Faculty Bibliography

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.

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.

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.

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.

BACKGROUND:Previous studies have demonstrated that elevated neutrophil-to-lymphocyte ratios and platelet-to-lymphocyte ratios (PLRs) are associated with the presence of various malignancies. The present study evaluated various hematologic parameters and their association with renal tumor biopsy pathology. MATERIALS AND METHODS/METHODS:The clinical, hematologic, and pathologic parameters were obtained through a retrospective review of 475 diagnostic biopsy specimens of small renal masses from January 2001 to December 2013. The complete blood counts closest to and before the biopsies were obtained. The biopsy pathologic findings were divided into 3 groups: benign, primary renal malignancy, and nonrenal malignancy. The hematologic parameters were compared among the 3 groups. Receiver operating characteristic curves were constructed for the parameters that were significantly different among the groups. Multiple logistic regression models were used to assess whether the clinical and hematologic parameters were associated with benign or malignant pathologic findings. RESULTS:Hematologic parameters were available for 462 cases (97%). Pathologic examination of the biopsy specimens demonstrated benign, primary renal malignancy, and nonrenal malignancy in 114 (25%), 337 (73%), and 11 (2%) patients, respectively. The PLR was significantly (P = .010) different among the 3 groups and was significantly (P = .013) greater in those with nonrenal malignancies than in those with primary renal malignancies. Using a cutoff for the PLR of 202.9 gave a sensitivity of 63.6% and specificity of 82.2% for detecting a nonrenal malignancy. CONCLUSION/CONCLUSIONS:The hematologic parameters did not differ significantly between benign and primary renal malignant masses undergoing biopsy. The PLR might be useful as a simple and inexpensive marker to help distinguish nonrenal malignancies in the workup of a small renal mass.

OBJECTIVES/OBJECTIVE:To investigate the radiological features, diagnosis and management of screen-detected lobular neoplasia (LN) of the breast. MATERIALS AND METHODS/METHODS:392 women with pure LN alone were identified within the prospective UK cohort study of screen-detected non-invasive breast neoplasia (the Sloane Project). Demography, radiological features and diagnostic and therapeutic procedures were analysed. RESULTS:Non-pleomorphic LN (369/392) was most frequently diagnosed among women aged 50-54 and in 53.5% was at the first screen. It occurred most commonly on the left (58.0%; p = 0.003), in the upper outer quadrant and confined to one site (single quadrant or retroareolar region). No bilateral cases were found. The predominant radiological feature was microcalcification (most commonly granular) which increased in frequency with increasing breast density. Casting microcalcification as a predominant feature had a significantly higher lesion size compared to granular and punctate patterns (p = 0.034). 326/369 (88.3%) women underwent surgery, including 17 who underwent >1 operation, six who had mastectomy and six who had axillary surgery. Two patients had radiotherapy and 15 had endocrine treatment. Pleomorphic lobular carcinoma in situ (23/392) presented as granular microcalcification in 12; four women had mastectomy and six had radiotherapy. CONCLUSION/CONCLUSIONS:Screen-detected LN occurs in relatively young women and is predominantly non-pleomorphic and unilateral. It is typically associated with granular or punctate microcalcification in the left upper outer quadrant. Management, including surgical resection, is highly variable and requires evidence-based guideline development.

A widespread approach to investigating the dynamical behaviour of complex social systems is via agent-based models (ABMs). In this paper, we describe how such models can be dynamically calibrated using the ensemble Kalman filter (EnKF), a standard method of data assimilation. Our goal is twofold. First, we want to present the EnKF in a simple setting for the benefit of ABM practitioners who are unfamiliar with it. Second, we want to illustrate to data assimilation experts the value of using such methods in the context of ABMs of complex social systems and the new challenges these types of model present. We work towards these goals within the context of a simple question of practical value: how many people are there in Leeds (or any other major city) right now? We build a hierarchy of exemplar models that we use to demonstrate how to apply the EnKF and calibrate these using open data of footfall counts in Leeds.

PURPOSE/OBJECTIVE:Oncocytomas are benign tumors often diagnosed incidentally on imaging. Small case series have suggested that the growth kinetics of oncocytomas are similar to those of malignant renal tumors. Biopsy material may be insufficient to exclude a diagnosis of chromophobe renal cell carcinoma. We evaluated and compared the growth rates of oncocytoma and chromophobe renal cell carcinoma to improve our understanding of their natural history. MATERIALS AND METHODS/METHODS:This was a single center, retrospective study of patients diagnosed with lesions suggestive of oncocytoma or chromophobe renal cell carcinoma between 2003 and 2014. The growth rates were estimated using a mixed effect linear model. Patient and lesion characteristics were tested using a similar model for association with growth rate. RESULTS:Of the 95 lesions (oncocytoma 81, chromophobe renal cell carcinoma 14) included in the analysis 98% were diagnosed on biopsy. The annual growth rate was 0.14 cm and 0.38 cm for oncocytoma (median followup 34 months) and chromophobe renal cell carcinoma (median followup 25 months), respectively (p=0.5). Baseline lesion size was significantly associated with growth (p <0.001). The majority of oncocytomas (74%) and chromophobe renal cell carcinomas (67%) followed up to the 3-year mark had grown. Of these, 8 underwent surgery (6 in the chromophobe renal cell carcinoma group). The initial diagnosis was confirmed in all. Overall 5 patients died, all of nonrenal related causes. CONCLUSIONS:Although the majority of oncocytic renal neoplasms will grow with time, surveillance appears to remain safe. Patients opting for this strategy should be made aware that a diagnosis of oncocytoma following biopsy is associated with some degree of uncertainty due to the difficulty of differentiating them from other oncocytic renal neoplasms.

Innovative technologies for digital imaging and telecommunications are changing the way we deliver health care. Telepathology collaborations are one example of how delivering remote pathology services to patients can benefit from leveraging this change. Over the years, several academic and commercial teleconsultation networks have been established. Herein, we review the landscape of these international telepathology efforts and highlight key supportive factors and potential barriers to successful cross-border collaborations. Important features of successful international telepathology programs include efficient workflows, dedicated information technology staff, continuous maintenance, financial incentives, ensuring that all involved stakeholders are satisfied, and value-added clinical benefit to patient care. Factors that plague such telepathology operations include legal/regulatory issues, sustainability, and cultural and environmental issues. Pathologists, vendors and laboratory accreditation agencies will need to embrace and capitalize on this new paradigm of international telepathology accordingly.