Histopathology最新文献

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.

Conflicting practice recommendations regarding the grading of intraductal carcinoma of the prostate (IDCP) from two leading uropathology societies, the Genitourinary Pathology Society (GUPS) and the International Society of Urological Pathology (ISUP), are confusing for both pathologists and treating clinicians. The objectives of this consultation were to clarify unresolved issues regarding IDCP and atypical intraductal proliferation (AIP) terminology, diagnostic criteria, grading, and management implications, as well as to develop uniform reporting guidelines for IDCP and AIP, endorsed by both societies. A 32-member expert panel, composed of five core members, 25 expert urological pathologists, and two expert urologists, employed a modified Delphi process consisting of multiple rounds of consultation and voting. These were supplemented by discussions at the 2025 United States and Canadian Academy of Pathologists Annual Meeting to achieve expert consensus (defined as at least 67% agreement). Consensus was reached on several key issues. IDCP was regarded most commonly as reflecting the retrograde spread of invasive prostate cancer (PCa). IDCP diagnosis should be based on the Guo and Epstein criteria, supported by basal cell immunohistochemistry in cases that are difficult to distinguish from invasive PCa. The term AIP should be used only in equivocal proliferations where IDCP is favoured but the criteria are not fully met, and these should be reported as ‘AIP, suspicious for IDCP’. In the presence of invasive PCa, IDCP should generally be incorporated into Gleason grading irrespective of Grade Group (GG). However, a significant minority (30%) favoured excluding IDCP from the Gleason score if the invasive component was solely Gleason pattern (GP) 3. Pure IDCP (not associated with invasive PCa) and AIP, suspicious for IDCP, should not be graded. IDCP should not be incorporated in the grading of invasive PCa when it is spatially distinct from invasive PCa. A second opinion from a senior or dedicated GU pathologist and discussion within a multidisciplinary management setting should be considered, in the rare settings of pure IDCP or GP3 + IDCP (formerly GG1 + IDCP scenario). This joint GUPS–ISUP consultation provides unified recommendations for the diagnosis, terminology, grading, and reporting of IDCP and AIP, and will pave the way for the development of future IDCP/AIP WHO guidelines. Their adoption should reduce interobserver variation, facilitate consistent communication with clinicians, and improve patient management.

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.