Diagnosis Of Prostatic Adenocarcinoma Research Articles

Benign mimickers and potential precursors of prostatic adenocarcinoma

The diagnosis of prostatic adenocarcinoma (PCa) in needle biopsy, especially when present in small amounts, is often challenging. Before making a malignant diagnosis, it is imperative to consider and rule out various benign processes that can simulate cancer. A useful method of classifying benign mimickers is in relationship to the major architectural patterns depicted in the Gleason diagram. The four major patterns are small gland, large gland, fused gland and solid nests and single cells. Most mimickers have small gland architecture and include atrophy, post-atrophic hyperplasia and atypical adenomatous hyperplasia. Normal anatomical and vestigial structures such as seminal vesicle/ejaculatory duct tissue, Cowper’s gland, verumontanum mucosal glands, mesonephric glands and paraganglionic tissue may be confused with PCa. Additionally, metaplastic and hyperplastic processes may be mistaken for PCa. Furthermore, inflammatory processes including non-specific granulomatous prostatitis, xanthoma and malakoplakia may simulate high-grade PCa. In addition to mimickers there are a number of putative precursors of PCa. High-grade prostatic intraepithelial neoplasia has been expensively studied and is thought to be a precursor of at least a subset of PCa. The pathologist’s awareness of the vast array of benign mimickers coupled with prudent use of immunohistochemistry is a critical step in the systematic approach to the diagnosis of PCa. Recognition of PCa precursors in pathological specimens may significantly impact patient management.

Frequencies of different nuclear morphological features in prostate adenocarcinoma

Diagnosis of prostate adenocarcinoma is primarily based on morphological analysis. Nucleomegaly, prominent nucleoli, and hyperchromasia constitute current nuclear diagnostic parameters but are seen in benign conditions, vary with Gleason grade, and pose diagnostic challenge in well-differentiated tumors with accompanying inflammation or equivocal architectural features. In such cases, other pleomorphic nuclear features such as variation in size and shape, irregular contours, nuclear membrane infoldings, and nonuniform chromatin, which are not incorporated in formal evaluation, may prove helpful. Our aim was to study different nuclear morphological features of prostate adenocarcinoma (including currently practiced ones) and highlight their variation with Gleason grades. We examined 84 cases of prostate adenocarcinoma using oil immersion microscopy where necessary. Commonest Gleason pattern observed was grade 4a accounting for 42.8% of cases. Nuclear enlargement (moderate to marked in 93.8%), nucleolar enlargement (62.1%), and nonuniform chromatin distribution (100%) could serve as useful diagnostic features but did not vary with tumor differentiation. Pleomorphism (moderate in 58.6%), nuclear overlapping (62.8%), nuclear membrane infoldings (66.2%), and irregular contours (frequent in 94.5%) were significant diagnostic features that increased in frequency and extent with increasing grade and could be used to differentiate low-grade from high-grade tumors. Worsening of nuclear morphology with advancing tumor grades indicated that nuclear anaplasia accompanies poor architectural differentiation. Coexistence of pale and dark nuclei signified variable chromatin density of no diagnostic significance.

Is There a Role for Fatty Acid Synthase in the Diagnosis of Prostatic Adenocarcinoma?

Our aim was to compare the usefulness of fatty acid synthase (FASn) with that of α-methylacyl coenzyme-A racemase (AMACR) in the diagnosis of prostatic adenocarcinoma. The expression of these 2 markers was compared in a tissue microarray containing 62 foci of benign glands and 36 foci of prostatic adenocarcinoma. Similar to AMACR, there was significantly higher FASn expression in adenocarcinoma compared with that in benign glands. The optimal accuracy rate and area under curve (AUC) by receiver operating characteristic analysis for FASn were not significantly different from those for AMACR (accuracy, 80% vs 87%; AUC, 0.942 vs 0.956; P for both, > .05). Moreover, in cases with coexistent malignant and benign glands on the same core, FASn could selectively distinguish a proportion of cases (17/21 [81%]) similar to using AMACR. We conclude that FASn may aid in the diagnosis of prostatic adenocarcinoma, at least to supplement AMACR as another positive marker of carcinoma and potentially increase diagnostic accuracy.

IGFBP2 as an Immunohistochemical Marker for Prostatic Adenocarcinoma

The aim of the study was to evaluate the immunohistochemical expression of insulin-like growth factor binding protein 2 (IGFBP2) in normal epithelium, high-grade prostatic intraepithelial neoplasia (HG-PIN), and prostatic adenocarcinoma (PAc), in patients hormonally untreated and in those having undergone complete androgen ablation. IGFBP2 expression was evaluated in PAc, HG-PIN, and normal-appearing epithelium in 40 radical prostatectomies from hormonally untreated patients and 10 radical prostatectomies from patients under complete androgen ablation before surgery. The study also included the initial biopsies of such patients, and an additional 10 simple prostatectomies from patients with bladder outlet obstruction. Statistics included receiver-operator characteristic curves, the Wilcoxon test, and the Spearman test. Results were compared with α-methylacyl-CoA racemase. The principal findings were: (1) IGFBP2 was not expressed in normal ducts and acini of the transition and peripheral zones; (2) IGFBP2 was expressed in the cytoplasm of untreated PAc and, to a lesser extent, in HG-PIN; (3) it was also expressed in PAc and HG-PIN after complete androgen ablation, but to a lesser extent than in the untreated neoplasms; (4) α-methylacyl-CoA racemase was expressed both in PAc and HG-PIN, the level being similar in both lesions and lower in the specimens from the patients having undergone androgen ablation. Results obtained show that IGFBP2 is expressed in invasive PAc, whereas its expression in HG-PIN is low. These findings can be helpful in the correct diagnosis of PAc both in biopsies and in surgical specimens, mainly in untreated patients.

A retrospective analysis after low-dose-rate prostate brachytherapy with permanent 125I seed implant: clinical and dosimetric results in 70 patients

To evaluate the biochemical disease-free survival (bDFS) rate after (125)I permanent-implant prostate brachytherapy. Patients with a diagnosis of prostate adenocarcinoma and adequate PSA follow-up were selected for this retrospective study. Brachytherapy with permanent (125)I seeds was performed as monotherapy, with a prescribed dose of 145 Gy to the prostate. Patients were stratified into recurrence risk groups according to the National Comprehensive Cancer Network (NCCN) guidelines. Biochemical failure was defined using the American Society of Therapeutic Radiology and Oncology (ASTRO) guidelines. The post-implant D90 (defined as the minimum dose covering 90% of the prostate) was obtained for each patient. Two cutoff points were used to test the correlation between D90 and bDFS results: 130 Gy and 140 Gy. bDFS was calculated from the implant date to the date of biochemical recurrence. Univariate and multivariate analysis were performed using the SPSS software and included clinical stage, pretreatment PSA, Gleason score (GS), androgen deprivation therapy, D90, and risk groups. In the univariate analysis we used a cutoff point of 5.89 ng/mL for PSA and 5 for GS. From June 2003 to April 2007, 70 patients were analyzed. The patients' distribution into recurrence risk groups was as follows: 39 patients (56%) in the low-risk group, 23 patients (33%) in the intermediate-risk group, and 8 patients (11%) in the high-risk group. At a median follow-up of 47 months (range, 19-70 months) bDFS was 88.4%, with a global actuarial 5-year bDFS of 86%. Disease-related factors including initial PSA level, GS and risk group were significant predictors of biochemical failure ( P = 0.01, P = 0.01, P = 0.006, respectively). In multivariate analysis, risk group (P = 0.005) and GS (P = 0.03) were statistically significant. Our data are in agreement with those in the literature and, despite the short follow-up, confirm the advantage of brachytherapy for patients at low and intermediate risk of recurrence.

Role of magnetic resonance spectroscopic imaging ([1H]MRSI) and dynamic contrast-enhanced MRI (DCE-MRI) in identifying prostate cancer foci in patients with negative biopsy and high levels of prostate-specific antigen (PSA)

The purpose of this study was to evaluate the role of magnetic resonance spectroscopic imaging (MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting tumour foci in patients with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (TRUS)-guided biopsy. This prospective randomised trial was conducted on 150 patients who underwent [¹H]MRSI and DCE-MRI and targeted biopsies of suspicious areas on MRI associated with random biopsies. After the second biopsy, the diagnosis of prostate adenocarcinoma was made in 64/150 cases. On a per-patient basis, MRSI had 82.8% sensitivity, 91.8% specificity, 88.3% positive predictive value (PPV), 87.8% negative predictive value (NPV) and 85.7% diagnostic accuracy. The sensitivity, specificity, PPV, NPV and accuracy for DCE-MRI was 76.5%, 89.5%, 84.5%, 83.7% and 82%, respectively. The combination of MRSI and DCE-MRI yielded 93.7% sensitivity, 90.7% specificity, 88.2% PPV, 95.1% NPV and 90.9% accuracy in detecting prostate carcinoma. The combined study with [¹H]MRSI and DCE-MRI showed promising results in guiding the biopsy of cancer foci in patients with an initial negative TRUS-guided biopsy.

Small-cell carcinoma of prostate: A case report and literature review

One case of small-cell carcinoma (SCC) of prostate was identified at Shangyu people’s hospital. This 70-year-old male had a prior diagnosis of prostatic adenocarcinoma when he was first admitted to the hospital and received anti-androgen treatment. 9 months later, he was readmitted to the hospital and was diagnosed as SCC through biopsy. The article was written to evaluate the clinical and pathological characteristics and treatment of SCC of prostate.

Influence of phosphoprotein associated with glycosphingolipid microdomains 1 on biologic behavior of human prostatic cancer cell line in-vitro

To investigate the mechanism of influence of phosphoprotein associated with glycosphingolipid microdomains 1 (PAG1) on the biological behavior of human prostatic cancer cell line PC-3M-1E8. The expression of GST-Raf1-RBD recombinant protein, a specific binding domain of active Ras (GTP-Ras), was induced by IPTG in JM109 bacterium. SDS-PAGE and coomassie brilliant blue staining were performed using cleaved product of the bacterium to determine the expression of the fusion protein. GST-pull down essay was designed to detect the level of active Ras in PGA1 and vector transfected, respectively and in the native PC-3M-1E8 cells. Western blotting was used to detect the expression levels of downstream proteins of Ras signal pathway which may be related to the function of PAG1. Phalloidine labeled by tetramethylrhodamine-5-(and-6) isothiocyanate (TRITC) was used for the staining of intracellular F-actin, Laser passing confocal microscopy was adopted for observing change of the cell morphology and the arrangement of F-actin. After IPTG induction, the GST-Raf1-RBD recombinant protein, with a molecular weight of 33 000, was noticed to be highly expressed in JM109 bacterium. GST-pull down assay revealed that the expression level of active Ras markedly decreased after PAG1-transfection while the total Ras remained unchanged. The expression of p-ERK and cyclin D1 in the PAG1-transfected cells decreased in accordance with the level of active Ras. However, the expression of p21(WAF1/CIP1) and p-Akt didn't show any variation. Additionally, the structure of F-actin was turbulent and the pseudopodia of cells diminished conspicuously after PAG1-transfection. There was a high expression of PAG1 in normal human prostate tissue, however, the positive rate of PAG1 immuno-staining decreased in cases of prostatic adenocarcinoma, correspondent with increasing of the grading index of cell differentiation established in the Gleason grading system for the diagnosis of prostate adenocarcinoma. An over-expression of PAG1 in PC-3M-1E8 cells effectively suppresses the activation of Ras and ERK, as well as the cyclin D1 expression, leading to an inhibition of the proliferation ability of tumor cells. The turbulence of F-actin and reduction of pseudopodia of cells result in an impairment of cell mobility, invasiveness and metastatic capability. In human prostate and prostatic adenocarcinoma tissues, the expression of PAG1 is related to the cellular differentiation and malignancy.

Acute myeloid leukemia incidence following radiation therapy for localized or locally advanced prostate adenocarcinoma

Introduction: The effect of radiation therapy on acute myeloid leukemia incidence among prostate cancer patients has not been sufficiently elucidated despite evidence that acute myeloid leukemia is a consequence of therapeutic radiation in other primary malignancies. Therefore, we investigated the effect of definitive therapy with radiation therapy (external beam radiation therapy [EBRT] or brachytherapy) on acute myeloid leukemia incidence in a population-based cohort of patients with localized or locally advanced prostate cancer. Methods: We utilized the Surveillance, Epidemiology, and End Results database to identify a cohort of men ( n = 168,612) with newly diagnosed prostate adenocarcinoma between January 1988 and December 2003. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of acute myeloid leukemia incidence following definitive therapy with EBRT alone, brachytherapy alone, or surgery alone compared to no definitive therapy (i.e. no EBRT, brachytherapy, or surgery). Results: The cohort yielded 184 acute myeloid leukemia cases during 1,064,820 person-years of follow-up after prostate adenocarcinoma diagnosis. Patients treated with EBRT had a higher adjusted relative risk of developing acute myeloid leukemia than patients treated with brachytherapy or surgery when each therapy group was compared to patients who were not treated with definitive therapy (EBRT: HR = 2.05, 95% CI 1.29, 3.26; brachytherapy: HR = 1.22, 95% CI 0.46, 3.22; surgery: HR = 1.24, 95% CI 0.77, 1.98). Conclusions: Our findings suggest that acute myeloid leukemia incidence is a greater concern for patients treated with EBRT than brachytherapy for localized or locally advanced prostate adenocarcinoma.

412 THE VALUE OF MANDATORY SECOND OPINION PATHOLOGY REVIEW IN THE INTERPRETATION OF PROSTATE NEEDLE BIOPSIES PRIOR TO RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Staging III1 Apr 2010412 THE VALUE OF MANDATORY SECOND OPINION PATHOLOGY REVIEW IN THE INTERPRETATION OF PROSTATE NEEDLE BIOPSIES PRIOR TO RADICAL PROSTATECTOMY Fadi Brimo, Luciana Schultz, and Jonathan Epstein Fadi BrimoFadi Brimo More articles by this author , Luciana SchultzLuciana Schultz More articles by this author , and Jonathan EpsteinJonathan Epstein More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.481AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We determined the value of mandatory second opinion pathology review in the interpretation of prostate needle biopsies prior to radical prostatectomy (RP). METHODS The original and reviewed needle biopsy pathology reports for all cases referred to our institution for RP over a 1 year period were compared. A major discrepancy in GS was defined as a change that places the patient in a different risk stratification category (GS of 6, 7, and 8-10). A significant difference in the reporting of the highest percentage of cancer in a single core was defined as a difference >30% between the two reports. RESULTS 855 cases were included. All had an original diagnosis of prostatic adenocarcinoma (PCa). Of these, 844/855 (98.8%) were diagnosed as carcinoma upon review. Nine (1%) cases were diagnosed as atypical and 2 (0.2%) as benign upon review. A major discrepancy in GS between the original and the reviewed reports was present in 124 (14.7%) of cases; of those the majority 67 (54%) were downgraded upon review. 80 cases (64.5%) of the disagreements were between GS 6 and 7. Of the 777 cases in which the number of positive cores was reported in both reports, 71 (9.1%) had discrepancies upon review; the difference was one core in 53/71 cases (75%). The number of positive cores was reported to be higher in 45/71 (63.4%) after review. A significant difference in the highest percentage of cancer in a single core was present in 76/844 (9%) evaluable cases; in all of these cases, the extent of cancer was underestimated in the original report. In 60/76 (78.9%) cases, cancer was reported to involve the core discontinuously on review. Perineural invasion was reported to be present in 138/844 (16.3%) cases after revision, from which this information was lacking in 37 of the original reports. Finally, in 4 cases, presence of extra-prostatic extension was noted on the needle biopsy only upon review. CONCLUSIONS Compared to a smaller study done over 10 years ago at our institution, the percent of cancers that could not be confirmed was identical at 1.2%. Also, a non-significant proportion of cases had a significant change in Gleason grade. This study is the first to analyze concordance upon review for number of positive cores and maximum percent positive in a core with a 9% discrepancy in both. Mandatory second opinion on prostate needle biopsies can, in a minority of cases, result in significantly different reports that may affect therapy. Baltimore, MD© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e163 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fadi Brimo More articles by this author Luciana Schultz More articles by this author Jonathan Epstein More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Reliability of the 34βE12, keratin 5/6, p63, bcl-2, and AMACR in the diagnosis of prostate carcinoma

Objective In this study, we aimed to investigate which basal cell marker should be used with α-methylacyl coenzyme A racemase (AMACR) to increase diagnostic accuracy in the diagnosis of prostate carcinoma. Materials and methods A total of 98 cases of prostate biopsy, comprising 65 cases with prostate adenocarcinoma and 33 cases without adenocarcinoma, were included in this study. Prostate-specific antigen (PSA) serum levels before biopsies were obtained. The number of cores with malignant glands and Gleason scores for each case were determined. Paraffin sections were stained immunohistochemically with 34βE12, keratin 5/6, p63, bcl-2, and AMACR. Results According to staining pattern, extensiveness, and intensity of basal cell markers in benign glands, 34βE12 gave the best results. As negative markers for prostate adenocarcinoma, the best markers were p63 and 34βE12. According to the AUC values in ROC curves for both extensiveness and intensity, the arrangement from the best to the worst was 34βE12, p63, bcl-2, and keratin 5/6. The 34βE12 had the best sensitivity and specificity values (95% and 98%, respectively). Staining extensiveness and intensity of keratin 5/6 in malignant glands, and those of bcl-2 in benign glands had statistically significant positive correlation with serum PSA levels. Even though AMACR is a negative marker for benignity, some of the benign glands also had positive immune reaction with AMACR. However, AMACR positivity was usually focal and weak. Nevertheless, intensively stained subjects were also present. No correlation was present between AMACR and basal cell markers. Conclusions As a result, we suggest that keratin 5/6 and bcl-2 should not be used to identify benign glands in prostate biopsy since they show high positivity in malignant glands and high negativity in benign glands. 34βE12 should be the first choice as a basal cell marker. p63 can be used together with 34βE12, but it may not give additional diagnostic information. When we evaluated the correlation of basal cell markers, we did not find any complementary staining results among basal cell markers. Our study showed that 34βE12 is the most appropriate negative marker to combine with AMACR as a positive marker for the diagnosis of prostate adenocarcinoma.

Prostate cancer screening in a Saudi population: an explanatory trial study

The aim of this study is to explore the actual situation of prostate cancer in a cohort of healthy population in Saudi Arabia and to show the feasibility of screening for this disease using the internationally agreed criteria. This study was conducted in the city of Riyadh, in the outpatient clinics of four different health facilities. All men presented to the outpatient clinics during the period of study, from January 2008 to December 2008, were invited to participate in the study, in which they were subjected to PSA blood testing and digital rectal examination (DRE). When either test was abnormal, transrectal ultrasound and multiple prostatic biopsies were performed for confirmation of the results. A total of 2100 healthy males who met the inclusion criteria of the study were evaluated. The highest percentage of men with PSA>/=4 ng ml(-1) was in the age group 61-70, 51-60 years (42.7 and 31.8%, respectively). The number of subjects with an elevated PSA only was 172 (8.1%). Those having both elevated PSA and an abnormal DRE were 51 (2.4%). The total number referred to biopsy was 223. Fifty two subjects had a positive diagnosis of prostatic adenocarcinoma, which compromised 2.5% of the cohort studied. The cancer in 27 (52%) persons was organ confined, whereas in 14 (26.9%), it was metastatic. The prevalence rate of prostate cancer detected by screening was higher than expected and the disease was advanced. Larger community-based larger studies are highly warranted specially among high-risk groups.

TU-D-210A-01: 3D Ultrasound Guided Prostate Interventions

Definitive clinical diagnosis of prostate adenocarcinoma (PCa) requires histopathological confirmation of a tissue sample drawn from a 2D transrectal ultrasound(TRUS) guided biopsy. The prostate biopsy procedure, however, is plagued by high false negative rates (up to 34%) as early‐stage PCa is generally not visible on ultrasound. As a result, a negative biopsy does not rule out a diagnosis of PCa, as many tumors are missed on initial biopsy. In such circumstances, patients will undergo multiple repeat prostate biopsy (RPBx) to find undetected PCa. In a repeat biopsy, the physician must either avoid previously biopsied tissue (in cases of prior negative biopsy) or target the same anatomical site for patients with non‐diagnostic, atypical small acinar proliferations (ASAP). In cases of ASAP, there is a 40–50% chance of finding PCa on RPBx in the same anatomic location, so accurate targeting of prior biopsy locations is essential. 3D TRUS is hypothesized to be superior to 2D TRUS for accurate guidance and recording of the prostate biopsy procedure. Patients undergoing RPBx might benefit most from the hypothesized improvements, as previous Bx core locations can be viewed in 3D and used to guide a RPBx. Accuracy is also important when suspicious findings exist on other diagnostic imaging modalities, such as MRI or PET, are used to direct a TRUS‐guided biopsy. In this paper, we describe a new method to guide prostate biopsy procedures using 3D ultrasound and extend it to prostate therapy. This new approach allows us to guide the biopsy to specific 3D targets in the prostate, record the biopsy locations in 3D, and register the intra‐biopsy procedural 3D ultrasoundimage with an MR image to guide the biopsy to specific locations in the prostate. Learning Objectives: 1. Understand the limitations of conventional TRUS‐guided prostate biopsy 2. Understand the methods that can be used to overcome the limitations of TRUS‐guided prostate biopsy 3. Understand the advantages of using MR images fused with 3D ultrasoundimages to guide prostate biopsy

Effectiveness of argon plasma coagulation in the treatment of chronic actinic proctitis

There are two kinds of actinic proctitis--one is acute and self-limited, and lasts about 3 months; the other is chronic and develops months to years after radiation therapy. The incidence of chronic actinic proctitis is about 5-20% of radiated prostate tumors. To evaluate the effectiveness of argon plasma coagulation in the treatment of chronic actinic proctitis. A retrospective search of patients with the diagnosis of actinic proctitis. The number of argon plasma coagulation therapies needed to achieve the symptom resolution was analyzed. We found 22 patients with a diagnosis of actinic proctitis. Nineteen were males (86.7%) and three (13.6%) were females. Nineteen patients (86.4%) had a diagnosis of prostate adenocarcinoma, one had a diagnosis of squamous-cell cervix carcinoma (4.5%), and two had a diagnosis of endometrial carcinoma (9.1%). The mean number of coagulation sessions needed for symptom resolution was 2.58 (absolute range 1-7) with a median of 2 sessions. Multiple treatments are described in the literature. None of them have shown promising results. Our results suggest that argon plasma coagulation is effective in the treatment of this condition, and achieves a rapid and sustained response with few sessions and a good safety profile.

Small-cell prostate carcinoma: A retrospective analysis of five newly reported cases

Five cases of small-cell carcinoma (SCC) of prostate were identified, at the Rhode Island Hospital and the Miriam Hospital from 1984 to 2006, with an average age of 71 years at the time of diagnosis. Three of these patients had a prior diagnosis of prostatic adenocarcinoma, with all of the five patients receiving anti-androgen treatment. The average time between the diagnosis of adenocarcinoma and of SCC in these patients was 6.7 years. The PSA levels varied greatly, with two patients possessing markedly elevated levels and the remaining patients with normal levels. Approximately 3/5 patients developed liver metastases, 2/5 patients had bone metastases, and 1/5 patients developed carcinomatous meningitis. Of the four patients who expired, the median survival time after diagnosis of SCC was 3.6 months (0.5–12 months).

Immunocytochemical study of urine cytological preparations from secondary prostatic adenocarcinoma involving the urinary bladder

Involvement of the urinary bladder by prostatic adenocarcinoma (PCA) occasionally occurs. In this study, we analyzed urine cytological findings in patients with secondary involvement of the urinary bladder by PCA with the help of the immunocytochemistry. The cases were divided into two groups: (1) prospective study group: three cases; and (2) retrospective study group: 12 cases which were retrieved from our cytopathological files. The urine cytology specimens (cytospins) from all cases were submitted for prostatic specific antigen (PSA) immunocytochemistry. Additional immunostaining for high-molecular-weight cytokeratin (HMWCK) was performed if PSA immunoreactivity was negative. All cytospin smears showed atypical cells characterized by large, round and uniform nuclei with prominent nucleoli and dense cytoplasm. They were present as single cells or in cell groups simulating urothelial carcinoma. The diagnosis of PCA was made if the atypical cells were either immunoreactive for PSA or nonreactive for HMWCK. The urothelial cells were PSA- and HMWCK+. The immunostaining supported the PCA diagnosis in all three cases from the prospective group and two cases in the retrospective group. The remaining 10 cases in the retrospective group were diagnosed as negative: 3, atypia: 5 urothelial carcinoma: 2. The positive diagnosis for PCA was based on the PSA immunoreactivity or nonreactivity to HMWCK and the cytological atypia. In conclusions, immunostaining for PSA and HMWCK performed on cytospins of urine specimens from patients with a prior history of high-grade and/or stage of PCA is helpful to make a positive diagnosis of secondary bladder involvement from PCA.

Histopathologic Review of Previously Negative Prostatic Core Needle Biopsies following a New Diagnosis of Adenocarcinoma of the Prostate by Core Needle Biopsies: Implications for Quality Assurance Programs

Programs for quality assurance are increasingly important in surgical pathology. Many quality assurance (QA) techniques for surgical pathology were adopted from procedures introduced in cytopathology. Surgical pathology specimens have diminished in size such that the majority of diagnostic biopsies of prostatic lesions are now core needle biopsies. These specimens raise issues similar to those of cytology specimens, including concerns regarding adequacy and the representative nature of the biopsy. Due to sample size, some neoplasms may not be diagnosed on initial biopsy, raising concerns regarding false negative results. Cytopathologists have instituted QA procedures including review of all previously negative slides received within five years prior to the new diagnosis of high grade squamous intraepithelial lesion or gynecologic malignancy. No such requirement exists in surgical pathology for review of core biopsies.The Department of Pathology at the University of Utah instituted a QA policy requiring review of prior negative prostatic needle biopsies following a new diagnosis of prostatic adenocarcinoma. We reviewed five years of QA records of prostate needle biopsy review. During this time, nine hundred and fifty-eight core biopsy sets were performed. Two hundred and ninety-five of these contained at least one biopsy with a diagnosis of adenocarcinoma. Two hundred and eight patients had a prior set of prostatic needle biopsies with a diagnosis of adenocarcinoma. The remaining 87 had prior biopsies with either a diagnosis of prostatic intraepithelial neoplasia (23), small atypical acinar proliferation (21) or no evidence of malignancy (43). QA review of these 87 cases revealed two biopsies which revealed foci of adenocarcinoma. Both had been initially diagnosed as no evidence of malignancy. The false negative rate for core biopsy was 0.68%. In an additional twenty-one cases, microscopic foci of atypical small acinar proliferations were found in core biopsies antedating the positive core biopsy (7.1%).

Evaluation of an immunohistochemcal combination for diagnosis of prostate adenocarcinoma

目的 探讨α-甲酰基辅A消旋酶(P504S)、前列腺特异性抗原(PSA)、前列腺酸性磷酸酶(PAP)、p63和高分子量角蛋白34βE12免疫组织化学组合检测诊断前列腺腺癌的价值.方法 采用免疫组织化学SP法检测前列腺增生及前列腺腺癌患者前列腺穿刺活检或电切组织中P504S、PSA、PAP、p63和34βE12的表达,并以ELISA法测定其血清PSA含量.结果 前列腺腺癌患者与前列腺增生者血清PSA含量差异无统计学意义(t=1.91,P=0.07).P504S诊断前列腺腺癌的灵敏度和特异度分别为95.6%(44/46)和96.15%(25/26).前列腺腺癌中PSA及PAP的阳性率分别为95.56%(43/45)和100%(23/23),而p63和34βE12阴性率分别为100%(43/43)和86.4(19/22).4.2%(1/24)前列腺增生患者p63呈阴性,13.6%(3/22)前列腺腺癌患者34βE12呈阳性.P504S、p63和34βE12在前列腺增生组与前列腺腺癌组间表达的差异均有统计学意义(P＜0.01),而PSA和PAP在此两组间表达的差异均无统计学意义(P＞0.05).P504S、PSA和PAP在前列腺腺癌中的表达强度与Gleason评分无相关性(P＞0.05).结论 P504S、PSA、PAP、p63和34βE12组合检测是辅助诊断前列腺腺癌的一种较好的方法。

Identification of patients with low‐risk for aneuploidy: Comparative discriminatory models using linear and machine‐learning classifiers in prostate cancer

Prostate needle biopsy (PNB) ploidy status has proven utility to predict adverse outcomes after prostatectomy. We sought to develop models to predict ploidy status using clinicopathologic variables. We identified a cohort of 169 patients with a diagnosis of prostatic adenocarcinoma on PNB, and estimated ploidy status (determined using Feulgen stained biopsy tissue) using four predictors, including age, prebiopsy PSA, highest Gleason score (GS), and the percentage of involvement by carcinoma at the biopsy site with the highest GS (PCARBX). Logistic regression (LR), Neural Network (NN), and CART classifiers were constructed. Univariate analyses revealed all four predictors to be significantly associated with ploidy status. On multivariable analyses, LR identified a 2-parameter model, including GS and PCARBX that had a significant ability to predict ploidy status with a 74% and 75% correct classification rate (CCR), respectively. Using the same variables, CART and NN yielded similar CCRs of 70.4%. Within GS = 6 cohort, the CART model classified over 90% of biopsies as diploid when patients had a PCARBX < 55% and a log(PSA) < 1.7. Our study demonstrates that models using GS and PCARBX are able to predict PNB ploidy status with acceptable accuracy. While machine learning classifier-derived models yield similar accuracy as LR-derived models, the latter methodology has the distinct advantage of being applicable in future datasets to estimate case-specific predictions. This information may be useful in identifying potentially aneuploid patients, who can then be targeted for more aggressive therapy.

Immunohistochemistry in the diagnosis of minimal prostate cancer

Summary The diagnosis of minimal prostatic adenocarcinoma can be challenging in prostate needle biopsy tissues, and immunohistochemistry may be needed to substantiate the diagnosis of prostatic adenocarcinoma and/or exclude one of its benign mimickers. Basal cell markers, such as those targeted by the 34 β E12 antibody, and antibodies directed against cytokeratin (CK) 5/6 or p63, are very useful for demonstrating basal cells as their presence argues against a diagnosis of invasive carcinoma. The detection of α -methylacyl-coenzyme-A racemase in the appropriate histological context, and with the concurrent use of basal cell markers, can be very useful in confirming an impression of adenocarcinoma. It is important to be aware of the different caveats associated with the use of these markers. Cutting and saving interval sections and performing immunohistochemistry on destained haematoxylin and eosin-stained sections are methods that can be used to increase the diagnostic yield of immunohistochemistry in the assessment of prostatic lesions.