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Jonathan I Epstein

Publications and source records attributed to Jonathan I Epstein.

At least 55 records · Page 3Linked to original sources
PubMed2006

Prostate basal cell lesions can be negative for basal cell keratins: a diagnostic pitfall.

BACKGROUND: Prostate basal cell lesions can have architectural and cytologic atypia that mimic prostate adenocarcinoma. Immunohistochemical stains for basal cell markers are most helpful in the differential diagnosis. All of the published studies show basal cell lesions are positive for basal cell keratins, whereas adenocarcinoma is negative for both. We reported two cases of prostate basal cell lesions with negative basal cell keratin expression by immunohistochemistry. STUDY DESIGN: We reported the histologic and immunohistochemical profiles of two cases of basal cell lesions of the prostate. RESULTS: Histologically, both cases were highly suspicious for prostate adenocarcinoma with infiltrative growth pattern and significant nuclear atypia. The atypical glands in both cases were negative for basal cell keratins. However, both lesions were positive for another basal cell marker, p63, confirming that they were basal cells in origin, rather than prostate adenocarcinoma. CONCLUSION: Prostate basal cell lesions can occasionally be negative for basal cell keratins by immunohistochemistry and therefore may be misdiagnosed as prostate adenocarcinoma. We recommend using both p63 and basal cell keratins simultaneously in the workup of atypical prostate lesions to avoid such a misdiagnosis.

Adenocarcinoma↗
PubMed2005

Promoter hypermethylation as an independent prognostic factor for relapse in patients with prostate cancer following radical prostatectomy.

PURPOSE: To analyze the prognostic significance of six epigenetic biomarkers (APC, Cyclin D2, GSTP1, TIG1, Rassf1A, and RARbeta2 promoter hypermethylation) in a homogeneous group of prostate cancer patients, following radical prostatectomy alone. PATIENTS AND METHODS: Biomarker analyses were done retrospectively on tumors from 74 prostate cancer patients all with a Gleason score of 3 + 4 = 7 and minimum follow-up period of 7 years. Using quantitative methylation-specific PCR, we analyzed six gene promoters in primary prostate tumor tissues. Time to any progression was the primary end point, and development of metastatic disease and/or death from prostate cancer was a secondary point. The association of clinicopathologic and biomolecular risk factors to recurrence was done using the log-rank test and Cox proportional hazards model for multivariate analysis. To identify independent prognostic factors, a stepwise selection method was used. RESULTS: At a median follow-up time of 9 years, 37 patients (50%) had evidence of recurrence: biochemical/prostate-specific antigen relapse, metastases, or death from prostate cancer. In the final multivariate analysis for time to progression (TTP), the significant factors were age > 60 [hazard ratio (HR), 0.4; 95% confidence interval (95% CI), 0.2-0.8; P = 0.01], hypermethylation of GSTP1 (HR, 0.23; 95% CI; 0.09-0.64; P = 0.004), and hypermethylation of APC (HR, 3.0; 95% CI, 1.42-6.32; P = 0.004). In another multivariate analysis, a profile of hypermethylation of APC and cyclin D2 hypermethylation was significant as well: if either any one was hypermethylated (HR, 1.84; 95% CI, 0.92-3.72; P = 0.09) or if both were hypermethylated (HR, 4.3; 95% CI, 1.52-12.33; P = 0.01). CONCLUSIONS: Methylation status of selected genes in the prostate cancer specimen may predict for time to recurrence in Gleason 3 + 4 = 7 patients undergoing prostatectomy. These results should be validated in a larger and unselected cohort.

Adenomatous Polyposis Coli Protein↗
PubMed2005

Stronger association between obesity and biochemical progression after radical prostatectomy among men treated in the last 10 years.

BACKGROUND: Prior prospective cohort studies found that obesity was associated with increased risk of prostate cancer death. However, in the last 20 years dramatic changes in both the extent of obesity and prostate cancer screening and treatment have occurred. Whether the association between obesity and aggressive disease has changed as a result of these temporal changes is unclear. METHODS: The study population consisted of 2,832 men treated by anatomic radical retropubic prostatectomy between 1985 and 2004 by a single surgeon. We evaluated the associations of obesity (body mass index > or =30 kg/m(2))with tumor stage and grade using logistic regression and with biochemical progression using Cox proportional hazards regression. We examined whether these associations have changed over the last 20 years. RESULTS: On multivariable analysis, the strength of the positive association between obesity and high-grade disease increased over time whereas the strength of the positive association between obesity and positive surgical margins decreased over time. The strength of the positive association between obesity and extraprostatic extension fluctuated over time, although the strongest and only statistically significant association was among men treated since 2000. The association between obesity and biochemical progression was strongest among men treated since 1995 (relative risk, 1.90; 95% confidence interval, 1.09-3.30; P = 0.02). CONCLUSIONS: In the current study, with the exception of positive surgical margins, the positive association between obesity and high-grade disease, advanced stage, and biochemical progression after radical retropubic prostatectomy was in general strongest among men treated in the last 10 years. The reasons for these findings are not clear, although factors possibly related to prostate-specific antigen-based screening and/or other temporal changes in prostate cancer diagnosis and treatment may play a role.

Body Mass Index↗
PubMed2005

Current practice of Gleason grading among genitourinary pathologists.

There is consensus that the Gleason system should be used for grading of prostate cancer. However, a number of controversial issues remain as regards how this grading is applied. A questionnaire was sent to 91 genitourinary pathologists in countries around the world with the purpose to survey current practice of Gleason grading. The response rate was 74%, including 43 North American pathologists and 24 from other continents. Of all participants, only 13% and 36%, respectively, ever diagnosed a Gleason score (GS) of 2 to 3 or 4 on needle biopsies (NBX), and 88% of those who did so assigned a GS 4 to <1% of cancers. Cribriform Gleason pattern (GP) 3 was acknowledged by 88% but a majority of them would classify < or =20% of cribriform patterns as GP 3. One third only accepted cribriform or fusion patterns as GP 4, but two thirds also included incomplete or poorly defined glands. For GP 5 to be identified on NBX, 83% required clusters of individual cells, strands, or nests seen at less than x40 lens magnification. Only 26% defined GS on NBX as primary + tertiary GP, and a majority would mention a tertiary pattern separately. For NBX, global or highest GS was reported by 40% and 10%, respectively, whereas 46% only gave a separate GS for each individual NBX core. In conclusion, there is a need to standardize practical application of Gleason grading both in terms of interpretation of patterns as well as how grading is reported. Our survey data provide information to general pathologists about the most common grading practices among genitourinary pathologists.

Adult↗
PubMed2005

Glomus tumor of renal pelvis: a case report and review of the literature.

Glomus tumors are uncommon benign perivascular neoplasms that have rarely been described outside of their usual peripheral soft tissue sites. We report a unique case of glomus tumor of the renal pelvis in a 53-year-old woman who presented with microscopic hematuria associated with obstruction of the ureteropelvic junction and marked hydronephrosis. At initial gross examination, the tumor mimicked a urothelial carcinoma.

Diagnosis, Differential↗
PubMed2005

The utility of Ki-67 expression in the differential diagnosis of prostatic intraepithelial neoplasia and ductal adenocarcinoma.

Cribriform and/or papillary prostatic lesions observed on limited tissue, such as needle biopsy, can pose diagnostic dilemmas. One such area of difficulty is the distinction between papillary and/or cribriform prostatic high-grade prostatic intraepithelial neoplasia (HG-PIN) and ductal adenocarcinoma. Over 48 months, we identified 17 cases of ductal adenocarcinoma and 17 cases of HG-PIN from radical retropubic prostatectomy specimens. The HG-PIN lesions were in all cases associated with an acinar prostatic adenocarcinoma component. For each case, we evaluated the proliferative activity, assessed by Ki-67 immunohistochemistry. The majority (82%) of ductal adenocarcinomas were composed of mixed papillary and cribriform patterns, with the remaining demonstrating pure papillary or cribriform patterns. The HG-PIN lesions showed a papillary, cribriform, or mixed papillary/cribriform architecture. The proliferative activity, defined as Ki-67 labeling index, was statistically higher in ductal adenocarcinoma (mean 33%, range 21%-66%) as compared with HG-PIN (mean 6%, range 2%-15%), with no overlap in the Ki-67 indices (P = 0001). A combination of histological features and measurements of cellular proliferation may be helpful to distinguish HG-PIN from ductal adenocarcinoma in limited prostatic tissue samples.

Adenocarcinoma↗
PubMed2005

Basal cell hyperplasia: an unusual diagnostic dilemma on prostate needle biopsies.

Basal cell hyperplasia (BCH) is a well-recognized entity on transurethral resection specimens, but it is an uncommon finding on prostatic needle biopsies, and the diagnostic difficulties with it have not been fully defined on this material. A 13-year (1991-2003) retrospective review of the consult files of one of the authors was performed. In all cases, the focus of BCH was referred for consultation to rule out adenocarcinoma. Thirty-three cases of prominent BCH were identified. The dominant pattern of BCH consisted of either glands (26/33) or solid nests (7/33). Other minor patterns included cribriform (5), pseudocribriform (4), cords (1), and adenoid basal (1). Twelve of 33 cases showed an infiltrative pattern. Other features of BCH included prominent nucleoli (14/33), abnormal secretions (17/33 with dense pink and/or blue mucin), mitoses (6/33), altered stroma with increased cellularity (6/33), calcifications (6/33), intraluminal crystalloids (3/33) and perineural invasion (1/33). By immunohistochemistry, 7 (100%) out of 7 were positive for p63 and 14 (88%) of 16 were positive for high molecular weight cytokeratin. No cases (0/6) were positive for alpha-methylacyl-coenzyme A racemase. Basal cell hyperplasia, as a mimicker of cancer, is an uncommon entity encountered on prostatic needle biopsies. Helpful features for its diagnosis include solid nests, pseudocribriform glands, multilayering of cells, calcifications, and cellular stroma. Immunohistochemistry can be useful for documenting the basal cell layer and demonstrating negative racemase staining.

Adenocarcinoma↗
PubMed2005

Number and location of nucleoli and presence of apoptotic bodies in diagnostically challenging cases of prostate adenocarcinoma on needle biopsy.

There is limited published data regarding the significance of the number or position of nucleoli and the presence of apoptotic bodies in diagnostically challenging cases of adenocarcinoma of the prostate on needle biopsy material. One hundred consecutive prostate cancers on needle biopsy were sent because of diagnostic difficulty to an expert in urological pathology, and the remaining normal benign prostatic glands on the same core were evaluated for the number and location of nucleoli and for the presence of mitotic figures and apoptotic bodies. The Gleason scores of the cases were 6 (86%), 7 (9%), and 8 to 10 (5%). For comparison, the same parameters were evaluated in mimickers of cancer on needle biopsy from other cases, including partial atrophy (n = 135), fully developed atrophy (n = 89), adenosis (n = 50), prostate glands with acute inflammation (n = 50), and high-grade prostatic intraepithelial neoplasia (n = 100). Findings were recorded under high dry magnification (x40) using hematoxylin and eosin-stained sections. Although the number and position of nucleoli did not discriminate between cancer and benign mimickers, mitotic figures and apoptotic bodies were more commonly seen in cancer. Apoptotic bodies in particular were seen fairly frequently (34%) in prostatic adenocarcinoma (also seen in 13% of high-grade prostatic intraepithelial neoplasia), yet rarely in benign mimickers on needle biopsy. Our findings indicate that the presence of apoptotic bodies should be added to the list of histological features that are helpful in the diagnosis of challenging cases of prostate cancer on needle biopsy.

Adenocarcinoma↗
PubMed2005

Anaplastic signet ring cell carcinoma arising in gastrocystoplasty.

Augmentation cystoplasty operations using segments of gastrointestinal tract are often necessary in neurogenic low-compliance bladders. Patients are usually rehabilitated with an increase in storage volume and normalization of the reduced compliance. However, gut mucosa-related early and late complications are not very uncommon. Malignancy, although rare, is known to occur after enterocystoplasty, but only one such case has been reported for gastrocystoplasty, a single patient who developed urothelial carcinoma. We describe what we believe to be the first case of signet ring cell carcinoma developing after gastrocystoplasty.

Adult↗
PubMed2005

Utility of saturation biopsy to predict insignificant cancer at radical prostatectomy.

OBJECTIVES: To determine whether potential candidates for watchful waiting have undersampling of more substantial cancer. METHODS: A total of 103 men were studied, who were predicted to have insignificant cancer in their radical prostatectomy (RP) specimen. All had limited cancer on routine needle biopsy (no core with more than 50% involvement; Gleason score less than 7, and fewer than 3 cores involved) with a serum prostate-specific antigen density of 0.15 or less. Insignificant tumor at RP was considered organ-confined tumor, no Gleason pattern 4 or 5, and a tumor volume of less than 0.5 cm3. Saturation biopsy (average 44 cores) and an alternate biopsy saturation scheme with one half the number of cores using an 18-gauge Biopty gun was performed in the pathology laboratory on totally embedded and serially sectioned RP specimens. RESULTS: Of the tumors, 97% were organ confined. The RP Gleason score was less than 7 in 84% of the cases. The RP tumor volume was 0.01 to 2.39 cm3 (median 0.14). Of the cancer specimens, 71% were insignificant and 29% had been incorrectly classified before surgery using standard biopsy schemes. Using the full saturation biopsy scheme, if we predicted significant cancer, the probability of having insignificant cancer was only 11.5% (false-positive rate). If the model predicted insignificant cancer, the probability of significant cancer was also only 11.5% (false-negative rate; sensitivity 71.9% and specificity 95.8%). Using the alternate biopsy sampling scheme, the false-positive rate was 8% and the false-negative rate was 11.4% (sensitivity 71.9% and specificity 97.1%). CONCLUSIONS: Saturation biopsy provides accurate predictability of prostate tumor volume and grade to select suitable candidates for watchful waiting therapy.

Adult↗
PubMed2005

Prognostic and predictive factors in prostate cancer: historical perspectives and recent international consensus initiatives.

An understanding of prognosis in cancer medicine is important for patient care, research and cancer control programs. In prostate cancer, prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic and biomolecular levels. Clinical stage and histologic grade have historically played major roles in defining heterogeneity in prostate cancer. More recently, serum prostate-specific antigen measurement has assumed a significant prognostic role. Over the last two decades there has been an explosion of research into biomarkers, many of which have been purported to have prognostic significance. In this paper we present an overview of the various consensus initiatives that have transpired over the last dozen years. Criteria for evaluating prognostic factors and classifications of predictive factors have emerged that have proven useful and advanced our understanding of the biology of prostate cancer. The results of these consensus initiatives form a foundation on which the current international consultation on prognosis (prediction) in prostate cancer is built. Advances in our understanding of the new and promising prognostic factors will require a more rigorous evidence-based approach to the analysis of published studies. Furthermore, appropriate mathematical models for the analysis of the multiple factors that influence a prognostic system will have to be employed.

Adenocarcinoma↗
PubMed2005

Prognostic and predictive factors and reporting of prostate carcinoma in prostate needle biopsy specimens.

The information provided in the surgical pathology report of a prostate needle biopsy of carcinoma has become critical in the subsequent management and prognostication of the cancer. The surgical pathology report should thus be comprehensive and yet succinct in providing relevant information consistently to urologists, radiation oncologists and oncologists and, thereby, to the patient. This paper reflects the current recommendations of the 2004 World Health Organization-sponsored International Consultation, which was co-sponsored by the College of American Pathologists. It builds on the existing work of several organizations, including the College of American Pathologists, the Association of Directors of Anatomic and Surgical Pathologists, the Royal Society of Pathologists, the European Society of Urologic Pathology and the European Randomized Study of Screening for Prostate Cancer.

Biomarkers, Tumor↗
PubMed2005

Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens.

This paper, based on the activity of the Morphology-Based Prognostic Factors Committee of the 2004 World Health Organization-sponsored International Consultation, describes various methods of handling radical prostatectomy specimens for both routine clinical use and research purposes. The correlation between radical prostatectomy findings and postoperative failure is discussed in detail. This includes issues relating to pelvic lymph node involvement, detected both at the time of frozen section and in permanent sections. Issues of seminal vesicle invasion, including its definition, routes of invasion and relationship to prognosis, are covered in detail. The definition, terminology and incidence of extra-prostatic extension are elucidated, along with its prognostic significance relating to location and extent. Margins of resection are covered in terms of their definition, the etiology, incidence and sites of positive margins, the use of frozen sections to assess the margins and the relationship between margin positivity and prognosis. Issues relating to grade within the radical prostatectomy specimen are covered in depth, including novel ways of reporting Gleason grade and the concept of tertiary Gleason patterns. Tumor volume, tumor location, vascular invasion and perineural invasion are the final variables discussed relating to the prognosis of radical prostatectomy specimens. The use of multivariate analysis to predict progression is discussed, together with proposed modifications to the TNM system. Finally, biomarkers to predict progression following radical prostatectomy are described, including DNA ploidy, microvessel density, Ki-67, neuroendocrine differentiation, p53, p21, p27, Bcl-2, Her-2/neu, E-cadherin, CD44, retinoblastoma proteins, apoptotic index, androgen receptor status, expression of prostate-specific antigen and prostatic-specific acid phosphatase and nuclear morphometry.

Biomarkers, Tumor↗
PubMed2005

Radical retropubic prostatectomy. How often do experienced surgeons have positive surgical margins when there is extraprostatic extension in the region of the neurovascular bundle?

PURPOSE: We determined the frequency of positive surgical margins (PSMs) in patients with extraprostatic extension (EPE) in the region of the neurovascular bundle (NVB) who underwent open radical retropubic prostatectomy by 2 experienced surgeons. MATERIALS AND METHODS: A total of 204 men with EPE in the region of the NVB underwent surgery by 2 experienced surgeons. The frequency of PSMs in the area of the NVB as well as the nerve sparing status of each lobe of the prostate were determined through a retrospective investigation of the pathology database as well as the physician's database. The recovery of sexual function was determined and compared to controls. RESULTS: The age, clinical stage, biopsy Gleason sum and serum prostate specific antigen of the patients operated on by surgeons 1 and 2 were similar. Surgeon 1 widely excised at least 1 neurovascular bundle in 16% of the patients and surgeon 2 in 63%. The overall frequency of PSMs at the NVB was 5.9% for surgeon 1 and 5.8% for surgeon 2. Of the evaluable patients followed for 12 months or longer 83.5% of those operated on by surgeon 1 were potent compared to 63.8% of those operated on by surgeon 2. CONCLUSIONS: Visual and tactile assessment during open surgery by an experienced surgeon provides valuable information on when and where it is safe to preserve the neurovascular bundle in patients with EPE in the region of the NVB. Surgical approaches in which tactile sensation is muted or absent, laparoscopic and robotic, need to undergo a similar evaluation to determine whether magnification of the operative field is sufficient to overcome the lack of haptic feedback and ability to palpate the tissue.

Adult↗
PubMed2005

Prediction of extraprostatic extension in the neurovascular bundle based on prostate needle biopsy pathology, serum prostate specific antigen and digital rectal examination.

PURPOSE: There are few studies on predictors of extraprostatic extension (EPE) in the region of the neurovascular bundle (NVB). We investigated whether clinical information and prostate biopsy data could predict EPE of clinical localized prostate cancer. MATERIALS AND METHODS: Through a retrospective analysis of the pathology database we identified 2,660 cases of clinically localized prostate cancer treated with radical retropubic prostatectomy without preoperative adjuvant therapy at The Johns Hopkins Hospital. The study sample involved a total of 3,006 lobes with prostate cancer including 2,070 with organ confined disease, 620 with EPE in the NVB at the posterolateral edge of the prostate and 316 with EPE in a region other than the NVB (EPE elsewhere). Through univariate and multivariate logistic regression analysis we determined whether patient age, year of surgery, serum prostate specific antigen, digital rectal examination, biopsy highest Gleason score, perineural invasion, percent of side specific biopsy cores with cancer, percent of each core involved with cancer and the maximum percent of a core involved with cancer was predictive of EPE in the NVB. RESULTS: Prostate specific antigen (10 or greater vs less than 10), biopsy Gleason score (7 or greater vs 6 or less), digital rectal examination (abnormal vs normal), percent of side specific cores with tumor (greater than 33.3% vs 33.3% or less) and average percent involvement of each positive core (greater than 20% vs 20% or less) were all found to be statistically significant independent predictors of NVB penetration in multivariate analysis. The generated model stratifies each of these variables into high and low risk. The probability of EPE in the NVB was less than 10% in cases with 1 or fewer of the higher risk variables and was 10% or greater in cases with more than 1 of the higher risk variables. CONCLUSIONS: The model generated in this study allows for the preoperative identification of patients with 10% or greater probability of EPE in the NVB. Our algorithm will help provide objective parameters that aid in the decision to spare the NVB safely.

Biopsy, Needle↗
PubMed2005

Serum leptin and pathological findings at the time of radical prostatectomy.

PURPOSE: Obesity has been associated with a higher risk of progression following radical prostatectomy (RP). Obese men have higher serum leptin, a hormone produced by adipocytes, which has also been shown to be an in vitro prostate cancer growth factor. We examined whether serum leptin correlates with advanced pathological findings at RP. MATERIALS AND METHODS: Preoperative serum from 225 men treated with RP between 1998 and 1999 was examined for serum leptin. Multivariate logistic regression analysis was used to determine whether serum leptin was predictive of extraprostatic extension (pT3a). RESULTS: Serum leptin highly correlated with body mass index (Spearman r = 0.602, p <0.001). Serum leptin was not associated with total or percent free prostate specific antigen (PSA), biopsy or prostatectomy Gleason score, age or height. On multivariate analysis with total and percent free PSA, clinical stage, age, biopsy Gleason score, body mass index, serum leptin, and height as variables considered for entry into the model, serum PSA (p = 0.009), clinical stage (p = 0.019) and serum percent free PSA (p = 0.041) were the only variables predictive of extraprostatic extension. Serum leptin was not significantly associated with pathological stage (pT3a). CONCLUSIONS: In the current study of predominantly white men with mainly low risk disease there was no statistically significant association between serum leptin and pathological stage (pT3a) at RP. In this cohort serum leptin was not a good biomarker for predicting advanced stage at RP.

Humans↗
PubMed2005

Patient and urologist driven second opinion of prostate needle biopsies.

PURPOSE: We reviewed second opinion prostate needle biopsies that were patient and urologist driven to determine how often an expert opinion resulted in a different diagnosis. MATERIALS AND METHODS: Of 3,155 prostate needle biopsy consultations received during a 6-month interval 684 were sent at the request of the patient or urologist. A significant change in outside diagnosis was one that could potentially result in a change in therapy or prognosis. RESULTS: The second opinion was requested by patients (21.6%), urologist (63.9%) and patients plus urologists (14.5%). The distribution of the 684 outside diagnoses was benign in 6.1%, HGPIN in 7.6%, atypical (ATYP) in 29.8% and cancer in 56.5%. In 241 cases (35.2%) a change in diagnosis was rendered upon expert review. We agreed with the majority of outside cancer, benign and HGPIN diagnoses, in contrast to only 36.8% of outside ATYP cases (p <0.0001). Uncommonly did a cancer diagnosis become a benign one or vice versa. Of changes affecting outside cancer diagnoses 73.5% were due to changes in Gleason score. The diagnosis was more likely to be changed when the consultation was requested by the urologist rather than by the patient (41.4% vs 25%, p <0.0001). CONCLUSIONS: Cases diagnosed as ATYP have the highest likelihood of being changed upon expert review. Urologists should consider sending such cases for consultation to attempt to resolve the diagnosis as definitively benign or malignant before subjecting the patient to repeat biopsy.

Adenocarcinoma↗