CXCL12 is a chemotactic cytokine that has pro-metastatic functions in several malignancies through interactions with its receptor, CXCR4. CXCL12 is an estrogen-regulated gene, and notably, estrogen is a major risk factor for endometrial cancer (EC) development. As few studies examine concurrent CXCL12, CXCR4, and estrogen receptor (ER) expression in EC patients, we examined this pathway in 199 EC patients with data from the University of Pittsburgh Medical Center Cancer Registry. Immunohistochemistry (IHC) was used to detect CXCR4, CXCL12, and ER protein expression. As CXCR4 expression was positive in all cases, this investigation focused on associations between CXCL12 and ER expression, clinicopathologic factors, and survival outcomes using chi-square tests, Kaplan-Meier graphs, and log-rank tests. CXCL12 expression was negative in 63 cases (32%) and positive in 136 cases (68%). Negative CXCL12 expression was borderline significantly associated with metastasis (χ2 p=0.07). ER expression was negative in 75 cases (38%) and positive in 124 cases (62%). Positive ER expression was significantly associated with low grade and early stage tumors (χ2 p<0.001). CXCL12 and ER were not significantly associated (χ2 p=0.11). Positive CXCL12 expression was associated with longer overall survival (OS) (log-rank p=0.006) and longer recurrence-free survival (RFS) (log-rank p=0.01) in ER negative patients, but not in ER positive patients. We identified a unique molecular signature associated with better OS and RFS in EC patients. In addition to pathological characteristics of the tumor, expression of CXCL12 and ER may be clinically useful for assigning adjuvant treatment to EC cases.
clear cell; papillary serous; prognostic biomarkers; chemokines; metastasis
Data protection and security are critical components of routine pathology practice because laboratories are legally required to securely store and transmit electronic patient data. With increasing connectivity of information systems, laboratory work-stations, and instruments themselves to the Internet, the demand to continuously protect and secure laboratory information can become a daunting task. This review addresses informatics security issues in the pathology laboratory related to passwords, biometric devices, data encryption, internet security, virtual private networks, firewalls, anti-viral software, and emergency security situations, as well as the potential impact that newer technologies such as mobile devices have on the privacy and security of electronic protected health information (ePHI). In the United States, the Health Insurance Portability and Accountability Act (HIPAA) govern the privacy and protection of medical information and health records. The HIPAA security standards final rule mandate administrative, physical, and technical safeguards to ensure the confidentiality, integrity, and security of ePHI. Importantly, security failures often lead to privacy breaches, invoking the HIPAA privacy rule as well. Therefore, this review also highlights key aspects of HIPAA and its impact on the pathology laboratory in the United States.
Antivirus; audit; biometrics; data backup; data integrity; encryption; firewall; health insurance portability and accountability act; internet; password; privacy; security; spyware; virtual private networks
Pathology informatics has evolved to varying levels around the world. The history of pathology informatics in different countries is a tale with many dimensions. At first glance, it is the familiar story of individuals solving problems that arise in their clinical practice to enhance efficiency, better manage (e.g., digitize) laboratory information, as well as exploit emerging information technologies. Under the surface, however, lie powerful resource, regulatory, and societal forces that helped shape our discipline into what it is today. In this monograph, for the first time in the history of our discipline, we collectively perform a global review of the field of pathology informatics. In doing so, we illustrate how general far-reaching trends such as the advent of computers, the Internet and digital imaging have affected pathology informatics in the world at large. Major drivers in the field included the need for pathologists to comply with national standards for health information technology and telepathology applications to meet the scarcity of pathology services and trained people in certain countries. Following trials by a multitude of investigators, not all of them successful, it is apparent that innovation alone did not assure the success of many informatics tools and solutions. Common, ongoing barriers to the widespread adoption of informatics devices include poor information technology infrastructure in undeveloped areas, the cost of technology, and regulatory issues. This review offers a deeper understanding of how pathology informatics historically developed and provides insights into what the promising future might hold.
History; pathology informatics; clinical informatics; electronic medical record; laboratory information systems; pathology education
Many pathology laboratories are implementing digital pathology systems. The image resolution and scanning (digitization) magnification can vary greatly between these digital pathology systems. In addition, when digital images are compared with viewing images using a microscope, the cellular features can vary in size. This article highlights differences in magnification and resolution between the conventional microscopes and the digital pathology systems. As more pathologists adopt digital pathology, it is important that they understand these differences and how they ultimately translate into what the pathologist can see and how this may impact their overall viewing experience.
Digital; magnification; pathology; resolution; whole slide image
This study attempted to distinguish primary bladder adenocarcinoma (PBA) from metastatic colonic adenocarcinomas (MCA), which is a difficult diagnostic and clinical problem.
Twenty-four cases of bladder adenocarcinomas (12 primary & 12 metastatic colorectal) were included in the study with urothelial carcinoma (UC) and colonic adenocarcinoma (CA) as controls. A panel of immunohistochemical (IHC) stains along with fluorescence in-situ hybridization (FISH), using the UroVysion probe set, was performed.
The majority of the PBAs presented with advanced disease. Enteric histologic subtype was the most common morphological variant. Strong nuclear with cytoplasmic-membranous staining of β-catenin was seen in 75% of MCA and only 16.7% PBA (<10% staining cells). Although abnormal nuclear staining with E-cadherin was seen in both PBA and MCA, it was more frequent in former. CK-7, CK-20, villin and CDX-2 stains were not helpful in distinguishing the two entities. FISH did not reveal any unique differences in chromosomal abnormality between the two groups.
Although there was a statistically significant difference in β-catenin and E-cadherin staining between two groups, we did not find any IHC or FISH marker that was specific for PBA. Distinction between PBA and MCA remains a diagnostic problem and clinical correlation is vital before rendering a diagnosis.
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1393156268152357
Bladder; Adenocarcinoma; Primary; Metastatic; Colorectal; Beta-catenin; E-cadherin
We report a scrotal epidermal inclusion cyst located outside the median raphe which a rare entity in the absence of trauma and few cases have been reported. 47 year old male presents with a complaint of right sided testicular swelling and discomfort. On examination a 3 cm mass was palpated between the scrotum and the medial thigh on the subcutaneous tissue with a positive slip sign. Complete surgical excision of the cyst was performed. Histopathology confirmed epidermal inclusion cyst with no evidence of malignancy.
Vitamin D has been shown to have anti-proliferative effects in a wide variety of cancers including lung cancer. The anticancer effects of Vitamin D are mediated primarily by its active metabolite, 1,25-dihydroxyvitamin D (calcitriol), through vitamin D receptor (VDR) signaling. However, thus far there have been no studies evaluating the association between VDR expression and survival outcome in lung cancer. Using immunohistochemical analysis, we evaluated VDR expression, separately in the nucleus and cytoplasm, in lung cancer samples from 73 non-small cell lung carcinoma (NSCLC) patients with no prior therapy, and investigated the association between VDR expression and overall survival (OS). Cox proportional hazard models were used for our primary analyses. There were 44 deaths during a median follow-up of 51 months (range 13-93 months). High nuclear VDR expression was associated with improved OS after adjusting for age, gender, stage, smoking status, and histology (adjusted hazard ratio, 0.36; 95% confidence interval, 0.17-0.79). There was no association between cytoplasmic VDR expression and OS. Our results suggest that nuclear VDR status may be a prognostic marker in NSCLC. Future large studies to replicate our findings and to assess the impact of VDR gene polymorphisms on VDR expression are required as therapies targeting the vitamin D signaling pathway may be influenced by VDR status in the target lung cancer tissue.
Vitamin D receptor; Non-small cell lung cancer; Biomarker; Survival; Prognosis
Sharing digital pathology images for enterprise- wide use into a picture archiving and communication system (PACS) is not yet widely adopted. We share our solution and 3-year experience of transmitting such images to an enterprise image server (EIS).
Gross pathology images acquired by prosectors were integrated with clinical cases into the laboratory information system's image management module, and stored in JPEG2000 format on a networked image server. Automated daily searches for cases with gross images were used to compile an ASCII text file that was forwarded to a separate institutional Enterprise Digital Imaging and Communications in Medicine (DICOM) Wrapper (EDW) server. Concurrently, an HL7-based image order for these cases was generated, containing the locations of images and patient data, and forwarded to the EDW, which combined data in these locations to generate images with patient data, as required by DICOM standards. The image and data were then “wrapped” according to DICOM standards, transferred to the PACS servers, and made accessible on an institution-wide basis.
In total, 26,966 gross images from 9,733 cases were transmitted over the 3-year period from the laboratory information system to the EIS. The average process time for cases with successful automatic uploads (n=9,688) to the EIS was 98 seconds. Only 45 cases (0.5%) failed requiring manual intervention. Uploaded images were immediately available to institution- wide PACS users. Since inception, user feedback has been positive.
Enterprise- wide PACS- based sharing of pathology images is feasible, provides useful services to clinical staff, and utilizes existing information system and telecommunications infrastructure. PACS-shared pathology images, however, require a “DICOM wrapper” for multisystem compatibility.
DICOM; digital image; LIS; PACS; pathology; wrapper
Pathology informatics encompasses digital imaging and related applications. Several specialized microscopy techniques have emerged which permit the acquisition of digital images (“optical biopsies”) at high resolution. Coupled with fiber-optic and micro-optic components, some of these imaging techniques (e.g., optical coherence tomography) are now integrated with a wide range of imaging devices such as endoscopes, laparoscopes, catheters, and needles that enable imaging inside the body. These advanced imaging modalities have exciting diagnostic potential and introduce new opportunities in pathology. Therefore, it is important that pathology informaticists understand these advanced imaging techniques and the impact they have on pathology. This paper reviews several recently developed microscopic techniques, including diffraction-limited methods (e.g., confocal microscopy, 2-photon microscopy, 4Pi microscopy, and spatially modulated illumination microscopy) and subdiffraction techniques (e.g., photoactivated localization microscopy, stochastic optical reconstruction microscopy, and stimulated emission depletion microscopy). This article serves as a primer for pathology informaticists, highlighting the fundamentals and applications of advanced optical imaging techniques.
2-photon microscopy; 4Pi microscopy; advanced imaging; confocal microscopy; digital; microscopy; optical coherence tomography; optics; photoactivated localization microscopy; spatially modulated illumination microscopy; stimulated emission depletion microscopy
For decades anatomic pathology (AP) workflow have been a highly manual process based on the use of an optical microscope and glass slides. Recent innovations in scanning and digitizing of entire glass slides are accelerating a move toward widespread adoption and implementation of a workflow based on digital slides and their supporting information management software. To support the design of digital pathology systems and ensure their adoption into pathology practice, the needs of the main users within the AP workflow, the pathologists, should be identified. Contextual inquiry is a qualitative, user-centered, social method designed to identify and understand users’ needs and is utilized for collecting, interpreting, and aggregating in-detail aspects of work.
Contextual inquiry was utilized to document current AP workflow, identify processes that may benefit from the introduction of digital pathology systems, and establish design requirements for digital pathology systems that will meet pathologists’ needs.
Materials and Methods:
Pathologists were observed and interviewed at a large academic medical center according to contextual inquiry guidelines established by Holtzblatt et al. 1998. Notes representing user-provided data were documented during observation sessions. An affinity diagram, a hierarchal organization of the notes based on common themes in the data, was created. Five graphical models were developed to help visualize the data including sequence, flow, artifact, physical, and cultural models.
A total of six pathologists were observed by a team of two researchers. A total of 254 affinity notes were documented and organized using a system based on topical hierarchy, including 75 third-level, 24 second-level, and five main-level categories, including technology, communication, synthesis/preparation, organization, and workflow. Current AP workflow was labor intensive and lacked scalability. A large number of processes that may possibly improve following the introduction of digital pathology systems were identified. These work processes included case management, case examination and review, and final case reporting. Furthermore, a digital slide system should integrate with the anatomic pathologic laboratory information system.
To our knowledge, this is the first study that utilized the contextual inquiry method to document AP workflow. Findings were used to establish key requirements for the design of digital pathology systems.
Anatomic pathology; contextual inquiry; workflow; digital pathology
Several modes of telepathology exist including static (store-and-forward), dynamic (live video streaming or robotic microscopy), and hybrid technology involving whole slide imaging (WSI). Telepathology has been employed at the University of Pittsburgh Medical Center (UPMC) for over a decade at local, national, and international sites. All modes of telepathology have been successfully utilized to exploit our institutions subspecialty expertise and to compete for pathology services. This article discusses the experience garnered at UPMC with each of these teleconsultation methods. Static and WSI telepathology systems have been utilized for many years in transplant pathology using a private network and client-server architecture. Only minor clinically significant differences of opinion were documented. In hematopathology, the CellaVision® system is used to transmit, via email, static images of blood cells in peripheral blood smears for remote interpretation. While live video streaming has remained the mode of choice for providing immediate adequacy assessment of cytology specimens by telecytology, other methods such as robotic microscopy have been validated and shown to be effective. Robotic telepathology has been extensively used to remotely interpret intra-operative neuropathology consultations (frozen sections). Adoption of newer technology and increased pathologist experience has improved accuracy and deferral rates in teleneuropathology. A digital pathology consultation portal (https://pathconsult.upmc.com/) was recently created at our institution to facilitate digital pathology second opinion consults, especially for WSI. The success of this web-based tool is the ability to handle vendor agnostic, large image files of digitized slides, and ongoing user-friendly customization for clients and teleconsultants. It is evident that the practice of telepathology at our institution has evolved in concert with advances in technology and user experience. Early and continued adoption of telepathology has promoted additional digital pathology resources that are now being leveraged for other clinical, educational, and research purposes.
Digital imaging; robotic; static; teleconsultation; telemicroscopy; telepathology; video microscopy; whole slide imaging
Male infertility is traditionally evaluated by tissue core biopsies of the testes. Touch preparations (TP) of these biopsies have been infrequently used. The aim of this study is to report our experience with using testicular biopsy TP for the evaluation of male infertility.
Materials and Methods:
A retrospective search was performed for cases of testes biopsies with concurrent TP. These cases were evaluated for clinical information, specimen adequacy, and cytological–histological correlation.
A total of 39 cases were identified from men with a mean age of 34 years (range 23 to 50 years). TP slides were satisfactory for evaluation in 31 (89%) cases, and less than optimal in four due to low cellularity, obscuring blood or air drying artifact. Cytopathology showed concordance with the biopsy in almost all cases. In one discordant case where the biopsies showed no active spermatogenesis, a rare sperm were identified on the TP.
TP of the testis is a helpful adjunct to biopsy because of its ability to clearly evaluate all stages of spermatogenesis. These data demonstrate that TP cytopathology of the testes in our experience has an excellent correlation with both normal testicular biopsies and those showing pathological spermatogenesis, and in rare cases may provide added benefit in evaluating the presence of spermatogenesis for male infertility. Albeit uncommon, cytopathologists may be required to identify and evaluate spermatogenic elements in cytology specimens being submitted from men with infertility.
Cytology; infertility; spermatogenesis; testis; touch preparation
BACKGROUND: Conflicting roles for Slit2, a protein involved in mediating the processes of cell migration and chemotactic response, have been previously described in prostate cancer. Here we use immunohistochemistry to evaluate the expression of Slit2 in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets). METHODS: Tissue microarrays were immunostained for Slit2. The staining intensities were quantified using automated image analysis software. The data was statistically analyzed using one-way analysis of variance with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Eleven cases of NDP, 35 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 106 cases of PCa, and 37 cases of Mets were analyzed. RESULTS: Specimens of PCa and HGPIN had the highest absolute staining for Slit2. Significant differences were seen between PCa and NDP (P < .05), PCa and NAC (P < .05), HGPIN and NDP (P < .05), and HGPIN and NAC (P < .05). Whereas the average Mets staining was not significantly different from NDP or NAC, several individual Mets cases featured intense staining. CONCLUSIONS: To our knowledge, this represents the first study comparing the immunohistochemical profiles of Slit2 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC. These findings suggest that Slit2 expression can be increased in HGPIN, PCa, and Mets, making it a potentially important biomarker for prostate cancer.
“Collision tumor” is an uncommon phenomenon characterized by coexistence of two completely distinct and independent tumors at the same site. Collision tumors have been reported in different sites in the body; however, these are particularly uncommon in the pelvic cavity. A 70-year-old man, with prior history of urothelial and prostate cancer, presented with a large pelvic mass detected on imaging studies. Pathological examination revealed a large liposarcoma with prostatic carcinoma embedded in it. Immunohistochemistry and florescence in situ hybridization studies were performed to reach to a conclusive diagnosis. To the best of our knowledge, this is the second case reported till date. We present the challenges encountered in the diagnosis of this case and review of pelvic collision tumors.
Distinguishing urothelial carcinoma (UC) from prostate carcinoma (PC) is important due to potential therapeutic and prognostic implications. However, this can be a diagnostic challenge when there is limited tissue and in poorly differentiated tumors. We evaluated the diagnostic utility of a dual immunohistochemical stain comprising p63 and P501S (prostein), applied sequentially on a single slide and visualized by double chromogen reaction, in differentiating these two cancers. Thus far, there have been no previous studies assessing the diagnostic utility of p63 and P501S combined together as a dual immunostain in distinguishing between these two cancers.
p63/P501S dual-color sequential immunohistochemical staining was performed on archival material from 132 patients with high-grade UC and 23 patients with PC, and evaluated for p63 (brown nuclear) and P501S (red cytoplasmic) expression. Both the staining intensity and percentage of positive tumor cells were assessed.
p63 was positive in 119/132 of UC and negative in PC. P501S was positive in 22/23 of PC and negative in UC. The p63+/P501S- immunoprofile had 90% sensitivity and 100% specificity for UC. The p63-/P501S+ immunoprofile had 96% sensitivity and 100% specificity for PC.
Our results indicate that double sequential immunohistochemical staining with p63 and P501S is highly specific and can be a useful tool in distinguishing UC from PC especially when there is limited diagnostic tissue as it can be performed on a single slide.
Rapid advances are occurring in the field of cytopathology, particularly in the field of digital imaging. Today, digital images are used in a variety of settings including education (E-education), as a substitute to multiheaded sessions, multisite conferences, publications, cytopathology web pages, cytology proficiency testing, telecytology, consultation through telecytology, and automated screening of Pap test slides. The accessibility provided by digital imaging in cytopathology can improve the quality and efficiency of cytopathology services, primarily by getting the expert cytopathologist to remotely look at the slide. This improved accessibility saves time and alleviates the need to ship slides, wait for glass slides, or transport pathologists. Whole slide imaging (WSI) is a digital imaging modality that uses computerized technology to scan and convert pathology and cytology glass slides into digital images (digital slides) that can be viewed remotely on a workstation using viewing software. In spite of the many advances, challenges remain such as the expensive initial set-up costs, workflow interruption, length of time to scan whole slides, large storage size for WSI, bandwidth restrictions, undefined legal implications, professional reluctance, and lack of standardization in the imaging process.
Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is an adapter protein which has been shown to play an active role in a wide variety of cellular processes, including interactions with proteins related to both tumor suppression and oncogenesis. Here we use immunohistochemistry to evaluate EBP50's expression in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets).
Tissue microarrays were immunohistochemically stained for EBP50, with the staining intensities quantified using automated image analysis software. The data were statistically analyzed using one-way ANOVA with subsequent Tukey tests for multiple comparisons. Eleven cases of NDP, 37 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 103 cases of PCa, and 36 cases of Mets were analyzed in the microarrays.
Specimens of PCa and Mets had the lowest absolute staining for EBP50. Mets staining was significantly lower than NDP (p = 0.027), BPH (p = 0.012), NAC (p < 0.001), HGPIN (p < 0.001), and PCa (p = 0.006). Additionally, HGPIN staining was significantly higher than NAC (p < 0.009) and PCa (p < 0.001).
To our knowledge, this represents the first study comparing the immunohistochemical profiles of EBP50 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC and suggests that EBP50 expression is decreased in Mets. Given that PCa also had significantly higher expression than Mets, future studies are warranted to assess EBP50's potential as a prognostic biomarker for prostate cancer.
Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets).
Tissue microarrays were immunohistochemically stained for claudin-3, with the staining intensities subsequently quantified and statistically analyzed using a one-way ANOVA with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Fifty-three cases of NAC, 17 cases of BPH, 35 cases of PIN, 107 cases of PCa, and 55 cases of Mets were analyzed in the microarrays.
PCa and Mets had the highest absolute staining for claudin-3. Both had significantly higher staining than BPH (p < 0.05 in both cases) and NAC (p < 0.05 in both cases). PIN had a lower, but non-significant, staining score than PCa and Mets, but a statistically higher score than both BPH and NAC (p < 0.05 for both cases). No significant differences were observed between PCa, Mets, and PIN.
To our knowledge, this represents one of the first studies comparing the immunohistochemical profiles of claudin-3 in PCa and NAC to specimens of PIN, BPH, and Mets. These findings provide further evidence that claudin-3 may serve as an important biomarker for prostate cancer, both primary and metastatic, but does not provide evidence that claudin-3 can be used to predict risk of metastasis.
Some members of the Protein 4.1 superfamily are believed to be involved in cell proliferation and growth, or in the regulation of these processes. While the expression levels of two members of this family, radixin and moesin, have been studied in many tumor types, to our knowledge they have not been investigated in prostate cancer.
Tissue microarrays were immunohistochemically stained for either radixin or moesin, with the staining intensities subsequently quantified and statistically analyzed using One-Way ANOVA or nonparametric equivalent with subsequent Student-Newman-Keuls tests for multiple comparisons. There were 11 cases of normal donor prostates (NDP), 14 cases of benign prostatic hyperplasia (BPH), 23 cases of high-grade prostatic intraepithelial neoplasia (HGPIN), 88 cases of prostatic adenocarcinoma (PCa), and 25 cases of normal tissue adjacent to adenocarcinoma (NAC) analyzed in the microarrays.
NDP, BPH, and HGPIN had higher absolute staining scores for radixin than PCa and NAC, but with a significant difference observed between only HGPIN and PCa (p = < 0.001) and HGPIN and NAC (p = 0.001). In the moesin-stained specimens, PCa, NAC, HGPIN, and BPH all received absolute higher staining scores than NDP, but the differences were not significant. Stage 4 moesin-stained PCa had a significantly reduced staining intensity compared to Stage 2 (p = 0.003).
To our knowledge, these studies represent the first reports on the expression profiles of radixin and moesin in prostatic adenocarcinoma. The current study has shown that there were statistically significant differences observed between HGPIN and PCa and HGPIN and NAC in terms of radixin expression. The differences in the moesin profiles by tissue type were not statistically significant. Additional larger studies with these markers may further elucidate their potential roles in prostatic neoplasia progression.
The Transfusion Medicine Service (TMS) covers diverse clinical and laboratory-based services that must be delivered with accuracy, efficiency and reliability. TMS oversight is shared by multiple regulatory agencies that cover product manufacturing and validation standards geared toward patient safety. These demands present significant informatics challenges. Over the past few decades, TMS information systems have improved to better handle blood product manufacturing, inventory, delivery, tracking and documentation. Audit trails and access to electronic databases have greatly facilitated product traceability and biovigilance efforts. Modern blood bank computing has enabled novel applications such as the electronic crossmatch, kiosk-based blood product delivery systems, and self-administered computerized blood donor interview and eligibility determination. With increasing use of barcoding technology, there has been a marked improvement in patient and specimen identification. Moreover, the emergence of national and international labeling standards such as ISBT 128 have facilitated the availability, movement and tracking of blood products across national and international boundaries. TMS has only recently begun to leverage the electronic medical record to address quality issues in transfusion practice and promote standardized documentation within institutions. With improved technology, future growth is expected in blood bank automation and product labeling with applications such as radio frequency identification devices. This article reviews several of these key informatics issues relevant to the contemporary practice of TMS.
Blood bank; barcode; computer; donor; electronic crossmatch; FDA; informatics; transfusion medicine; virtual
Quality assurance (QA) programs in cytopathology laboratories in the USA currently primarily involve the review of Pap tests per clinical laboratory improvement amendments of 1988 federal regulations. A pre-signout quality assurance tool (PQAT) at our institution allows the laboratory information system (LIS) to also automatically and randomly select an adjustable percentage of non-gynecological cytopathology cases for review before release of the final report. The aim of this study was to review our experience and the effectiveness of this novel PQAT tool in cytology.
Materials and Methods:
Software modifications in the existing LIS application (CoPathPlus, Cerner) allow for the random QA of 8% of cases prior to signout. Selected cases are assigned to a second QA cytopathologist for review and all agreement and disagreements tracked. Detected errors are rectified before the case is signed out. Data from cases selected for PQAT over an 18-month period were collected and analyzed.
The total number of non-gynecological cases selected for QA review was 1339 (7.45%) out of 17,967 cases signed out during this time period. Most (1304) cases (97.4%) had an agreement in diagnosis. In 2.6% of cases, there were disagreements, including 34 minor and only 1 major disagreement. Average turnaround time of cases selected for review was not significantly altered.
The PQAT provides a prospective QA mechanism in non-gynecological cytopathology to prevent diagnostic errors from occurring. This LIS-driven tool allows for peer review and corrective action to be taken prior to reporting without delaying turnaround time, thereby improving patient safety.
Cytopathology; error; laboratory information system; patient safety; quality assurance
Statement of Translational Relevance
Although benzodiazepines have been used clinically for over 50 years, their application as a form of cancer therapy is largely unexplored. Here we show that lorazepam, a benzodiazepine commonly prescribed to treat anxiety disorders and acts on both central and peripheral receptors, inhibits prostate cancer cell growth and survival. Our studies further elucidate the mechanism by which Translocator Protein (TSPO) antagonists alter cancer cell function. Antagonists for TSPO are already used in the clinic for other indications and demonstrate very minor side effects. Because lorazepam is a commonly prescribed FDA-approved drug, the translation of our preclinical results to the prostate cancer patient population could be readily achieved. Our studies could lead to a significant change in the management of prostate cancer by providing a treatment option with minimal toxicity for use after failure of androgen-deprivation therapy and could ultimately prevent prostate cancer deaths.
The transmembrane molecule, Translocator Protein (TSPO) has been implicated in the progression of epithelial tumors. TSPO gene expression is high in tissues involved in steroid biosynthesis, neurodegenerative disease and in cancer and overexpression has been shown to contribute to pathologic conditions including cancer progression in several different models. The goal of our study was to examine the expression and biological relevance of TSPO in prostate cancer and demonstrate that the commonly prescribed benzodiazepine lorazepam, a ligand for TSPO, exhibits anti-cancer properties.
Immunohistochemical analysis using tissue microarrays was used to determine the expression profile of TSPO in human prostate cancer tissues. To demonstrate the effect of benzodiazepines (lorazepam and PK11195) in prostate cancer, we utilized cell proliferation assays, apoptosis ELISA, prostate cancer xenograft study, and immunohistochemistry.
TSPO expression is increased in prostatic intraepithelial neoplasia, primary prostate cancer, and metastases compared to normal prostate tissue and benign prostatic hyperplasia. Furthermore, TSPO expression correlates with disease progression, as TSPO levels increased with increasing Gleason sum and stage with prostate cancer metastases demonstrating the highest level of expression among all tissues examined. Functionally, we have demonstrated that lorazepam has anti-proliferative and pro-apoptotic properties in vitro and in vivo. Additionally, we have shown that TSPO overexpression in nontumorigenic cells conferred susceptibility to lorazepam-induced growth inhibition.
These data suggest that blocking TSPO function in tumor cells induces cell death and denotes a survival role for TSPO in prostate cancer and provide the first evidence for the use of benzodiazepines in prostate cancer therapeutics.
TSPO; Prostate Cancer; PBR; benzodiazepine; lorazepam; PK11195
Clinical studies have confirmed that renal oncocytoma (RO) is a benign neoplasm with excellent prognosis. In diagnostically challenging cases of renal oncocytic epithelial neoplasms, fluorescent in-situ hybridization (FISH) is increasingly being used and its ability to distinguish RO from chromophobe renal cell carcinoma (ChRCC) has been documented. In this study, we evaluated the differential diagnostic contribution of FISH in cases of RO.
Clinicopathologic data and glass slides from 73 patients with RO were reviewed; 20 cases of ChRCC were included for comparison. FISH analysis of formalin-fixed, paraffin-embedded sections was performed using centromeric probes for chromosomes 1, 2, 7 and 17. FISH analysis revealed ROs had frequent loss of signal for chromosome 1 (56%) and 17 (44%). Tumors with more than one loss were common (41%) and 10% cases showed loss of all chromosomes examined. A total of 18% cases did not show any abnormality.
Our study shows that chromosomal abnormalities in both ROs and ChRCCs are common with frequent loss of chromosomes 1 and 17. No association was found between overall patient survival and the extent of chromosomal abnormalities. FISH results, even those showing significant chromosomal abnormalities, should not alter the primarily morphology-based diagnosis of RO.
Automated, high-speed, high-resolution whole slide imaging (WSI) robots are becoming increasingly robust and capable. This technology has started to have a significant impact on pathology practice in various aspects including resident education. To be sufficient and adequate, training in pathology requires gaining broad exposure to various diagnostic patterns through teaching sets, which are traditionally composed of glass slides.
A teaching set of over 295 glass slides has been used for resident training at the Division of Genitourinary Pathology, Department of Pathology, University of Pittsburgh Medical Center. Whole slide images were prepared from these slides using an Aperio ScanScope CS scanner. These images and case-related information were uploaded on a web-based digital teaching model.
The web site is available at: https://www.secure.opi.upmc.edu/genitourinary/index.cfm. Once logged in, users can view the list of cases, or search cases with or without diagnoses shown. Each case can be accessed through an option button, where the clinical history, gross findings are initially shown. Whole slide images can be accessed through the links on the page, which allows users to make diagnoses on their own. More information including final diagnosis will display when the diagnosis-button is clicked.
The web-based digital study set provides additional educational benefits to using glass slides. Residents or other users can remotely access whole slide images and related information at their convenience. Searching and sorting functions and self-testing mode allow a more targeted study. It would also prepare residents with competence to work with whole slide images. Further, the model can be expanded to include pre-rotation and post-rotation exams, and/or a virtual rotation system, which may potentially make standardization of pathology resident training possible in the future.
Digital teaching set; pathology education; whole slide imaging