Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

[Epidemiology, classification and risk factors of endometrial cancer]. / Instabilité des microsatellites dans les cancers de l'endomètre.

MICROSATELLITE INSTABILITY IN ENDOMETRIAL CANCERS The microsatellite instability reflects genetic instability that can be sought in tumors, using two methods, immunohistochemistry and molecular biology. Currently in France, a systematic evaluation of microsatellites is recommended in any endometrial cancer from diagnosis. The interest of this evaluation is threefold: diagnostic, prognostic and therapeutic. The presence of microsatellite instability in endometrial cancer allows to detect Lynch syndrome, a hereditary cancer predisposition syndrome, in some patients. The microsatellite status is essential for establishing the molecular classification of endometrial cancers, a classification which has a well-established prognostic value, and finally it determines the eligibility for immunotherapy.

INSTABILITÉ DES MICROSATELLITES DANS LES CANCERS DE L'ENDOMÈTRE L'instabilité des microsatellites est le reflet d'une instabilité génétique que l'on peut rechercher dans les tumeurs, grâce à deux techniques : l'immunohistochimie et la biologie moléculaire. Actuellement, en France, une évaluation systématique des microsatellites est recommandée dans tout cancer de l'endomètre dès le diagnostic. L'intérêt de cette évaluation est triple : diagnostique, pronostique et thérapeutique. La présence d'une instabilité des microsatellites dans un cancer de l'endomètre permet de détecter chez quelques patientes un syndrome de Lynch, syndrome héréditaire de prédisposition au cancer. Le statut microsatellitaire est indispensable à l'établissement de la classification moléculaire des cancers de l'endomètre, classification qui a une valeur pronostique bien établie, et qui permet de déterminer l'éligibilité à une immunothérapie.

The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review.

The objective of this systematic review was to summarize our current knowledge of the role of immunohistochemistry (IHC) markers for identifying mismatch repair-deficient (MMRd) tumors in endometrial cancer (EC). Identification of MMRd tumors, which occur in 13% to 30% of all ECs, has become critical for patients with colorectal and endometrial cancer for therapeutic management, clinical decision making, and prognosis. This review was conducted by two authors applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the following terms: "immunohistochemistry and microsatellite instability endometrial cancer" or "immunohistochemistry and mismatch repair endometrial cancer" or "immunohistochemistry and mismatch repair deficient endometrial cancer". Among 596 retrieved studies, 161 fulfilled the inclusion criteria. Articles were classified and presented according to their interest for the diagnosis, prognosis, and theragnostics for patients with MMRd EC. We identified 10, 18, and 96 articles using IHC expression of two, three, or four proteins of the MMR system (MLH1, MSH2, MHS6, and PMS2), respectively. MLH1 promoter methylation was analyzed in 57 articles. Thirty-four articles classified MMRd tumors with IHC markers according to their prognosis in terms of recurrence-free survival (RFS), overall survival (OS), stage, grade, and lymph node invasion. Theragnostics were studied in eight articles underlying the important concentration of PD-L1 in MMRd EC. Even though the role of IHC has been challenged, it represents the most common, robust, and cheapest method for diagnosing MMRd tumors in EC and is a valuable tool for exploring novel biotherapies and treatment modalities.

Ulipristal Acetate Modifies miRNA Expression in Both Superficial and Basal Layers of the Human Endometrium.

(1) Background: Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) widely used for emergency contraception and mid- to long-term leiomyoma treatment. The aim of this study was to identify modifications of miRNA expression in superficial and basal layers of the human endometrium at the end of the UPA treatment for at least 3 months. (2) Methods: Microarray miRNA analysis of formalin-fixed, paraffin-embedded hysterectomy tissue samples was conducted, followed by an Ingenuity Pathway Analysis. Samples were divided into three groups: women having had 3 months of UPA treatment (n = 7); and two control groups of UPA-naïve women in the proliferative (n = 8) or secretory (n = 6) phase. (3) Results: The UPA modified the expression of 59 miRNAs involved in the processes of cell cycle, carcinogenesis, and inflammation. Their expression profiles were different in the basal and superficial layers. Most of the processes influenced by the UPA in the basal layer were connected to the cell cycle and immune regulation. (4) Conclusion: Specific changes were observed in both layers of the endometrium in the UPA group. However, the miRNA expression in the basal layer was not consistent with that in the superficial layer. Other large studies analysing the long-term impact of SPRM on endometrial miRNA expression are necessary.

Standardizing immunohistochemistry methodology for evaluation of PD-1 and PDL-1 expression in upper tract urothelial carcinoma.

INTRODUCTION: Controversy regarding the prognostic and/or predictive role of PD-1 and PD-L1 expression for upper tract urothelial carcinoma (UTUC) could partly be explained by inconsistencies in the immunohistochemistry (IHC) methodology. Objective is to standardize the methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC patients. MATERIALS AND METHODS: Twenty-two cases treated with radical nephroureterectomy between 1996 and 2015 at 11 French hospitals were randomly selected to compare different methodologies for evaluation of PD-1 and PD-L1 expression. IHC was carried out on whole tissue sections and 0.6 mm- or 2 mm-core tissue micro-arrays (TMAs) using PD-1 NAT105 and PD-L1 28.8 or E1L3N on both tumor cells and tumor-infiltrating immune cells (TILs). Results obtained with whole tissue sections (WTS) were compared to those obtained with 0.6 mm- and 2 mm-core TMAs. Concordance was evaluated using Kappa coefficient. RESULTS: For evaluation of PD-1 and PD-L1 expression, the best concordance with WTS was observed using the PD-1 NAT105 and PD-L1 28.8 antibody on 2 mm-core TMAs, with 5% cut off for positivity on TILs and tumor cells, respectively (Kappa = 0.8). CONCLUSIONS: The most accurate methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC may be based on 2 mm-core TMAs using NAT105 and 28.8 antibodies with a 5% cut off for positivity on TILs and tumor cells, respectively.

PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases.

Therapeutic strategies for epithelial ovarian cancers are evolving with the advent of immunotherapy, such as PD-L1 inhibitors, with encouraging results. However, little data are available on PDL-1 expression in ovarian cancers. Thus, we set out to determine the PD-L1 expression according to histological subtype. We evaluated the expression of two PD-L1 clones - QR1 and E1L3N - with two scores, one based on the percentage of labeled tumor cells (tumor proportion score, TPS) and the other on labeled immune cells (combined proportion score, CPS) in a consecutive retrospective series of 232 ovarian cancers. PD-L1 expression was more frequent in high grade serous carcinoma (27.5% with E1L3N clone and 41.5% with QR1 clone), grade 3 endometrioid carcinoma (25% with E1L3N clone and 50% with QR1 clone), and clear-cell carcinomas (27.3% with E1L3N clone and 29.6% with QR1 clone) than other histological subtypes with CPS score. Using the CPS score, 17% of cases were labeled with E1L3N vs 28% with QR1. Using the TPS score, 14% of cases were positive to E1L3N vs 17% for QR1. For TPS and CPS, respectively, 77% and 78% of the QR1 cases were concordant with E1L3N for the thresholds of 1%. Overall and progression-free survival between PD-L1 positive and PD-L1 negative patients were not different across all histological types, and each subtype in particular for serous carcinomas expressing PD-L1. Expression of PD-L1 is relatively uncommon in epithelium ovarian tumors. When positive, usually <10% of tumor cells are labeled. QR1 clone and CPS appear the best tools to evaluate PD-L1 expression.

Pathological reporting of cystectomy lymph nodes: a retrospective analysis of experience in Paris.

PURPOSE: Pathological evaluation of pelvic lymph node (LN) dissection (PLND) is important for management of cystectomy patients. However, challenges such as unclear interobserver variability of LN counting remain. Here, we assess interobserver variability of LN measures and their clinical utility, with a focus on variant histology. METHODS: We retrieved radical cystectomy cases with PLND between 2010 and 2016 and reevaluated pathological parameters; number of total and metastatic LN, LN density (LND), length of metastatic LN and metastases, extranodal extension (ENE). RESULTS: We report 96 patients: median age of 71a, 34 cases pN+, 36 cases with any extent of variant histology, median follow-up 10 months. Perivesical LN were only rarely identified, but frequently metastatic (4/9). Variant histology (34 cases) frequently exhibited LN metastasis (53% of pN+ cases). Interobserver variance was poor for total LN (kappa = 0.167), excellent for positive LN (0.85) and pN staging (0.96), and mediocre for LND (0.53). ROC analysis suggests that both LND and the sum of LN metastasis length may predict outcome (AUC 0.83 and 0.75, respectively). CONCLUSION: Our study confirms the notion of LND as a prognostic measure, but cautions due to strong interobserver variance of LN counts. The sum length of LN metastases could be a measure that is independent of LN counts. We find that microscopically identified perivesical LN merit particular attention. In summary, our study highlights current challenges in pathological reporting of PLND, confirms previous observations and forms a basis for further studies.

[Lymph node management in endometrial cancer]. / Stratégies ganglionnaires dans les cancers de l'endomètre.

In 2018, around 382,100 new cases of endometrial cancer (EC) were reported worldwide, accounting for about 4.4% of all new cases of cancer in women. In France, in 2018, the EC is the first gynecological cancer in incidence and the fourth cancer in women. The rationale for the therapeutic management of EC is based on the estimation of a theoretical risk of recurrence and lymph node metastasis using MRI and preoperative biopsy criteria. However, lymph node status remains the determining factor of adjuvant treatment. In order to reduce the morbidity of lymphadenectomy, the concept of sentinel lymph node biopsy (SLN) has been developed. The SLN technique has evolved in recent years, thanks to the advent of robotics and the creation of fluorescence detection cameras. It has been shown that detection of SLN with Indocyanine Green (ICG) allows for more frequent bilateral migration of 88 to 100% and better detection of pelvic GS in 97% of cases with a decrease in morbidity. Recently, in view of the absence of a therapeutic role of lymph node staging, the operational risks and the delay of adjuvant treatments, in case of pelvic lymph node metastasis on definitive histological examination, the question of secondarily performing paraaortic lymphadenectomy arises. The SLN procedure, extended to all early-stage endometrial cancers, should lead to a major reduction in the use of secondary staging and better adaptation of adjuvant therapy.

Cervical cancer recurrence: Proposal for a classification based on anatomical dissemination pathways and prognosis.

INTRODUCTION: Precise definitions of recurrences and optimal treatment strategy are yet to be clearly defined among patients with cervical cancer (CC). The purpose of this study was to develop a reproducible classification of CC recurrence. MATERIEL AND METHODS: Data of women with FIGO stages I-IV CC treated between January 2000 and January 2015 were retrospectively abstracted from nine French institutions. We proposed a rTNM classification for recurrence: locoregional (rT), nodal (rN), or distant organ (rM). According to rTNM prognosis, we then defined a rSTAGE classification (I, II, IIIA, IIIB, IVA, IVB). RESULTS: Among the 1028 women treated for FIGO stages I-IV CC during the study period, 216 recurrences were observed (21%). The 3-year survival after recurrence was 38.8%, with a median time to recurrence of 9 months (95% CI, 30.9-48.7). A trend for a lower 3-year survival after recurrence was observed in women with multiple-site vs single-site recurrence (p = 0.1). Among the women in the rT group, a difference in 3-year survival after recurrence was found between rT1 single site, rT2 single site and rT3 single site (p = 0.02). The 3-year survival after recurrence was 69.1%, 49.2%, 37.5%, 34.2%, 23.1% and 24.4% for rStage I, II, IIIA, IIIB, IVA and IVB, respectively (p = 0.007). CONCLUSION: rTNM classifications and rSTAGE are discriminatory and allow all recurrence modalities to be classified.

Absence of predictable long-term molecular effect of ulipristal acetate (UPA) on the endometrium.

RESEARCH QUESTION: What are the effects of ulipristal acetate (UPA) on the expression of endometrial proliferation and maturation markers? DESIGN: A total of 45 endometrium-containing blocks of hysterectomy samples from non-menopausal women with a diagnosis of moderate to severe symptoms of uterine fibroids: 14 women operated on at the end of a 3-month course of UPA; four women who had discontinued UPA treatment 1-12 months before surgery; 27 control unexposed samples (14 in the proliferative and 13 in the secretory phase). Immunohistochemical staining of Ki67, vascular endothelial growth factor-receptor 2 (VEGFR2), oestradiol receptor, progesterone receptor, interleukin-15 (IL-15), indoleamin-2,3-dioxygenase (IDO) and C-C motif chemokine ligand-2 (CCL2) markers were analysed in both endometrial compartments and layers. RESULTS: Under UPA, oestradiol receptor and progesterone receptor expression is similar to the proliferative phase in both layers, although with a decrease in cell proliferation. IL-15, IDO and CCL2 expressions are similar to the proliferative phase, suggesting a progesterone-antagonist effect of UPA. VEGFR2 staining suggests a trend to a mixed agonist-antagonist effect. No significant difference is observed in the post-UPA proliferative phase group compared with the control group in both layers of the endometrium. CONCLUSION: The effect of 3-month UPA treatment is mostly progesterone receptor antagonist-like. After treatment is discontinued, there are no signs of any long-term effects of this molecule on endometrial proliferation and maturation. Therefore, UPA may be administered to women willing to conceive in the short term without consequences for further implantation.

[Comparison of UICC and AJCC 8th edition TNM classifications in uropathology]. / Comparaison des classifications TNM des 8es éditions de l'UICC et de l'AJCC en uropathologie.

The pTNM stage is one of the most important parameters in the handling of tumor patients. The pathologist plays a major role in the determination of the stage. The classifications undergo an evolution according to the state of art. The TNM system is used worldwide and allows to precise the tumor (T) and lymph node stage and the presence of distant metastasis. This system helps to stratify patient groups and determine their prognosis. In 2017, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) published their 8th edition. Unluckily several differences exist between both classifications. The UICC neglected to make several recommendations according to the International Society of Urological Pathology (ISUP) decisions, which organises the consensus in uropathology.

Patterns of recurrence and prognosis in locally advanced FIGO stage IB2 to IIB cervical cancer: Retrospective multicentre study from the FRANCOGYN group.

INTRODUCTION: Evidence-based data describing patterns of recurrence and prognosis in women with FIGO stage IB2 to IIB locally advanced cervical cancer (LACC) are scarce. The purpose of this study was to analyse patterns of recurrence in LACC and their correlation with prognosis, depending on FIGO stage, lymph node (LN) status and treatment modalities. The endpoints of this study were the type of recurrence (locoregional or distant, and time to recurrence), the recurrence free survival, the overall survival and the cumulative incidence for both locoregional and distant recurrence. MATERIALS AND METHODS: Data of women with FIGO stage IB2 to IIB CC treated between April 1996 and May 2016 were retrospectively abstracted from nine French institutions. RESULTS: The median follow-up for the 501 women included was 35.6 months. Recurrences were observed in 158 (31.5%), with a mean time to recurrence of 20.7 months. Women with IIB CC had poorer prognosis, lower 3-year RFS and higher 3-year cumulative incidence of both locoregional and distant recurrences. Women with positive or unknown LN status had poorer prognosis with higher 3-year cumulative incidence of distant recurrence. Women who underwent concomitant chemo-radiotherapy ±â€¯vaginal brachytherapy had poorer prognosis, with lower 3-year RFS and higher 3-year cumulative incidence of distant recurrence. CONCLUSIONS: Recurrence location and time to recurrence differ widely depending on the FIGO stage, LN status and treatment modalities, with potential impact on follow-up modalities and therapeutic approaches.

Comparison of pelvic and para-aortic lymphadenectomy versus para-aortic lymphadenectomy alone for locally advanced FIGO stage IB2 to IIB cervical cancer using a propensity score matching analysis: Results from the FRANCOGYN study group.

INTRODUCTION: Pre-treatment evaluation of nodal status is crucial in women presenting with locally advanced cervical cancer (LACC). However, the prognostic impact of surgical staging remains to be proved, as published results comparing surgical versus radiological staging are contradictory. The aim of this study was to compare the prognosis of women with FIGO stage IB2-IIB CC who underwent surgical nodal staging including either exclusive para-aortic lymphadenectomy (PAL) or comprehensive pelvic + para-aortic lymphadenectomy (P-PAL). MATERIALS AND METHODS: Data of 314 women with FIGO stage IB2 to IIB CC treated between January 2000 and January 2015 were retrospectively abstracted from nine French institutions. The prognosis and outcomes were compared by Propensity score (PS) matching (PSM) analysis. RESULTS: The median follow-up was 33 months (2-114). When comparing women who underwent PAL vs P-PAL, the recurrence rates were 26% (37/144) and 28% (41/144), respectively (p = 0.595). The respective 3-year recurrence free survival (RFS) for P-PAL and PAL were 72.9% (95% CI, 65.7-81.0) and 70.7% (95% CI, 62.4-80.2), (p = 0.394). The respective 3-year overall survival (OS) rates for P-PAL and PAL were 86.8% (95% CI, 81.1-92.9) and 78.6% (95% CI, 70.4-87.7) (p = 0.592). In the sub-group of women with lymph node metastases, RFS was improved for women who underwent P-PAL compared to those with exclusive PAL (p = 0.027), with no difference in OS (p = 0.187). CONCLUSIONS: Comprehensive P-PAL does not seem to be of significant therapeutic benefit compared to exclusive PAL.

Comparison of cell cycle progression score with two immunohistochemical markers (PTEN and Ki-67) for predicting outcome in prostate cancer after radical prostatectomy.

PURPOSE: Previous studies of the cell cycle progression (CCP) score in surgical specimens of prostate cancer (PCa) in patients treated by radical prostatectomy (RP) demonstrated significant association with time to biochemical recurrence (BCR). In this study, we compared the ability of the CCP score and the expression of PTEN or Ki-67 to predict BCR in a cohort of patients treated by RP. Finally, we constructed the best predictive model for BCR, incorporating biomarkers and relevant clinical variables. MATERIALS AND METHODS: The study population consisted of 652 PCa patients enrolled in a retrospective cohort and who had RP surgery in French urological centers from 2000 to 2007. RESULTS: Among the 652 patients with CCP scores and complete clinical data, BCR events occurred in 41%, and the median time from surgery to the last follow-up among BCR-free patients was 72 months. In univariate Cox analysis, the continuous CCP score and positive Ki-67 predicted recurrence with a HR of 1.44 (95% CI 1.17-1.75; p = 5.3 × 10-4) and 1.89 (95% CI 1.38-2.57; p = 1.6 × 10-4), respectively. In contrast, PTEN expression was not associated with BCR risk. Of the three biomarkers, only the CCP score remained significantly associated in a multivariable Cox model (p = 0.026). The best model incorporated CAPRA-S and CCP scores as predictors, with HRs of 1.32 and 1.24, respectively. CONCLUSION: The CCP score was superior to the two IHC markers (PTEN and Ki-67) for predicting outcome in PCa after RP.

A practical guide to bladder cancer pathology.

Pathological assessment of bladder cancer is becoming an increasingly complex task owing to the growing availability of molecular data for different histological subtypes and the appreciation of their importance in determining outcomes of neoadjuvant chemotherapy. Urologists are aware of the need to closely collaborate with pathologists, and comprehensive sharing of information is crucial to achieve optimal patient management. Numerous steps towards this goal have been made during the past years. Important advances in the assessment and reporting of grading and staging, especially substaging of pT1 urothelial carcinomas, have been made. As part of the International Collaboration on Cancer Reporting (ICCR), an international expert group has suggested worldwide reporting standards for urothelial lesions. Nevertheless, several issues remain unresolved, for example, regarding the reporting of heterogeneous lesions and substaging as well as the gross handling and the reporting for lymphadenectomy specimens. During the past few years, major insights have been gained into the molecular changes that occur during bladder cancer development, but a consensus on how to integrate these data into daily practice has not been achieved.

Large nested variant of urothelial carcinoma: a clinicopathological study of 36 cases.

AIMS: The large nested variant of urothelial carcinoma (LNUC) has been added to the World Health Organization (WHO) 2016 classification. Scant data exist, and little is known about its clinical behaviour. MATERIAL AND RESULTS: Cases fulfilling the morphological criteria of LNUC were collected. Pure and mixed cases (i.e. with other patterns of invasive UC) were studied. Immunohistochemical staining with cytokeratin (CK)7, p63, GATA-3, CK20, p53 and Ki-67 was performed. Included were 26 cystectomies (RC) and 10 resections (TURB) belonging to 36 patients with an average age of 66.7 years. Fourteen (39%) were pure LNUCs, and 22 (61%) displayed mixed features. Seventy per cent of the TURBs had pT2 tumours, while 58% of RCs had extravesical disease (≥pT3 and/or ≥pN1), with the rate of advanced disease being higher in mixed (69%) in comparison to pure cases (40%). Similarly, 38% of mixed cases had nodal metastases in comparison to 20% of pure cases. Overall, eight patients (24%) died of disease at a mean interval time of 21.7 months and seven patients (21%) showed recurrence or metastases. Disease progression was significantly higher in mixed cases (55 and 31% in mixed and pure cases, respectively). Positive staining was: CK7 = 87.5%, CK20 = 72%, GATA-3 = 91%, P63 = 100%, p53 = 56% and Ki-67 = mean of 16%. CONCLUSION: Despite the bland cytological appearance and deceptive pattern of invasion of the LNUC, our study validates its fully malignant potential with metastatic spread and tumour-related deaths. Distinguishing mixed from pure LNUCs seems to be of value. LNUCs show comparable immunophenotype to both conventional urothelial carcinoma and the nested variant of urothelial carcinoma.

HOXB13 a useful marker in pleomorphic giant cell adenocarcinoma of the prostate: a case report and review of the literature.

We report the case of an 81-year-old patient with a pleomorphic giant cell adenocarcinoma of the prostate. After diagnosis, he rapidly developed bone metastasis and died within 1 year. This variant of acinar adenocarcinoma is extremely rare and prognosis is poor. This entity has been included into the 2016 WHO classification. The principal differential diagnosis is urothelial carcinoma. To assess the prostatic origin, routine immunohistochemistry can be problematic. Loss of epitopes in this poorly differentiated entity can occur, such as loss of expression of PSA and p504s. We recently described a very sensitive and specific marker of prostate cancer, HOXB13, which once again has proven to be highly specific and sensitive. This is the first description of a pleomorphic giant cell prostate cancer expressing HOXB13.

Urothelial carcinoma in first histological diagnosis of patients over 80 years has distinctive histological features: a retrospective single-institution study of 185 patients.

Few histological data are known about patients with a first diagnosis of bladder cancer (BC) at the age ≥80 years. We describe the largest series in this patient group and their distinctive histological features. This unicentric retrospective study included patients at the age ≥80 years with a first diagnosis of bladder cancer between 2005 and 2015. All diagnosis was made by one senior uropathologist according to the WHO 2016 classification, pTNM 7th edition 2009. We examined samples of 185 patients, sex ratio M:W = 2.49:1, with ≥80 years at the time of first diagnosis of BC. The mean age was 85.1 years (84.8 for men and 85.8 for women). One hundred sixteen patients were diagnosed with NMIBC (non-muscle invasive bladder cancer) (62.7%). Sixty-nine patients were detected with MIBC (muscle invasive bladder cancer) (37.3%). In the MIBC, 20 (29.0%) cases, a divergent differentiation was reported. No patient had primary carcinoma in situ (Cis) at time of diagnosis, and concomitant Cis was observed in 18.9% (35 cases). According to our results, the histopathological findings are different from those of other patients' groups. The study shows a higher number of MIBC and a high percentage of histological variants. We could show distinctive pathological features in this patient group.