Antonio Lopez-Beltran

• MD, PhD
• University of Córdoba

Aims A hybrid‐three tier system with low grade (LG), high grade‐ G2 (HG‐G2), high grade‐ G3 (HG‐G3) has been proposed in recognition of, and to help address, the clinical heterogeneity within high grade WHO 2004/2022. We assessed interobserver reproducibility amongst international uropathologists using this three‐tier approach. Methods and Results...

PURPOSE With the aid of ever-increasing computing resources, many deep learning algorithms have been proposed to aid in diagnostic workup for clinicians. However, existing studies usually selected informative patches from whole-slide images for the training of the deep learning model, requiring labor-intensive labeling efforts. This work aimed to i...

This study aimed to evaluate the prognostic significance of programmed cell death (PD)-1/PD-ligand 1 (PD-L1), PD-ligand 2 (PD-L2), and Fibroblast growth factor receptor 3 (FGFR3) expression in bladder cancer (BC). Material and Methods A retrospective study was conducted on BC patients who underwent transurethral resection (TUR) between 2005 and 201...

To the Editor In 2022, Dr. Suzanne Koven published a book entitled Letter to a Young Female Physician, Notes from a Medical Life. W.W. Norton & Company, Inc, New York. The book starts with a letter written by the author while participating in a 2017 orientation session...

Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonst...

A new era in cancer therapy emerged with the arrival of immune-checkpoint inhibitors (ICIs), followed by a new cadre of immune-related adverse events that affect up to 40% of patients. Literature on the pathological features associated with these events is still limited. Therefore, to expand our knowledge of the histopathologic spectrum of pulmonar...

According to the recently published paper by the Lancet Commission on prostate cancer (PCa) 1, the projections of new cases of PCa will rise from 1.4 million in 2020 to 2.9 million by 2040. Such a rise cannot be prevented by public health interventions and lifestyle changes. Late diagnosis of PCa is “widespread worldwide but especially in low-incom...

Pathologists have closely collaborated with clinicians, mainly urologists, to update the Gleason grading system to reflect the current practice and approach in prostate cancer diagnosis, prognosis, and treatment. This has led to the development of what is called patient advocacy and patient information. Ten common questions asked by patients to pat...

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 acceptabilit...

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor...

The influence of anatomical parameters on urinary continence (UC) after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) remains uncharted. Our objective was to evaluate their association with UC at 3, 6 and 12 months post-operatively. Data from patients who underwent RS-RARP were prospectively collected. Continence was defined as no...

Bladder cancer remains a leading cause of cancer death worldwide and is associated with substantial impacts on patient quality of life, morbidity, mortality, and cost to the healthcare system. Gross hematuria frequently precedes the diagnosis of bladder cancer. Non-muscle-invasive bladder cancer (NMIBC) is managed initially with transurethral resec...

Aim Primary mucinous adenocarcinoma of the urethra represents an extremely rare entity. We sought to characterise further these tumours’ clinicopathological, immunohistochemical and molecular features. Methods and results Thirty‐five cases were identified, occurring in 18 males and 17 females. The mean age at diagnosis was 65 years (28–89 years)....

Emerging data on T1 bladder cancer subcategorization (aka substaging) suggests a correlation with oncological outcomes. The International Society of Urological Pathology (ISUP) organized the 2022 consensus conference in Basel, Switzerland to focus on current issues in bladder cancer and tasked working group 3 to make recommendations for T1 subcateg...

Background: Grading of muscle-invasive bladder cancer (MIBC) according to the current World Health Organization (WHO) criteria is controversial due to its limited prognostic value. All MIBC cases except a tiny minority are of high grade. Objective: To develop a prognostic histological scoring system for MIBC integrating histomorphological phenot...

Background: Grade of non-muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1-3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinom...

The classification of the epithelial tumors of the male and female urethra includes benign and malignant neoplasms. Primary urethral carcinomas and adenocarcinomas of the accessory glands are the most relevant tumors, both from the morphologic and clinical point of view. An accurate diagnosis, grading and staging are essential for determining adequ...

Introduction: Cisplatin-based chemotherapy is currently considered the gold-standard treatment for metastatic urothelial carcinoma (mUC). Nevertheless, most mUC patients develop resistance to chemotherapy. Immune checkpoint inhibitors (ICI) have emerged as a therapeutic option for mUC. ICI are used as both first- and second-line therapy for patien...

Simple Summary Our study used NanoString technology, a high-throughput platform measuring gene expression at the mRNA level to identify a set of genes predictive of clinical outcomes in bladder cancer patients. Twenty-seven differentially expressed genes were correlated with clinicopathological variables including molecular subtypes (luminal, basal...

The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated TERT promoter and FGFR3 mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty eight patients presented with papillary urothelial hyperplasia and concurrent non-invasive papillary urothelial carcinoma...

Tumour grade used in conjunction with other prognostic parameters, such as tumour type, stage and biomarker status, is a critical determinant of patient management in several cancers, especially those that are organ-confined. Pathologists therefore strive for precise grading and there have been ongoing efforts to facilitate grading reproducibility....

The fifth-edition of World Health Organization (WHO) Classification of Tumors series for urinary and male genital tract tumors has been published, six years later the fourth-edition. In these years, new treatment approaches have been implemented and new molecular data on urological cancers are known. Morphology remains the groundwork for taxonomy o...

Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has emerged as a surgical option for patients with prostatic cancer in high-volume centers. The objective is to assess oncological and functional outcomes when implementing RS-RARP in a medium-volume center without previous experience of robotic surgery. This is a prospective observatio...

We report on the clinicopathologic features of 27 pleomorphic giant cell carcinoma (PGCC) cases of the prostate identified in 20 patients with an age range of 51 to 84 years (68 ± 9; median 71 years). Charlson comorbidity index ranged from 3 to 12. Serum PSA ranged from 4.30 to 662 ng/mL (median 13 ng/mL). On histologic examination, bizarre giant c...

Over the past two decades, the global efforts for the early detection and intervention of prostate cancer seem to have made significant progresses in the basic researches, but the clinic outcomes have been disappointing: (1) prostate cancer is still the most common non-cutaneous cancer in Europe in men, (2) the age-standardized prostate cancer rate...

Starting in the mid-1970s, we formed a group of pathologists with a major interest in uropathology. Originally, it included 2 (R.M. and M.S.). In the years the followed, the group was enlarged to include 4 more people, 2 in the mid- and late-1980s (A.L.B. and L.C.) and another in the mid-1990s (R.Ma.); a sixth (A.C.) joined the group ∼5 years ago....

The telomerase reverse transcriptase (TERT) promoter mutations are associated with increased TERT mRNA and TERT protein levels, telomerase activity, and shorter but stable telomere length. TERT promoter mutation is the most common mutation that occurs in approximately 60-80% of bladder cancer patients. The TERT promoter mutations occur in a wide sp...

The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed....

The seminal vesicle (SV) mucosa can show epithelial and stromal tumors. The epithelial tumors include both cystadenoma and carcinomas, adenocarcinoma being the most common. Squamous carcinoma may arise in the SV (1). Rarely mixed epithelial and stromal tumors (MESTs) can occur. Incipient lesions, i.e., primary precursor or preinvasive lesions givin...

Molecular classification of bladder carcinoma is a relevant topic in modern bladder cancer oncology due to its potential to improve oncological outcomes. The available molecular classifications are generally based on transcriptomic profiles, generating highly diverse categories with limited correlation. Implementation of molecular classification in...

Risk stratification of COVID-19 patients is essential for pandemic management. Changes in the cell fitness marker, hFwe-Lose, can precede the host immune response to infection, potentially making such a biomarker an earlier triage tool. Here, we evaluate whether hFwe-Lose gene expression can outperform conventional methods in predicting outcomes (e...

The 2021 novelties in prognostic and therapeutic tissue markers in patients with prostate cancer (PCa) can be subdivided into two major groups. The first group is related to prognostic markers based on morphological and immunohistochemical evaluations. The novelties in this group can then be subdivided into two subgroups, one involving morphologic...

Approximately 23% of metastatic castration-resistant prostate cancers (mCRPC) harbor deleterious aberrations in DNA repair genes. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) therapy has shown improvements in overall survival in patients with mCRPC who harbor somatic and/or germline alterations of homology recombination repair (HRR) genes...

The current personalized oncology era has witnessed significant efforts to integrate clinical, pathological, and molecular classifications. The growing need for molecular biomarkers to feed personalized oncology, together with the unprecedented wealth of knowledge on the molecular basis of bladder cancer, has led to a novel approach to this disease...

Immuno-oncology (IO) agents (anti–programmed cell death 1 (PD-1) and anti–programmed cell death-ligand 1 (PD-L1)) are approved as first- and second-line treatments for metastatic UC. PD-L1 expression levels in UC tumors help clinicians determine which patients are more likely to respond to IO therapies. Assays for approved IO agents use different a...

Telomerase reverse transcriptase (TERT) promoter mutations have been implicated in urothelial carcinogenesis and are present in 60–80% of conventional and variants of urothelial carcinomas. We investigated the prevalence of TERT promoter mutations in 46 cases of bladder nonurachal adenocarcinoma, 30 cases of urothelial carcinoma with glandular diff...

Context Grading is the mainstay for treatment decisions for patients with non–muscle-invasive bladder cancer (NMIBC). Objective To determine the requirements for an optimal grading system for NMIBC via expert opinion. Evidence acquisition A multidisciplinary working group established by the International Society of Urological Pathology reviewed a...

In 1952, renal cell carcinomas had been divided into 2 categories-clear cell or granular cell-depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic locati...

The American Joint Committee of Cancer (AJCC) tumor-node-metastasis (TNM) classification, with its periodical updates and modifications, has represented and still represents the basis of cancer staging. The historical, long-standing limitations of anatomic-based TNM staging have been recently "threatened" by the impressive amount of data derived fr...

Over the last few years efficacy of immunotherapy using immune checkpoint inhibitors (ICI) has been investigated in patients with bladder cancer (BC) at all stages. The present article aims to assess new therapeutic options with emerging agents in BC patients, shedding light on ICI-based treatments encompassing all disease stages, from non-muscle i...

The Gleason grading system, proposed by Dr. Donald F. Gleason in 1966, is one of the most important prognostic factors in men with prostate cancer (PCa). At consensus conferences held in 2005 and 2014, organized by the International Society of Urological Pathology (ISUP), the system was modified to reflect the current diagnostic and therapeutic app...

Despite several clinical trials have assessed different agents in the adjuvant setting, renal cell carcinoma (RCC) still remains a disease orphan of an effective adjuvant treatment. In fact, systemic therapies targeting angiogenesis that have been observed to be effective in metastatic setting failed to show an improvement in terms of clinical outc...

Prostate cancer represents the most frequent tumor in men, accounting for the 21% of all diagnosed tumors, with 191,930 new cases and 33,330 deaths estimated in 2020. Advanced prostate cancer represents a heterogeneous disease, ranging from hormone naive or hormone sensitive to castration resistant. The therapeutic armamentarium for this disease ha...

Introduction Signal Transducer and Activator of Transcription 3 (STAT3) is involved in cancer initiation and resistance to chemo-radiation therapies and targeted agents. The role of STAT3 in inflammation and immunity together with its involvement in a variety of diseases including genitourinary, gastrointestinal, lung, ovarian and brain tumors make...

Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features. 131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up. Fifty (38%) participants completed the survey. 46 of...

A number of immune checkpoint inhibitors (ICIs) have been approved as first-line therapy in case of cisplatin-ineligible patients or as second-line therapy for patients with metastatic urothelial carcinoma (mUC) of the bladder. About 30% of patients with mUC will respond to ICIs immunotherapy. Programmed death-ligand 1 (PD-L1) expression detected b...

Gains of genetic material or internal rearrangements of chromosome 12p, including 12p overrepresentation or isochromosome 12p [i(12p)], are observed in virtually all germ cell tumors (GCT), in all histologic subtypes, and from various body locations. The chromosomal region involved in these alterations contains the growth and survival promoting onc...

Testicular germ cell tumors are among the most common malignancies seen in children and young adults. Genomic studies have identified characteristic molecular profiles in testicular cancer, which are associated with histologic subtypes and may predict clinical behavior including treatment responses. Emerging molecular technologies analyzing tumor g...

The wide range of novelties reported in this Special Issue of the journal Cells on prostate cancer (PCa) diagnosis, prognosis, and prediction to response to therapy, has led us to a series of considerations related to a better understanding of the current and future role of effective molecular biomarkers in individual patients with PCa [...]

Aims: To capture the complex relationships between risk factors and cancer incidences in the US and predict future cancer burden. Materials & methods: Two artificial neural network (ANN) algorithms were adopted: a multilayer feed-forward network (MLFFNN) and a nonlinear autoregressive network with eXogenous inputs (NARX). Data on the incidence of t...

Around 80–90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient’s response to androgen ablation therapy is variable, and 20–30% of PCa...

The current World Health Organization (WHO) classification of adenocarcinoma of the urinary tract including the urethra includes uncommon Müllerian-derived carcinomas such as clear cell and endometrioid adenocarcinomas. The concept of primary mesonephric (Wolffian-derived) adenocarcinoma (MA) in the urethra (and urinary tract in general) is current...

Immune checkpoint inhibitors have radically changed the treatment approach to metastatic renal cell carcinoma (mRCC). In the present article, we reported and discussed the available data with immunocombinations in mRCC, offering new perspectives in the treatment landscape of these patients. We discussed the main results of pivotal clinical trials o...

Intraductal carcinoma of the prostate (IDC-P), a clinicopathological entity characterized by malignant prostatic epithelial cells growing within ducts and/or acini, has a distinct architectural pattern, cytological features, and biological behavior. Whereas most IDC-P tumors could be derived from adjacent high-grade invasive cancer via retrograde s...

Accurate pathological staging is crucial for patient management. Patients with T1 bladder cancer are at risk of recurrence, progression, and death of cancer. Recognition of early invasion (stage T1 disease) in urothelial carcinoma remains one of the most challenging areas in urological surgical pathology practice. A logical roadmap to T1 diagnosis...

Background: A microscopic analysis of tissue is the gold standard for cancer detection. Hematoxylin-eosin (HE) for the reporting of prostate biopsy (PB) is conventionally based on fixation, processing, acquisition of glass slides, and analysis with an analog microscope by a local pathologist. Digitalization and real-time remote access to images co...

In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials assessing programmed death receptor 1 (PD-1) and cytot...

We have witnessed successive stages since the Seventies in the advancements towards digital pathology. We agree with Dr Pallua et al on the tremendous changes that are taking place in pathology, all leading toward greater role of digitalization in the field of pathology, both in terms of consultation and teaching. In particular, distance teaching u...

Introduction Despite significant advances in the treatment of metastatic urothelial carcinoma, including the advent of immune checkpoint inhibitors, this disease is still challenging to treat and associated poor outcomes remain. Genomic characterization of advanced-stage urothelial carcinoma is widening the field of potential treatments due to the...

Context Whole-mount histopathology, that is, large format histology or whole-mount sectioning, refers to the histopathological examination of tissue sections from specimens processed with large tissue cassette. In some institutions, it is applied routinely to specimens with genitourinary cancers. Objective To give an overview of the application of...

We report on the clinicopathologic features of 115 cases of high-grade urothelial carcinoma of the upper urinary tract with variant histology present in 39 (34%). Variant histology was typically seen in high pathological stage (pT2-pT4) (82%, 32 cases) patients with lower survival rate (70%, 27 cases, median survival 31 months) and consisted in uro...

Most patients with bladder carcinoma are diagnosed with non-muscle-invasive disease, stage Ta, and pT1. Stage remains as the single most important prognostic indicator in urothelial carcinoma. Among the pT1 bladder cancer patients, recurrence and progression of disease occur in 50% and 10%, respectively. The identification of high-risk patients wit...

Medical treatment for metastatic castration-resistant prostate cancer (mCRPC) patients has progressively been evolving from a nonspecific clinical approach to genomics-oriented therapies. The scientific community is in fact increasingly focusing on developing DNA damage repair (DDR) defect-driven novel molecules, both as single-agent therapy and in...

Current developments in the treatment of genitourinary tumors underline the unmet clinical need for biomarkers to improve decision-making in a challenging clinical setting. The detection of circulating tumor cells (CTCs) has become one of the most exciting and important new approaches to identifying biomarkers at different stages of disease in a no...

The prostate gland, a male reproductive organ, is located posterior to the inferior symphysis pubis, superior to the urogenital diaphragm, and anterior to the rectum. McNeal has identified three zones. The transition zone surrounds the urethra between the colliculus and bladder neck; it is the usual location of benign prostatic hyperplasia. The per...