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Pathologica Feb 2022In 2022, after a six-year interval, the International Agency for Research on Cancer (IARC) has published the 5th edition of the WHO Classification of Urinary and Male... (Review)
Review
In 2022, after a six-year interval, the International Agency for Research on Cancer (IARC) has published the 5th edition of the WHO Classification of Urinary and Male Genital Tumors, which provides a comprehensive update on tumor classification of the genitourinary system. This review article focuses on prostate carcinoma and underscores changes in the prostate chapter as well as those made across the entire series of the 5th edition of WHO Blue Books. Although no major alterations were made to this chapter, some of the most notable updates include restructure of contents and introduction of a new format; standardization of mitotic counts, genomic nomenclatures, and units of length; refined definition for the terms "variant", "subtype", and "histologic pattern"; reclassification of prostatic intraepithelial neoplasia (PIN)-like adenocarcinoma as a subtype of prostatic acinar adenocarcinoma; and recognition of treatment-related neuroendocrine prostatic carcinoma as a distinct tumor type. Evolving and unsettled issues related to grading of intraductal carcinoma of the prostate and reporting of tertiary Gleason pattern, the definition and prognostic significance of cribriform growth pattern, and molecular pathology of prostate cancer will also be covered in this review.
Topics: Humans; Male; Prostate; Prostatic Neoplasms; Adenocarcinoma; Prognosis; World Health Organization; Neoplasm Grading
PubMed: 36645399
DOI: 10.32074/1591-951X-822 -
Nature Communications Jun 2018Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a...
Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
Topics: Adenocarcinoma; Computational Biology; Disease Progression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Prostate; Prostatectomy; Prostatic Neoplasms; RNA, Messenger; Stromal Cells; Transcriptome; Tumor Microenvironment
PubMed: 29925878
DOI: 10.1038/s41467-018-04724-5 -
Modern Pathology : An Official Journal... Jan 2018Neuroendocrine (NE) differentiation in tumors of the prostate or in the setting of prostate cancer (PCa) is rare. A survey of these lesions is presented, including usual... (Review)
Review
Neuroendocrine (NE) differentiation in tumors of the prostate or in the setting of prostate cancer (PCa) is rare. A survey of these lesions is presented, including usual PCa with focal NE marker-positive cells, Paneth cell-like change, prostatic 'carcinoid', high-grade NE carcinoma, as well as other tumors that do not fit neatly into these categories. The most significant clinical and pathologic features, emerging molecular evidence and the importance of differentiating NE tumors involving the prostate from secondary involvement are highlighted.
Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoid Tumor; Carcinoma, Neuroendocrine; Humans; Immunohistochemistry; Male; Neuroendocrine Cells; Neuroendocrine Tumors; Prostate; Prostatic Neoplasms
PubMed: 29297494
DOI: 10.1038/modpathol.2017.164 -
Modern Pathology : An Official Journal... Jan 2018Benign mimics present either as common challenges in daily routine practice or may cause diagnostic dilemmas because some are less commonly seen and one may be less... (Review)
Review
Benign mimics present either as common challenges in daily routine practice or may cause diagnostic dilemmas because some are less commonly seen and one may be less familiar in recognizing them. There are a multitude of mimics of prostatic adenocarcinoma, which may represent normal gland structures, benign proliferations, atrophic lesions, hyperplastic or metaplastic changes, and inflammatory processes. Some of them are preferentially found in certain anatomic areas of the prostate, either confined to the prostate, or outside of the gland. Various benign mimics of prostatic carcinoma may be also evaluated based on their morphologic similarity to Gleason patterns 3-5 of prostatic adenocarcinoma. Most of the mimics are easily recognizable in larger specimens, such as TUR of the prostate or radical prostatectomy specimens, but they may pose diagnostic problems when the evaluation is done on limited tissue, such as needle-core biopsies or if prostate specimens are infrequently encountered in practice. Therefore, before signing out a report with a diagnosis of prostatic carcinoma, pathologists should carefully consider and rule out the various benign lesions that may mimic carcinoma. This is particularly relevant in the current prostate biopsy practice which relies on using extended biopsy core templates. The awareness and familiarity with the characteristic features of the mimics and judicial use of additional ancillary tests, including immunohistochemistry can prevent overdiagnosis and false-positive interpretation. This review provides a contemporary update on the broad spectrum of the benign prostatic lesions that can mimic prostate adenocarcinoma, outlines their key morphologic and immunohistochemical diagnostic features, and provides a diagnostic, pattern-based approach in establishing a correct diagnosis and distinguishing them reliably from prostatic adenocarcinoma.
Topics: Adenocarcinoma; Atrophy; Biopsy, Large-Core Needle; Consensus; Diagnosis, Differential; Humans; Hyperplasia; Immunohistochemistry; Male; Metaplasia; Neoplasm Grading; Prostate; Prostatic Neoplasms
PubMed: 29297489
DOI: 10.1038/modpathol.2017.136 -
International Journal of Molecular... Sep 2023Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their... (Review)
Review
Extracellular vesicles (EVs)-including apoptotic bodies, microvesicles, and exosomes-are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.
Topics: Male; Humans; Carcinoma, Renal Cell; Prostate; Prostatic Neoplasms, Castration-Resistant; Clinical Relevance; Kidney Neoplasms; Neoplasm Recurrence, Local; Extracellular Vesicles; Exosomes
PubMed: 37834162
DOI: 10.3390/ijms241914713 -
Pathology Jan 2021The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance... (Review)
Review
The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance and many do not need to be reported. Their clinical relevance lies in the risk that they are misinterpreted as cancer. This review presents the histopathological features of benign mimics and discusses their distinction from cancer. The lesions that are most often misdiagnosed as cancer are atrophy and its variants, including simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations are a group of lesions with crowded small glands with no or little nuclear atypia. The most problematic entity of this group is adenosis, which may have a more alarming architecture than some cancers. A diagnostic problem with atrophy and several of the benign proliferations is that the glands often have a discontinuous or absent basal cell layer. Hyperplastic and metaplastic lesions include basal cell hyperplasia. Basal cell hyperplasia may especially mimic prostate cancer with its small dark glands, variable nuclear atypia and a pseudoinfiltrative pattern, which may be present. The anatomical structure that most often causes diagnostic problems is the seminal vesicle. The mucosa of the seminal vesicle contains small acini, often with very pronounced nuclear atypia that may be misinterpreted as cancer. Pathologists need to be familiar with these mimics, as a false positive diagnosis of prostate cancer may lead to unnecessary radical treatment.
Topics: Adenocarcinoma; Atrophy; Diagnosis, Differential; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms
PubMed: 33070957
DOI: 10.1016/j.pathol.2020.08.006 -
Modern Pathology : An Official Journal... Jan 2018The diagnosis of prostate cancer is based on microscopic criteria. Presently, prostate needle biopsy interpretation can be a challenge for the pathologist due to the... (Review)
Review
The diagnosis of prostate cancer is based on microscopic criteria. Presently, prostate needle biopsy interpretation can be a challenge for the pathologist due to the increased number of specimens with limited amount of suspicious glands and minimal atypia. It is critical for the pathologist to have an organized methodical approach when considering the morphological features enabling a definitive diagnosis of prostate cancer. Although several diagnostic criteria and supportive features have been advocated, only few findings are absolutely specific and diagnostic of prostate cancer. The diagnosis of prostate cancer relies on a combination of architectural and cytological features that are reviewed in detail herein. Infiltrative growth pattern, prominent nucleoli and lack of basal cells are the most useful diagnostic criteria. Perineural invasion, glomerulation and mucinous fibroplasia are pathognomonic features of prostate cancer, although uncommon on small prostate cancer foci. The role of immunohistochemistry in establishing a diagnosis of limited prostate is addressed.
Topics: Adenocarcinoma; Biopsy, Needle; Diagnosis, Differential; Humans; Immunohistochemistry; Male; Membrane Proteins; Mucins; Neoplasm Invasiveness; Prostate; Prostatic Neoplasms; Racemases and Epimerases
PubMed: 29297490
DOI: 10.1038/modpathol.2017.139 -
Detecting Neuroendocrine Prostate Cancer Through Tissue-Informed Cell-Free DNA Methylation Analysis.Clinical Cancer Research : An Official... Mar 2022Neuroendocrine prostate cancer (NEPC) is a resistance phenotype that emerges in men with metastatic castration-resistant prostate adenocarcinoma (CR-PRAD) and has...
PURPOSE
Neuroendocrine prostate cancer (NEPC) is a resistance phenotype that emerges in men with metastatic castration-resistant prostate adenocarcinoma (CR-PRAD) and has important clinical implications, but is challenging to detect in practice. Herein, we report a novel tissue-informed epigenetic approach to noninvasively detect NEPC.
EXPERIMENTAL DESIGN
We first performed methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq) on a training set of tumors, identified differentially methylated regions between NEPC and CR-PRAD, and built a model to predict the presence of NEPC (termed NEPC Risk Score). We then performed MeDIP-seq on cell-free DNA (cfDNA) from two independent cohorts of men with NEPC or CR-PRAD and assessed the accuracy of the model to predict the presence NEPC.
RESULTS
The test cohort comprised cfDNA samples from 48 men, 9 with NEPC and 39 with CR-PRAD. NEPC Risk Scores were significantly higher in men with NEPC than CR-PRAD (P = 4.3 × 10-7) and discriminated between NEPC and CR-PRAD with high accuracy (AUROC 0.96). The optimal NEPC Risk Score cutoff demonstrated 100% sensitivity and 90% specificity for detecting NEPC. The independent, multi-institutional validation cohort included cfDNA from 53 men, including 12 with NEPC and 41 with CR-PRAD. NEPC Risk Scores were significantly higher in men with NEPC than CR-PRAD (P = 7.5×10-12) and perfectly discriminated NEPC from CR-PRAD (AUROC 1.0). Applying the predefined NEPC Risk Score cutoff to the validation cohort resulted in 100% sensitivity and 95% specificity for detecting NEPC.
CONCLUSIONS
Tissue-informed cfDNA methylation analysis is a promising approach for noninvasive detection of NEPC in men with advanced prostate cancer.
Topics: Carcinoma, Neuroendocrine; Cell-Free Nucleic Acids; DNA Methylation; Humans; Male; Neuroendocrine Tumors; Prostate; Prostatic Neoplasms
PubMed: 34907080
DOI: 10.1158/1078-0432.CCR-21-3762 -
Developmental Biology Apr 2015The prostate gland plays an important role in male reproduction, and is also an organ prone to diseases such as benign prostatic hyperplasia (BPH) and prostate cancer.... (Review)
Review
The prostate gland plays an important role in male reproduction, and is also an organ prone to diseases such as benign prostatic hyperplasia (BPH) and prostate cancer. The prostate consists of ducts with an inner layer of epithelium surrounded by stroma. Reciprocal signaling between these two cell compartments is instrumental to normal prostatic development, homeostasis, regeneration, as well as tumor formation. Hedgehog (HH) signaling is a master regulator in numerous developmental processes. In many organs, HH plays a key role in epithelial-mesenchymal signaling that regulates organ growth and tissue differentiation, and abnormal HH signaling has been implicated in the progression of various epithelial carcinomas. In this review, we focus on recent studies exploring the multipotency of endogenous postnatal and adult epithelial and stromal stem cells and studies addressing the role of HH in prostate development and cancer. We discuss the implications of the results for a new understanding of prostate development and disease. Insight into the cellular and molecular mechanisms underlying epithelial-mesenchymal growth regulation should provide a basis for devising innovative therapies to combat diseases of the prostate.
Topics: Adult Stem Cells; Animals; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Developmental; Hedgehog Proteins; Humans; Male; Mice; Prostate; Prostatic Neoplasms; Signal Transduction; Species Specificity
PubMed: 25641695
DOI: 10.1016/j.ydbio.2015.01.019 -
Archives of Pathology & Laboratory... Aug 2018- The presence of cribriform glands/ducts in the prostate can pose a diagnostic challenge. Cribriform glands/ducts include a spectrum of lesions, from benign to... (Review)
Review
CONTEXT
- The presence of cribriform glands/ducts in the prostate can pose a diagnostic challenge. Cribriform glands/ducts include a spectrum of lesions, from benign to malignant, with vastly different clinical, prognostic, and treatment implications.
OBJECTIVE
- To highlight the diagnostic features of several entities with a common theme of cribriform architecture. We emphasize the importance of distinguishing among benign entities such as cribriform changes and premalignant to malignant entities such as high-grade prostatic intraepithelial neoplasia, atypical intraductal cribriform proliferation, intraductal carcinoma of the prostate, and invasive adenocarcinoma (acinar and ductal types). The diagnostic criteria, differential diagnosis, and clinical implications of these cribriform lesions are discussed.
DATA SOURCES
- Literature review of pertinent publications in PubMed up to calendar year 2017. Photomicrographs obtained from cases at the University of California at Irvine and authors' collections.
CONCLUSIONS
- Although relatively uncommon compared with small acinar lesions (microacinar carcinoma and small gland carcinoma mimickers), large cribriform lesions are increasingly recognized and have become clinically and pathologically important. The spectrum of cribriform lesions includes benign, premalignant, and malignant lesions, and differentiating them can often be subtle and difficult. Intraductal carcinoma of the prostate in particular is independently associated with worse prognosis, and its presence in isolation should prompt definitive treatment. Patients with atypical intraductal cribriform proliferation, intraductal carcinoma of the prostate, or even focal cribriform pattern of invasive adenocarcinoma in biopsies would not be ideal candidates for active surveillance because of the high risk of adverse pathologic findings associated with these entities.
Topics: Diagnosis, Differential; Humans; Male; Prostate; Prostatic Diseases
PubMed: 30040459
DOI: 10.5858/arpa.2018-0005-RA