AIM: Primary malignant melanomas in the bladder or urethra are exceedingly rare. Diagnosing these tumours presents substantial challenges due to their close resemblance in gross appearance and histology to urothelial car...AIM: Primary malignant melanomas in the bladder or urethra are exceedingly rare. Diagnosing these tumours presents substantial challenges due to their close resemblance in gross appearance and histology to urothelial carcinomas. METHODS: A retrospective review of our department archives from 2000 to 2023 identified four cases of primary malignant melanoma in the urinary tract. Demographic and clinical data were extracted from electronic medical records. RESULTS: This retrospective case series investigates the clinical presentations, histopathological characteristics, immunohistochemical profiles and molecular features of four unique cases of primary malignant melanoma in the bladder or urethra. CONCLUSION: Our analysis aims to deepen the understanding of the diagnostic and management strategies for this extremely rare disease.
AIMS: This study was undertaken to compare and expand the clinicopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumour (SMARCA4-dUT) and switch/sucrose non-fermentable-deficient non-small cel...AIMS: This study was undertaken to compare and expand the clinicopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumour (SMARCA4-dUT) and switch/sucrose non-fermentable-deficient non-small cell lung carcinomas (SWI/SNF-dNSCLC) and to address cases with intermediate features. METHODS: The pathology department archive was searched for all primary mediastinal, pleural and lung-based malignancies that showed aberrant expression of two SWI/SNF proteins the Brahma (BRM) aka and/or (Brahma-related gene 1 (BRG1) aka . Patient demographics, treatment and clinical outcomes were collected from records and telephonic interviews. Differences in histopathological features and immunohistochemical stains were analysed. Cases with characteristics intermediate between both tumour entities were sequenced to advance our understanding of their biology and to assign them a more accurate classification. RESULTS: We identified 50 tumours with SMARCA4 and/or SMARCA2 deficiencies, including 23 (46%) SMARCA4-dUT, 18 (36%) SMARCA4-dNSCLC and 2 (4%) SMARCA2-dNSCLC. Dyscohesive or undifferentiated cellular morphology versus frank gland formation along with keratin, claudin-4 and expression of >1 stem cell marker helped classify the SWI/SNF deficient tumours as SMARCA4-dUT or SWI/SNF-dNSCLC (p<0.05). Seven (14%) cases with BRG1 deficiency displayed 'intermediate' features of both SMARCA4-dNSCLC and SMARCA4-dUT and had the shortest overall survival. The smoking-related gene signature was observed on sequencing in all four cases examined. CONCLUSION: Tumours with intermediate features between SMARCA4-dUT and SWI/SNF-dNSCLC exist and portend an equally poor prognoses. Immunostains, including keratin, claudin-4, TTF1, HepPar1, stem cell markers, along with BRG1 and BRM testing, are essential adjuncts to morphology, while molecular studies can offer supplementary evidence in challenging cases.
There is an ongoing explosion of new information regarding the underlying molecular alterations driving a variety of salivary gland neoplasms. The volume of this emerging data makes it difficult to keep up with and may c...There is an ongoing explosion of new information regarding the underlying molecular alterations driving a variety of salivary gland neoplasms. The volume of this emerging data makes it difficult to keep up with and may cause pathologists to believe that salivary gland neoplasms cannot be diagnosed without genetic analysis. This review focuses on the practical diagnostic applications of molecular tools in surgical pathology specimens.
AIMS: To investigate the clinicopathological features and molecular characteristics of sporadic hypertrophic and nodular port-wine stains (PWS). METHODS: We analysed the clinicopathological and molecular characteristics...AIMS: To investigate the clinicopathological features and molecular characteristics of sporadic hypertrophic and nodular port-wine stains (PWS). METHODS: We analysed the clinicopathological and molecular characteristics of 27 sporadic hypertrophic and nodular PWS retrieved from our pathology database from 2013 to 2023 and reviewed the relevant literature. RESULTS: There were 13 men and 14 women who ranged in age from 10 to 66 years. The main sites were the head and neck (23/27, 85%), which showed irregular thickening and darkening of purplish-red patches on the skin surface and the development of nodularity. Histologically, immature venule-like channels with irregular dilation are arranged in clusters or honeycombs, which are widely distributed primarily in the papillary layer and deep dermis and partly extend into the subcutaneous fat layer and other deep tissues. Dilated vessels with irregular shapes often exhibit fibrous thickening and an increased number of large vessels without vascular endothelial cell proliferation. All vessels showed similar characteristics, with positive staining for CD34, ERG and GNAQ in the endothelial cells, and negative staining for elastic fibres. Nine patients had somatic mutations (9/11, 82%), including exon four mutations (6 cases, p.R183Q), exon five mutations (2 cases, p.Q209R) and exon two mutations (one case, p.G48V). Two patients had somatic corepressor-like 1 () gene mutations (2/11, 18%), including exon 3 mutations (p.T1111M) and exon 7 mutations (p.G1391R). CONCLUSIONS: Sporadic hypertrophic and nodular PWS are mostly related to somatic mutations. This is the first study to identify the Rare and somatic mutations.
Domonkos L, Yusenko M, Kovacs G
… +1 more, Banyai D
J Clin Pathol
· 2025 May · PMID 39433307
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AIMS: During detailed analysis of H&E-stained histological slides of 710 unbiased conventional renal cell carcinomas (cRCCs), 141 tumours displayed partial regressive changes showing strong similarity to that of wound he...AIMS: During detailed analysis of H&E-stained histological slides of 710 unbiased conventional renal cell carcinomas (cRCCs), 141 tumours displayed partial regressive changes showing strong similarity to that of wound healing. We aimed to analyse the molecular processes occurring in regressive tumours. METHODS: Immunohistochemistry was applied to analyse the signalling molecules in 12 selected tumours, and statistical analysis was used to estimate the correlation between regression and the outcome of the disease. RESULTS: The regressive areas displayed inflammatory granulation tissue expressing transforming growth factor beta-1 (TGFB1), interleukin-1 beta and interleukin-6 (IL1B and IL6), proliferation of alpha smooth muscle actin (αSMA) positive naïve activated fibroblasts and a diffuse fibronectin 1 (FN1) network. In the central areas of regressive tissues, parallel-running myofibroblasts showed FN1, collagen type I alpha 1 (COL1A1) and collagen type III alpha 1 (COL3A1) positive immunoreaction. Partial tumour regression is associated with a better postoperative course of the disease. CONCLUSIONS: Partial regression is a frequent event in cRCCs. Recognising complex molecular processes involved in tumour regression might help to find a way towards 'healing' cRCC.
Molero A, Hernandez S, Alonso M
… +4 more, Peressini M, Curto D, Lopez-Rios F, Conde E
J Clin Pathol
· 2025 Jun · PMID 39419594
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AIMS: To study programmed death ligand 1 (PD-L1) expression and tumour infiltrating lymphocytes (TILs) in patients with early-stage non-small cell lung carcinoma (NSCLC) with artificial intelligence (AI) algorithms. METH...AIMS: To study programmed death ligand 1 (PD-L1) expression and tumour infiltrating lymphocytes (TILs) in patients with early-stage non-small cell lung carcinoma (NSCLC) with artificial intelligence (AI) algorithms. METHODS: The study included samples from 50 early-stage NSCLCs. PD-L1 immunohistochemistry (IHC) stained slides (clone SP263) were scored manually and with two different AI tools (PathAI and Navify Digital Pathology) by three pathologists. TILs were digitally assessed on H&E and CD8 IHC stained sections with two different algorithms (PathAI and Navify Digital Pathology, respectively). The agreement between observers and methods for each biomarker was analysed. For PD-L1, the turn-around time (TAT) for manual versus AI-assisted scoring was recorded. RESULTS: Agreement was higher in tumours with low PD-L1 expression regardless of the approach. Both AI-powered tools identified a significantly higher number of cases equal or above 1% PD-L1 tumour proportion score as compared with manual scoring (p=0.00015), a finding with potential therapeutic implications. Regarding TAT, there were significant differences between manual scoring and AI use (p value <0.0001 for all comparisons). The total TILs density with the PathAI algorithm and the total density of CD8+ cells with the Navify Digital Pathology software were significantly correlated (τ=0.49 (95% CI 0.37, 0.61), p value<0.0001). CONCLUSIONS: This preliminary study supports the use of AI algorithms for the scoring of PD-L1 and TILs in patients with NSCLC.
AIMS: This study aims to summarise published cases of reactive plasmacytosis to provide a resource to aid haematopathologists and clinicians in the diagnostic workup of reactive plasmacytosis. METHODS: We searched publis...AIMS: This study aims to summarise published cases of reactive plasmacytosis to provide a resource to aid haematopathologists and clinicians in the diagnostic workup of reactive plasmacytosis. METHODS: We searched published articles on reactive plasmacytosis on PubMed, Scopus and Google Scholar. Data were screened following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Cases were classified into six categories, namely: (1) infection, (2) angioimmunoblastic T-cell lymphoma (AITL), (3) other malignancies, (4) drug associated, (5) autoimmune diseases and (6) others. Plasma cell percentage in peripheral blood and/or bone marrow was tabulated. Descriptive statistics were reported as median with IQR, using JASP Team. RESULTS: 87 articles which reported on 146 patients were included. Infectious diseases represented most cases associated with reactive plasmacytosis (n=46, 31% of all cases), with viral infections being the most frequent (n=31, 21% of all cases). AITL was the second most frequent aetiology (n=34, 23% of all cases), followed by medications (n=28, 19% of all cases), other malignancies (n=18, 12% of all cases), miscellaneous aetiologies (n=11, 7% of all cases) and autoimmune diseases (n=9, 6% of all cases). The absolute and relative levels of plasma cells in each diagnostic category showed marked variation and ranges largely overlapped between categories. CONCLUSIONS: In patients with an increase in the number and/or proportion of plasma cells in peripheral blood and/or bone marrow, clinical context and a broad differential diagnosis are necessary to direct further evaluation and arrive at a correct diagnosis. Our literature review suggests that evaluation for infectious causes and AITL may be of the greatest yield in many cases.
AIMS: Structured reporting in pathology is not universally adopted and extracting elements essential to research often requires expensive and time-intensive manual curation. The accuracy and feasibility of using large la...AIMS: Structured reporting in pathology is not universally adopted and extracting elements essential to research often requires expensive and time-intensive manual curation. The accuracy and feasibility of using large language models (LLMs) to extract essential pathology elements, for cancer research is examined here. METHODS: Retrospective study of patients who underwent pathology sampling for suspected hepatocellular carcinoma and underwent Ytrrium-90 embolisation. Five pathology report elements of interest were included for evaluation. LLMs (Generative Pre-trained Transformer (GPT) 3.5 turbo and GPT-4) were used to extract elements of interest. For comparison, a rules-based, regular expressions (REGEX) approach was devised for extraction. Accuracy for each approach was calculated. RESULTS: 88 pathology reports were identified. LLMs and REGEX were both able to extract research elements with high accuracy (average 84.1%-94.8%). CONCLUSIONS: LLMs have significant potential to simplify the extraction of research elements from pathology reporting, and therefore, accelerate the pace of cancer research.
Microscopic review of tissue sections is of foundational importance in pathology, yet the traditional chemistry-based histology laboratory methods are labour intensive, tissue destructive, poorly scalable to the evolving...Microscopic review of tissue sections is of foundational importance in pathology, yet the traditional chemistry-based histology laboratory methods are labour intensive, tissue destructive, poorly scalable to the evolving needs of precision medicine and cause delays in patient diagnosis and treatment. Recent AI-based techniques offer promise in upending histology workflow; one such method developed by PictorLabs can generate near-instantaneous diagnostic images via a machine learning algorithm. Here, we demonstrate the utility of virtual staining in a blinded, wash-out controlled study of 16 cases of lymph node excisional biopsies, including a spectrum of diagnoses from reactive to lymphoma and compare the diagnostic performance of virtual and chemical H&Es across a range of stain quality, image quality, morphometric assessment and diagnostic interpretation parameters as well as proposed follow-up immunostains. Our results show non-inferior performance of virtual H&E stains across all parameters, including an improved stain quality pass rate (92% vs 79% for virtual vs chemical stains, respectively) and an equivalent rate of binary diagnostic concordance (90% vs 92%). More detailed adjudicated reviews of differential diagnoses and proposed IHC panels showed no major discordances. Virtual H&Es appear fit for purpose and non-inferior to chemical H&Es in diagnostic assessment of clinical lymph node samples, in a limited pilot study.
AIMS: The field of molecular pathology has undergone significant advancements in the clinical impact of sarcoma diagnosis, resulting in challenges to nosology of bone and soft tissue tumours. The surge in molecular data...AIMS: The field of molecular pathology has undergone significant advancements in the clinical impact of sarcoma diagnosis, resulting in challenges to nosology of bone and soft tissue tumours. The surge in molecular data has led to the identification of novel fusions and description of new 'entities'. To illustrate this, we have selected five emerging entities with novel fusions: clear cell stromal tumour of the lung with fusion, fusion spindle cell neoplasm, -rearranged sarcomas, -rearranged sarcomas and calcified chondroid mesenchymal neoplasms. METHODS: Literature for the relevant case reports and case series of these five entities were reviewed and clinicopathological data was collected. Additionally, this review includes a table format of recently described fusion-associated mesenchymal neoplasms. RESULTS: The morphological and immunohistochemical features, along with diagnostic challenges, are discussed for each entity. CONCLUSIONS: Here, we have provided a review of selected emerging mesenchymal neoplasms, which of these neoplasms will meet the threshold to be 'new entities' remains to be determined.
Falleni M, Dal Lago M, Tosi D
… +6 more, Ghilardi G, De Pasquale L, Saibene AM, Felisati G, Cozzolino M, Gianelli U
J Clin Pathol
· 2025 Nov · PMID 39288990
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AIMS: Evaluation of 'alternative' vascularisation in human cancer is considered an important prognostic parameter; the 2022 WHO classification of parathyroid tumours despite progresses in clinical triaging of patients st...AIMS: Evaluation of 'alternative' vascularisation in human cancer is considered an important prognostic parameter; the 2022 WHO classification of parathyroid tumours despite progresses in clinical triaging of patients strongly emphasises new histopathological parameters to properly stratify these lesions. 'Alternative' and 'classic' vessels were here investigated for the first time in parathyroid tumours for their possible histopathological and clinical relevance during progression. METHODS: Using a double CD31/PAS staining, microvessel density (MVD, 'classic' CD31+ vessels), mosaic vessel density (MoVD, 'alternative' CD31+/-vessels) and vessel mimicry density (VMD, 'alternative' CD31-/PAS+ vessels) were evaluated in 4 normal parathyroid glands (N), 50 Adenomas (A), 35 Atypical Tumours (AT) and 10 Carcinomas (K). RESULTS: Compared with N, MVD significantly increased in A (p=0.012) and decreased in K (p=0.013) with vessel counts lower than in AT and A (p<0.001). MoVs and VMs, absent in normal tissue, were documented in non-benign parathyroid lesions (AT, K) (p<0.001), with MoVs and VMs most represented in AT and K, respectively (p<0.001), in peripheral growing areas. Vessel distribution was correlated to neoplastic progression (r=-0.541 MVD; r=+0.760 MoVD, r=+0.733 VMD), with MVD decrease in AT and K inversely related to MoVD and VMD increase (r=-0.503 and r=-0.456). CONCLUSIONS: 'Alternative' vessel identification in parathyroid tumours is crucial because it: (1) explains the paradox of non-angiogenic tumours, consisting in a new bloody non-endothelial vessel network and (2) helps pathologists to unmask worrisome lesions. Furthermore, detection of alternative vascular systems in human tumours might explain the limited success of antiangiogenic therapies and encourage new oncological studies.
AIMS: Widespread use of immune checkpoint inhibitors (ICIs) for treatment of advanced malignancies led to an increase in number of immune-related adverse events such as ICI gastrointestinal (GI) injury (ICIGI). The resul...AIMS: Widespread use of immune checkpoint inhibitors (ICIs) for treatment of advanced malignancies led to an increase in number of immune-related adverse events such as ICI gastrointestinal (GI) injury (ICIGI). The resulting immune dysregulation of the GI mucosa is believed to predispose patients to viral infections. We characterised the histopathological features of ICIGI and the frequency of viral infections such as cytomegalovirus (CMV), adenovirus, and Epstein-Barr virus (EBV). METHODS: Single-centre retrospective study (2011-2020). RESULTS: 81 GI biopsies from 31 patients with ICIGI (65% male (20/31), 35% female (11/31)) with advanced malignancies were reviewed. Most patients received ipilimumab and nivolumab (14/31, 45%), followed by pembrolizumab (9/31, 29%), ipilimumab (4/31, 13%), nivolumab (2/31, 6%) and combination of all three medications (2/31, 6%). Average regimen prior to incidence of diarrhea was three cycles. Evidence of colitis or erythema by endoscopy was present in 77% of cases, while 23% showed normal endoscopy. Histologically, the predominant ICIGI findings were active inflammation (84%), including cryptitis (77%), crypt abscesses (65%), lymphocytic colitis-like (LCL) pattern (61%), increase in epithelial apoptosis (74%) and/or surface injury (81%). Only one case showed diffuse CMV positivity (3%) with characteristic CMV viral cytopathic effects present on H&E stain and four cases were positive for rare EBV (13%). Adenovirus infection was not identified. CONCLUSION: While our cohort is small, ICIGI generally demonstrates active inflammation including cryptitis and crypt abscesses in the colon, LCL pattern, and an increase in epithelial apoptosis. Upfront immunohistochemistry for viral infection without high-degree of clinical and histologic suspicion is not recommended.
Even though the average surgical pathologist reviews far more non-neoplastic orthopaedic pathology on a daily basis, most current research focuses on rare tumours and their even less frequent molecular events. Our experi...Even though the average surgical pathologist reviews far more non-neoplastic orthopaedic pathology on a daily basis, most current research focuses on rare tumours and their even less frequent molecular events. Our experiences among consults and focused conferences strongly suggest that there remains a practice gap regarding knowledge and diagnosing specific non-neoplastic orthopaedic conditions. One of the most frequent intraoperative consultations performed in the USA, among both academic and private institutions, relates to revision arthroplasty and the determination of infection in periprosthetic joints. Pathologists play a critical role in this algorithm, helping determine intraoperatively whether patients require antibiotic spacers prior to reimplantation. Many pathology departments have abandoned the examination of arthroplasty specimens because they (and their surgeons) mistakenly believe there is little clinically relevant information to be gained by thorough pathological examination. However, recent literature has challenged this concept, emphasising the importance of distinguishing avascular necrosis (from osteoarthritis/degenerative joint disease with secondary osteonecrosis), subchondral insufficiency fracture, septic arthritis (from so-called 'sterile' osteomyelitis/pseudoabscesses), underlying crystalline diseases and incidental/occult neoplasia. Histological evaluation of historically insignificant orthopaedic specimens, such as tenosynovium from carpal tunnel syndrome/trigger finger, is now seen as valuable in early diagnosis of cardiac amyloidosis. Not infrequently, orthopaedic conditions like haemosiderotic synovitis, osteocartilaginous loose bodies or rheumatoid nodules, may histologically mimic bona fide neoplasms, notably diffuse tenosynovial giant cell tumour, synovial chondromatosis and epithelioid sarcoma, respectively. Here is a review of the more common non-neoplastic orthopaedic conditions, those likely to be examined by the practising surgical pathologist, with updates and guidelines for establishing clinically relevant diagnoses.
is the most commonly rearranged gene in mesenchymal neoplasia, and its myriad chimeric oncoproteins drive widely disparate neoplasms. Here, we survey selected rearrangements, including well-described fusions with CREB...is the most commonly rearranged gene in mesenchymal neoplasia, and its myriad chimeric oncoproteins drive widely disparate neoplasms. Here, we survey selected rearrangements, including well-described fusions with CREB family members, and , as well as fusions in emerging entities such as mesenchymal neoplasms with and fusions. We also discuss recent data demonstrating the imperfect specificity of and, possibly, fusions.