RESUMEN
BACKGROUND: Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress. METHODS: The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake. RESULTS: Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations. CONCLUSIONS: We observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.
Asunto(s)
Adiposidad , Biomarcadores , Frutas , Humanos , Masculino , Reino Unido/epidemiología , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Estudios Transversales , Estudios Prospectivos , Bancos de Muestras Biológicas , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo Cardiometabólico , Dieta/estadística & datos numéricos , Adulto , Estrés Oxidativo/fisiología , Lípidos/sangre , Biobanco del Reino UnidoRESUMEN
AIMS: Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe. METHODS AND RESULTS: A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy. CONCLUSION: In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility.
RESUMEN
OBJECTIVES: In the face of unprecedented demand, the Welsh Ambulance Services University NHS Trust developed 'Blue Light Hub': a new app to educate primary school-aged children about emergency services. Our overarching aim was to examine the effectiveness of the app. DESIGN: Primary school-aged children from three schools in South Wales, UK, played with the app for 2 hours over 2 weeks in class time. Children completed quizzes to assess their knowledge and awareness of, and confidence in engaging with, emergency services before and after using the app. PARTICIPANTS: Our evaluation focused on N=393 children who completed both the pre-test and post-test quizzes. On average, children were 8-9 years old (median school year, Year 4); 47.8% were male and 50.9% were female. RESULTS: After using the app, there was a significant increase in the proportion of children who knew of appropriate actions to take in non-emergency scenarios, χ2(1) = 26.01, and could provide a question a call handler would ask them if they called 999, χ2(1) = 13.79. There was also an increase in the proportion of children who could identify an National Health Service (NHS) service that could help them if they were unwell, χ2(1) = 33.31, name different roles in the NHS, χ2(1) = 12.80 and knew how dialling 111 could help them χ2(1) = 90.05 (all p values<0.001). CONCLUSION: To our knowledge, Blue Light Hub is the first app of its kind designed to educate primary school-aged children about emergency services. Our findings provide preliminary evidence that the app supports children's knowledge and awareness of emergency services.
Asunto(s)
Servicios Médicos de Urgencia , Aplicaciones Móviles , Humanos , Niño , Femenino , Masculino , Gales , Conocimientos, Actitudes y Práctica en Salud , Educación en Salud/métodos , Ambulancias , Luz AzulRESUMEN
Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2â mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.
RESUMEN
Preoperative biopsy for retroperitoneal sarcoma (RPS) enables appropriate multidisciplinary treatment planning. A systematic review of literature from 1990 to June 2022 was conducted using the population, intervention, comparison and outcome model to evaluate the local recurrence and overall survival of preoperative biopsy compared to those that had not. Of 3192 studies screened, five retrospective cohort studies were identified. Three reported on biopsy needle tract seeding, with only one study reporting biopsy site recurrence of 2â¯%. Two found no significant difference in local recurrence and one found higher 5-year local recurrence rates in those who had not been biopsied. Three studies reported overall survival, including one with propensity matching, did not show a difference in overall survival. In conclusion, preoperative core needle biopsy of RPS is not associated with increased local recurrence or adverse survival outcomes.
Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias Retroperitoneales , Sarcoma , Humanos , Australia/epidemiología , Biopsia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/epidemiología , Nueva Zelanda/epidemiología , Guías de Práctica Clínica como Asunto , Cuidados Preoperatorios/normas , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/mortalidad , Neoplasias Retroperitoneales/cirugía , Neoplasias Retroperitoneales/diagnóstico , Sarcoma/mortalidad , Sarcoma/patología , Sarcoma/diagnóstico , Sarcoma/terapiaRESUMEN
A small subset of testicular sex cord-stromal tumors, designated as Sertoli-stromal cell tumors (SSCTs), comprises a mixture of Sertoli, spindle, and/or Leydig cells. The clinicopathologic features of these tumors have not been studied in any detail, and their molecular features are unknown. We, therefore, assessed the morphologic and genomic features of 14 SSCTs, including 1 tumor with features similar to the ovarian Sertoli-Leydig cell tumor (SLCT) with retiform tubules. The median age of the patients was 24 years (range, 10-55 years), and the median tumor size was 2.3 cm (range, 0.7-4.7 cm). All tumors showed Sertoli-like sex cord cells arranged in variably developed tubular structures, typically also forming nests and cords. These imperceptibly blended with a neoplastic spindle cell stroma or, in the SLCT, vacuolated to eosinophilic Leydig cells. Genomic analysis demonstrated the presence of a hotspot loss-of-function DICER1 mutation in the SLCT (patient 1) and hotspot gain-of-function CTNNB1 mutations in the tumors of patients 2 and 3, with both CTNNB1 variants being interpreted as possible subclonal events. The mutations were the only relevant findings in the tumors of patients 1 and 2, whereas the tumor of patient 3 harbored concurrent chromosomal arm-level and chromosome-level copy number gains. Among the remaining 11 tumors, all of those that had interpretable copy number data (9 tumors) harbored multiple recurrent chromosomal arm-level and chromosome-level copy number gains suggestive of a shift in ploidy without concurrent pathogenic mutations. The results of the present study suggest that CTNNB1 mutations (likely subclonal) are only rarely present in SSCTs; instead, most of them harbor genomic alterations similar to those seen in testicular sex cord-stromal tumors with pure or predominant spindle cell components. A notable exception was a testicular SLCT with morphologic features identical to the ovarian counterpart, which harbored a DICER1 mutation.
Asunto(s)
Neoplasias Ováricas , Tumor de Células de Sertoli-Leydig , Tumores de los Cordones Sexuales y Estroma de las Gónadas , Neoplasias Testiculares , Masculino , Femenino , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Tumor de Células de Sertoli-Leydig/genética , Tumor de Células de Sertoli-Leydig/patología , Neoplasias Testiculares/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/genética , Tumores de los Cordones Sexuales y Estroma de las Gónadas/química , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Aberraciones Cromosómicas , Ribonucleasa III/genética , ARN Helicasas DEAD-box/genéticaRESUMEN
Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumour of intermediate (rarely metastasising) malignant potential, which harbours EWSR1/FUS gene fusions. These tumours can express anaplastic lymphoma kinase (ALK) in the absence of gene rearrangement or copy number alteration and can also coexpresses Pan-TRK immunohistochemistry (IHC). All EWSR1/FUS-rearranged AFH were retrieved from the files of three institutions and Pan-TRK (EPR17341), ALK and BRAF V600E IHC were performed. Fourteen AFH cases were identified, which included three cases of intracranial mesenchymal tumours with FET-CREB fusions. PanTRK and ALK positive immunostaining was identified in 9 (64.2%) and 12 (85.7%) cases, respectively. No NTRK or ALK translocations or increased copy number/amplification were identified in all eight cases which had fluorescence in situ hybridisation and/or next generation sequencing for NTRK1-3 and ALK available for assessment. None of the cases expressed BRAF-V600E.Although our study is limited, our report is the first to document PanTRK expression in AFH in the absence of identifiable NTRK1-3 gene alterations.
Asunto(s)
Neoplasias Encefálicas , Histiocitoma Fibroso Benigno , Histiocitoma Fibroso Maligno , Humanos , Histiocitoma Fibroso Benigno/genética , Proteínas Proto-Oncogénicas B-raf/genética , Histiocitoma Fibroso Maligno/genética , Histiocitoma Fibroso Maligno/patología , Neoplasias Encefálicas/patología , Reordenamiento Génico , Proteínas Tirosina Quinasas Receptoras/genéticaAsunto(s)
Enfermedades Autoinmunes , Prostatitis , Masculino , Humanos , Prostatitis/diagnóstico , Inmunoglobulina G , PatólogosRESUMEN
Spermatocytic tumor (ST) is a rare type of germ cell tumor that occurs exclusively in the postpubertal testis and typically affects elderly men. Most STs are benign, but rare cases exhibit aggressive clinical behavior, often in association with transition to sarcomatoid histology. Limited molecular analyses have been performed on STs; therefore, their genomic and epigenomic features remain incompletely described. Twenty-seven samples from 25 individual patients were analyzed with a combination of DNA sequencing panels, genomic methylation profiling, SNP array, isochromosome (12p) [i(12p)] FISH, and immunohistochemistry. The series included five metastasizing tumors (three with sarcomatoid transformation, one anaplastic, and one conventional) and 20 non-metastasizing tumors (14 anaplastic and six conventional). Anaplastic tumors comprised a monomorphic population of intermediate-sized neoplastic cells, as previously described. Multiomic analyses demonstrated that there were two genomic subgroups of STs: one with diploid genomes and hotspot RAS/RAF variants and the other with global ploidy shift and absence of recurrent mutations. Relative gain of chromosome 9 was a consistent finding in both subgroups. A comparison of metastasizing and non-metastasizing cases demonstrated that aggressive behavior was associated with the acquisition of pathogenic TP53 mutations and/or relative gains of 12p/i(12p). In cases with sarcomatoid transformation, TP53 mutations seem to underlie the transition to sarcomatoid histology. Genomic methylation analysis demonstrated that aggressive cases with gains of 12p cluster closer to pure seminomas than to STs without gains of 12p. In conclusion, STs include two genomic subgroups, characterized by global ploidy shifts without recurrent mutations and diploid genomes with RAS/RAF hotspot mutations, respectively. Biologic progression was associated with relative gains of 12p and TP53 mutations. The findings in STs with relative gains of 12p suggest that they may exhibit biologic characteristics akin to those seen in germ cell neoplasia in situ-related germ cell tumors rather than non-germ cell neoplasia in situ-derived STs. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Asunto(s)
Productos Biológicos , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Anciano , Seminoma/genética , Neoplasias Testiculares/metabolismo , Neoplasias de Células Germinales y Embrionarias/genética , Genómica , Cromosomas Humanos Par 12/metabolismoRESUMEN
While women pathologists have made up over one-third of pathologists in the Australian workforce for over 15 years and at least 50% since 2019, they are under-represented in senior leadership roles, scientific publications, grant recipients, editorial boards, key presentations, and professional awards. This is not unique to pathology and is seen in the broader medical and academic community. Barriers to gender equity and equality in pathology, medicine and academia include gender stereotypes, gender-based discrimination, structural and organisational barriers as well as broader social and cultural barriers. A diverse leadership reflective of the whole professional body and the broader community is important for optimal health outcomes. It is the responsibility and moral duty of individuals and organisations to address any gender disparities, inequities, and inequalities by monitoring, identifying, and acting on gender biases and systemic barriers that hinder appropriate levels of representation by women.
Asunto(s)
Equidad de Género , Sexismo , Femenino , Humanos , Australia , Recursos HumanosRESUMEN
To elucidate the spectrum of metastatic solid tumors to the testis and their clinicopathologic features. The databases and files of 26 pathology departments from 9 countries on 3 continents were surveyed to identify metastatic solid tumors to the testis and to characterize their clinicopathologic features in detail. We compiled a series of 157 cases of metastatic solid tumors that secondarily involved the testis. The mean patient age at diagnosis was 64 years (range, 12-93 years). Most patients (127/144; 88%) had clinical manifestation of the disease, with testicular mass/nodule (89/127; 70%) being the most common finding. The main mechanism of testicular involvement was metastasis in 154/157 (98%) cases. Bilateral testicular involvement was present in 12/157 (8%) patients. Concurrent or prior extratesticular metastases were present in 78/101 (77%) patients. The diagnosis was made mainly in orchiectomy specimens (150/157; 95%). Different types of carcinomas (138/157; 87%), most commonly adenocarcinoma (72/157; 46%), were the most common malignancies. The most common primary carcinomas included prostatic (51/149; 34%), renal (29/149; 20%), and colorectal (13/149; 9%). Intratubular growth was identified in 13/124 (11%) cases and paratesticular involvement was found in 73/152 (48%) cases. In patients with available follow-up (110/157; 70%), more than half (58/110; 53%) died of disease. In this largest series compiled to date, we found that most secondary tumors of the testis represent metastases from the genitourinary and gastrointestinal tract carcinomas and typically occur in the setting of disseminated disease.
Asunto(s)
Adenocarcinoma , Carcinoma , Neoplasias Primarias Secundarias , Neoplasias Testiculares , Masculino , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Neoplasias Testiculares/patología , Adenocarcinoma/secundarioRESUMEN
BACKGROUND: Optimal management of sarcoma requires multidisciplinary team input throughout the process of diagnosis, treatment and follow up. This systematic review aimed to evaluate the impact of surgery performed at specialised sarcoma centres on outcomes. METHODS: A systematic review was conducted using the population, intervention, comparison and outcome (PICO) model. Medline, Embase, Cochrane Central databases were queried for publications that evaluated the local control, limb salvage rate, 30-day and 90-day surgical mortality, and overall survival in patients undergoing surgery in a specialist sarcoma centre compared with non-specialist centre. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed. RESULTS: Sixty-six studies were identified. The majority of studies were Level III-3 as assessed by the NHMRC Evidence Hierarchy, whilst just over half of the studies were of good quality. Definitive surgery performed at specialised sarcoma centres was associated with improved local control as defined by lower rate of local relapse, higher rate of negative surgical margins, improved local recurrence free survival and higher limb conservation rate. Available evidences show a favourable pattern of lower 30-day and 90-day mortality rates, and greater overall survival when surgery was performed in specialist sarcoma centres compared with non-specialised centres. CONCLUSIONS: Evidences support better oncological outcomes when surgery is performed at specialised sarcoma centre. Patients with suspected sarcoma should be referred early to a specialised sarcoma centre for multidisciplinary management, which includes planned biopsy and definitive surgery.
Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Nueva Zelanda , Estudios Retrospectivos , Recurrencia Local de Neoplasia/epidemiología , Sarcoma/cirugía , Sarcoma/diagnóstico , Neoplasias de los Tejidos Blandos/cirugía , AustraliaRESUMEN
AIMS: To elucidate the spectrum of metastatic tumours to the penis and their clinicopathologic features. METHODS: The databases and files of 22 pathology departments from eight countries on three continents were queried to identify metastatic solid tumours of the penis and to characterize their clinical and pathologic features. RESULTS: We compiled a series of 109 cases of metastatic solid tumours that secondarily involved the penis. The mean patient age at diagnosis was 71 years (range, 7-94 years). Clinical presentation commonly included a penile nodule/mass (48/95; 51%) and localised pain (14/95; 15%). A prior history of malignancy was known in 92/104 (89%) patients. Diagnosis was made mainly on biopsy (82/109; 75%), or penectomy (21/109; 19%) specimens. The most common penile locations were the glans (45/98; 46%) and corpus cavernosum (39/98; 39%). The most frequent histologic type was adenocarcinoma (56%). Most primary carcinomas originated in the genitourinary (76/108; 70%) and gastrointestinal (20/108; 18%) tracts, including prostate (38/108; 35%), urinary bladder (27/108; 25%), and colon/rectum (18/108; 17%). Concurrent or prior extrapenile metastases were identified in 50/78 (64%) patients. Clinical follow-up (mean 22 months, range 0-171 months) was available for 87/109 (80%) patients, of whom 46 (53%) died of disease. CONCLUSION: This is the largest study to date of metastatic solid tumours secondarily involving the penis. The most frequent primaries originated from the genitourinary and gastrointestinal tracts. Metastatic penile tumours usually presented with penile nodules/masses and pain, and they often occurred in the setting of advanced metastatic disease, portending poor clinical outcomes.
Asunto(s)
Adenocarcinoma , Neoplasias del Pene , Masculino , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Pene/patología , Neoplasias del Pene/patología , Adenocarcinoma/patología , BiopsiaRESUMEN
Our aim was to utilise a 241-gene RNA hybridisation capture sequencing (CaptureSeq) gene panel to identify unexpected fusions in undifferentiated, unclassified or partly classified sarcomas of young individuals (<40 years). The purpose was to determine the utility and yield of a large, targeted fusion panel as a tool for classifying tumours that do not fit typical diagnostic entities at the time of the original diagnosis. RNA hybridisation capture sequencing was performed on 21 archival resection specimens. Successful sequencing was obtained in 12 of 21 samples (57%), two of which (16.6%) harboured translocations. A novel NEAT1::GLI1 fusion, not previously reported in the literature, presented in a young patient with a tumour in the retroperitoneum, which displayed low grade epithelioid cells. The second case, a localised lung metastasis in a young male, demonstrated a EWSR1::NFATC2 translocation. No targeted fusions were identified in the remaining 83.4% (n=10) of cases. Forty-three per cent of the samples failed sequencing as a result of RNA degradation. RNA-based sequencing is an important tool, which helps to redefine the classification of unclassified or partly classified sarcomas of young adults by identifying pathogenic gene fusions in up to 16.6% of the cases. Unfortunately, 43% of the samples underwent significant RNA degradation, falling below the sequencing threshold. As CaptureSeq is not yet available in routine pathology practice, increasing awareness of the yield, failure rate and possible aetiological factors for RNA degradation is fundamental to maximise laboratory procedures to improve RNA integrity, allowing the potential identification of significant gene alterations in solid tumours.
Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Adulto Joven , Humanos , Masculino , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patología , Fusión Génica , Factores de Transcripción/genética , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Reordenamiento Génico , Proteínas de Fusión Oncogénica/genéticaRESUMEN
Large cell calcifying Sertoli cell tumour (LCCSCT) is a type of testicular sex cord-stromal tumour that may occur sporadically or in the context of Carney complex and other genetic syndromes. A subset is clinically malignant, and the molecular mechanisms that drive such aggressive behaviour remain unknown. METHODS AND RESULTS: We analysed 21 samples from 20 patients with LCCSCT (12 non-metastasising and eight metastasising) using PRKAR1A immunohistochemistry (IHC) and next-generation sequencing. All tumours except two (cases 17 and 20, both metastasising) demonstrated loss of PRKAR1A expression. Among 11 cases with interpretable sequencing results, all harboured pathogenic single nucleotide variants of PRKAR1A. Evidence of loss of heterozygosity (LOH) of PRKAR1A was present in all tumours with interpretable zygosity data, but the mechanisms of LOH were different for non-metastasising and metastasising tumours. Non-metastasising tumours demonstrated only copy-neutral LOH, while metastasising tumours demonstrated a spectrum of mechanisms of LOH, including copy-loss LOH, two concurrent mutations or copy-neutral LOH. Relevant molecular findings in non-metastasising LCCSCT were limited to PRKAR1A variants. In contrast, all metastasising LCCSCTs with interpretable data harboured additional pathogenic variants, including (but not restricted to) BRCA2 mutations with evidence of LOH and bi-allelic CDKN2A/B deletions. Three patients harboured PRKAR1A variants of inferred germline origin, including one with Carney complex and two without known syndromic features. CONCLUSIONS: This study further confirms that PRKAR1A IHC is a useful diagnostic tool for both non-metastasising and metastasising tumours and suggests that molecular analyses can be helpful to identify non-metastasising tumours with malignant potential in selected patients. Importantly, these results highlight that germline assessment could be beneficial for all patients presenting with LCCSCT.
Asunto(s)
Complejo de Carney , Tumor de Células de Sertoli , Tumores de los Cordones Sexuales y Estroma de las Gónadas , Neoplasias Testiculares , Masculino , Humanos , Tumor de Células de Sertoli/genética , Tumor de Células de Sertoli/química , Neoplasias Testiculares/metabolismo , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , MutaciónRESUMEN
The pathological grade of prostate cancer is the strongest predictor of recurrence. It is unclear whether the better predictor is the composite of all carcinomas within the prostate, or the highest grade lesion (index). The purpose of this study was to determine whether composite or index grade group better predicts biochemical recurrence (BCR). We undertook a retrospective analysis from a prospective institutional cohort study of men who underwent radical prostatectomy for localised prostate cancer between 2009 and 2020, in which an index and composite grade group was reported. The index grade in this study was defined as the highest grade of any tumour, usually with the highest stage, regardless of volume. Multivariate analysis and Kaplan-Meier plots were utilised. A total of 2024 men underwent radical prostatectomy during the study period; we analysed 1605 with composite grade group 2 or 3 prostate cancer. Median preoperative prostate specific antigen (PSA) was 5.9 ng/L, mean follow up was 56.8 months, 54% were pT2, 76% had multifocal disease and 16% had discordant index and composite grades. Patients with discordant index grade group had a higher risk of BCR [hazard ratio (HR) 2.22, p<0.0001]. The prevalence of BCR in the discordant group was higher at 1, 3, 5 and 7 years (4.7% vs 8.9%, 8.3% vs 18.1%, 14.5% vs 28.8% and 22.5% vs 49.5%, respectively). In cases of discordance, a higher index grade group is associated with increased rates of BCR after radical prostatectomy. Index rather than composite grade group should be used to counsel men post-operatively regarding prognosis and follow-up.
Asunto(s)
Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/patología , Estudios Retrospectivos , Estudios de Cohortes , Estudios Prospectivos , Prostatectomía , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patologíaAsunto(s)
Melanoma , Neoplasias Primarias Secundarias , Tumores Neuroendocrinos , Neoplasias de Células Epitelioides Perivasculares , Sarcoma , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patologíaRESUMEN
Introduction. Epithelioid hemangioma is a benign vascular neoplasm associated with FOS and/or FOSB protein overexpression detected by immunohistochemistry (IHC). Methods. The aim of our study was to determine the co-expression or independent IHC expression of FOS and FOSB in a cohort of epithelioid hemangiomas. We also included two cohorts of other vascular lesions: papillary endothelial hyperplasia and lobular capillary hemangioma / pyogenic granuloma. Results. We identified 50 cases of epithelioid hemangioma, 84% of which were cutaneous and the remaining involved other anatomic locations. Over two thirds of all cases expressed FOSB (68%; 34/50) while FOS immunoreactivity was identified in 46% of all cases. Co-expression of FOSB and FOS occurred in 37% of cases while 76% of all cases stained for at least one of the antibodies. Fifty-eight percent (n = 14/24) and 33% (8/24) of all cases of papillary endothelial hyperplasia expressed FOS and FOSB, respectively. Thirty-two per cent of lobular capillary hemangiomas (n = 8/25) were positive for either FOS or FOSB. Conclusion. In summary, we present the largest cohort of epithelioid hemangiomas assessed with both FOS and FOSB and demonstrated that the use of both antibodies increases the detection rate of these proliferations by 10%. Nonetheless, the use of thresholds may not be appropriate, as only a subset of lesional endothelial cells label with FOS/FOSB. Over half of all cases of papillary endothelial hyperplasia and a third of lobular capillary hemangiomas also displayed immunoreactivity with FOS and/or FOSB.
Asunto(s)
Granuloma Piogénico , Hemangioma Capilar , Hemangioma , Neoplasias Vasculares , Humanos , Inmunohistoquímica , Hiperplasia/patología , Células Endoteliales/patología , Hemangioma/diagnóstico , Granuloma Piogénico/patología , Neoplasias Vasculares/patología , Hemangioma Capilar/patología , Proteínas Proto-Oncogénicas c-fosRESUMEN
Myoid gonadal stromal tumours (MGST) represent a rare type of testicular sex cord-stromal tumour that has recently been recognised as a distinct entity by the World Health Organization (WHO) classification of genitourinary tumours. MGSTs affect adult men and have been reported to behave in an indolent fashion. Histologically, MGSTs are pure spindle cell neoplasms that coexpress SMA and S100 protein. Given that the molecular features of these neoplasms remain largely undescribed, we evaluated a multi-institutional series of MGSTs using DNA and RNA sequencing. This study included 12 tumours from 12 patients aged 28 to 57 years. Tumour sizes ranged from 0.6 to 4.3 cm. Aggressive histologic features, such as vascular invasion, necrosis, invasive growth, and atypical mitoses were invariably absent. Mitotic activity was low, with a median of less than 1 mitosis per 10 high power fields (HPF; maximum: 3 mitoses per 10 HPF). Molecular analyses did not identify recurrent mutations or gene fusions. All cases with interpretable copy number variant data (9/10 cases sequenced successfully) demonstrated a consistent pattern of chromosome arm-level and whole-chromosome-level copy number gains indicative of ploidy shifts, with recurrent gains involving chromosomes 3, 6, 7, 8, 9, 11, 12, 14q, 15q, 17, 18q, 20, and 21q. Similar findings have also been recognised in pure spindle cell and spindle-cell predominant sex cord-stromal tumours without S100 protein expression. MGSTs are characterised by ploidy shifts and may be part of a larger spectrum of spindle cell-predominant sex cord-stromal tumours, including cases without S100 protein expression.