Hypertensive nephrosclerosis (HN) and diabetic nephropathy (DN) are the leading global causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Both conditions share overlapping clinical and histopathological features, particularly in patients with concurrent hypertension and diabetes, making accurate differentiation challenging. This narrative review synthesizes current evidence on the pathophysiology, histopathology, diagnostic criteria, and therapeutic implications of HN and DN, with emphasis on areas of morphological and clinical overlap. HN is driven by chronic vascular injury from sustained hypertension, resulting in ischemic glomerulosclerosis, arteriolar hyalinosis, and interstitial fibrosis. DN, in contrast, is primarily mediated by hyperglycemia-induced metabolic and hemodynamic stressors, producing diffuse and nodular mesangial expansion, glomerular basement membrane thickening, and bilateral arteriolar hyalinosis. While certain histological features, such as Kimmelstiel-Wilson nodules and efferent arteriole involvement, favor DN, mixed lesions are common in long-standing type 2 diabetes with hypertension. Accurate differentiation is clinically significant, as it guides the application of disease-specific interventions such as intensive glycemic control and emerging pharmacotherapies for DN, versus targeted vascular risk reduction in HN. Future advances in biomarkers, imaging, and genomics hold promise for earlier, noninvasive diagnosis.

Neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) are characterized by progressive neuronal dysfunction, yet their underlying mechanisms remain incompletely understood. Emerging evidence implicates epigenetic dysregulation as a central contributor to the pathogenesis of these disorders. A thematic literature review was conducted across major databases using targeted search terms related to epigenetics and neurodegeneration. Studies were selected based on relevance, methodological quality, and contribution to mechanistic understanding, in accordance with Scale for the Assessment of Narrative Review Articles (SANRA) guidelines. Across AD, PD, and HD, distinct yet overlapping patterns of epigenetic alterations were identified. In AD, dysregulated DNA methylation and histone acetylation affect genes linked to amyloid and tau pathology. In PD, hypomethylation of SNCA and altered histone acetylation contribute to α-synuclein overexpression and neuronal loss. In HD, mutant huntingtin protein disrupts chromatin remodeling by sequestering histone acetyltransferases and altering microRNA expression. These changes disrupt neuronal identity, synaptic function, and inflammatory responses, often forming feedback loops that exacerbate disease progression. Epigenetic mechanisms play a pivotal role in neurodegeneration by mediating gene-environment interactions and perpetuating neuropathological changes. Their reversible nature presents opportunities for therapeutic intervention, though challenges related to specificity, delivery, and timing remain. Continued research into epigenetic biomarkers and precision-targeted epigenetic therapies holds promise for advancing early diagnosis and disease modification in NDDs.

Diabetic nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal disease worldwide, characterized by progressive injury across all renal compartments. Traditionally considered a glomerular disorder marked by basement membrane thickening, mesangial expansion, and nodular sclerosis, DN is now recognized as a multifaceted process involving tubulointerstitial, vascular, and podocyte pathology. This narrative review integrates current histopathological insights, highlighting key glomerular lesions, tubular basement membrane thickening, interstitial fibrosis, arteriolar hyalinosis, and podocyte injury, as well as atypical and advanced patterns. The role of kidney biopsy in diagnosis, the application of the Renal Pathology Society classification, and differentiation from mimicking conditions such as amyloidosis and monoclonal deposition disease are discussed. Emerging biomarkers and advanced imaging modalities offer promise for earlier detection and risk stratification. Understanding the full histological spectrum of DN is critical for accurate diagnosis, prognostication, and the development of targeted therapies. Future directions include molecular classification, non-invasive diagnostics, and precision medicine approaches to improve patient outcomes.

Glomerular diseases represent a diverse group of conditions that significantly contribute to chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. Understanding the histopathological patterns of glomerular injury is essential for accurate diagnosis, prognosis, and targeted therapy. This comprehensive review explores the morphologic, immunopathologic, and clinical characteristics of major glomerular disorders, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, immunoglobulin A nephropathy, lupus nephritis, and others. Histological classification is integrated with clinical syndromes, such as nephrotic and nephritic presentations, emphasizing the role of light microscopy, immunofluorescence, and electron microscopy in renal biopsy interpretation. Recent advances in molecular diagnostics, digital pathology, and artificial intelligence are also discussed, highlighting their transformative impact on precision nephrology. Through a multidisciplinary lens, this review underscores the prognostic and therapeutic implications of distinct histologic patterns and advocates for the continued evolution of clinicopathologic correlation in glomerular disease management.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and represent a paradigm of precision oncology in which histopathology and molecular profiling directly inform diagnosis, prognosis, and therapeutic strategy. Arising from the interstitial cells of Cajal or their precursors, GISTs display a wide morphological spectrum, including spindle cell, epithelioid, mixed, and rare histologic variants, often requiring immunohistochemical confirmation with KIT (CD117), DOG1, and CD34. Molecular characterization reveals a limited but clinically decisive range of driver mutations, most commonly in KIT and PDGFRA, with additional subsets involving SDH deficiency, NF1 alterations, and rare mutations such as BRAF, KRAS, or NTRK fusions. These molecular signatures underpin distinct biological behaviors, prognostic categories, and therapeutic sensitivities. Risk stratification incorporates tumor size, mitotic rate, anatomical location, and tumor rupture to predict recurrence and guide adjuvant therapy decisions. Targeted tyrosine kinase inhibitors (TKIs) have transformed GIST management, with imatinib as the foundational first-line therapy and subsequent agents, sunitinib, regorafenib, avapritinib, and ripretinib, addressing primary or secondary resistance driven by diverse mutational patterns. Nevertheless, challenges persist, including imatinib-resistant PDGFRA D842V mutations, SDH-deficient tumors lacking actionable kinase alterations, and the emergence of polyclonal secondary resistance due to heterogeneous KIT adenosine triphosphate (ATP)-binding pocket or activation loop mutations. Emerging therapeutic directions include next-generation kinase inhibitors, heat shock protein inhibitors, immunotherapy, metabolic and epigenetic targeting, and biomarker-driven individualized treatment strategies. This review synthesizes contemporary advances in the histopathological, molecular, and therapeutic landscape of GISTs, emphasizing an integrated diagnostic approach and highlighting ongoing efforts to overcome therapeutic resistance and optimize personalized care.

Kidney transplantation is the treatment of choice for end-stage renal disease; however, long-term graft survival continues to be jeopardized by rejection, chronic allograft injury, and infection. Histopathological assessment of renal allograft biopsies remains the diagnostic gold standard, yet interpretation variability has historically hindered consistency across institutions and clinical trials. To address this, international consensus efforts established the Banff Classification, with biennial updates refining and expanding its scope. This review outlines the evolution of renal allograft pathology classification systems, emphasizing key Banff revisions that introduced diagnostic criteria for T cell-mediated and antibody-mediated rejection (ABMR), borderline changes, chronic active rejection, and polyomavirus nephropathy. Modern frameworks increasingly incorporate morphology, immunohistochemistry, and emerging molecular diagnostics to improve accuracy and reproducibility. In clinical practice, the Banff system informs immunosuppressive strategies, guides treatment response monitoring, supports prognostication, and standardizes endpoints in clinical trials. Ongoing challenges include interobserver variability, sampling limitations, and restricted access to advanced molecular and digital technologies in resource-limited settings. Future directions point toward integrating multi-omics, digital pathology, and artificial intelligence to create a unified, patient-centered diagnostic platform that extends Banff’s legacy of consensus and adaptability.