Histopathology最新文献

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.

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.

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.

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.

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.

Histopathology parameters are generally critical for the management of prostate cancer. Current practice is focussed on accuracy, precision, reproducibility, standardization and completeness of this data collection. This review discusses issues with this reporting practice and suggests a simpler alternative approach focussed on the clinical utility of pathology data and effective communication of the histopathology ‘message’. The principles of prostate cancer detection and management are significantly different from those of other cancers. These differences could have important implications for the histopathological diagnosis and reporting of prostate cancer. Management decisions are often based on pathology data from nontargeted prostate biopsies that are subject to significant sampling error, which precludes accurate determination of tumour size and grade. In contrast to other solid tumours, definitive tumour size, grade, and stage are available only in the minority of patients who have undergone complete tumour excision (radical prostatectomy). The availability of a serum marker (prostate-specific antigen) for monitoring patients after prostate biopsy or prostatectomy would also significantly impact the clinical utility of histopathological data in these specimens. While it is necessary to report all mandatory data items, pathologists should focus their resources on data that are of clinical significance in an individual case. A pragmatic approach to prostate biopsy reporting with less emphasis on precise determination of tumour extent and grade is recommended.

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.

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.

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.

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.