Primary pulmonary Langerhans cell histiocytosis (PLCH) is a rare entity. To characterize its clinicopathological and molecular features, 13 cases (15 specimens) were retrospectively analyzed, incorporating clinical infor...Primary pulmonary Langerhans cell histiocytosis (PLCH) is a rare entity. To characterize its clinicopathological and molecular features, 13 cases (15 specimens) were retrospectively analyzed, incorporating clinical information, imaging findings, histopathological features, immunohistochemical results, BRAFV600E mutation status, and DNA-based next-generation sequencing data. The patients ranged in age from 17 to 59 years (mean, 30 years), with a male-to-female ratio of 12:1; all male patients were smokers. Computed tomography demonstrated multiple pulmonary cysts in 12 cases, including pneumothorax in 3 cases, and a solitary nodular mass in 1 case. Histologically, 11 cases exhibited classic morphological features, whereas two small biopsy specimens showed subtle nuclear grooves and sparse background eosinophils, leading to an initial misdiagnosis of reactive lesions. Immunohistochemical analysis confirmed expression of S-100 (15/15), CD1a (15/15), Langerin (15/15), and cyclin D1 (3/3) in all cases. BRAFV600E mutation analysis was positive in one of four tested cases. Next-generation sequencing performed in six cases (seven lesions) revealed a non-frameshift BRAF deletion in one case, concurrent MAP2K1 and DUSP4 missense mutations in one case, an isolated DUSP4 missense mutation in one case, and RRAS mutations in two separate specimens from one patient. Four cases exhibited abnormalities in genes associated with DNA damage repair. Additional alterations involved multiple other signaling pathways, as well as abnormalities in hematopoietic regulation, epigenetic modulation, and related molecules. At a median follow-up of 23 months, all twelve patients were alive, although one patient developed extrapulmonary lesions. In conclusion, PLCH predominantly affects adult smokers, shows a marked male predominance, and generally carries a favorable prognosis. In cases with atypical morphology, immunohistochemical and molecular analyses should be integrated with characteristic imaging findings to avoid misdiagnosis. Furthermore, this study provides additional insights into the molecular pathogenesis of PLCH.
BCL2 follicular lymphomas (FLs) of grades 1-3A are defined as classic FL, and duodenal and skin FLs are known as special subtypes. To clarify the natural history of BCL2 FLs, we analyzed the tumor site, histological grad...BCL2 follicular lymphomas (FLs) of grades 1-3A are defined as classic FL, and duodenal and skin FLs are known as special subtypes. To clarify the natural history of BCL2 FLs, we analyzed the tumor site, histological grade, and histological transformation rate. We analyzed 2260 FL grade 1-3B samples from 1389 patients. BCL2 expression was positive in 94 % (2115/2260) of the samples, with higher positivity in gastrointestinal (GI) (98 % [duodenum, 99 %]) and bone marrow (BM) (97 %) FLs than in lymph node (LN) (92 %) and extranodal (EN) (93 %) FLs (P = 3.4E-06). Histological grade increased in the order of BM and duodenum, GI (excluding duodenum) and EN, and LN. The histological transformation rate in the same biopsy sample diagnosed with FL was the highest in GI (excluding duodenum) (12 %), followed by LN (10 %), EN (5 %), BM (1 %), and duodenum (0.5 %). No significant differences were observed between duodenal and BM FLs regarding BCL2-positivity rate (P = 0.326), histological grade (P = 0.131), and histological transformation rate (P = 0.408). In EN sites, FLs most commonly involved skin, ocular adnexa, connective tissue, bone, and paravertebra. No specific organ showed a particularly low BCL2 percentage (range, 67 %-100 %). Because both primary (88 %) and secondary (95 %) skin FLs showed a high incidence of BCL2 expression, most skin FLs may represent one aspect of BCL2 FL. These findings suggest that BM and duodenum FLs may represent early-phase BCL2 FL, whereas EN, GI (excluding duodenum), and LN FLs may correspond to more advanced phases.
BACKGROUND: The diagnosis of bone and soft tissue tumors is challenging due to their rarity, overlapping morphology, and limited access to specialized immunohistochemistry (IHC) in routine practice. Because many of these...BACKGROUND: The diagnosis of bone and soft tissue tumors is challenging due to their rarity, overlapping morphology, and limited access to specialized immunohistochemistry (IHC) in routine practice. Because many of these tumors are fusion-driven, targeted RNA sequencing may improve diagnostic accuracy, but its use is not yet established in Japan. METHODS: We retrospectively analyzed 90 cases of bone and soft tissue tumors, including benign lesions, using the TruSight RNA Pan-Cancer Panel (1385 genes) on FFPE samples. Fusion detection was combined with expression-based clustering. Diagnostic impact was assessed by comparing initial histological impressions with integrated diagnoses incorporating targeted RNA panel findings. RESULTS: Fusion transcripts were detected in 63 cases (69.2 %), of which 46 were in-frame. Twenty-five cases harbored well-characterized pathogenic fusions that directly contributed to diagnostic confirmation or refinement. Twenty-one cases showed fusion transcripts of uncertain significance, and ten of these were reclassified as likely pathogenic after additional validation. Three cases exhibited complex fusion patterns suggestive of chromothripsis or chromoplexy, warranting further genome-wide analysis. RNA expression clustering distinguished several tumor subtypes and provided complementary support for diagnostically challenging cases, such as undifferentiated pleomorphic sarcoma. CONCLUSIONS: Targeted RNA panel testing enabled robust detection of clinically relevant fusions and provided expression-based insights into tumor classification. When integrated with histopathology, this approach improved diagnostic accuracy in rare tumors and offered a practical triage strategy for extended genomic analysis, highlighting its clinical utility in pathology practice.
BACKGROUND: The frequency and prognostic significance of prostate cancer (PCa) metastasis to the prostatic anterior fat pad (PAFP) remain unclear. We evaluated the incidence of lymph nodes and metastatic involvement with...BACKGROUND: The frequency and prognostic significance of prostate cancer (PCa) metastasis to the prostatic anterior fat pad (PAFP) remain unclear. We evaluated the incidence of lymph nodes and metastatic involvement within the PAFP and assessed the impact of PAFP lymph node metastasis on nodal staging accuracy and long-term outcomes in patients undergoing radical prostatectomy. METHODS: We retrospectively analyzed 4028 patients who underwent radical prostatectomy with concurrent PAFP and pelvic lymph node (PLN) dissection between January 2010 and May 2021. Lymph nodes within the PAFP and PLN specimens, along with relevant histopathologic features, were evaluated. Patients were stratified into three groups based on the location of lymph node metastasis: (Group 1) PAFP-only metastasis, (Group 2) PLN-only metastasis, and (Group 3) metastasis involving both regions. Biochemical recurrence-free survival and overall survival were compared, and Kaplan-Meier analysis and multivariable Cox regression were used. RESULTS: Among all patients, lymph nodes were identified in the prostatic anterior fat pad in 295 cases (7.30 %), of those, 23 patients had isolated PAFP lymph node metastasis (0.57 % of the entire cohort and 7.80 % of patients with PAFP lymph nodes). PLNs were reported in 3874 patients (96.18 %), of whom 70 patients had isolated PLN metastasis (1.73 % of the entire cohort and 1.8 % of patients with PLN). Nine patients (0.22 % overall) demonstrated metastatic involvement of both PAFP and PLN. The metastatic positivity rate for isolated metastasis was significantly higher in PAFP lymph nodes than in PLN (Z = 6.7), with a relative risk of 4.32 (95 % CI, 2.73-6.75). Biochemical recurrence occurred in 77.8 % of patients in Group 1, 72.7 % in Group 2, and 66.7 % in Group 3. All-cause mortality was observed in 21.7 %, 7.2 %, and 22.2 % of patients in Groups 1, 2, and 3, respectively. Kaplan-Meier analysis and multivariable Cox regression demonstrated no significant differences in biochemical recurrence-free survival or overall survival between groups. Excision of the prostatic anterior fat pad resulted in lymph node upstaging in approximately 1 % of all patients. Biochemical recurrence-free survival and overall survival were comparable between patients with isolated PAFP and isolated PLN metastases. CONCLUSIONS: Routine excision and pathological evaluation of the prostatic anterior fat pad during radical prostatectomy improve nodal staging by identifying otherwise unrecognized N1 disease, without an associated adverse impact on oncologic outcomes, compared with pelvic lymph node evaluation alone.
Herein, we have provided select updates targeted towards practicing pathologists pertaining to the pathology of kidney, testis, and penile cancer. This includes discussion of diagnostic criteria, evolution of nomenclatur...Herein, we have provided select updates targeted towards practicing pathologists pertaining to the pathology of kidney, testis, and penile cancer. This includes discussion of diagnostic criteria, evolution of nomenclature, emerging immunohistochemistry markers, diagnostic pitfalls, and improved understanding of prognostic significance of biomarkers and/or staging parameters. For kidney tumors, specific topics of discussion include a summary of the recent literature pertaining to the biology and diagnostic criteria for conventional and non-conventional FLCN-mutated tumors, utility of GPNMB immunohistochemistry, and diagnostic pitfalls relevant to eosinophilic solid and cystic renal cell carcinoma. Testicular/paratesticular updates address diagnostic criteria for mesothelium-derived lesions of the tunica vaginalis, recommended immunohistochemical panels for testicular sex cord-stromal tumors, and recommended nomenclature, specifically the use of "embryonic-type neuroectodermal tumor" rather than primitive neuroectodermal tumor (PNET) in the context of somatic transformation of testicular germ cell tumors. For penile squamous cell carcinoma, the summary emphasizes prognostic biomarkers, notably TP53 alterations and high risk HPV status, and nuances pertaining to pathologic staging.
Endocrine pathology is continuously advancing with with new classification systems and an increased understanding the underlying pathogenesis and genetic alterations, whether somatic or germline, in endocrine diseases. M...Endocrine pathology is continuously advancing with with new classification systems and an increased understanding the underlying pathogenesis and genetic alterations, whether somatic or germline, in endocrine diseases. Many changes have recently occurred in the classification of thyroid carcinoma, the most complex of which involve the new category of "high-grade follicular cell derived non anaplastic thyroid carcinoma" which encompasses both poorly differentiated thyroid carcinomas and differentiated high-grade thyroid carcinomas. The word "hyperplasia" is no longer used with primary multiglandular parathyroid disease due to increased understanding of its clonal nature. New terminology of "atypical parathyroid tumor" has been introduced for tumors highly worrisome for malignancy but without definitive invasion. "Parafibromin deficient parathyroid tumor" is now used for parathyroid neoplasms that show complete loss of nuclear parafibromin all tumor cells. Newer classification systems are increasingly used in the classification of adult and pediatric adrenal cortical neoplasms. The utility of CYP11B2 immunostain is being increasing reread recognized in the diagnosis of primary unilateral aldosteronism. This update focus on selected complex and significant areas in endocrine pathology that have undergone recent changes.
Resections from the mobile tongue, the oropharynx and neck dissections constitute a large proportion of routine head and neck pathology workload. Histologically detected proximity to margins and prognostic factors like d...Resections from the mobile tongue, the oropharynx and neck dissections constitute a large proportion of routine head and neck pathology workload. Histologically detected proximity to margins and prognostic factors like depth of invasion, perineural or lymphovascular invasion, or extranodal extension guide adjuvant radiotherapy and/or chemotherapy. This review discusses practical approaches to macroscopic examination of the various types of tongue and oropharyngeal resections and neck dissections. Differential inking and radial sections demonstrate proximity of tumour to margins. The macroscopic examination and sampling should then be directed towards identifying remaining adverse prognostic features including the maximum extent of invasion at the primary site and extranodal extension, nodal matting or soft tissue deposits in the neck dissections. The diagnostic challenges differ in the tongue and oropharynx. The diagnosis of tongue SCC is relatively easy, however, precursor oral epithelial dysplasia can be challenging. Architectural and cytologic clues assisting in identifying dysplasia and practical clues distinguishing it from reactive changes are discussed. In contrast, dysplasia is not diagnosed in the oropharynx. p16 immunostaining and detection of human papillomavirus (HPV) play a critical role in the diagnosis and prognosis of oropharyngeal SCC. Nuances in the implementation and interpretation of p16 immunostaining and HPV assays are discussed.
Endometrial gastric (gastrointestinal)-type mucinous adenocarcinoma (EGMA) is a rare histologic subtype of endometrial carcinoma that is challenging to recognize as a distinct entity. Mucinous differentiation has been ob...Endometrial gastric (gastrointestinal)-type mucinous adenocarcinoma (EGMA) is a rare histologic subtype of endometrial carcinoma that is challenging to recognize as a distinct entity. Mucinous differentiation has been observed in endometrial carcinomas since the 1980s. However, the definitive characterization of endometrial carcinomas with mucinous differentiation has been unclear in the past. Since its formal inclusion in the latest 5th edition of the World Health Organization (WHO) Classification of Female Genital Tumors, and with increasing awareness of this rare entity, more case reports and studies on EGMAs have emerged in the recent years. Some studies sought to understand the expression of gastrointestinal immunohistochemical markers in neoplastic and/or normal endometrium, while others performed comprehensive clinicopathologic characterization of EGMAs, including their molecular characteristics. However, there still exist challenges in the diagnosis of EGMA, with considerable overlaps in morphologic features and immunohistochemical phenotype existing between EGMAs and the other differential diagnoses. This review sought to summarize the known clinical presentation, radiological findings and pathologic features of EGMA to date. We also discuss in detail the salient differential diagnoses to consider, and evaluate the utility of immunohistochemistry in the workup of this entity.
Diagnostic pathology of the upper gastrointestinal tract continues to evolve as molecular insights, clinical practices, and updated international standards improve our understanding of disease. The World Health Organizat...Diagnostic pathology of the upper gastrointestinal tract continues to evolve as molecular insights, clinical practices, and updated international standards improve our understanding of disease. The World Health Organization (WHO) classification of digestive system tumors, now in its 6th edition, includes several important changes, including incorporating esophageal epidermoid metaplasia as a separate section, and modifying the approach to metaplastic and dysplastic gastric lesions. These updates reflect a broader trend toward simplified terminology, clearer definitions of precursor lesions, and more consistent grading systems across the digestive tract. At the same time, increased use of immunotherapy has introduced new patterns of injury. Beyond immune checkpoint inhibitors, several agents, including rituximab and chimeric antigen receptor T-cell therapy have been associated with distinctive upper-GI mucosal alterations that can resemble infectious or immunologic diseases. Failure to recognize these patterns of injury can carry significant clinical implications, including treatment delay or discontinuation, and require careful histologic evaluation to avoid misclassification. This review summarizes select upper-GI updates from the 6th edition of the WHO classification and outlines emerging therapy-related injuries with a focus on rituximab- and CAR-T-associated changes. The aim is to provide a practical and contemporary guide for pathologists navigating these evolving diagnostic challenges.
Colloid cyst of the 3rd ventricle (CC) is an unusual cystic lesion of uncertain histogenesis, occurring exclusively in the 3rd ventricle close to the foramen Monro. In the past, its pathogenic relationship to neurenteric...Colloid cyst of the 3rd ventricle (CC) is an unusual cystic lesion of uncertain histogenesis, occurring exclusively in the 3rd ventricle close to the foramen Monro. In the past, its pathogenic relationship to neurenteric cyst (NEC) of central nervous system or Rathke cleft cyst (RCC) has been suggested. Thus, we evaluated expression of selected tissue-specific transcription factors and other proteins to assess its putative origin. Tissue samples of 15 CCs (8 females and 7 males, mean age 46.7 years), 7 RCCs (7 females, mean age 45.6 years), 8 neurenteric cysts (5 females and 2 males, mean age 42.1 years, including 1 recurrent case), and 10 craniopharyngiomas (2 papillary and 8 adamantinomatous) were included. Immunohistochemical detections of PAX8 with C-terminus specific antibody, TTF1, SOX17, and cadherin 17 were performed in all the samples. The immunoreactivity was scored based on extent (0 %; <10 %; 10-50 %; >50 %) and intensity (weak, moderate, strong). All 15 cases of CCs were PAX8 positive (moderate to strong expression in >50 % in 13/15 cases), while no RCC, NEC or craniopharyngioma showed PAX8 immunoreactivity. Rare PAX8-positive cells were also observed in single cells of 50 % (3/6) of the choroid plexuses. No expression of TTF1 or SOX17 was detected in any of the cases and weak cadherin 17 expression was seen in scattered cells (<10 %) of one CC and RCC. Colloid cysts of the 3rd ventricle are consistently PAX8-positive, while they lack signs of thyroid, müllerian or enteric differentiation. Furthermore, PAX8 can be used to distinguish CC from NEC, RCC, and craniopharyngiomas.
OBJECTIVE: A heavy admixture of inflammatory cells is observed in extranodal NK/T-cell lymphoma (ENKTL), but granuloma formation is typically absent. We aimed to describe the clinicopathological features of this rare gra...OBJECTIVE: A heavy admixture of inflammatory cells is observed in extranodal NK/T-cell lymphoma (ENKTL), but granuloma formation is typically absent. We aimed to describe the clinicopathological features of this rare granulomatous variant of ENKTL. METHODS: Four cases of the granulomatous variant of ENKTL were retrospectively analyzed, combined with a review of four cases reported in the literature. RESULTS: The four cases in our institution comprised one female and three male patients aged 57-65 years (median: 61 years). One patient had a nasal lesion, while three exhibited extranasal disease. All were diagnosed at stage III/IV. Histopathology showed extensive epithelioid granulomas, but lacked typical features such as angiocentricity and angiodestruction. Scattered atypical lymphoid cells with varying degrees of cytological atypia were observed between granulomas. Immunohistochemistry confirmed T or NK cell lineage with expression of CD3ε and cytotoxic markers. Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization (ISH) confirmed an Epstein-Barr virus (EBV) association in all cases. Three cases were CD56-positive, and two were CD5-negative. Three showed CD4-/CD8-, and one showed CD4-/CD8+. Mutations in DNMT3A, KMT2D, and KMT2A in Case #3 and a B2M mutation in Case #4 were revealed by next-generation sequencing (NGS). Combined with literature, granulomatous ENKTL most frequently involved the skin (6/8 cases). Notably, five of these eight cases were initially misdiagnosed as chronic inflammation. CONCLUSIONS: ENKTL encompasses a variety of morphological features and a broad biological spectrum. Heightened awareness of this granulomatous variant is critical for preventing diagnostic delays and ensuring timely therapeutic intervention.
Leydig cell tumors (LCTs) and Sertoli cell tumors (SCTs) are the two most common sex cord-stromal tumors of the testis, and can exhibit overlapping histologic and immunophenotypic features, creating diagnostic challenges...Leydig cell tumors (LCTs) and Sertoli cell tumors (SCTs) are the two most common sex cord-stromal tumors of the testis, and can exhibit overlapping histologic and immunophenotypic features, creating diagnostic challenges. Currently, differential diagnosis of these two tumors relies primarily on histological features, with no reliable immunohistochemical markers available. B72.3 is a widely used immunohistochemical antibody recognizing tumor-associated glycoprotein 72 (TAG-72) expressed in a broad range of normal and tumor tissues. Incidentally, we observed that B72.3 specifically stains the Leydig cells, but not Sertoli cells, in normal testis, suggesting its potential utility as a diagnostic marker for testicular LCTs. In this study, we identified 35 patients with testicular LCTs (primary: n = 28; metastatic: n = 7) and 12 with testicular SCTs (primary: n = 10; metastatic: n = 2). B72.3 immunohistochemistry was performed on 17 testicular LCTs and 7 SCTs. Positive B72.3 staining was observed in 9 of 17 LCTs (53 %), including 8 of 12 primary tumors (67 %) and 1 of 5 metastatic tumors (20 %). Among the positive LCTs, 2 exhibited diffuse staining, 2 showed patchy positivity, and 5 had focal staining. By contrast, all 7 SCTs and 1 Sertoli cell nodule were negative for B72.3. These findings indicate that B72.3 may serve as a useful diagnostic marker for testicular LCTs and can aid in distinguishing LCTs from SCTs in challenging cases.
The classification of lung adenocarcinoma (LADC) subtypes is important for understanding disease heterogeneity and has potential implications for diagnosis and treatment planning, yet the complexity and heterogeneity of...The classification of lung adenocarcinoma (LADC) subtypes is important for understanding disease heterogeneity and has potential implications for diagnosis and treatment planning, yet the complexity and heterogeneity of histopathological images pose significant challenges for automated classification. This study proposes an efficient deep learning model that integrates Depthwise Separable Residual Block (DSResBlock), RefConv, Channel Attention Pooling (CAP), and Multidimensional Collaborative Attention (MCA) modules into the EfficientNetV2-S architecture to improve subtype classification of LADC histopathological images. DS-EffNet model optimizes feature extraction and modeling of complex pathological patterns through depthwise separable convolutions and attention mechanisms. Experimental results demonstrate that the model achieves an accuracy of 95.1 %, an F1-score of 0.938, and an area under the curve (AUC) of 0.994 on the primary experimental dataset, outperforming other baseline models. Furthermore, the model attains 100 % generalization accuracy on the LC25000 dataset, indicating promising cross-institutional performance. Ablation studies demonstrate the synergistic contributions of each module, with MCA particularly effective in modeling complex features and RefConv significantly reducing computational complexity. This study provides a novel design paradigm for medical image classification, extendable to other histological tasks, and may assist pathologists by providing rapid subtype-level information, potentially supporting future diagnostic research and aiding treatment stratification studies.
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a high risk of early recurrence after surgery. We evaluated the utility of circulating tumour DNA (ctDNA) analysed at different time points as a prognostic tool....INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a high risk of early recurrence after surgery. We evaluated the utility of circulating tumour DNA (ctDNA) analysed at different time points as a prognostic tool. Secondary aims were prognostic value of ctDNA combined with plasma carbohydrate antigen (CA) 19-9 and prognostic value of peritoneal tumour DNA (ptDNA). METHODS: A total of 75 patients were included. Plasma samples were obtained preoperatively, 1 month, and 7-9 months after resection. Peritoneal lavage fluid (PLF) was collected preoperatively and 7-9 months after resection. Cell-free DNA (cfDNA) from plasma and ptDNA were analysed using mutation specific digital droplet PCR assays in a tumour-informed apprach. Kaplan-Meier survival curves, univariable, and multivariable Cox proportional hazard models were used to assess overall survival (OS) and recurrence-free survival (RFS). RESULTS: Preoperatively, detectable ctDNA was an independent risk factor for OS (HR = 1.88, p = 0.047). Detectable ctDNA 7-9 months after surgery was an independent risk factor for RFS (HR = 4.48, p = 0.017). Detectable ctDNA 1 month after surgery showed decreased RFS (HR = 1.98, p = 0.055). Preoperative, 1-month, and 7-9 months postoperative positivity for ctDNA and/or CA 19-9 showed a significantly worse median OS (p = 0.024, p = 0.008, and p = 0.0003). We did not find association of ptDNA with OS or RFS, but ptDNA detection 7-9 months after surgery was associated with peritoneal RFS (p = 0.003). CONCLUSION: Our data indicate that detectable ctDNA in plasma taken before and 7-9 months after surgery holds independent prognostic value in PDAC. Combination of ctDNA with CA-19-9 may be a particularly strong prognosticator, which should be confirmed in future studies.
In last few decades our understanding of bone and soft tissue tumors has evolved significantly, expanding and clarifying our current classification system. Due largely to increased utilization of ancillary testing, parti...In last few decades our understanding of bone and soft tissue tumors has evolved significantly, expanding and clarifying our current classification system. Due largely to increased utilization of ancillary testing, particularly molecular tools, new entities are continually emerging and/or being further refined. In addition to morphological and molecular differences, in many instances, the recognition of a new entity carries significant prognostic and potentially therapeutic relevance. In this review on practice updates, we endeavor to discuss five recently described tumors including pseudoendocrine sarcoma, NUT-rearranged sarcoma, VGLL3-rearranged spindle cell rhabdomyosarcoma of head and neck, superficial neurocristic FET::ETS fusion tumors, and NFATC1/2-rearranged epithelioid vascular tumors.
The field of central nervous system (CNS) tumor diagnostics continues to evolve and expand with the emergence and integration of diagnostic, prognostic, and predictive genomic markers. Despite such ever-increasing comple...The field of central nervous system (CNS) tumor diagnostics continues to evolve and expand with the emergence and integration of diagnostic, prognostic, and predictive genomic markers. Despite such ever-increasing complexity, it remains within the ability of practicing surgical pathologists to perform an informed assessment of a majority of CNS tumors. In this review, we provide practical guidelines to evaluate the most common primary malignant and benign CNS tumor entities - high-grade diffuse glioma and meningioma.
Accurate grading, staging, and classification are essential components of bladder and prostate cancer pathology, directly influencing clinical management and patient outcomes. Recent initiatives by the International Soci...Accurate grading, staging, and classification are essential components of bladder and prostate cancer pathology, directly influencing clinical management and patient outcomes. Recent initiatives by the International Society of Urological Pathology (ISUP) and the Genitourinary Pathology Society (GUPS) have produced key consensus updates aimed at refining diagnostic criteria and resolving long-standing controversies. This review highlights high-impact developments in bladder and prostate pathology, including updated grading systems and T1 substaging in bladder tumors, the proposed hybrid grading approach, and the classification of urachal carcinoma. Evolving perspectives in prostate pathology are also discussed, encompassing intraductal carcinoma of the prostate (IDC-P), neuroendocrine and aggressive variant tumors, and the clinical relevance of Grade Group 1 (GG1) disease in the context of active surveillance. Recent literature and consensus statements are summarized with attention to diagnostic challenges and practical implementation. These focused updates highlight the dynamic nature of urologic pathology and reflect a broader movement toward greater diagnostic precision, reproducibility, and clinical relevance, with adoption of ISUP and GUPS frameworks essential for improving patient outcomes.