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Endometrial carcinoma is a heterogeneous group of malignancies characterized by distinct histopathological features and genetic underpinnings. The 2020 WHO classification has provided a comprehensive framework for the categorization of endometrial carcinoma. However, it has not fully addressed the spectrum of uncommon entities that are currently not recognized by the 2020 WHO and have only been described in the form of small case series and case reports. These neoplasms represent a real diagnostic challenge for pathologists; furthermore, their therapeutic management still remains controversial and information regarding tumor prognosis is very limited. This review aims to elucidate these lesser-known variants of endometrial carcinoma. We discuss the challenges of identifying these rare subtypes and the molecular alterations associated with them. Furthermore, we propose the need for expanded classification systems that include these variants to enhance clinical outcomes and research efforts. We believe that a better histological typing characterization of these entities may lead to more reproducible and accurate diagnoses and more personalized treatments. By raising awareness of these rare entities, we also hope to encourage further investigation and integration into clinical practice to improve patient care in endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Among the four endometrial cancer (EC) TCGA molecular groups, the MSI/hypermutated group represents an important percentage of tumors (30%), including different histotypes, and generally confers an intermediate prognosis for affected women, also providing new immunotherapeutic strategies. Immunohistochemistry for MMR proteins (MLH1, MSH2, MSH6 and PMS2) has become the optimal diagnostic MSI surrogate worldwide. This review aims to provide state-of-the-art knowledge on MMR deficiency/MSI in EC and to clarify the pathological assessment, interpretation pitfalls and reporting of MMR status. [ABSTRACT FROM AUTHOR]

Digital imaging, including the use of artificial intelligence, has been increasingly applied to investigate the placenta and its related pathology. However, there has been no comprehensive review of this body of work to date. The aim of this study was to therefore review the literature regarding digital pathology of the placenta. A systematic literature search was conducted in several electronic databases. Studies involving the application of digital imaging and artificial intelligence techniques to human placental samples were retrieved and analyzed. Relevant articles were categorized by digital image technique and their relevance to studying normal and diseased placenta. Of 2008 retrieved articles, 279 were included. Digital imaging research related to the placenta was often coupled with immunohistochemistry, confocal microscopy, 3D reconstruction, and/or deep learning algorithms. By significantly increasing pathologists' ability to recognize potentially prognostic relevant features and by lessening inter-observer variability, published data overall indicate that the application of digital pathology to placental and perinatal diseases, along with clinical and radiology correlation, has great potential to improve fetal and maternal health care including the selection of targeted therapy in high-risk pregnancy. [ABSTRACT FROM AUTHOR]

High-grade serous ovarian carcinoma (HGSOC) is the most aggressive subtype of epithelial ovarian cancer and a leading cause of mortality among gynecologic malignancies. This review aims to comprehensively analyze the morphological, immunohistochemical, and molecular features of HGSOC, highlighting its pathogenesis and identifying biomarkers with diagnostic, prognostic, and therapeutic significance. Special emphasis is placed on the role of tumor microenvironment (TME) and genomic instability in shaping the tumor's behavior and therapeutic vulnerabilities. Key advancements, such as the identification of TP53 and BRCA mutations, the classification of homologous recombination repair (HRR) deficiencies, and the clinical implications of biomarkers like folate receptor alpha (FRα) and PD-L1 are discussed. These findings reveal actionable insights into targeted therapies, including immune checkpoint inhibitors and PARP inhibitors, which hold promise for improving outcomes in HGSOC. This synthesis of knowledge aims to bridge gaps in understanding HGSOC's multifaceted biology, enhance clinical decision-making, and foster the development of precision therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Endometrial carcinoma (EC) is the commonest gynecological cancer affecting women in Western populations. To predict patient risk, the 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract stressed the importance of integrated histo-molecular classification of the disease. This survey analysis poses attention on the most frequently used immunohistochemical and molecular markers adopted in daily categorization of ECs in European laboratories., Methods: We analyzed data collected through questionnaires administered to 40 Italian, 20 Spanish, 3 Swiss and 6 United Kingdom (UK) laboratories. We collected information regarding daily practice in EC evaluation, specifically concerning mismatch repair status (MMR) and microsatellite instability (MSI). Summary and descriptive statistical analyses were carried out to evaluate the current practice of each laboratory., Results: The results show that MMR status is mainly evaluated by using immunohistochemistry (IHC) on most EC samples. The most frequent approach for the analysis of MMR status is IHC of four proteins (PMS2, MSH6, MSH2, MLH1). MSI analysis by molecular methods is uncommon but useful as a supplemental tool in specific conditions. MLH1 promoter hypermethylation and BRAF V600 mutations analysis are performed in case of negative expression of MLH1/PMS2. Other markers (mainly p53 followed by POLE and PTEN) are investigated in particular in Spain and Switzerland in a consistent number of cases., Conclusion: Guidelines consultation and standardization of laboratory procedures are efficient means for EC prognostic risk stratification and improving the quality of care., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Objective: Endometrial carcinoma (EC) is the most common gynecological malignant disease in high income countries. The 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract underlines the important clinical implications of the new integrated histo-molecular classification system, in order to correctly define the specific prognostic risk group. This survey analysis will focus on the most commonly adopted immunohistochemical and molecular biomarkers used in daily clinical characterization of a diagnosed endometrial carcinoma in Italian labs., Methods: An evaluation questionnaire was distributed to 41 Italian pathology laboratories. Normal habits in EC evaluation, especially regarding mismatch repair status (MMR) and microsatellite instability (MSI), were collected. A summary and a descriptive statistical analysis were used to show the current practice of each laboratory., Results: The analysis of MMR status by immunohistochemistry (IHC) is carried out on the majority of all EC samples. The most frequent strategy for the analysis of MMR status in EC is IHC of four proteins (PMS2, MSH6, MSH2, MLH1). MSI analysis by molecular method in endometrial cancer is rarer and more restricted to some circumstances. Hypermethylation of the MLH1 promoter by methylation-specific PCR and pyrosequencing was analyzed in case of negative expression of MLH1/PMS2. Also, the analysis of p53 in EC is performed in the majority of cases. POLE mutational profiling is adopted only in a limited number of laboratories. Fifty-five percent of Italian laboratories refer to national/international guidelines when analyzing biomarkers in EC (among those, 45% use the ESGO Guidelines, 18% ASCO-CAP, 18% AIOM, 14% WHO, 5% British Association of Gynaecological Pathologist, 5% ESMO, 5% NCCN)., Conclusions: Adoption of guidelines and standardization of pre-analytical and analytical procedures are effective tools for adequate EC prognostic risk stratification and high quality standard of care., (Copyright © 2022 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Background: The accumulation of cyclin-dependent kinase inhibitor 2A (p16 ink4a ) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16 ink4a and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed., Methods: Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports. Immunostaining results were classified as positive, negative, inconclusive, or inadequate. After evaluation of the first set of slides and before circulation of the second set, the results were discussed in a plenary meeting. The 10 slides with the most discordant results were evaluated again by selected expert cytopathologists., Results: The overall κ value was 0.612 (95% confidence interval [CI], 0.523-0.701), it was higher for the positive and negative categories (κ = 0.692 and κ = 0.641, respectively), and it was almost null for the inconclusive category (κ = 0.058). Considering only readers from laboratories with documented experience, the κ value was higher (κ = 0.747; 95% CI, 0.643-0.839) compared with nonexperienced centers (κ = 0.498; 95% CI, 0.388-0.616). The results were similar in both sets of slides (κ = 0.505 [95% CI, 0.358-0.642] and κ = 0.521 [95% CI, 0.240-0.698] for the first and second sets, respectively). Reinterpretation of the slides with the most discordant results did not provide any improvement (first evaluation, κ = 0.616 [95% CI, 0.384-0.866]; second evaluation, κ = 0.403 [95% CI, 0.182-0.643])., Conclusions: Dual staining for p16 ink4a and Ki-67 demonstrated good reproducibility, confirming its robustness, which is a necessary prerequisite for its adoption as a triage test in cervical cancer screening programs that use human papillomavirus DNA as a primary test. Cancer Cytopathol 2017;125:212-220. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Accurate classification of nonsmall cell lung cancers is of paramount clinical relevance, as novel chemotherapeutic agents show different efficacy in adenocarcinomas (ADCs) compared with squamous cell carcinomas (SQCCs). Cyto and histomorphology may sometimes be insufficient for this distinction and immunohistochemistry may improve diagnostic accuracy. The measurement of miR-205 may be another tool for the distinction between ADC and SQCC. The aim of our study was to compare morphologic and immunohistochemical classification with the relative quantification of miR-205 and miR-21 insurgically resected and well-characterized lung tumors (25 ADCs, 24 SQCCs, 1 adenosquamous). The miR-21 relative levels were similar in SQCC and ADC, whereas the miR-205 relative levels were lower in ADC (P<0.0001). The miR-205 sample score value, determined according to Lebanony et al, was higher in ADC (range, 2.8 to 9.08) compared with SQCC (range, -4.17 to 2.445) (P<0.0001). Accordingly, 22 tumors were classified as ADC and 28 tumors as SQCC, although 8 cases (2 SQCCs and 6 ADCs) were in the range of "near cutoff values." Four cases classified as SQCC (according to the sample score method) corresponded to cases classified as ADC on the basis of morphoimmunohistochemical evaluation. In conclusion, the relative quantification of miR-205 and miR-21 seems to be a promising diagnostic tool. However, the molecular approach is still not completely satisfactory as it may misclassify a non-negligible percentage of cases. Therefore, it cannot be used as a substitute of accurate morphologic and immunophenotypical characterization of tumors, but could be used as an adjunctive diagnostic criterion in selected cases.