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To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio.

Chondroid syringoma (CS) is a rare cutaneous tumor characterized by mixte epithelial and mesenchymal component. The confident histological diagnosis can be obtained by immuno-histochemistry study. Here we present 10 new cases with their clinico-hystological characteristics.The 10 cases were observed between January 2000 and august 2013, in Fort-de-France and Louis-Mourier universitary hospitals. For all the cases a controlled histological study was performed by a dermatopathologist expert and immuno-histochemistry was added. Clinical and immuno-histological data were analyzed.The lesions were almost localized on the face (3/10) and the extremities (3/10). The size was about 1.2 to 5.2cm. Every case was treated by surgery, no malignant case was diagnosed. Histologically, all the 10 cases presented as a well-limited dermic tumor with a mixte epithelial and mesenchymal component. The stroma was myxo-chondroid, and the epithelial component consisted in epithelial cavities lined by one or two cell layers with eccrine (4/10) or apocrine (5/10) features. Immuno-chemistry study reveals positivity for EMA, ACE and CK7 for the internal cells, and positivity for S100 protein and vimentin of the extern cell layer.Chondroid syringoma is characterized by a mixte epithelial with eccrine and apocrine cells and a myxo-chondroid stroma. Our study has some clinical and histological particularities (lesions on the extremities, epidermic connecting…). The main differentials diagnoses are the other annexial tumors. The treatment is surgical.The histological diagnosis of CS is quite easy, but in case of doubt, immuno-chemistry will help, showing a double mesenchymal and epithelial differentiation.

Anal intraepithelial lesions are caused by chronic infection with oncogenic types of human papillomavirus. Their incidence and prevalence are increasing, especially among patients with HIV infection. Their natural history is not well known, but high-grade intraepithelial lesions seem to have an important risk to progress to squamous cell carcinoma. Their treatment can be achieved by many ways (surgery, coagulation, imiquimod, etc.) but there is a high rate of recurrent lesions. Pretherapeutic evaluation should benefit from high-resolution anoscopy. Periodic physical examination and anal cytology may probably be interesting for screening the disease among patients with risk factors. Vaccine against oncogenic types of papillomavirus may prevent the development of anal intraepithelial neoplasia.

Juxtaglomerular-cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derives from specialized smooth-muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as single-case reports or small series. JGCTs are considered benign, but the clinical follow-up has been short in most reported cases. Only one metastatic case has been reported to date, raising the question of tumors of uncertain malignant potential rather than clearly benign neoplasms. Genomic features have been studied in only two cases that showed gains on chromosome 10 as well as deletions on chromosomes 9, 11q and X. The present work studied the genomic characteristics of two additional cases of JGCT by CGH. Similarly to the two previously reported cases, these two tumors showed losses on chromosomes 9 and 11, suggesting recurrent chromosomal imbalances. In addition, one case showed gains and losses of entire chromosomes similar to a previous case studied by karyotyping. Such an aneuploid karyotype may reflect a potential for malignancy as previously reported. Thus, JGCT might be better considered as a tumor of uncertain malignant potential consequently requiring a prolonged follow-up. Future clinicopathologic and genomic studies of large retrospective and prospective series may help to better understand the biology of this fascinating entity.

The identification of fusion genes provides new insights into the initial mechanisms of molecular events implicated in the tumorigenesis of prostate cancer. The presence of TEMPRSS2-ETS fusion in up to half of all human prostate cancers makes it perhaps the most common genetic rearrangement in human epithelial tumors. Some data suggest that TMPRSS2-ERG fusion prostate cancers have a more aggressive phenotype which may affect cancer progression and outcome in localized tumors treated with prostatectomy. This discovery should pave the way towards future targeted therapies.

The histological grading system of prostate cancer proposed by David Gleason in 1966 remains, more than 40 years after its princeps use, an essential tool of communication between the pathologists and urologists. We present here the principal modifications of this score proposed in 2005 by the International Society of Uropathology.

Total prostatectomy remains the main treatment for intermediate risk prostate cancer with a life expectancy greater than 10 years. In other cases non-surgical treatments can be proposed: external radiotherapy (exclusive or combined anti-androgen therapy), brachytherapy with permanent implants, high frequency ultrasounds (HIFU, Ablatherm), cryotherapy or exclusive hormonal treatment. For such patients in case of biological recurrence, prostate biopsies are usually performed in order to affirm the local recurrence. The histological confirmation of persistent tumor is usually required before any treatment: salvage surgery, cryotherapy, and brachytherapy or high intensity focused ultrasound (HIFU). Pathologists must be aware of the histological modifications induced by these different treatments in order to ensure an optimal interpretation of the biopsies. In this review, we describe the modifications observed in the normal prostate and in cancers after these various therapeutic methods, and also after alpha reductase inhibitors proposed as treatment of benign prostate hypertrophy and prostate cancer chemoprevention.

Prostate biopsies remain the only way to confirm the presence of prostate cancer. Nevertheless, the ideal number of biopsies needed to establish the diagnosis is prone to controversy. The current European guidelines recommend 12 sextant biopsies. Few recommendations concerning how the biopsies should be handled have been published. In France, in order to avoid the loss of histological specimens, it was strongly recommended to transmit each core biopsy to the pathology department in an independent container. Performing a large number of biopsies means an increase in the number of containers transmitted and consequently a technical overload of the transmission network, which occurs without any financial counterpart. Since the current tarification system establishes cost allotment by activity, there is no room for an increased technical workload schedule. New approaches must be developed in order to increase productivity. The main aim of our study was to search for answers to the question whether it would be possible to use only one container per sextant irrespective of the number of biopsies performed. For this purpose, we performed various series of one, two, three, four or six biopsies from fresh total prostatectomies with an automatic prostate biopsy gun. All the biopsies were paraffin embedded after a 4% formalin fixative procedure. All the cores were measured after fixing, and on HES slides. The 48 series were as follow: 10 cases with one core, 16 cases with two cores, 13 cases with three cores, five cases with four cores and three cases with six cores. The average length of each core before inclusion varied from 11,8mm to 16,3mm. The average length on HES slides from 9,7 to 11,5mm. A significant difference was observed only for the blocks containing six biopsies (p=0.02). Inclusion of one to three cores from each sextant, did not lead to a loss of information or loss of chances for the patient.

Prostate cancer with 60,000 new cases a year is a public health problem which requires adapted and effective responses. The era of PSA screening dramatically increased the number of prostate biopsies that pathologists have to screen and consequently the number of difficult cases requiring analysis. Immunohistochemistry with anti-AMACR/p504s is useful for detecting prostate cancer in the full range of prostate specimens encountered in needle biopsies. In particular, studies to date with AMACR/p504s clearly demonstrate the ability of this marker to support a diagnosis of malignancy in prostate needle biopsies, combined with negative staining for a basal cell marker, such as p63. This study conducted by the Prostate Committee of the French Association of quality assurance in pathological anatomy and cytology (AFAQAP), reports the evaluation of the current practices with available anti-p63 and -p504s antibodies. The results of this investigation show a correct evaluation of the immunostaining procedure. Overall, from the 39/56 structures tested, the value of the test was positive in 85%. The best results were obtained after antigenic restoration with TRIS-EDTA pH 9, p504s (13H4, 1/200) and p63 (A4A, 1/100).

The two major genes responsible for autosomal dominant polycystic kidney disease and complex tuberous sclerosis are located on chromosome 16 at position 16p13.3, separated by only a few nucleotides. A simultaneous loss of both genes has been termed "the TSC2/PKD1 contiguous gene syndrome". It has been described essentially in young children. We report 2 new cases in French adults, in whom the diagnosis has been made fortuitously on the macroscopic and microscopic examination of the nephrectomy specimen. This diagnosis should be considered for the association of a polycystic kidney disease and numerous angiomyolipomas. It is necessary to set up a specific follow-up of both diseases.

The diagnosis of prostate cancer is based on histological examination of prostatic biopsies using histological criteria identified on standard stains. In certain lesions mimicking prostate cancer, the pathologist must perform immunohistochemical studies looking for loss of basal cells and antibodies directed against cytokeratin CK 903 (34bE12) or CK5/6, which sometimes give inconclusive results leading to a diagnosis of suspicious site. The discovery of overexpression of alpha-méthylacyl CoA racemase in prostate cancer using a microarray technique has allowed the development and marketing of an antibody (P504S /AMACR) which, in combination with a new basal cell marker (p63), is a very valuable tool for the pathologist in the management of suspicious sites and cancers less than 1 mm in diameter detected on prostatic biopsies.

The treatment of prostate cancer by endocrine therapy induces histological changes of benign or malignant prostate glands. Treated cancers often have a more suspicious architecture, resulting in a higher Gleason score, while their nuclear grade (WHO) appears to be more reliable due to a reduction of the size of nuclei. Most authors appear to agree that cancers discovered by biopsy in patients treated with endocrine therapy should not be graded. A review of the literature appears to indicate that finasteride has less marked histomorphological consequences than other hormone-suppressor treatments and could have a lesser effect on the Gleason score. This paper, based on a review of the literature on this subject, emphasizes: (1) the extent of histological changes after androgen deprivation endocrine therapy; (2) histological changes after Finasteride and the difficulties of histological interpretation, particularly the risk of overestimating the Gleason histoprognostic score; (3) the need for urologists to indicate any treatment by 5-alpha-reductase inhibitors or androgen deprivation when requesting histological examination; (4) the value of collecting and documenting cases observed in the Uropathology Club in collaboration with the Oncology committee of the Association Française d'Urologie.

Diagnosis of renal epithelial tumours of adult is often easily made. Nevertheless, it can be difficult to distinguish clear cell carcinoma (CCC) and chromophobe carcinoma (CCHRO), or the eosinophilic variants of CCC and CCHRO with papillary carcinoma (CTP) and oncocytoma (ONCO). The objective is to study and validate immunohistochemical phenotypes of these tumours and to evaluate if they are helpful and to define a diagnostic strategy.310 tumours (75 CCC, 89 CTP, 50 CCHRO and 96 ONCO) were collected and put on 4 tissue-arrays blocks. Immunohistochemical stainings were performed with some usual antibodies: pancytokeratin AE1-AE3, EMA, vimentin, CD10, CK7, CK20 and RCC (Renal Cell Carcinoma).Pancytokeratin AE1-AE3 is expressed mainly in CTP (82.5%). The cytoplasmic staining of EMA is seen in almost all CCHRO (98%) and more than half of CTP (57%). Vimentin is rather specific of CCC (54.5%) and CTP (85%) whereas it is negative in ONCO and CCHRO. CD10 is expressed in the majority of CCC (86.5%) and in some of CTP and CCHRO 65 and 39% respectively. CK7 is rather specific of CTP and CCHRO with 79 and 81.5% of positivity rate. Based on statistical analysis, we have built a diagnostical tree allowing to distinguish 79% of tumours using only three antibodies: CK7, vimentin and CD10.CCC are CK7-/Vim-/CD10+ or CK7-/Vim+; CTP are CK7+/Vim+; CCHRO are CK7+/Vim-; and ONCO CK7-/Vim-/CD10-. In the oncocytoma/chromophobe group, ONCO are more often CK7-/EMA- and CCHRO CK7+/EMA+.

Pelvic lymphadenectomy for localized prostate cancer (stage T1-T2) provides prognostic information. It can be performed by laparoscopy or by open surgery. Systematic lymphadenectomy is controversial and should be performed according to the stage of the tumour and the type of management. Frozen section examination of lymph nodes during total prostatectomy is also controversial due to its low sensitivity (66%). The objective of this article is to define the indications for lymphadenectomy and frozen section examination.Systematic review of the literature.Recommendations concerning the indications for bilateral pelvic lymphadenectomy and frozen section examination for stage T1-T2 prostate cancer as a function of the risk of lymph node metastases. A low risk (5%) of lymph node metastases is defined by an initial PSA10 ng/ml, a Gleason score of biopsies7 (3 + 4 or50% of grade 4) and possibly non-suspicious lymph node imaging. In this case, prior pelvic lymphadenectomy either some time before or immediately before local treatment is optional (Level of Evidence III-2). Due to the morbidity related to lymphadenectomy, the benefit of the procedure is not justified. However, the following situations are distinguished for open or laparoscopic total prostatectomy: --if open total prostatectomy is considered, exploration of the lymph nodes by palpation at the beginning of the operation is recommended. If exploration does not suggest any lymph node invasion, lymphadenectomy is then optional (without frozen section examination). If exploration shows induration or a mass deforming the shape of the lymph nodes, lymphadenectomy is recommended. Frozen section examination is requested only when the surgeon decides not to perform prostatectomy in the case of lymph node invasion. Lymphadenectomy without frozen section examination is optional in the case of laparoscopic total prostatectomy. Macroscopic examination of any lymph node invasion is less accurate via laparoscopy. A high risk (5%) of lymph node metastases is defined by a PSA10 ng/ml and/or a Gleason score7 (4 + 3 or50% of grade 4), and/or suspicious lymph node imaging. Pelvic lymphadenectomy is then recommended (Level of Evidence III-2). The following situations can be distinguished according to the type of treatment envisaged (total prostatectomy or external radiotherapy): when the surgeon decides not to perform total prostatectomy in the case of microscopic or macroscopic lymph node invasion (pN1), lymphadenectomy (open or laparoscopic) may be performed either before or at the same time as prostatectomy with frozen section examination. In the case of external radiotherapy, laparoscopic (or open) lymphadenectomy is recommended (without frozen section examination) when it is decided to extend the irradiation field to pelvic lymph nodes in the case of stage pN1 (1st option) or withhold radiotherapy (2nd option). Lymphadenectomy is optional in other cases, as lymphadenectomy induces considerable morbidity and the benefit of systematic pelvic lymph node irradiation has not been demonstrated. It should be stressed that all indications for lymphadenectomy for localized prostate cancer proposed in the literature are based on the results of standard or limited pelvic lymphadenectomy. These indications could be revised if it is confirmed that lymphadenectomy extended to the internal iliac nodes, for patients at high risk of lymph node invasion, is truly informative and contributive to the treatment decision.

Numerous lesions of the prostate, such as atrophy, adenomatous atypical hyperplasia (adenosis) or PIN can be misdiagnosed with prostatic cancer, and confused with ASAP, leading to perform additional biopsies. In such lesions, the pathologist can perform an immunohistochemical study with the anti-high molecular weight cytokeratin antibody CK903 (34bE12), which confirms the absence of basal cells and supports the diagnosis of prostatic cancer.To compare markers of basal cells (cytokeratin 5/6, p63) and the marker of prostatic carcinomatous glands (p504s) or alpha methylacyl-CoA racemase (AMACR).Retrospective study of 44 cases of paraffin-embedded prostatic specimens (36 biopsies, 4 PER, 1 adenomectomy and 3 radical prostatectomies), consisting in 20 cases of prostatic carcinomas (2 intraductal, 12 Gleason 6 (3+3), 4 Gleason 7 (4+3), 2 Gleason 8 (4+4)), 11 ASAP, 9 PIN (2 low grade, 7 high grade (2 isolated)), and 10 benign lesions (8 atrophy, 1 atypical adenomatous hyperplasia and 1 case of clear cell cribriform hyperplasia). All cases were tested with antibodies to CK 5/6, and with a cocktail to p63 and p504s, after heat antigenic retrieval on NEXES Ventana processor.Basal cells of normal prostatic glands stained with CK5/6 and p63 in 91,3% and 100% of cases, independently from the fixation procedure (Bouin or Formalin). Carcinomas had a p63-/p504s+ profile, PIN were p63+/p504s+, and benign lesions were p63+/p504s-. We observed an increase in sensitivity: p63/p504s (100%), CK5/6 (80%), p63 (90%), p504s (95%), and specificity: p53/p504s (90%), CK5/6 (87.5%), p63 (90.5%), p504s (90.9%).Our results show that the use of a cocktail to p63/p504s is more specific than the use of CK5/6 alone this technique supports a diagnosis of prostatic cancer in 40% of cases previously considered as ASAP.

Objectif : Analyser la répartition des différents génotypes de Papillomavirus Humain (HPV) à partir de frottis présentant des anomalies cytologiques, diagnostiquées entre janvier 2014 et décembre 2016, au Centre Hospitalier Universitaire de Martinique (CHUM), et étudier l’adéquation entre les types d’HPV observés et ceux pris en compte par les différents vaccins disponibles.Méthode : Il s’agit d’une étude rétrospective descriptive monocentrique qui s’est déroulée sur trois ans au sein des services d’Anatomie et Cytologie Pathologiques (ACP) et de Virologie du CHUM. Elle a concerné 208 femmes âgées de 17 à 84 ans, résidant en Martinique, et qui avait un frottis cervico-utérin (FCU) qui présentait des lésions intra-épithéliales avec possibilité de génotypage HPV sur le reliquat du milieu liquide. Les données ont été recueillies à partir des logiciels DIAMIC pour la cytologie et CYBERLAB pour la virologie. L’analyse cytologique a été décrite selon la classification Bethesda 2014, et le génotypage d’HPV a été effectué en utilisant les kits Papillocheck® de Greiner Bio-One®.Résultats : 195 patientes ont été incluses dans l’analyse des résultats. Les lésions de haut grade (20% des cas) sont majoritairement imputables aux HPV à haut risque (HPV-HR) de génotypes 16, 35, 53, 58 (par ordre décroissant de prévalence), puis de manière égale aux HPV 31, 51, 52, 68, 70, et enfin aux HPV 18, 33, 39, 56, 59. Les résultats montrent que concernant la couverture totale d’HPV-HR, le vaccin GARDASIL 9® a un taux de protection globale estimé à 30,3%, qui est supérieur de manière significative aux vaccins CERVARIX® et GARDASIL®.Conclusion : Le nouveau vaccin GARDASIL 9®, qui contient neuf génotypes d’HPV dont sept à haut risque (6, 11, 16, 18, 31, 33, 45, 52, 58), a un taux de protection deux fois plus élevé que les vaccins CERVARIX® et GARDASIL® que ce soit en terme de protection totale [IC 95 (1,47;3,84)] (p < 0,05) ou vis à vis d’au moins un HPV à haut risque [IC 95 (1,58;2,80)] (p < 0,05). Ce vaccin semble plus adapté à l’écologie virale retrouvée dans la population concernée par notre étude en Martinique, et pourrait être le vaccin de choix que les médecins généralistes devraient proposer dans le cadre de la prévention primaire dans notre département, en complément du dépistage du cancer du col par la réalisation de FCU.