Prostatic Neoplasms: Epstein JI

Kramer BS, Hagerty KL, Justman S, Somerfield MR, Albertsen PC, Blot WJ, Ballentine Carter H, Costantino JP, Epstein JI, Godley PA, Harris RP, Wilt TJ, Wittes J, Zon R, Schellhammer P, Anonymous00093, Anonymous00094. · National Institutes of Health, Bethesda, MD, USA. · J Clin Oncol. · Pubmed #19252137 No free full text.

Abstract: PURPOSE To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. Results The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION Asymptomatic men with a prostate-specific antigen (PSA) <or= 3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.

Kramer BS, Hagerty KL, Justman S, Somerfield MR, Albertsen PC, Blot WJ, Carter HB, Costantino JP, Epstein JI, Godley PA, Harris RP, Wilt TJ, Wittes J, Zon R, Schellhammer P, Anonymous00066. · National Institutes of Health, Bethesda, MD, USA. · J Urol. · Pubmed #19249063 No free full text.

Abstract: PURPOSE: To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS: The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. RESULTS: The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION: Asymptomatic men with a prostate-specific antigen (PSA) </=3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.

Kawachi MH, Bahnson RR, Barry M, Carroll PR, Carter HB, Catalona WJ, Epstein JI, Etzioni RB, Hemstreet GP, Howe RJ, Kopin JD, Lange PH, Lilja H, Mohler J, Moul J, Nadler RB, Patterson S, Pollack A, Presti JC, Stroup AM, Urban DA, Wake R, Wei JT, Anonymous00333. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #17692177 No free full text.

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Epstein JI, Srigley J, Grignon D, Humphrey P, Otis C. · The Johns Hopkins Hospital, 401 N Broadway St, Rom 2242, Baltimore, MD 21231, USA. · Virchows Arch. · Pubmed #17674043 No free full text.

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Epstein JI. · No affiliation provided · Am J Surg Pathol. · Pubmed #10757394 No free full text.

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Epstein JI. · No affiliation provided · Hum Pathol. · Pubmed #10667412 No free full text.

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Epstein JI. · Departments of Pathology, Urology and Oncology, The Johns Hopkins Hospital, 401 N. Broadway St., Rm 2242, Baltimore, MD, 21231, USA. · Virchows Arch. · Pubmed #19048290 No free full text.

Abstract: High-grade prostatic intraepithelial neoplasia (PIN) is the one well-documented precursor to adenocarcinoma of the prostate. This review article defines both low- and high-grade PIN. Unusual variants of high-grade PIN are illustrated. Benign lesions that may be confused with high-grade PIN, including central zone histology, clear cell cribriform hyperplasia, and basal cell hyperplasia are described and illustrated. High-grade PIN is also differentiated from invasive acinar (usual) and ductal adenocarcinoma. The incidence of high-grade PIN, its relationship to carcinoma (including molecular findings), and risk of cancer on rebiopsy are covered in detail. Finally, intraductal carcinoma of the prostate, a controversial entity, is discussed and differentiated from high-grade PIN.

Samaratunga H, Epstein JI. · Department of Anatomical Pathology, Sullivan Nicolaides Pathology, 134 Whitmore Street, Taringa, Brisbane, QLD, 4068, Australia. · World J Urol. · Pubmed #18408932 No free full text.

Abstract: OBJECTIVES: Low-risk prostate cancer is defined as a clinical T1c or T2a tumor with a Gleason score of </=6 and PSA <10 ng/ml. This is a pretreatment diagnosis and the patient can turn out to have either significant or insignificant disease. With methods currently available in practice it may not be possible to differentiate between these groups. Numerous molecular pathological changes have been described in prostate carcinoma. This review was to evaluate which of these changes may be useful to distinguish the group of patients likely to have significant carcinoma within the low risk category. MATERIALS AND METHODS: The literature on molecular pathology of prostate cancer was reviewed using MEDLINE and reference lists of relevant publications focusing on early and late molecular events and available molecular biomarkers in prostate cancer. RESULTS: There are a variety of molecular markers with the potential to be clinically utilized for assessment of low risk prostate cancer. One of the most promising is TMPRSS2: ETS fusion, which is a homogeneous event occurring early in prostate carcinogenesis. Other promising markers include p27, EZH2 and c-MYC. CONCLUSIONS: FISH analysis or RT-PCR based assays to detect TMPRSS2: ETS fusion and immunohistochemical assessment of p27, EZH2 and c-MYC may become useful ancillary tests in patients with low risk prostate cancer. Some serum biomarkers have promise for future use. Large prospective studies followed by clinical trials are necessary before these molecular markers could be integrated into clinical practice.

Epstein JI, Srigley J, Grignon D, Humphrey P, Anonymous00049. · Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. · Hum Pathol. · Pubmed #17707261 No free full text.

Abstract: It has been evident for decades that pathology reports are very variable even within a single institution. Standardization of reporting is the optimal way to insure that information necessary for patient management, prognostic and predictive factor assessment, grading, staging, analysis of outcomes, and tumor registries are included in pathology reports. The ADASP has chosen a pathologist expert in each field to assemble a group from within the pathology community (with clinician input if desired) to write specific cancer protocols. These were then approved by the ADASP council and subsequently by the membership. The American College of Surgery Commission on Cancer (COC) accredits cancer centers in the United States. Recently, the COC decided to require elements, deemed as essential by the CAP, to be described in all pathology reports in their accredited cancer centers as of January 2004. Importantly, they do not require that the specific College of Pathologists (CAP) protocols or synoptic reports be used. ADASP has updated all of its protocols to comply with the COC requirements in the form of uniform checklists. The checklists use the staging criteria cited in the American Joint Committee on Cancer 2002 staging manual (sixth edition) but include a variety of other references listed in each of the checklists. Moreover, the checklists are formatted for ease of use. They may be used as templates for uniform reporting and are designed to be compatible with voice-activated transcription. The different elements in these revised ADASP diagnostic checklists have been divided into Required and Optional. The term Required in this context only signifies compliance with the COC guidelines. ADASP realizes that specimens and practices vary, and it will not be possible to report these elements in every case. However, ADASP hopes that pathologists will find these checklists useful in daily clinical practice while facilitating compliance with the new COC requirements.

Hansel DE, Herawi M, Montgomery E, Epstein JI. · Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA. · Mod Pathol. · Pubmed #17170745 links to  free full text

Abstract: Prostatic spindle cell lesions are diagnostically challenging and encompass a broad array of benign and malignant processes. A subset of these lesions arises only within the prostate and generally represents entities that originate from the prostate epithelium or stroma, such as sclerosing adenosis, sarcomatoid carcinoma, stromal tumors of uncertain malignant potential (STUMP), and stromal sarcoma. Another subset of spindle cell tumors that involve the prostate are also found at other sites and include solitary fibrous tumor, leiomyosarcoma, and neural lesions among others. Finally, tumors may secondarily involve the prostate yet present as primary prostatic processes, as is evident with several cases of gastrointestinal stromal tumors (GIST). The utility of ancillary studies, including immunohistochemistry, is often limited and the main criteria for diagnosis are the morphologic findings by routine H&E stain. This review addresses the various entities that may present as spindle cell tumors within the adult prostate and discusses the functional aspects of the differential diagnosis of these lesions.

Epstein JI. · Departments of Disease, Urology, and Oncology, The Johns Hopkins Hospital, 401 N. Broadway, Baltimore, MD 21231, USA. · Curr Opin Urol. · Pubmed #16679850 No free full text.

Abstract: PURPOSE OF REVIEW: Issues relating to the disease are critical in the diagnosis, management, and prognostication of prostate cancer. RECENT FINDINGS: New data have emerged regarding the disease of prostate cancer and its precursors. The diagnosis of prostate cancer on needle biopsy has been refined because of the recent discovery of alpha-methylacyl-CoA racemase, which preferentially labels adenocarcinoma of the prostate. Modifications and additions to the Gleason grading system were published based on a consensus conference of urological pathologists. Various models have been proposed using Gleason score, clinical findings, as well as measurements of tumor volume on needle biopsy to enhance the prediction in men undergoing radical prostatectomy and to predict "insignificance". Several studies have confirmed that certain findings in radical prostatectomy are adverse, yet conflicting studies were published as to the independent prognosis of tumor volume. The risk of cancer following a diagnosis of high-grade prostatic intraepithelial neoplasia on needle biopsy has decreased to the point at which this author does not recommend a routine repeat needle biopsy within the first year following the diagnosis of high-grade prostatic intraepithelial neoplasia. SUMMARY: This review summarizes developments over the last year in the disease of prostate cancer and its precursors.

Epstein JI, Herawi M. · Department of Pathology, The Johns Hopkins University School of Medicine, The James Brady Urological Institute, The Johns Hospital, Baltimore, Maryland 21231, USA. · J Urol. · Pubmed #16469560 No free full text.

Abstract: PURPOSE: We identified information critical for patient treatment on prostate needle biopsies diagnosed with prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma. MATERIALS AND METHODS: A search was performed using the MEDLINE database and referenced lists of relevant studies to obtain articles addressing the significance of finding PIN or atypical foci suspicious for carcinoma on needle biopsy. RESULTS: There were certain results concerning PIN. 1) Low grade PIN should not be documented in pathology reports due to poor interobserver reproducibility and a relatively low risk of cancer following re-biopsy. 2) The expected incidence of HGPIN on needle biopsy is between 5% and 8%. 3) Although the diagnosis of HGPIN is subjective, interobserver reproducibility for its diagnosis is fairly high among urological pathologists, and yet only moderate among pathologists without special expertise in prostate pathology. 4) The median risk recorded in the literature for cancer following the diagnosis of HGPIN on needle biopsy is 24.1%, which is not much higher than the risk reported in the literature for repeat biopsy following a benign diagnosis. 5) The majority of publications that compared the risk of cancer in the same study following a needle biopsy diagnosis of HGPIN to the risk of cancer following a benign diagnosis on needle biopsy show no differences between the 2 groups. 6) Clinical and pathological parameters do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. 7) A major factor contributing to the decreased incidence of cancer following a diagnosis of HGPIN on needle biopsy in the contemporary era is related to increased needle biopsy core sampling, which detects many associated cancers on initial biopsy, such that re-biopsy, even with good sampling, does not detect many additional cancers. 8) It is recommended that men do not need routine repeat needle biopsy within the first year following the diagnosis of HGPIN, while further studies are needed to confirm whether routine repeat biopsies should be performed several years following a HGPIN diagnosis on needle biopsy. There were certain results concerning atypical glands suspicious for carcinoma. 1) An average of 5% of needle biopsy pathology reports are diagnosed as atypical glands suspicious for carcinoma. 2) Cases diagnosed as atypical have the highest likelihood of being changed upon expert review and urologists should consider sending such cases for consultation in an attempt to resolve the diagnosis as definitively benign or malignant before subjecting the patient to repeat biopsy. 3) Ancillary techniques using basal cell markers and AMACR (alpha-methyl-acyl-coenzyme A racemase) can decrease the number of atypical diagnoses, and yet one must use these techniques with caution since there are numerous false-positive and false-negative results. 4) The average risk of cancer following an atypical diagnosis is approximately 40%. 5) Clinical and pathological parameters do not help predict which men with an atypical diagnosis have cancer on repeat biopsy. 6) Repeat biopsy should include increased sampling of the initial atypical site, and adjacent ipsilateral and contralateral sites with routine sampling of all sextant sites. Therefore, it is critical for urologists to submit needle biopsy specimens in a manner in which the sextant location of each core can be determined. 7) All men with an atypical diagnosis need re-biopsy within 3 to 6 months. CONCLUSIONS: It is critical for urologists to distinguish between a diagnosis of HGPIN and that of atypical foci suspicious for cancer on needle biopsy. These 2 entities indicate different risks of carcinoma on re-biopsy and different recommendations for followup.

Epstein JI, Allsbrook WC, Amin MB, Egevad LL, Anonymous00202. · Department of Pathology, Urology and Oncology, Johns Hopkins Hospital, Baltimore, MD 21231, USA. · Am J Surg Pathol. · Pubmed #16096414 No free full text.

This publication has no abstract.

Epstein JI, Amin M, Boccon-Gibod L, Egevad L, Humphrey PA, Mikuz G, Newling D, Nilsson S, Sakr W, Srigley JR, Wheeler TM, Montironi R. · Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland 21231, USA. · Scand J Urol Nephrol Suppl. · Pubmed #16019758 No free full text.

Abstract: 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.

Amin M, Boccon-Gibod L, Egevad L, Epstein JI, Humphrey PA, Mikuz G, Newling D, Nilsson S, Sakr W, Srigley JR, Wheeler TM, Montironi R. · Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. · Scand J Urol Nephrol Suppl. · Pubmed #16019757 No free full text.

Abstract: 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.

Srigley JR, Amin M, Boccon-Gibod L, Egevad L, Epstein JI, Humphrey PA, Mikuz G, Newling D, Nilsson S, Sakr W, Wheeler TM, Montironi R. · Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. · Scand J Urol Nephrol Suppl. · Pubmed #16019756 No free full text.

Abstract: 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.

Parwani AV, Cao D, Epstein JI. · Department of Pathology, The Johns Hopkins Hospital, Baltimore, Md 21231, USA. · Arch Pathol Lab Med. · Pubmed #15270627 No free full text.

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De Marzo AM, DeWeese TL, Platz EA, Meeker AK, Nakayama M, Epstein JI, Isaacs WB, Nelson WG. · Department of Oncology, The Johns Hopkins University School of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21231-1000, USA. · J Cell Biochem. · Pubmed #14755677 No free full text.

Abstract: Prostate cancer is an increasing threat throughout the world. As a result of a demographic shift in population, the number of men at risk for developing prostate cancer is growing rapidly. For 2002, an estimated 189,000 prostate cancer cases were diagnosed in the U.S., accompanied by an estimated 30,200 prostate cancer deaths [Jemal et al., 2002]. Most prostate cancer is now diagnosed in men who were biopsied as a result of an elevated serum PSA (>4 ng/ml) level detected following routine screening. Autopsy studies [Breslow et al., 1977; Yatani et al., 1982; Sakr et al., 1993], and the recent results of the Prostate Cancer Prevention Trial (PCPT) [Thompson et al., 2003], a large scale clinical trial where all men entered the trial without an elevated PSA (<3 ng/ml) were subsequently biopsied, indicate the prevalence of histologic prostate cancer is much higher than anticipated by PSA screening. Environmental factors, such as diet and lifestyle, have long been recognized contributors to the development of prostate cancer. Recent studies of the molecular alterations in prostate cancer cells have begun to provide clues as to how prostate cancer may arise and progress. For example, while inflammation in the prostate has been suggested previously as a contributor to prostate cancer development [Gardner and Bennett, 1992; Platz, 1998; De Marzo et al., 1999; Nelson et al., 2003], research regarding the genetic and pathological aspects of prostate inflammation has only recently begun to receive attention. Here, we review the subject of inflammation and prostate cancer as part of a "chronic epithelial injury" hypothesis of prostate carcinogenesis, and the somatic genome and phenotypic changes characteristic of prostate cancer cells. We also present the implications of these changes for prostate cancer diagnosis, detection, prevention, and treatment.

Epstein JI. · Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Mod Pathol. · Pubmed #14739905 links to  free full text

Abstract: The diagnosis of limited adenocarcinoma of the prostate is one of the more difficult challenges in surgical pathology. This paper highlights the methodological approach to diagnosing limited cancer, based on a constellation of features more commonly present in adenocarcinoma than benign glands. In assessing small foci of atypical glands on needle biopsy, one looks for differences between the benign glands and the atypical glands in terms of nuclear features, cytoplasmic features, and intraluminal contents. Only a few features, such as glomerulations, mucinous fibroplasia (collagenous micronodules), and perineural invasion are diagnostic in and of themselves for prostate cancer. Immunohistochemistry may be a useful adjunct in the diagnosis of limited adenocarcinoma of the prostate, although as with any immunohistochemical studies, there are problems with both sensitivity and specificity. Basal cell markers, such as high molecular weight cytokeratin and more recently, p63, highlight basal cells found in benign glands, yet are absent in adenocarcinoma of the prostate. However, not all benign glands label uniformly with basal cell markers. Certain mimickers of adenocarcinoma of the prostate are even less frequently labeled uniformly with these stains. Consequently, negative staining in a small focus of atypical glands for basal cell markers is not diagnostic of adenocarcinoma of the prostate. More recently, a marker has been identified that relatively selectively labels adenocarcinoma of the prostate. AMACR will label the cytoplasm of approximately 80% of limited adenocarcinoma of the prostate cases on needle biopsy. In positive cases, not all of the glands will be positive and those that are positive are often not intensely positive. Certain variants of adenocarcinoma of the prostate that are a little more difficult to recognize, such as foamy glands adenocarcinoma, pseudohyperplastic adenocarcinoma, and atrophic adenocarcinoma, are labeled with AMACR in only approximately 60-70% of cases. In addition to problems with sensitivity, AMACR is not entirely specific for adenocarcinoma, and will label almost all cases of high-grade prostatic intraepithelial neoplasia, some foci of adenosis, and even some entirely benign glands. Finally, this paper will briefly cover the significance of atypical or suspicious prostate needle biopsies, and how to report the key diagnostic and prognostic information on needle biopsy.

Zhou M, Epstein JI. · Department of Anatomic Pathology, The Cleveland Clinic Foundation, Cleveland, OH, USA. · Pathology. · Pubmed #14660096 No free full text.

Abstract: Prostate needle biopsy remains the gold standard for diagnosing prostate cancer. Prostate cancer on needle biopsy can be evaluated by numerous techniques of quantifying tumour extent, Gleason score, and the presence of perineural invasion (PNI). These modalities can help clinicians in assessing the risk of extraprostatic disease, progression likelihood, and in helping men with prostate cancer choose among therapeutic options. This review details the information that should be included in the routine pathology report. Recent advances in molecular biology of prostate carcinogenesis have identified many molecular markers for prostate cancer. While several are extremely promising as diagnostic immunohistochemical markers, other prognostic markers are not yet ready to be used in routine practice until they are validated by large prospective studies.

Weir EG, Epstein JI. · Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Md 21231, USA. · Arch Pathol Lab Med. · Pubmed #12708899 No free full text.

Abstract: CONTEXT: Incidental non-Hodgkin lymphoma is often unrecognized at the time of radical prostatectomy in patients with prostate cancer because of nonspecific symptoms and an inconspicuous pathology. The early identification of lymphoma allows optimal long-term management and prevention of significant morbidity. OBJECTIVE: To show the subtlety of pathologic findings in cases of non-Hodgkin lymphoma in pelvic lymph nodes and the need for scrupulous attention to detail for diagnostic accuracy. DESIGN: Histologic and immunohistochemical profiles of 18 consecutive cases of small lymphocytic lymphoma (SLL) incidentally identified in pelvic lymph node dissections were reviewed and compared with 22 cases of benign pelvic lymph node dissections. RESULTS: Malignant nodes were grossly enlarged and averaged 3.2 cm in their greatest dimension. Histologically, 16 of the SLL cases were characterized by diffuse architectural effacement with obliterated sinuses and rare cortical follicles. Twelve of these cases showed evidence of pseudofollicles. Two cases showed an interfollicular growth pattern with occasional small pseudofollicles. In contrast, benign pelvic lymph nodes averaged 1.7 cm in their greatest dimension. Although most were architecturally distorted by fibrosis, all benign nodes were notable for patent sinuses. Immunohistochemistry was diagnostically helpful in several cases with equivocal morphology. All malignant cases had a B-cell phenotype with aberrant coexpression of T-cell-related antigens typical of SLL. CONCLUSION: Incidental low-grade non-Hodgkin lymphoma identified at radical prostatectomy is often overlooked by both the urologist and the pathologist. Although malignant pelvic lymph node dissections frequently lack overt manifestations of lymphoma, attention to subtle morphologic features coupled with lymph node size and immunohistochemical findings should permit diagnostic accuracy.

DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI. · Department of Pathology, Johns Hopkins' University School of Medicine, Johns Hopkins' Hospital, Baltimore, MD 21231, USA. · Lancet. · Pubmed #12648986 No free full text.

Abstract: This review focuses on new findings and controversial issues in the the pathology and molecular biology of adenocarcinoma of the prostate. Since management of high-grade prostatic intraepithelial neoplasia on needle biopsy--the most common precursor lesion to prostate cancer--is the crucial issue with this lesion, we discuss the risk of cancer subsequent to this histological diagnosis and the issue of whether such neoplasia should be regarded as carcinoma-in-situ. We also look at prostate cancer itself, starting with its diagnosis, reporting on needle biopsy, and reviewing how the most frequently used grading system, the Gleason grading system, affects treatment. The molecular basis of prostate cancer includes inheritable and somatic genetic changes (tumour suppressor genes, loss of heterozygosity, gene targets and regions of chromosomal gain, CpG island promoter methylation, invasion and metastasis suppressor genes, telomere shortening, and genetic instability). Changed gene expression (eg, proliferation-related genes, changes in the androgen receptor, apoptosis and stress-response genes) have potential as biomarkers and therapeutic targets in prostate cancer.

Epstein JI. · Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Urol Clin North Am. · Pubmed #11590815 No free full text.

Abstract: Despite the wealth of information obtained by conventional histology, long-term studies are needed to provide novel information on the correlation of pathologic findings with prognosis. Findings need to be correlated not only with PSA progression but with the more clinically important parameters of distant metastases and survival. Although conventional histology still will have a role in the evaluation of prostate cancer at radical prostatectomy and its correlation with outcome, it undoubtedly will be augmented by newer techniques. These developments must be approached critically and rationally to determine whether they provide additional prognostic information beyond that currently available using more conventional parameters.

Han M, Partin AW, Pound CR, Epstein JI, Walsh PC. · James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. · Urol Clin North Am. · Pubmed #11590814 No free full text.

Abstract: In a large series of 2404 men with a mean follow-up of 6.3 plus or minus 4.2 years (range, 1-17) after anatomic RRP for clinically localized prostate cancer, 412 men (17%) have recurred. A detectable PSA was the only evidence of recurrence in 9.7%, whereas 1.7% and 5.8% had local recurrence and distant metastasis, respectively. The overall actuarial 5-, 10-, and 15-year recurrence-free survival rates for these men were 84%, 74%, and 66%, respectively. As demonstrated in the authors' previous reports, the actuarial likelihood of a postoperative recurrence increased with advancing clinical stage, Gleason-score, preoperative PSA level, and pathologic stage. Subdivision of men with Gleason 7 tumors resulted in better stratification. There was a similar actuarial likelihood of postoperative recurrence for men with Gleason 4 + 3 and Gleason score 8 to 10 disease. The actuarial rate of recurrence of tumor for men with Gleason 3 + 4 disease was statistically different from the rate for men with Gleason score 6 or Gleason 4 + 3 disease. The overall actuarial metastasis-free survival rates at 5, 10, and 15 years were 96%, 90%, and 82%, respectively. The overall actuarial cancer-specific survival rates at 5, 10, and 15 years were 99%, 96%, and 90%, respectively. This study provides long-term outcome of patients with clinically localized cancer who underwent RRP between 1982 and 1999. Recognizing that this long-term study includes many patients with more advanced disease diagnosed before the PSA era, caution must be exercised in comparing these results with the outcomes for cohorts of patients treated since 1989. Anatomic RRP is an effective way to manage clinically localized prostate cancer. Excellent long-term results can be obtained with RRP for early stage disease. The proportion of men with early stage prostate cancer will continue to increase with wide use of serum PSA testing and digital rectal examination.

Epstein JI, Potter SR. · Brady Urological Institute and Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA. · J Urol. · Pubmed #11458037 No free full text.

Abstract: PURPOSE: The widespread use of prostate specific antigen testing and digital rectal examination has lead to the increasing application of prostate needle biopsy. A larger proportion of men undergoing biopsy have small foci of cancer, which coupled with the overall increase in needle biopsy has led to a surge in the number of equivocal biopsy specimens interpreted. MATERIALS AND METHODS: We reviewed the literature with an overview of the topic of prostate needle biopsy pathology results with an emphasis on current controversies. RESULTS: The diagnosis rendered on prostate needle biopsy pay be placed into 4 major categories, including 1) benign, 2) prostatic intraepithelial neoplasia, 3) atypical and suspicious for cancer, and 4) prostate cancer. Prostatic intraepithelial neoplasia or a diagnosis of atypical and suspicious for cancer mandates re-biopsy in a search for occult prostate cancer. Biopsy findings, including the location of positive cores, may help to guide re-biopsy strategies. Prostate cancer on needle biopsy may be evaluated by numerous techniques of quantifying tumor extent, Gleason score and perineural invasion. These modalities may help clinicians to assess the risk of extraprostatic disease and progression likelihood, and help men with prostate cancer choose among therapeutic options. CONCLUSIONS: The pathology reports returned on needle biopsy specimens may provide a wealth of information beyond the simple presence or absence of prostate cancer that may aid clinicians in patient treatment and counseling.