Faculty Bibliography

AIMS/OBJECTIVE:Despite efforts to standardise grading of prostate cancer, even among experts there is still a considerable variation in grading practices. In this study we describe the use of Pathology Imagebase, a novel reference image library, for setting an international standard in prostate cancer grading. METHODS AND RESULTS/RESULTS:The International Society of Urological Pathology (ISUP) recently launched a reference image database supervised by experts. A panel of 24 international experts in prostate pathology reviewed independently microphotographs of 90 cases of prostate needle biopsies with cancer. A linear weighted kappa of 0.67 (95% confidence interval = 0.62-0.72) and consensus was reached in 50 cases. The interobserver weighted kappa varied from 0.48 to 0.89. The highest level of agreement was seen for Gleason score (GS) 3 + 3 = 6 (ISUP grade 1), while higher grades and particularly GS 4 + 3 = 7 (ISUP grade 3) showed considerable disagreement. Once a two-thirds majority was reached, images were moved automatically into a public database available for all ISUP members at www.isupweb.org. Non-members are able to access a limited number of cases. CONCLUSIONS:It is anticipated that the database will assist pathologists to calibrate their grading and, hence, decrease interobserver variability. It will also help to identify instances where definitions of grades need to be clarified.

PURPOSE/OBJECTIVE:The aim of this study was to compare biopsy detection of intraductal (IDC) and cribriform (CR) pattern invasive prostate carcinoma (PCa) in mpMRI positive and negative regions of the prostate. MATERIAL AND METHODS/METHODS:A prospectively maintained single institution database was queried to identify patients who underwent mpMRI/US fusion targeted biopsy (MRI-TBx) and concurrent systematic sextant biopsy of MRI negative regions (SMN-Bx) between January 2013 and May 2016. All mpMRI targets were reviewed retrospectively by 2 readers for PIRADS v2 score, maximum dimension, ADC parameter and positive or negative DCE sequence. Biopsy slides were reviewed by two urologic pathologists for Gleason score/Grade group (GS/GG) and presence or absence of IDC/CR pattern. RESULTS:154 patients were included in the study. MRI-TBx and SMN-Bx were both negative for PCa in 51 patients, leaving 103 patients for mpMRI and IDC/CR pattern correlation. PCa was identified by MRI-TBx in 93 cases and by SMN-Bx in 76 (p=0.008). IDC/CR+ tumor was detected in 23 cases; in MRI-TBx site in 22 cases and in SMN-Bx site in 3 cases (p<0.001). IDC/CR pattern was significantly associated with PIRADS score of 5 (p=0.008) and decreasing ADC value (p=0.005). In 19/23 cases with IDC/CR, prior 12-core standard systematic biopsy was either negative (n=8) or had shown GG1 disease (n=11). CONCLUSION/CONCLUSIONS:MRI-TBx was associated with significantly increased detection of IDC/CR positive PCa compared to SMN-Bx sampling of mpMRI negative regions, supporting the role of MRI to enhance detection of clinically aggressive IDC/CR positive PCa.

Nonsurgical treatments for prostate cancer include androgen-deprivation therapy (ADT), radiation therapy (RT), ablative therapies, chemotherapy, and newly emerging immunotherapies. These approaches can be used alone or in combination depending on the clinical scenario. ADT is typically reserved for high-risk locally or systemically advanced disease that is not amenable to curative surgery. Radiation therapy can be used instead of surgery as primary therapy with curative intent for low-intermediate-risk disease as well as for control of locally advanced disease not suitable for surgery. Ablative therapies can be used as primary therapy for low-intermediate-risk disease or as salvage therapy for clinically localized disease where RT has failed. Chemotherapy and immune-based therapies are currently used for androgen-independent disease, although the indications for these approaches may well change as new data from clinical trials accrue. Pathologists should be able to recognize tissue changes associated with these treatments to provide information that will optimize patient management. This is particularly true in situations where clinical history of recent or remote nonsurgical treatment is not provided with the specimen. In the absence of this information, pathologists encountering the features described herein are encouraged to review patient records or communicate directly with clinical colleagues to determine how a given patient was treated and when.

AIMS/OBJECTIVE:The current World Health Organization classification categorises high-grade neuroendocrine (NE) carcinomas of the prostate into small-cell and large-cell types. A distinct form of carcinoma showing synchronous dual exocrine and NE differentiation, termed amphicrine carcinoma, has been described at various other sites, primarily within the gastrointestinal tract. The aim of this study was to investigate the clinicopathological features of a series of metastatic prostate carcinoma (PCa) cases with amphicrine features. METHODS AND RESULTS/RESULTS:Five cases of high-grade PCa showing an amphicrine immunohistochemical phenotype were prospectively collected. The serum prostate-specific antigen (PSA) level at diagnosis ranged from 38 ng/ml to 992 ng/ml (median 200 ng/ml). All five patients had metastatic disease, four at initial presentation. Microscopically, the tumours showed a solid/nested growth pattern composed of cells with amphophilic cytoplasm, vesicular nuclei, and macronucleoli. Morphological features of small-cell or large-cell NE carcinoma were absent. As compared with conventional high-grade PCa, the tumour cells showed a higher level of nuclear pleomorphism, brisk mitotic activity, and a high Ki67 proliferation index (median 50%). All cases showed immunohistochemical positivity for PSA, androgen receptor, and prostate-specific acid phosphatase, combined with diffuse or confluent/non-focal positivity for chromogranin-A and synaptophysin. Two hormone-naive cases showed a clinical response to androgen deprivation therapy. CONCLUSION/CONCLUSIONS:This series highlights a previously undefined, clinically aggressive variant of PCa showing dual exocrine and NE differentiation, for which we are proposing the term PCa with amphicrine features. Increased recognition of these tumours may lead to a better understanding of their biology, and ultimately improve their clinical management.

AIMS/OBJECTIVE:Despite efforts to standardize histopathology practice through the development of guidelines, the interpretation of morphology is still hampered by subjectivity. We here describe Pathology Imagebase, a novel mechanism for establishing an international standard for the interpretation of pathology specimens. METHODS AND RESULTS/RESULTS:The International Society of Urological Pathology (ISUP) established a reference image database through the input of experts in the field. Three panels were formed, one each for prostate, urinary bladder and renal pathology, consisting of 24 international experts. Each of the panel members uploaded microphotographs of cases into a non-public database. The remaining 23 experts were asked to vote from a multiple-choice menu. Prior to and while voting, panel members were unable to access the results of voting by the other experts. When a consensus level of at least two-thirds or 16 votes was reached, cases were automatically transferred to the main database. Consensus was reached in a total of 287 cases across five projects on the grading of prostate, bladder and renal cancer and the classification of renal tumours and flat lesions of the bladder. The full database is available to all ISUP members at www.isupweb.org. Non-members may access a selected number of cases. CONCLUSIONS:It is anticipated that the database will assist pathologists in calibrating their grading, and will also promote consistency in the diagnosis of difficult cases.

PURPOSE/OBJECTIVE:While prostate cancer is primarily a disease of older men, young age prostate cancer represents an important clinical subgroup which has not been adequately studied. We evaluated the histopathological features and associated clinical behavior of prostate cancer in a cohort of younger men treated with radical prostatectomy. MATERIALS AND METHODS/METHODS:The study included 171 men younger than 50 years with prostate cancer who were treated with radical prostatectomy at an academic institution between 2001 and 2015. Comprehensive pathology review was performed. Clinical and followup data were obtained from a prospectively maintained institutional database. RESULTS:Median age was 43 years (range 38 to 49). Of the tumors 42% were Gleason score 3 + 3 and 45% were 3 + 4 while Gleason score 4 + 3, 4 + 4 and 4 + 5 disease comprised 10.5%, 0.5% and 1% of cases, respectively. Mucinous carcinoma (greater than 25% extracellular mucin), an uncommon histological variant which comprises 0.2% of prostate cancers, was noted in 11 of our cases (6%). A further 21 cases (12%) of acinar adenocarcinoma had a less than 25% mucinous component. Followup data were available on 156 men (91%). Biochemical recurrence developed in 12 patients (19%) but there was no documented postoperative metastasis or death from disease in the cohort. All cases of mucinous carcinoma were associated with favorable clinicopathological characteristics. CONCLUSIONS:Our findings provide additional evidence that younger men with prostate cancer who are treated with radical prostatectomy mostly have favorable disease characteristics and outcomes. While the histopathological features in our series were generally comparable to those of older onset carcinoma, our cohort was enriched for tumors with a mucinous phenotype. Correlation with molecular-genetic analysis in this subset of tumors may be valuable.

CONTEXT/BACKGROUND:- There is growing interest in the use of digital pathology, especially whole slide imaging, for diagnostic purposes. Many issues need to be considered when incorporating this technology into a clinical laboratory. The College of American Pathologists (CAP) established a Digital Pathology Committee to support the development of CAP programs related to digital pathology. One of its many initiatives was a panel discussion entitled "Implementing Whole-Slide Imaging for Clinical Use: What to Do and What to Avoid," given for 3 years at the CAP annual meetings starting in 2014. OBJECTIVES/OBJECTIVE:- To review major issues to consider when implementing whole slide imaging for clinical purposes as covered during the panel discussion. DESIGN/METHODS:- The views expressed and recommendations given are based primarily on the personal experience of the authors as early adopters of this technology. It is not intended to be an exhaustive review of digital pathology. RESULTS:- Implementation is best approached in phases. Early efforts are directed toward identifying initial clinical applications and assembling an implementation team. Scanner selection should be based on intended use and budget. Recognizing pathologist concerns over the use of digital pathology for diagnostic purposes, ensuring adequate training, and performing appropriate validation studies will enhance adoption. Once implemented, the transition period from glass slide to image-based diagnostics will be associated with challenges, especially those related to a hybrid glass slide-digital slide workflow. CONCLUSIONS:- With appropriate preparation, planning, and stepwise implementation, whole slide imaging can be used safely and reliably for frozen sections, consultation, quality assurance, and primary diagnosis.

The development of whole-slide imaging has paved the way for digitizing of glass slides that are the basis for surgical pathology. This transformative technology has changed the landscape in research applications and education but despite its tremendous potential, its adoption for clinical use has been slow. We review the various niche applications that initiated awareness of this technology, provide examples of clinical use cases, and discuss the requirements and challenges for full adoption in clinical diagnosis. The opportunities for applications of image analysis tools in a workflow will be changed by integration of whole-slide imaging into routine diagnosis.