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Integrating Molecular, Digital, and Morphological Insights: The Unavoidable Future of Oncologic Diagnostics Hasibuan, Arie Widiansyah; Delyuzar, Delyuzar
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1620

Abstract

The remarkable progress of Anatomical Pathology over recent decades has fundamentally reshaped the landscape of oncologic diagnostics. From the early era when microscopic interpretation of routine hematoxylin-eosin (HE) stained sections formed the diagnostic cornerstone, the discipline has evolved into a complex hub of integrated biological data. This journey began with mastery of histopathological and cytological morphology and expanded to the use of histochemical and immunohistochemical stains, enabling precise visualization of specific proteins. The transformation continued as molecular technologies became routinely implemented in major laboratories, extending diagnostic capacity far beyond the limits of the optical microscope [1]. Advances in molecular techniques have opened a new dimension in cancer understanding. Polymerase chain reaction (PCR), real-time quantitative PCR, and reverse transcription PCR enable highly sensitive detection of gene mutations or transcripts, including EGFR mutations in pulmonary adenocarcinoma and BCR-ABL fusion transcripts in leukemia. Fluorescence in situ hybridization (FISH) adds the ability to visualize gene amplification or chromosomal rearrangements directly within cell nuclei, for example, to confirm HER2 amplification in breast carcinoma or ALK rearrangements in lung carcinoma. The most dramatic leap has come with next-generation sequencing (NGS), which uses massively parallel sequencing. It can interrogate hundreds to thousands of genes simultaneously. Targeted gene panels, whole-exome sequencing, and even whole-genome sequencing facilitate identification of driver mutations, copy number variations, and gene fusions in a single analysis. Tumor mutational burden and microsatellite instability status have now been recognized as critical biomarkers in selecting patients for immunotherapy. Moreover, transcriptomics, proteomics, and metabolomics, collectively referred to as “omics”, provide comprehensive insight into the interplay of genes, proteins, and metabolites that govern tumor biology and allow detection of germline mutations for familial risk assessment. The emergence of liquid biopsy, through analysis of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), adds the ability to dynamically monitor the development of resistance mutations and therapeutic response without invasive procedures [1,2]. At the same time, digital technologies and artificial intelligence (AI) are revolutionizing the practice of pathology. Digital pathology using whole slide imaging (WSI) replaces glass slides with high-resolution digital files that can be stored, shared, and algorithmically analyzed. Deep-learning algorithms are now capable of highlighting tumor areas, quantifying proliferation indices such as Ki-67, and even predicting genetic mutations directly from HE images. Integration of AI not only accelerates diagnosis and reduces interobserver variability but also transforms histomorphologic images into quantitative data that can be correlated with clinical outcomes. These developments reposition the pathologist from a mere “slide reader” to an integrator of biological information combining morphology, molecular data, and digital analytics [2–5,7]. Despite the force of these innovations, morphology remains an irreplaceable foundation. Evaluation of tissue architecture in histopathology and cytology, and the recognition of growth patterns, continue to provide essential biological context that cannot be fully supplanted by genomic data. Histologic grading systems such as Nottingham for breast carcinoma and Gleason for prostate carcinoma remain critical determinants of risk stratification and therapeutic planning. Assessment of surgical margins, selection of representative tumor areas for further molecular analysis, and correlation with radiologic findings require the pathologist’s expertise as curator of tissue. Without quality control anchored in microscopic evaluation, molecular results risk being misleading [1]. Thus, the prediction that “pathologists will abandon the microscope” is only literally true because optical devices may be replaced by WSI monitors. It does not signify abandonment of morphological analysis itself [3–5]. This paradigm shift carries broad implications for every branch of oncology. Medical oncologists rely on molecular findings to guide targeted therapy; surgeons require accurate information to determine resection margins; and genetic counselors assess familial risk based on germline alterations. The concept of “integrated diagnosis” emphasized in the 5th edition of the World Health Organization classification of tumors provides the modern framework: the final diagnosis synthesizes morphology, immunohistochemistry, and molecular data into a single comprehensive report [1]. Contemporary cancer therapy decisions from the selection of tyrosine kinase inhibitors to checkpoint inhibitor immunotherapy can only be reached through such multidimensional interpretation [2]. Adoption of these advanced technologies demands robust infrastructure, significant financial investment, and personnel with bioinformatics expertise. Disparities between major referral centers and regional hospitals must be addressed so that progress does not widen gaps in cancer care. Issues of genomic data privacy, clinical validation of analytic pipelines, and legal responsibility for AI-assisted decisions require careful attention. Governments, educational institutions, and hospitals must invest in molecular pathology and bioinformatics curricula and prepare appropriate regulatory frameworks [7]. Anatomical Pathology is now entering an era in which the role of the pathologist has shifted from mere microscopic examiner to architect of integrated cancer biology data. The strengths of NGS, FISH, advanced PCR, omics, and liquid biopsy have opened new perspectives on cancer pathogenesis, precision therapy, and dynamic disease monitoring. Yet these advances do not diminish the role of morphology; rather, they reinforce its status as the foundation upon which molecular analysis and AI applications depend [1-5,7]. All oncology stakeholders must work together to build infrastructure and collaborative networks so that cancer services in Indonesia are fully prepared for the era of precision diagnostics, where molecular, digital, and morphological integration becomes the gold standard of modern cancer management.
Relationship of the Number of Black Dots in the Nuclei of Argyrophilic Nucleolar Organizing Regions (AgNORs) Expressed Epithelial Cells with Nottingham Grading System in Invasive Breast Carcinoma of No Special Type (IBC-NST) Basrul, Mohd. Yuwanda; Delyuzar, Delyuzar; Intan, T. Kemala; Soekimin, Soekimin; Alferraly, T. Ibnu
Majalah Patologi Indonesia Vol. 35 No. 1 (2026): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.55816/mpi.v35i1.669

Abstract

Background Breast cancer is a malignant disease in women. The high number of breast cancer cases is caused by multiple factors, including barriers to early detection of breast cancer, socio-economic and geographical factors, and the difficulty of affordable, timely and effective health services. IBC-NST has the highest incidence among breast cancer cases with a 10 year survival rate (65-78%). AgNORs parameters have been shown to represent a reliable tool for determining the clinical outcome of cancer diseases, being an independent prognostic factor in many types of tumors.   Method Descriptive analytics research was carried out on slides from 31 patients with IBC-NST. Each slide was stained with H&E stainning to assess the Nottingham grading system and stained with AgNORs to assess the number of black dots in epithelial cell nuclei that expressed AgNORs. All clinicopathological data were taken from medical records/pathology archives. Logistic regression test (p<0.005) was used to assess the relationship between the number of black dots in epithelial cell nuclei expressing AgNORs and the Nottingham grading system in IBC-NST.   Results The highest cases were in the age group ≤40-50 years (range: 50.1 years), the highest grading was in grade 3 of the Nottingham grading system (48.8%), the lowest number of black dots was 576 dots and the highest was 1,036 dots (mean 798.80, median 710.0 and standard deviation 144.71) and the highest number of black dots was in grade 3 of the Nottingham grading system.   Conclusion Assessment of the number of black dots in the nuclei of epithelial cells expressing AgNORs associated with Nottingham grading system can be used as an indication of prognosis in patients with IBC-NST.
Comparative immunohistochemical expression of α-smooth muscle actin in pediatric indirect inguinal hernia and hydrocele Nugraha, Anshari Dwi; Fikri, Erjan; Delyuzar, Delyuzar
Jurnal SAGO Gizi dan Kesehatan Vol 7, No 1 (2026): April
Publisher : Poltekkes Kemenkes Aceh

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30867/gikes.v7i1.3189

Abstract

Background: Indirect inguinal hernia and hydrocele, with reported incidences of up to 4% and 0.0034%, respectively, are consequences of incomplete obliteration of the processus vaginalis. Although both conditions share a similar embryological origin, the molecular mechanisms driving their distinct clinical presentations remain unclear. Alpha-smooth muscle actin (α-SMA) is a widely used marker of myofibroblast activity and tissue remodeling. This study aimed to compare the expression of α-SMA in the processus vaginalis tissue of pediatric patients with indirect inguinal hernia and hydrocele.Methods: An observational analytical study with a cross-sectional approach was conducted at the H. Adam Malik General Hospital between January and June 2025. Processus vaginalis tissues were collected from 50 male pediatric patients (25 hernia and 25 hydrocele cases). The expression of α-SMA was evaluated through semi-quantitative immunohistochemical analysis, assessing both staining intensity and distribution. Data were analyzed using the chi-square test, and p < 0.05 was considered statistically significant.Results: A total of 50 patients were enrolled in the study, with a mean age of 3.98 ± 3.78 y. Statistical analysis revealed a highly significant difference in α-SMA expression between the two groups (p < 0.001). Strong α-SMA expression was observed in 96% of the indirect inguinal hernia group, whereas 96% of the hydrocele group exhibited weak expression (OR 576; 95% CI 34.0–9751.0; p < 0.001). The magnitude of this association indicates a strong relationship between clinical diagnosis and α-SMA expression.Conclusion:α-SMA expression differed significantly between indirect inguinal hernias and hydroceles, with a strong expression predominating in hernia specimens. These findings support an association between indirect inguinal hernias and increased α-SMA–positive stromal elements in the processus vaginalis.
Co-Authors Alamanda, Intan Nefia Alferraly, Ibnu Alferraly, T. Ibnu Basrul, Mohd. Yuwanda betty betty Chairani, Rizki Chrestela, Jessy Chrestella, Jessy CINDY CLARA AWE Dahlan, Nadjib Dedy Suryadi DITA ANNISA DIARA NASUTION Edi Kerina Sembiring, Edy Fachrial Eka Airlangga Emita Sabri Endang Sjamsudin Erjan Fikri Feby Yanti Harahap Fiandani, Fatma Fitri Dewi Ismida fitriani Lumongga Harahap, Rini Syahrani Hasibuan, Arie Widiansyah HENDRA SUTYSNA Hidayat Hidayat Hidayat Hilda Fitriyani Humairah Medina Liza Lubis Ibnu Alferally Indri Mahrani Indriani Saragih, Septina Intan, T. Kemala Jessy Chrestella Joko S. Lukito Kadri, Sayed Muhammad Kharismawaty, Dina Laksmi, Lidya Imelda Lidya Imelda Laksmi Lita Feriyawati Lokot Donna Lubis Lubis, Fahrurrozi Lubis, Nenni Dwi Aprianti Lukito, Joko S Lukito, Joko S. M. Nadjib D. Lubis Mariedina, Causa Trisna Masriana Masriana, Masriana Muhammad Nadjib D Lubis Muhammad Ramli Nadjib Dahlan Lubis Nasution, Annio Indah Lestari Nugraha, Anshari Dwi Nurcahaya Sinaga Nurlela Nurlela P. Poida B. Gurning Ren Astrid Allail Siregar Reza Aditya Digambiro Rita Juliana Pohan Riza, Ahyar Rizki, Diana Roza Rita S Lukito, Joko S. Lukito, Joko Sihotang, Marisi Cintya Debby sinambela, Roy Herbon Siregar, Ren Astrid Allail Soekimin Soekimin Soekimin Soekimin Soekimin, Soekimin Sri Amelia, Sri Sufitni Sunarti Sunarti Syafruddin Ilyas T Kemala Intan T. Ibnu Alferally T. Ibnu Alferally T. Ibnu Alferraly tengku ibnu alferraly Tri Widyawati Urip Harahap Utami, Tania Mulia