Histopathology最新文献

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.

The cover image is based on the reviews Molecular subtypes of metastatic prostate cancer: from pathophysiology to diagnosis by Jeanne M Dsouza et al., https://doi.org/10.1111/his.70033 and Advances in non-germ cell tumours of the testis: focus on new molecular developments in sex cord-stromal tumours by João Lobo and Andres M Acosta, https://doi.org/10.1111/his.70006.

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.

Molecularly defined renal carcinomas (MDRC) represent a heterogeneous group of tumours characterized by disease-defining genetic alterations, and the documentation of these mutations is necessary for their diagnosis. This group includes TFE3-rearranged renal cell carcinoma (RCC), TFEB-rearranged RCC, TFEB-amplified RCC, fumarate hydratase (FH)-deficient RCC, succinate dehydrogenase (SDH)-deficient RCC, SMARCB1-deficient renal medullary carcinoma (RMC), ALK-rearranged RCC, and ELOC-mutated RCC. Although they account for only about 5% of RCC, they are clinically significant due to distinctive biology, frequent diagnostic pitfalls, and therapeutic implications. Many pathology laboratories lack immediate access to fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) to confirm MDRC; this review emphasizes morphologic recognition and immunohistochemical surrogates, followed by rational triage for ancillary testing when available.

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.