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Barnes J.L.,Audie Murphy Memorial Veterans Administration Hospital | Barnes J.L.,University of Texas Health Science Center at San Antonio | Glass II W.F.,Bostwick Laboratories Inc.
Contributions to Nephrology | Year: 2011

Interstitial fibrosis is a common feature of chronic kidney disease, regardless of the etiology of the primary renal syndrome. Moreover, interstitial fibrosis is the strongest morphologic predictor of clinical outcome and is most tightly linked to progression of disease, even though the primary disease may be of glomerular origin. Also, the presence of an interstitial component in chronic kidney disease often indicates an ominous outcome. The incidence of chronic kidney disease has reached epidemic proportions; thus, understanding the pathophysiology of interstitial renal disease is paramount for the development of new therapeutic approaches to slowing progression. Experimental models of renal fibrosis have been essential in determining the mechanisms and sequence of progression of fibrogenesis, including the roles of endothelium, infiltrating leukocytes and myofibroblasts; of profibrogenic cytokine and growth factor release; of tubular injury and atrophy; and of interstitial extracellular matrix accumulation. Over the last decade, considerable attention has been paid to the origin of the myofibroblast, the cell type most responsible for interstitial matrix accumulation. However, the origin(s) of myofibroblasts and how they gain access to the peritubular interstitium has become a matter of controversy and debate. Interstitial myofibroblasts have been proposed to originate from one or more of five sources: resident fibroblasts (pericytes), adventitial fibroblasts, circulating fibrocytes, tubular epithelial-mesenchymal transition (EMT) or endothelial/ mesenchymal transition. To date, EMT has become the pre-eminent theory of the origin of myofibroblasts; however, a role for EMT in renal fibrosis is rigorously challenged by anecdotal and recent scientific evidence. This chapter will briefly discuss the experimental models used to explore interstitial renal disease in general and will then focus on the controversy related to the origin of myofibroblasts. Copyright © 2011 S. Karger AG, Basel.


Cheng L.,Indiana University | Montironi R.,Marche Polytechnic University | Bostwick D.G.,Bostwick Laboratories Inc. | Lopez-Beltran A.,University of Cordoba, Spain | Berney D.M.,Barts Cancer Center
Histopathology | Year: 2012

Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes. © 2011 Blackwell Publishing Limited.


Bostwick D.G.,Bostwick Laboratories Inc. | Kahane H.,Bostwick Laboratories Inc.
Annals of Diagnostic Pathology | Year: 2013

No standard method exists for sampling prostate needle biopsies, although most reports claim to embed 3 cores per block and obtain 3 slices from each block. This study was undertaken to determine the extent of histologic sectioning necessary for optimal examination of prostate biopsies. We prospectively compared the impact on cancer yield of submitting 1 biopsy core per cassette (biopsies from January 2010) with 3 cores per cassette (biopsies from August 2010) from a large national reference laboratory. Between 6 and 12 slices were obtained with the former 1-core method, resulting in 3 to 6 slices being placed on each of 2 slides; for the latter 3-core method, a limit of 6 slices was obtained, resulting in 3 slices being place on each of 2 slides. A total of 6708 sets of 12 to 18 core biopsies were studied, including 3509 biopsy sets from the 1-biopsy-core-per-cassette group (January 2010) and 3199 biopsy sets from the 3-biopsy-cores-percassette group (August 2010). The yield of diagnoses was classified as benign, atypical small acinar proliferation, high-grade prostatic intraepithelial neoplasia, and cancer and was similar with the 2 methods: 46.2%, 8.2%, 4.5%, and 41.1% and 46.7%, 6.3%, 4.4%, and 42.6%, respectively (P =.02). Submission of 1 core or 3 cores per cassette had no effect on the yield of atypical small acinar proliferation, prostatic intraepithelial neoplasia, or cancer in prostate needle biopsies. Consequently, we recommend submission of 3 cores per cassette to minimize labor and cost of processing. © 2013 Elsevier Inc. All rights reserved.


Bostwick D.G.,Bostwick Laboratories Inc.
Annals of Diagnostic Pathology | Year: 2013

Improved methods such as radiofrequency identification (RFID) are needed to optimize specimen tracking in anatomical pathology. We undertook a study of RFID in an effort to optimize specimen tracking and patient identification, including the following: (1) creation of workflow process maps, (2) evaluation of existing RFID hardware technologies, (3) creation of Web-based software to support the RFID-enabled workflow, and (4) assessment of the impact with a series of prostate biopsies. We identified multiple steps in the workflow process in which RFID enhanced specimen tracking. Multiple product choices were found that could withstand the harsh heat and chemical environments encountered in pathology processing, and software that was compatible with our laboratory information system was designed in-house. A total of 1067 prostate biopsies were received, and 78.3% were successfully processed with the RFID system. Radiofrequency identification allowed dynamic specimen tracking throughout the workflow process in anatomical pathology. © 2013 Published by Elsevier Inc.


Herrera G.A.,Bostwick Laboratories Inc. | Turbat-Herrera E.A.,Bostwick Laboratories Inc.
Archives of Pathology and Laboratory Medicine | Year: 2010

Nephrocor, Bostwick Laboratories Arizona, 1700 N Desert Dr, Tempe, AZ 85281abs Most renal diseases with organized deposits are relatively uncommon conditions, and proper pathologic characterization determines the specific diagnosis. Different entities with specific clinical correlates have been recognized, and their correct diagnosis has an impact on patient management, treatment options, and determination of prognosis. Objective.-The diagnosis of these conditions depends on careful evaluation of the findings by light microscopy together with immunofluorescence and electron microscopy. The objective of this manuscript is to delineate an algorithmic approach helpful in the pathologic assessment of these conditions at the light microscopic level. In some diseases, the immunomorphologic parameters short of electron microscopy provide solid information to suggest or make a definitive diagnosis. Nevertheless, electron microscopy plays a crucial role, because the criteria to separate these entities often are heavily influenced by the electron microscopic findings. Accepted diagnostic criteria for each of these conditions are discussed. Design.-Information used for this manuscript is gathered from published data and the authors' experience. Results.-The most common of these conditions is amyloidosis, which may account for as many as 5% to 8% of all renal biopsies in some renal pathology practices. Fibrillary, immunotactoid, and cryoglobulinemic glomerulopathies together represent, at most, 1% of all renal biopsies performed for medical renal diseases. Diabetic fibrillosis also is uncommon. Glomerulopathies associated with fibronectin deposits and collagenofibrotic glomerulopathy are extremely rare. Conclusions.-A systematic, algorithmic approach to the evaluation of the renal biopsies from patients with these disorders is very helpful to rule out certain conditions in the early stages of the evaluation of the biopsies. However, it is not uncommon for the final definitive diagnosis to be reached only after electron microscopic evaluation.


Turbat-Herrera E.A.,Bostwick Laboratories Inc.
Contributions to Nephrology | Year: 2011

This manuscript presents the usefulness of various experimental models in research with the purpose to elucidate mechanisms of disease and help create treatment modalities. The emphasis is on the use of models primarily for the study and treatment of amyloidosis. This is a rare condition that has attracted much attention recently. Amyloidosis is a disease in which the information obtained in the research laboratory has played a key role in advancing our understanding of the mechanisms associated with this group of disorders and in the development of new avenues for therapeutic intervention. Both in-vivo and in-vitro models are addressed. The early animal models and the more recent transgenic models are presented along with their usefulness to study the pathogenesis and dissect gene expression profiles where appropriate. Their pros and cons of the various experimental settings are highlighted. In-vitro models are presented with examples from the literature as to how they have or are being used to study a variety of conditions, renal as well as others. They also serve the purpose of resolving questions primarily relating to patho-genesis and to test the value of novel interventions prior to using in vivo models that are generally more expensive and difficult to work with. Since all models have their limitations, perhaps the best way is to utilize both in-vitro and in-vivo platforms, selecting them depending upon the questions to be answered. Employing a large variety of experimental techniques can serve to obtain and validate the data. The advantages of this approach will become obvious in the book chapters that follow. Copyright © 2011 S. Karger AG, Basel.


Bostwick D.G.,Bostwick Laboratories Inc. | Cheng L.,Indiana University
Histopathology | Year: 2012

High-grade prostatic intraepithelial neoplasia (PIN) is the only accepted precursor of prostatic adenocarcinoma, according to numerous studies of animal models and man; other proposed precursors include atrophy and malignancy-associated changes (with no morphologic changes). PIN is characterized by progressive abnormalities of phenotype and genotype that are intermediate between benign prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. The only method of detection of PIN is biopsy because it does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultrasonography. The mean incidence of PIN in biopsies is 9% (range, 4%-16%), representing about 115000 new cases of isolated PIN diagnosed each year in the United States. The clinical importance of PIN is its high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent carcinoma, especially when multifocal or observed in association with atypical small acinar proliferation (ASAP). Carcinoma develops in most patients with PIN within 10years. Androgen deprivation therapy and radiation therapy decrease the prevalence and extent of PIN, suggesting that these forms of treatment may play a role in prevention of subsequent cancer. Multiple clinical trials to date of men with PIN have had modest success in delaying or preventing subsequent cancer. © 2011 Blackwell Publishing Limited.


Bostwick D.G.,Bostwick Laboratories Inc. | Hossain D.,Bostwick Laboratories Inc.
Diagnostic Cytopathology | Year: 2014

Urine cytology is routinely used for early diagnosis and monitoring of patients with hematuria or a history of urothelial carcinoma, but its clinical utility is greatly diminished by a high frequency of "atypical" specimens, reportedly around 20% in the literature. We compared our results with double-stained urine cytology specimens (papanicolaou and acid hematoxylin stains) with published results with only a single or double papanicolaou stain. The acid hematoxylin stain enhanced nuclear chromatin staining, eliminated significant background debris, and improved visibility of diagnostic cells in the presence of obscuring blood. Medical records of all urine cytologies received between 2005 and 2012 in our laboratories were reviewed. The study group consisted of all cases with bladder biopsy follow-up within one year of cytology. Of 43,131 urine cytologies diagnosed in our laboratories, biopsy follow-up results were available within one year in 10,473 cases, including 852 for symptoms and 1,461 for follow-up of bladder cancer. An additional 6,427 cases had cystoscopy results in which no biopsy was obtained. Cases were classified as negative (81.6%), atypical, favor reactive (2.9%), atypical, favor neoplastic (7.3%), suspicious (5.7%), and malignant (2.5%), with subsequent frequencies for urothelial cancer on biopsy of 13.3%, 31.1%, 37.6%, 53.6%, and 74.3%, respectively. No significant difference was found if atypical was subdivided into two categories: favor reactive and favor neoplastic. Subdivision of the atypical category did not improve diagnostic accuracy. Addition of the acid hematoxylin stain decreased the incidence of atypical urine cytologies from about 20% to 10.2%. © 2014 Wiley Periodicals, Inc.


Cheng L.,Indiana University | Bostwick D.G.,Bostwick Laboratories Inc.
Histopathology | Year: 2010

Aims: Sclerosing adenosis of the prostate is a benign, small, acinar proliferation in dense spindle cell stroma, with a distinct immunohistochemical profiles. It is incidentally found in about 2% of transurethral resection specimens. The aim was to describe cases with significant cytological atypia mimicking cancer, which have not been previously reported. Methods and results: We describe five cases of sclerosing adenosis with significant cytological atypia, referred to as atypical sclerosing adenosis (ASA), which were initially considered suspicious or diagnostic of adenocarcinoma. Seven other cases of typical sclerosing adenosis were used as controls. All cases of typical and atypical sclerosing adenosis displayed an intact basal cell layer, which was immunoreactive for high-molecular-weight keratin, S100 protein, smooth muscle actin, and prostate-specific antigen, with no differences between ASA and the control group. Alpha-methylacyl-coenzyme A racemase was negative. Three of four cases of ASA had aneuploid DNA content by digital image analysis. All cases of typical sclerosing adenosis were diploid. During a mean follow-up of 33 months (range 5-73 months), none developed recurrence or prostatic cancer. Conclusions: ASA is an unusual small, acinar proliferation of the prostate that may be mistaken for adenocarcinoma, and should be distinguished from other mimics, including atypical adenomatous hyperplasia, mesonephric remnant hyperplasia, and post-atrophic hyperplasia. ASA is a benign lesion and aggressive treatment is unwarranted. © 2010 Blackwell Publishing Limited.


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