 (95% CI: 1.02–2.62) for patients with low KM grades compared to those with high KM grades. Conclusions: Low KM grades are associated with more aggressive tumor characteristics and poorer prognosis in GC patients. The KM score may serve as a valuable, cost-effective histological marker for assessing tumor aggressiveness and could aid in risk stratification when applied to routine H&E-stained slides. While it does not replace immunohistochemical or molecular analyses, integrating the KM score into pathological assessment may enhance prognostic accuracy and support identifying patients who might benefit from immunotherapy. Full article
(This article belongs to the Special Issue Towards Improved Cancer Diagnosis: New Developments in Histopathology)
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17 pages, 3490 KiB  
Article
ATRX, OLIG2, MGMT, and IDH2 in Glioblastoma: Essential Molecular Mechanisms and Therapeutic Significance
by Andrea Pop-Crisan, Radu Pirlog, Lavinia-Lorena Pruteanu, Constantin Busuioc, Ovidiu-Laurean Pop, Deo Prakash Pandey, Cornelia Braicu and Ioana Berindan-Neagoe
Medicina 2025, 61(4), 697; https://doi.org/10.3390/medicina61040697 - 10 Apr 2025
Viewed by 500
Abstract
Background and Objectives: Glioblastoma (GBM) is among the most aggressive and lethal primary brain tumors, characterized by high heterogeneity, invasive growth, and resistance to conventional therapies. The 2021 WHO classification highlights the importance of molecular diagnostics, integrating genetic, transcriptomic, and epigenetic alterations [...] Read more.
Background and Objectives: Glioblastoma (GBM) is among the most aggressive and lethal primary brain tumors, characterized by high heterogeneity, invasive growth, and resistance to conventional therapies. The 2021 WHO classification highlights the importance of molecular diagnostics, integrating genetic, transcriptomic, and epigenetic alterations alongside histological and immunohistochemical criteria. Materials and methods: Key molecular regulators, including ATRX, OLIG2, MGMT, and IDH2, play critical roles in chromatin remodeling, transcriptional reprogramming, DNA repair, and metabolic adaptation. However, their specific expression patterns and functional roles in GBM remain incompletely understood. This study utilizes publicly available data from The Cancer Genome Atlas (TCGA) to assess the transcriptional profiles of ATRX, OLIG2, MGMT, and IDH2 in GBM, aiming to identify potential biomarkers and therapeutic targets. Results: The expression analysis revealed that ATRX is downregulated at the gene level but overexpressed at the protein level, while OLIG2 is consistently overexpressed at both levels. MGMT showed no statistically significant changes in either gene or protein expression, whereas IDH2 was not significantly altered at the gene level but was downregulated at the protein level (p < 0.05). These discrepancies suggest potential post-transcriptional regulatory mechanisms influencing GBM molecular profiles. Notably, OLIG2 and MGMT expression correlated significantly with patient survival (p < 0.05), whereas ATRX and IDH2 did not reach statistical significance. Conclusions: Understanding these molecular relationships provides valuable insights into potential therapeutic strategies, paving the way for precision oncology approaches and combination therapies targeting multiple pathways simultaneously. Full article
(This article belongs to the Special Issue Towards Improved Cancer Diagnosis: New Developments in Histopathology)
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Review

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15 pages, 6092 KiB  
Review
From Biopsy to Diagnosis: Navigating Aggressive B-Cell Lymphomas in Practice
by Georgian Halcu, Anca Evsei-Seceleanu, Mihai Cerbu, Marina Alina Bara, Andrei Turbatu and Mihail Constantin Ceausu
Medicina 2025, 61(5), 842; https://doi.org/10.3390/medicina61050842 - 2 May 2025
Viewed by 297
Abstract
Diffuse large B-cell lymphoma (DLBCL), recognized as the most prevalent variant of adult non-Hodgkin lymphoma, presents considerable challenges in diagnosis owing to its diverse morphological features and frequent extranodal involvement, which may frequently mimic nonhematopoietic neoplasms. The 2022 WHO Classification of Lymphoid and [...] Read more.
Diffuse large B-cell lymphoma (DLBCL), recognized as the most prevalent variant of adult non-Hodgkin lymphoma, presents considerable challenges in diagnosis owing to its diverse morphological features and frequent extranodal involvement, which may frequently mimic nonhematopoietic neoplasms. The 2022 WHO Classification of Lymphoid and Hematopoietic Tissues provides essential updates, highlighting the necessity of combining morphology, immunohistochemistry, cytogenetics, and molecular testing for precise subclassification. This review presents a practical method for differentiating DLBCL from other aggressive B-cell neoplasms, such as Burkitt lymphoma, B-lymphoblastic lymphoma, and mantle cell lymphoma. It highlights vital diagnostic tools, including CD45, B/T-cell markers, germinal center markers, and the Hans algorithm, as well as the role of FISH in identifying rearrangements of key genes MYC, BCL2, and BCL6, which are significant for recognizing double-hit and triple-hit lymphomas. Special focus is given to EBV-associated DLBCL and uncommon subtypes featuring plasmablastic or ALK-positive traits. This review aims to enhance diagnostic accuracy and ensure appropriate treatment strategies for patients with large B-cell lymphomas by emphasizing thorough morphological evaluation, specific adjunct testing, and adherence to the most recent classification standards. Full article
(This article belongs to the Special Issue Towards Improved Cancer Diagnosis: New Developments in Histopathology)
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