Variants and new entities of bladder cancer Lopez‐Beltran, Antonio; Henriques, Vanessa; Montironi, Rodolfo ...
Histopathology,
January 2019, Letnik:
74, Številka:
1
Journal Article
Recenzirano
Pathological evaluation of bladder cancer typically reveals great tumour heterogeneity, and therefore the common observation of urothelial carcinoma exhibiting a wide variety of histopathological ...patterns is not surprising. Some of these patterns are so distinctive that they have been recognised as specific variants of urothelial carcinoma. Classifications have recently been revised in the 2016 World Health Organisation (WHO) classification of tumours of the urinary system and male genital organs. The current WHO classifications clarify terminological issues and provide better definition criteria, but also incorporate some new entities. Many of these variants have important prognostic or therapeutic implications worth knowing by the urologist and oncologist, but also represent diagnostic challenges in daily pathology practice. This review will discuss the features of variants of urothelial carcinoma in the context of our current clinical practice. Histological variations and new entities of bladder cancer not included in the current WHO classification of urothelial tumours will be briefly discussed.
Staging of bladder cancer Magers, Martin J; Lopez‐Beltran, Antonio; Montironi, Rodolfo ...
Histopathology,
January 2019, Letnik:
74, Številka:
1
Journal Article
Recenzirano
Urothelial carcinoma of the urinary bladder is a heterogeneous disease with multiple possible treatment modalities and a wide spectrum of clinical outcome. Treatment decisions and prognostic ...expectations hinge on accurate and precise staging, and the recently published American Joint Committee on Cancer (AJCC) Staging Manual, 8th edition, should be the basis for staging of urinary bladder tumours. It is unfortunate that the International Union Against Cancer (UICC) 8th edition failed to incorporate new data which is considered in the AJCC 8th edition. Thus, the AJCC 8th edition is the focus of this review. Several critical changes and clarifications are made by the AJCC 8th edition relative to the 7th edition. Although the most obvious changes in the 8th edition are in the N (i.e. perivesical lymph node involvement now classified as N1) and M (i.e. M1 is subdivided into M1a and M1b) categories, several points are clarified in the T category (e.g. substaging of pT1 should be attempted). Further optimisation, however, is required. No particular method of substaging pT1 is formally recommended. In this review, these modifications are discussed, as well as points, which require further study and optimisation.
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). The main presentation symptoms were haematuria and urinary outlet obstruction. Microscopic analysis revealed that all 35 tumours have stromal dissection by mucin. Ten tumours showed villoglandular dysplasia, nine showed mucinous metaplasia, two showed adenocarcinoma in situ and four showed signet ring cell features. All tumours were immunopositive for CEA, while immunonegative for nuclear β‐catenin; 19 of 23 (83%) expressed high molecular weight cytokeratin; 19 of 33 (58%) CK7; 28 of 34 (82%) CK20; 32 of 35 (91%) CDX2; 22 of 27 (81%) cadherin‐17 (CDH‐17); 26 of 29 (90%) SATB2; and one of 31 (3%) GATA3. Mismatch repair gene products, including MLH1, PMS2, MSH2 and MSH6, were immunopositive, suggesting the MSI‐low genotype of mucinous adenocarcinoma of the urethra. BRAF V600E and ALK rearrangements were not detected. During the mean follow‐up of 20 months, nine patients either developed distant metastasis or succumbed to the illness.
Conclusion
Our study, encompassing the most extensive series of 35 cases of primary mucinous adenocarcinoma of the urethra, provides crucial insights into its precise diagnosis, management and potential targeted treatments. We found a greater CDX2, SATB2 and CDH17 sensitivity in these urethral tumours for the first time, to our knowledge. We identified characteristics such as an MSI‐low profile, non‐V600E BRAF mutations and an absence of ALK rearrangements.
Primary mucinous adenocarcinoma of the urethra represents an extremely rare entity. In our study, we further characterise the clinicopathological, immunohistochemical and molecular features of these tumours and suggest that mucinous adenocarcinoma of the urethra is characterised by an MSI‐low profile, non‐V600E BRAF mutations and the absence of ALK rearrangements.
The classification of kidney tumors in adults expands rapidly with new categories recently incorporated. This will result in the modification of the current 2004 World Health Organization (WHO) ...classification of the adult renal epithelial neoplasms. Emphasis should be placed in defining risk groups categorized as malignant or benign tumors, including a category of tumors with low malignant potential to accommodate recently recognized categories with extremely good prognosis after surgery. Unusual tumors such as familial renal cell carcinoma (RCC), translocation RCC, renal cell carcinoma after neuroblastoma, tubular mucinous and spindle cell carcinoma, and mixed epithelial and stromal tumors are also presented. A number of recently described entities and morphologic variants of classical categories deserve recognition since they can be important in differential diagnosis. This review emphasizes clinical, pathological and genetic features defining renal epithelial tumors in adults.
Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors ...is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms 'BRAF,' 'mutation,' and 'cancer/tumor.' These results were filtered to include manuscripts that focused on diagnostic tests for determining BRAF mutation status. Numerous BRAF testing methods were identified, including DNA-based companion diagnostic tests and DNA- and protein-based laboratory-developed tests. Herein we review the characteristics of each method and highlight the strengths and weaknesses that should be considered before use and when interpreting results for each patient. Molecular profiling has shown that mutation load increases with melanoma tumor progression and that unique patterns of genetic changes and evolutionary trajectories for different melanoma subtypes can occur. Discordance in the BRAF mutational status between primary and metastatic lesions, as well as intratumoral heterogeneity, is known to occur. Additionally, the development of acquired resistance to combination BRAF and MEK inhibitor therapy is still a formidable obstacle. Therefore, tumor heterogeneity and the development of acquired resistance have important implications for molecular testing and ultimately the treatment of patients with advanced-stage melanoma. Overall, this information may help community oncologists more accurately and effectively interpret results of diagnostic tests within the context of recent data characterizing melanoma tumor progression.
Since the last World Health Organization (WHO) classification scheme for tumours of the urinary tract and male genital organs, there have been a number of advances in the understanding, ...classification, immunohistochemistry and genetics of testicular germ cell tumours. The updated 2016 draft classification was discussed at an International Society of Urological Pathology Consultation on Testicular and Penile Cancer. This review addresses the main updates to germ cell tumour classification. Major changes include a pathogenetically derived classification using germ cell neoplasia in situ (GCNIS) as a new name for the precursor lesion, and the distinction of prepubertal tumours (non‐GCNIS‐derived) from postpubertal‐type tumours (GCNIS‐derived), acknowledging the existence of rare benign prepubertal‐type teratomas in the postpubertal testis. Spermatocytic tumour is adopted as a replacement for spermatocytic seminoma, to avoid potential confusion with the unrelated usual seminoma. The spectrum of trophoblastic tumours arising in the setting of testicular germ cell tumour continues to expand, to include epithelioid and placental site trophoblastic tumours analogous to those of the gynaecological tract. Currently, reporting of anaplasia (seminoma or spermatocytic tumour) or immaturity (teratoma) is not required, as these do not have demonstrable prognostic importance. In contrast, overgrowth of a teratomatous component (somatic‐type malignancy) and sarcomatous change in spermatocytic tumour indicate more aggressive behaviour, and should be reported.
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 practice is typically limited due to the high complexity of the required technology, the elevated costs, and the limited availability of this technology worldwide. We have conducted a gene expression analysis using a four-gene panel related to luminal and basal subtypes in a series of 91 bladder cancer cases. NanoString-based gene expression analysis using typically luminal (GATA3+/KRT20+) and basal markers (KRT14+/KRT5+/GATA3low/-/KRT20low/-) classified urothelial bladder carcinoma samples as luminal, basal, and a third category (KRT14-/KRT5-/GATA3-/KRT20-), null/double negative (non-luminal/non-basal). These three categories were meaningful in terms of overall cancer-specific survival (p < 0.0001) or when classified as conventional urothelial carcinoma and variant histology urothelial carcinoma (p < 0.0001), NMIBC vs. MIBC (p < 0.001), or by AJCC stage category Ta (p = 0.0012) and T1 (p < 0.0001) but did not reach significance in T2-T4 (p = 0.563). PD-L1 expression (low vs. high) was also different according to molecular subtype, with high PD-L1 expression mostly seen in basal and null subtypes and carcinomas with variant histology (p = 0.002). Additionally, the luminal subtype was enriched in NMIBC with favorable cancer-specific survival (p < 0.0001). In contrast, basal and null subtypes resulted in aggressive MIBC tumors with shorter cancer-specific survival (p < 0.0001), some of which presented variant histology. In conclusion, a comprehensive evaluation of a gene classifier related to molecular taxonomy using NanoString technology is feasible. Therefore, it might represent an accessible and affordable tool in this rapidly expanding area of precision genomics.
In this study, we have examined 67 cytology specimens from patients from 2014 to 2016. The ratio man to women was 4:1 with a median age of 75 years (range: 55–87 years). Thin‐Prep processed urinary ...cytology specimens demonstrated large urothelial cells, with cytologic features of malignancy, thus including hypochromatic nuclei with occasional peripherally accentuated chromatin rim. The cytological diagnosis of High Grade Urothelial Carcinoma (HGUC) was made in 55 patients while 12 specimens were classified as Atypical Urothelial Cells (AUC). This cases represent the 15% of the HGUC and the 4% of the AUC cases diagnosed in our department between 2016 to 2018. Of note, is the fact that in AUC cases, hypochromatic irregular urothelial cells were the only type of cells with malignant features observed in the specimen, and therefore, according to the Paris System criteria, the absence of nuclear hyperchromasia precludes a diagnosis of suspicious high grade urothelial carcinoma (SHGUC) or High Grade Urothelial Carcinoma (HGUC). Subsequent biopsy diagnosis of high grade urothelial carcinoma confirmed the cytological diagnosis of HGUC in 55 patients but also in all 12 patients with a AUC cytologic diagnosis. Our study series support the hypothesis that malignant urothelial cells with hypochromatic nuclei seen in urine cytologic specimens can be diagnostic for HGUC based on their very large nuclei, high nuclear cytoplasmatic ratio (N/C) >0.7, irregular nuclear outlines and coarse (frequently peripheral) chromatin in the absence of hyperchromasia.
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 by immunohistochemistry seems to predict response to immune checkpoint inhibitors in patients with mUC as supported by the objective response rate (ORR) and overall survival (OS) associated with the response observed in most clinical trials. Pembrolizumab, an anti-PD-1 antibody, demonstrated better OS respective to chemotherapy in a randomized phase 3 study for second-line treatment of mUC. Nivolumab, a PD-1 antibody, also demonstrated an OS benefit when compared to controls. Atezolizumab, Durvalumab, and Avelumab antibodies targeting PD-L1 have also received approval as second-line treatments for mUC with durable response for more than 1 year in selected patients. Atezolizumab and Pembrolizumab also received approval for first-line treatment of patients that are ineligible for cisplatin. A focus on the utility of ICIs in the adjuvant or neoadjuvant setting, or as combination with chemotherapy, is the basis of some ongoing trials. The identification of a clinically useful biomarker, single or in association, to determine the optimal ICIs treatment for patients with mUC is very much needed as emphasized by the current literature. In this review, we examined relevant clinical trial results with ICIs in patients with mUC alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting. The current landscape of selected biomarkers of response to ICIs including anti-PD-L1 immunohistochemistry is also briefly reviewed.
Staging of prostate cancer Cheng, Liang; Montironi, Rodolfo; Bostwick, David G ...
Histopathology,
01/2012, Letnik:
60, Številka:
1
Journal Article
Recenzirano
Cheng L, Montironi R, Bostwick D G, Lopez‐Beltran A & Berney D M (2012) Histopathology 60, 87–117 Staging of prostate cancer
Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and ...mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three‐tiered T2 classification system for organ‐confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size‐based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node‐positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.
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