Histopathology[JOURNAL]
Sun
200 papers
Diagnostic potential of a novel immunohistochemical marker, GFPT2, in differentiating mesothelioma from its morphological mimics.
Wei J, Ma X, Chen G … +3 more , Wang Y, Fan Q, Gong Q
Histopathology · 2026 Apr · PMID 41392993 · Publisher ↗
AIMS: Mesothelioma (MESO) is a rare and aggressive tumour originating from mesothelial cells, primarily affecting the pleura and peritoneum. Its diagnosis remains challenging due to non-specific clinical, radiological an...
AIMS: Mesothelioma (MESO) is a rare and aggressive tumour originating from mesothelial cells, primarily affecting the pleura and peritoneum. Its diagnosis remains challenging due to non-specific clinical, radiological and histopathological features, compounded by morphological diversity and overlapping immunohistochemical profiles with other tumours. Building on our previous finding that GFPT2 is highly expressed in MESO tissues, we evaluated its diagnostic utility in distinguishing MESO from histological mimics. METHODS AND RESULTS: We conducted an immunohistochemical analysis of GFPT2 in 101 MESO cases and 266 histological mimics, including 100 non-small cell lung cancer (NSCLC), 40 high-grade serous ovarian cancer (HGSOC), 6 epithelioid hemangioendothelioma (EHE), 33 solitary fibrous tumour (SFT), 23 aggressive fibromatosis (AF), 6 synovial sarcoma (SS), 7 dedifferentiated liposarcoma (DDLPS), 6 leiomyosarcoma (LMS), 4 malignant peripheral nerve sheath tumour (MPNST), 8 sarcomatoid carcinoma, 20 reactive mesothelial hyperplasia (RMH) and 13 well-differentiated papillary mesothelial tumour (WDPMT) cases. GFPT2 positivity was detected in 85.15% (86/101) of MESO cases, significantly higher than in RMH (0%, 0/20), WDPMT (0%, 0/13), NSCLC (0%, 0/100), HGSOC (0%, 0/40), EHE (16.7%, 1/6), SFT (0%, 0/33), AF (21.74%, 5/23), SS (0%, 0/6), LMS (0%, 0/6), MPNST (25%, 1/4) and sarcomatoid carcinoma (12.5%, 1/8). However, DDLPS (85.7%, 6/7) showed high GFPT2 positivity. CONCLUSIONS: This study demonstrates GFPT2's diagnostic utility in MESO, effectively overcoming tumour heterogeneity challenges. It distinguishes malignant mesothelial lesions from benign/borderline ones (RMH/WDPMT), differentiates epithelioid MESO from epithelioid malignances(NSCLC/HGSOC/EHE) and aids in sarcomatoid MESO versus spindle cell tumours (SFT/AF/SS/LMS/MPNST/sarcomatoid carcinoma), though limited for DDLPS. In summary, GFPT2 is a promising novel antibody demonstrating 85.2% sensitivity and 94.7% specificity.
Immunohistochemical characterization of peritoneal inclusion cysts with squamous metaplasia.
Chen-Yost HI, Chapel DB, Hrycaj SM … +4 more , Perry WR, Konopka KE, Myers JL, Huang T
Histopathology · 2026 Jan · PMID 41392656 · Full text
AIMS: Peritoneal inclusion cysts (PICs) are mesothelial-lined cysts that can uncommonly develop squamous metaplasia. Here, we describe the immunophenotype of PICs with squamous metaplasia using a comprehensive immunohist...
AIMS: Peritoneal inclusion cysts (PICs) are mesothelial-lined cysts that can uncommonly develop squamous metaplasia. Here, we describe the immunophenotype of PICs with squamous metaplasia using a comprehensive immunohistochemical (IHC) panel. METHODS AND RESULTS: We collected surgical excisions of PICs with squamous metaplasia from our institution and cases sent to our extramural consultation service. An IHC panel was used to characterize the immunophenotype, which included antibodies to claudin 4, WT-1, D2-40, calretinin, CK5/6, p40/p63, PAX8, BAP1, MTAP and merlin. 10 cases of PICs with squamous metaplasia were identified. The average age was 51 years, with 8 females and 2 males. On histology, all PICs (n = 10) showed diffuse squamous metaplasia. The cyst lining cells exhibited a squamous epithelial phenotype with diffuse expression of claudin 4 and p63/p40 in the suprabasal cells that also showed consistent co-expression of WT1 in all cases. In contrast, the basal layer displayed a mesothelial phenotype, demonstrating immunoreactivity to WT1 and D2-40 and lacking expression of claudin 4. Calretinin showed complete loss of expression in both the basal and parabasal cells. All cases showed retained expression of BAP1, MTAP and merlin. CONCLUSIONS: PICs with squamous metaplasia express a unique mixed epithelial and mesothelial immunophenotype. The basal layer shows an immunophenotype consistent with mesothelial cells, and the suprabasal layers show an immunophenotype consistent with epithelial/squamous cells. Knowing the detailed immunophenotype of PIC with squamous metaplasia is helpful for correctly recognizing this lesion.
A new Editor arrives, but what is the plan?
Feakins R
Histopathology · 2026 Jan · PMID 41392647 · Publisher ↗
Abstract loading — click title to view on PubMed.
Pathological features, differential diagnosis, prognosis, and diagnostic challenges in the classification of penile squamous neoplasia.
Rodriguez I, Fernandez-Nestosa MJ, Sanchez D … +1 more , Cubilla AL
Histopathology · 2026 Jan · PMID 41384715 · Publisher ↗
Approximately 50% of penile squamous cell carcinomas are of the usual (conventional) type, resembling their counterparts in the skin or other organs. The remaining half comprises a heterogeneous group of histological var...
Approximately 50% of penile squamous cell carcinomas are of the usual (conventional) type, resembling their counterparts in the skin or other organs. The remaining half comprises a heterogeneous group of histological variants, some of which exhibit highly distinctive morphological features. Current classification models recognize more than 14 subtypes of penile squamous cell carcinoma. Pathological guidelines recommend histological subtyping of penile carcinomas in diagnostic reports. This practice is clinically significant because specific subtypes carry distinct prognostic implications. However, diagnostic challenges may arise in certain cases due to overlapping histological features. While most subtypes of penile intraepithelial neoplasia (PeIN) are readily identifiable, a subset of cases presents diagnostic challenges. A notable example is distinguishing benign condylomas from low grade minimally atypical warty PeIN. Among invasive carcinomas, the most significant diagnostic difficulties arise in classifying verruciform tumours, due to their overlapping morphological features. Warty carcinomas may simulate giant condylomas; verrucous carcinoma may simulate giant condylomas or Papillary NOS carcinomas. Conversely, this tumour may be confused with low grade warty carcinomas. With some experience, histological classification using H&E stain is possible in about 70% of the cases. The remainder 30%, however, presents diagnostic difficulties even for experienced pathologists. The use of immunostaining and HPV genotyping are crucial aids in the differential diagnosis. By describing and illustrating in detail their morphological features, suggesting treatment options, and emphasizing diagnostic difficulties in the differential diagnosis, we aimed to assist our colleagues in improving their penile neoplasia classification skills.
Recent developments in eosinophilic renal neoplasms: what's new, true and important?
Trpkov K, Siadat F, Saleeb R
Histopathology · 2026 Jan · PMID 41384711 · Full text
We focus in this review on the latest developments on several eosinophilic renal entities, aiming to provide an update on this topic that was previously addressed by the Genitourinary Pathology Society in their consensus...
We focus in this review on the latest developments on several eosinophilic renal entities, aiming to provide an update on this topic that was previously addressed by the Genitourinary Pathology Society in their consensus papers on existing renal entities, and on novel, emerging, and provisional renal entities, and in the World Health Organization 2022 Classification of Renal Cell Tumours (5th Edition). The scope of this review includes an update on more recently described eosinophilic renal entities, including low-grade oncocytic renal tumour (LOT), eosinophilic vacuolated tumour (EVT), folliculin (FLCN) mutated tumour, succinate dehydrogenase (SDH)-deficient renal cell carcinoma, epithelioid angiomyolipoma/epithelioid PEComa (eAML/ePEComa), eosinophilic solid and cystic renal cell carcinoma (ESC RCC), anaplastic lymphoma kinase (ALK)-rearranged RCC, fumarate hydratase (FH)-deficient RCC, papillary renal neoplasm of reversed polarity (PRNRP), tubulocystic RCC (TC-RCC), and thyroid-like follicular carcinoma of kidney (TLFCK). These renal entities fall within the spectrum of eosinophilic renal tumours, in addition to the more common ones with eosinophilic features that will not be covered in this review, such as clear cell renal RCC, papillary RCC, chromophobe RCC, TFE3 rearranged RCC, and TFEB-altered RCC. Pathologists need to consider these less common renal entities in the differential of any eosinophilic renal tumour to be able to diagnose them for the benefit of their patients. The recent developments and acquired knowledge on newer renal entities with eosinophilic cytoplasm opened insights into the clinical, pathological, immunohistochemical, molecular, epidemiological aspects, and the prognosis of these entities. We emphasize the role of routine morphology, aided by appropriate and select immunohistochemistry, as essential keys for diagnosing eosinophilic renal tumours.
Treatment-related changes in the prostate: past, present and future therapies.
Collins K, Cheng L
Histopathology · 2026 Jan · PMID 41384710 · Full text
A broad spectrum of therapies is available for the management of prostate cancer, ranging from well-established interventions like radical prostatectomy, androgen deprivation therapy (ADT) and radiation therapy (RT), to...
A broad spectrum of therapies is available for the management of prostate cancer, ranging from well-established interventions like radical prostatectomy, androgen deprivation therapy (ADT) and radiation therapy (RT), to emerging modalities such as focal ablative treatments and targeted molecular therapies. These therapies can induce profound histologic alterations in both benign and malignant prostate tissue. Hormonal and radiation therapies are particularly known for their distinctive and often extensive morphologic effects, which have been well documented across needle biopsies, transurethral resection of the prostate (TURP) or enucleation specimens and prostatectomy samples. Novel ablative techniques-including cryotherapy, high-intensity focused ultrasound (HIFU), photodynamic therapy (PDT) and interstitial laser thermotherapy-are gaining traction, yet the histologic consequences of these newer modalities are still being characterized. These treatment-induced changes can obscure residual carcinoma, complicate tumour grading and staging and sometimes render traditional parameters such as Gleason scoring unreliable. As therapies evolve, pathologists must remain informed about the spectrum of post-treatment changes to accurately interpret prostate specimens. Diagnostic accuracy hinges not only on recognizing these morphologic effects but also on integrating clinical history, particularly when treatment details are not readily available. This review provides an overview of current and investigational prostate cancer therapies, their histologic impact and practical guidance for post-treatment evaluation.
Molecular pathology of bladder cancer.
Lopez-Beltran A, Blanca A, Downes MR … +3 more , Cimadamore A, Montironi R, Cheng L
Histopathology · 2026 Jan · PMID 41384708 · Publisher ↗
Significant progress has been achieved in elucidating the molecular underpinnings of bladder cancer initiation and progression. Translational research has identified mutations in chromatin-modifying genes such as KMT2D a...
Significant progress has been achieved in elucidating the molecular underpinnings of bladder cancer initiation and progression. Translational research has identified mutations in chromatin-modifying genes such as KMT2D and KDM6A, which facilitate colonization of larger regions of the urothelium. Subsequent mutations in TP53, PIK3CA, FGFR3 or RB1 drive malignant transformation. Advances in personalized oncology now integrate clinical, pathological and molecular classifications in bladder cancer, representing a paradigm shift in the management of locally advanced and metastatic disease. Alterations in FGFR3, commonly found in the luminal-papillary molecular subtype associated with low response to immunotherapy, are the target of erdafitinib. Enfortumab vedotin, which targets Nectin-4 (expressed in >95% of urothelial carcinomas), is approved for patients who progress after chemotherapy and/or immunotherapy. Evidence suggests that Nectin-4 gene amplification may further refine patient stratification. Sacituzumab govitecan, an antibody-drug conjugate directed against Trop-2, is effective in basal, luminal and stroma-rich subtypes but not in neuroendocrine carcinomas. In addition, therapies developed for HER2-positive breast cancer have shown efficacy in urothelial carcinoma, with recent data from the DESTINY pan-tumour phase II trial leading to FDA approval of trastuzumab deruxtecan for HER2-overexpressing metastatic urothelial carcinoma. This paper is a comprehensive review of the molecular pathology of bladder cancer, highlighting advances in molecular classification, biomarkers and personalized therapies. The transition from morphology-based classifications to combined morphological and molecular approaches, with therapeutic implications, is also addressed.
MiT family translocation carcinomas of the kidney and related entities.
Argani P
Histopathology · 2026 Jan · PMID 41384707 · Publisher ↗
The MiT subfamily of transcription factors includes TFE3, TFEB, TFEC and MITF. Gene fusions involving two of these transcription factors have been well characterized in two subtypes of renal cell carcinoma (RCC): TFE3-re...
The MiT subfamily of transcription factors includes TFE3, TFEB, TFEC and MITF. Gene fusions involving two of these transcription factors have been well characterized in two subtypes of renal cell carcinoma (RCC): TFE3-rearranged RCC (also known as Xp11 translocation RCC) and TFEB-rearranged RCC (which typically harbour a t(6;11)(p21;q12) translocation). TFE3 and TFEB have overlapping functional activity, which explains why these two subtypes of translocation RCC have many morphologic similarities and express similar downstream targets. Therefore, these two neoplasms are grouped together under the heading of 'MiT family translocation RCC'. TFE3-rearranged PEComas and TFEB-amplified RCC are more recently described related neoplasms harbouring alterations in these same genes. This review summarizes our current knowledge of these molecularly defined neoplasms, and differential diagnostic considerations.
Pathology of adrenal tumours: recent advances.
Erickson LA, Gupta S, Whaley RD
Histopathology · 2026 Jan · PMID 41384706 · Publisher ↗
Changes in the nomenclature and classification of adrenal gland diseases are the result of advances in understanding the pathogenesis, germline susceptibility and the clonal-neoplastic nature of diseases of the adrenal g...
Changes in the nomenclature and classification of adrenal gland diseases are the result of advances in understanding the pathogenesis, germline susceptibility and the clonal-neoplastic nature of diseases of the adrenal gland. Although numerous classification systems have been proposed, the Weiss system remains the standard for distinguishing benign from malignant adult adrenal cortical tumours, but the Helsinki system and the reticulin algorithm are proving to be increasingly useful in difficult cases. Subtypes of adrenal cortical neoplasms, such as myxoid and oncocytic, as well as those occurring in children require special consideration as their classification systems are different from those for standard adult adrenal cortical neoplasms. The importance of proliferative activity is central to the evaluation of adrenal cortical neoplasms. As for primary unilateral aldosteronism, CYP11B2 immunostain is increasingly studied to identify sites of aldosterone production with the hope of finding staining patterns predictive of clinical outcomes. Awareness of the clonal-neoplastic nature of adrenal cortical nodules and underlying germline susceptibilities has also advanced the classification of adrenal cortical nodular disease. For the adrenal medulla, pheochromocytomas (intra-adrenal paragangliomas) are all regarded as malignant tumours as they all have potential for metastases and are often associated with genetic susceptibilities.
Urologic surgical pathology in the era of precision medicine.
Cheng L, Berney DM
Histopathology · 2026 Jan · PMID 41384705 · Publisher ↗
Abstract loading — click title to view on PubMed.
Second edition ICCR dataset for testicular germ cell tumours: a reporting guide for histopathological diagnosis of orchiectomy specimens.
Bremmer F, Webster F, Daugaard G … +10 more , Hamilton RJ, Idrees MT, Kao CS, Miyai K, Raspollini MR, Srigley JR, Tickoo S, Yilmaz A, Wagner T, Berney DM
Histopathology · 2026 Jan · PMID 41384704 · Full text
To summarise the content and significance of the recently published second edition International Collaboration on Cancer Reporting (ICCR) histopathology dataset for testicular germ cell tumours, covering the Orchiectomy...
To summarise the content and significance of the recently published second edition International Collaboration on Cancer Reporting (ICCR) histopathology dataset for testicular germ cell tumours, covering the Orchiectomy specimen dataset. We highlight key updates from the first editions, including alignment with the 5th edition World Health Organization (WHO) Classification, revised staging criteria, clarified core data elements versus non-core elements and the evidentiary basis underpinning these changes. A review of the ICCR 2nd edition dataset for Orchiectomy specimens of primary testicular tumours was performed, focusing on their development by an international expert committee using a consensus-based approach. Core (required) and non-core (recommended) data elements were identified along with the level of evidence supporting each, following National Health and Medical Research Council (NHMRC) criteria. Changes from the first edition were extracted by comparing dataset content and notes, informed by up-to-date literature through July 2024. The 2nd edition Orchiectomy dataset provides an integrated, harmonised framework for reporting testicular germ cell tumours. The dataset incorporates the WHO 5th Edition Classification of Urinary and Male Genital Tumours. Pathological staging criteria have been updated to align with the 8th edition Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) definitions. The second edition of this dataset includes changes to align the dataset with the WHO Classification of Tumours, Urinary and Male Genital Tumours, 5th edition, 2022. The ICCR dataset includes the 5th edition Corrigenda, July 2024. It was agreed that this dataset is not suitable for non-germ cell tumours, with the hope that a new dataset, especially for sex-cord stromal tumours, would be developed. The 2nd edition Orchiectomy dataset represents an authoritative, up-to-date standard for pathology reporting of primary testicular germ cell tumours. By incorporating the WHO 5th edition classifications, current TNM staging and the latest evidence on prognostic factors, this dataset facilitates uniform reporting and prognostication. The ICCR dataset underscores core data required for patient management decisions (e.g., adjuvant therapy in Stage I disease, post-chemotherapy management) while providing flexibility through non-core elements for additional useful information. Adoption of this internationally vetted dataset will enhance consistency, assist multidisciplinary treatment planning and align pathology reports with modern consensus guidelines and classifications. The dataset can be used in both high-resource and limited-resource settings without compromising the essential reporting standards.
Grading of bladder cancer: updates, controversies and practical solutions.
Downes MR, van der Kwast TH, Lopez-Beltran A … +1 more , Cheng L
Histopathology · 2026 Jan · PMID 41384703 · Full text
Bladder cancer grading provides important prognostic information to clinicians, and the assigned grade is used as a variable in risk stratification models. There have been multiple proposed grading schemes over the last...
Bladder cancer grading provides important prognostic information to clinicians, and the assigned grade is used as a variable in risk stratification models. There have been multiple proposed grading schemes over the last century, with the most widely utilized in contemporary practice being the World Health Organization (WHO) 1973 and 2004 schemes, with WHO 2004 used almost exclusively in North America, and dual grading using both 2004 and 1973 is in widespread use in Europe. Recently, there has been increased interest in hybrid grading schemes for papillary bladder cancer. These combine features from both aforementioned schemes and have demonstrated prognostic performance that exceeds WHO 2004 and WHO 1973. In this article, we review the historical background and new concepts in bladder cancer grading, highlight the opinions and perspectives of clinicians and pathologists, and assess the challenges along with evidence for and against different grading schemes. We discuss the potential contribution of hybrid 3-tier grading of bladder cancer and how this could impact the classification of papillary urothelial neoplasms and shape future grading scheme proposals.
Advances in non-germ cell tumours of the testis: focus on new molecular developments in sex cord-stromal tumours.
Lobo J, Acosta AM
Histopathology · 2026 Jan · PMID 41384702 · Full text
Testicular sex cord-stromal tumours (TSCSTs) represent ~4%-8% of all testicular neoplasms. Most show a Leydig or Sertoli cell phenotype and exhibit benign clinical behaviour. However, a subset of ~10% is malignant and cl...
Testicular sex cord-stromal tumours (TSCSTs) represent ~4%-8% of all testicular neoplasms. Most show a Leydig or Sertoli cell phenotype and exhibit benign clinical behaviour. However, a subset of ~10% is malignant and clinically problematic, as TGCTs do not respond to systemic therapy. Classification of TSCSTs has relied on morphology, with several entities being defined based on their resemblance to more common ovarian counterparts (e.g. granulosa cell tumours). In recent years, multiple clinicopathologic and molecular studies have improved our understanding of the mechanisms that underlie pathogenesis and progression in TSCSTs, providing data that can be useful to refine classification and prognostication. In this review, we summarise the major recent advances in TSCSTs, focusing on molecular alterations and biomarkers relevant for diagnosis, classification and prognosis.
Molecular pathology of testicular germ cell tumours: an update for practicing pathologists.
Fichtner A, Zschäbitz S, Nettersheim D … +1 more , Bremmer F
Histopathology · 2026 Jan · PMID 41384700 · Full text
Testicular tumours are a diverse group of tumours, but most cases fall into the category of testicular germ cell tumours (TGCT). TGCTs are classified as either derived from a germ cell neoplasia in situ (GCNIS) or unrela...
Testicular tumours are a diverse group of tumours, but most cases fall into the category of testicular germ cell tumours (TGCT). TGCTs are classified as either derived from a germ cell neoplasia in situ (GCNIS) or unrelated to GCNIS. Based on the development, molecular alterations and onset of development, TGCTs can further be divided into three groups. Type I TGCTs include prepubertal-type teratoma and yolk-sac tumour. Type II TGCTs are the only GCNIS-related tumours in this classification and include seminomas, embryonal carcinoma, choriocarcinoma, yolk-sac tumour and teratoma of postpubertal type. Type III TGCTs only include spermatocytic tumours. While genetic alterations are helpful in the diagnostic routine, they have not yet been useful in determining treatment options, as targetable alterations are very rare. Type I TGCTs most commonly exhibit chromosomal aberrations and rarely display alterations related to the Wnt signalling pathway. A common molecular alteration in type II TGCTs is the presence of an isochromosome 12p or gain of 12p material. It is thought that the isochromosome 12p develops during the progression of a GCNIS to an invasive TGCT. Seminomas can also exhibit c-Kit mutations or KRAS mutations. Alterations associated with the formation of a somatic-type malignancy and/or the development of cisplatin resistance include TP53 mutations or MDM2 gene amplifications as well as epigenetic alterations. In advanced cases, some of these genes might be useful as targeted therapies (e.g. KRAS G12C or BRAF V600E), but as these mutations are rare, studies on larger groups of patients are not possible. Amplification of chromosome 9 including the DMRT1 gene, or Ras mutations is common in spermatocytic tumours. Overlapping molecular alterations, including those on chromosome 12, have recently been discovered in some type III TGCT. Tumour serum markers (e.g. alpha-fetoprotein, beta-subunit of human gonadotropin and microRNAs) are helpful in the diagnosis and for follow-up analysis to detect recurrent disease or disease progression. This review article provides an overview of the current classification of testicular tumours and their molecular classification. Furthermore, it provides information on biomarkers that are helpful in the diagnostic setting. Additionally, we will provide guidance on how to examine a testicular tumour specimen histopathologically to reach an accurate diagnosis. Finally, we will outline the importance of the content of a histopathological report for the urologists and oncologists.
The Paris system for reporting urinary cytology: what worked and what still needs to be improved.
Wojcik EM
Histopathology · 2026 Jan · PMID 41384697 · Full text
Urine cytology has long been a challenging diagnostic modality due to its low sensitivity for low-grade urothelial neoplasms and high interobserver variability. The introduction of The Paris System (TPS) in 2016 marked a...
Urine cytology has long been a challenging diagnostic modality due to its low sensitivity for low-grade urothelial neoplasms and high interobserver variability. The introduction of The Paris System (TPS) in 2016 marked a pivotal shift towards standardisation, with a primary focus on detecting high-grade urothelial carcinoma (HGUC). This review evaluates the impact of TPS on diagnostic accuracy, reproducibility, and clinical utility. It also highlights the system's limitations, including issues with nuclear-to-cytoplasmic (N/C) ratio estimation, cellular degeneration, and the underrepresentation of HGUC variants. The second edition of TPS (TPS 2.0) addresses many of these concerns, offering refined criteria and visual aids. However, further improvements are needed, particularly in the integration of molecular diagnostics and artificial intelligence.
Artificial intelligence in genitourinary pathology.
Patel AU, Parwani AV, Satturwar S
Histopathology · 2026 Jan · PMID 41384695 · Full text
Artificial intelligence (AI) is now a practical, value-generating tool in genitourinary (GU) pathology. Real-world deployments report up to 65% time-savings and multi-million-dollar returns on investment within 3 years a...
Artificial intelligence (AI) is now a practical, value-generating tool in genitourinary (GU) pathology. Real-world deployments report up to 65% time-savings and multi-million-dollar returns on investment within 3 years at high-volume centres. Across prostate, bladder, renal and testicular systems, contemporary algorithms equal or exceed expert accuracy for cancer detection, grading and prognostication. Foundation models trained on millions of whole-slide images now match specialized organ-specific tools without bespoke tuning. High AI-pathologist concordance is widely regarded as a surrogate marker of safety and clinical acceptability, yet no universally codified regulatory threshold for sensitivity, specificity or concordance has been issued. Because internationally recognized guidelines still omit detailed instructions for safe roll-out and sustained performance, we distilled insights from real-world deployments and pioneering pilot studies into two complementary roadmaps: the nine-step VALIDATED framework, which focuses on governance and safety oversight, and the 11-principle ORCHESTRATE blueprint, which guides day-to-day implementation. By 2030, we anticipate AI will automate ~80% of routine quantification, allowing pathologists to assume the role of diagnostic orchestrators who integrate multimodal data streams, helping offset a ~40% workforce shortfall and reducing inter-observer variability across practice settings. This review distils the evidence, economics and practical guidance required for successful AI adoption in GU pathology. Institutions following the VALIDATED-ORCHESTRATE pathway can harness efficiency gains while maintaining diagnostic excellence and achieving positive ROI within 5 years.
Neuroendocrine tumours of the urinary bladder: recent advances.
Akbulut D, Al-Ahmadie H
Histopathology · 2026 Jan · PMID 41384692 · Publisher ↗
Small cell carcinoma is the most frequently encountered neuroendocrine tumour (NET) of the urinary bladder, and it may present as either pure or in combination with urothelial carcinoma or other histological subtypes. La...
Small cell carcinoma is the most frequently encountered neuroendocrine tumour (NET) of the urinary bladder, and it may present as either pure or in combination with urothelial carcinoma or other histological subtypes. Large cell neuroendocrine carcinoma is increasingly recognized in this location, but it is not yet fully characterized. Well-differentiated NET and paraganglioma of the bladder are rare neuroendocrine neoplasms. Advances in the molecular characterization of these tumours have enhanced our understanding of their biology and can provide better classification and more accurate risk stratification for clinical decision-making.
Renal cell tumours with papillary architecture: evolving concepts, classification and new emerging entities.
Alruwaii ZI, Williamson SR, Cheng L … +1 more , Al-Obaidy KI
Histopathology · 2026 Jan · PMID 41384691 · Publisher ↗
Renal cell carcinoma (RCC) with papillary architecture encompasses a diverse group of renal epithelial tumours. The entity papillary RCC is thought to be the second most common subtype of renal cell carcinoma. Although i...
Renal cell carcinoma (RCC) with papillary architecture encompasses a diverse group of renal epithelial tumours. The entity papillary RCC is thought to be the second most common subtype of renal cell carcinoma. Although initially categorized into type 1 and type 2 subtypes based on histology, clinicopathological observations in conjunction with molecular advancements have reshaped the above categorization, suggesting that a significant number of the former type 2 tumours can be reclassified. This review traces the historical classification of papillary RCC, discusses emerging entities and reviews the recently recognized molecularly defined RCCs, highlighting diagnostic challenges, morphologic features and key immunohistochemical and genetic features.
Pathology of the upper urinary tract tumours: Histologic subtypes, genetics, biomarker testing.
Compérat E, Shariat S, Cussenot O … +1 more , Kläger J
Histopathology · 2026 Jan · PMID 41384690 · Publisher ↗
In the past few years, upper tract urothelial carcinoma (UTUC) has moved more towards the centre of interest in uro-oncology. Specific guidelines exist, and although these tumours are still rare, handling becomes more co...
In the past few years, upper tract urothelial carcinoma (UTUC) has moved more towards the centre of interest in uro-oncology. Specific guidelines exist, and although these tumours are still rare, handling becomes more common, especially in centres specialized in this type of tumour. Most of the time, conventional urothelial carcinoma (UC) can be diagnosed, but subtypes of UC as well as other carcinoma types exist, which might be more complicated to report. These other tumour morphologies are rare, but recognizing them is of great importance. With the evolution towards personalized medicine, biomarkers have been found; some are evaluated on a protein level using immunohistochemistry, and some require molecular testing. This review will focus on which marker to take. Additionally, major efforts have been taken in order to characterize UTUC on a molecular basis, with some alterations encountered regularly, but others are less frequent. In order to progress with biomarker identification and hence potential new therapeutic options and personalized patient management, the underlying mechanisms must be understood in detail.
Molecular subtypes of metastatic prostate cancer: from pathophysiology to diagnosis.
Dsouza JM, Sayar E, Schweizer MT … +7 more , Harmon S, Morrissey C, Beltran H, Nelson PS, Cheng L, Ding CC, Haffner MC
Histopathology · 2026 Jan · PMID 41384688 · Publisher ↗
Metastatic prostate cancer (mPC) is characterized by molecular and phenotypic heterogeneity. With increasing guideline-driven use of metastatic biopsies, more mPC specimens are being evaluated in surgical pathology. Howe...
Metastatic prostate cancer (mPC) is characterized by molecular and phenotypic heterogeneity. With increasing guideline-driven use of metastatic biopsies, more mPC specimens are being evaluated in surgical pathology. However, unlike localized prostate cancer, no standardized framework currently exists to guide the diagnostic workup of metastatic biopsies or reliably determine phenotypic subtypes. While many mPCs retain conventional acinar features, a growing subset exhibits phenotypic plasticity - including loss of prostate epithelial identity and emergence of neuroendocrine or other divergent lineages. This phenotypic diversity often occurs in castration-resistant prostate cancer as a mechanism of resistance to chronic androgen receptor pathway inhibition and is characterized by genomic alterations and epigenetic reprogramming. This review outlines the histologic and molecular spectrum of mPC and proposes a practical, pathology-informed diagnostic approach integrating morphologic assessment and immunohistochemistry. Adoption of a standardized diagnostic framework and multidisciplinary integration will be useful for employing precision oncology in advanced mPC.
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