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Bile duct brushing (BDB) is used to evaluate pancreatobiliary lesions as it widely samples lesions with a low complication rate. Cytological evaluation of BDB is a specific but insensitive test. There is limited literature on the use of post-cytocentrifuged (PCC) samples, which are usually discarded, for next-generation sequencing (NGS) as an adjunct to cytological diagnosis of BDB. In this study we investigate whether molecular analysis by NGS of PCC specimens improves the sensitivity of diagnosis. PCC samples from 100 consecutive BDB specimens spanning 93 unique patients were retained. DNA was extracted and mutational analysis was performed agnostic of morphologic or clinical findings. Each BDB specimen was characterized as negative, atypical or positive based on morphological analysis by trained cytopathologists. Performance characteristics for mutational profiling and morphological analysis were calculated on the basis of clinicopathologic follow-up. There was sufficient clinicopathologic follow-up to classify 94 of 100 cases as either malignant (n = 43) or benign (n = 51). Based on morphologic analysis of cytology, these 94 cases were classified as either benign (n = 55), atypical (n = 18), or as at least suspicious or positive for malignancy (n = 21). Morphologic analysis of cytology showed a sensitivity of 49% and a specificity of 100% if atypical cases were considered negative. NGS revealed oncogenic alterations in 40/43 (93%) of malignant cases based on clinicopathologic follow-up. The most common alterations were in KRAS and TP53, observed in 77% and 49% of malignant cases respectively. No alterations were observed in the 51 benign cases classified based on clinicopathologic follow-up. Supplementing cytomorphologic analysis with molecular profiling of PCC by targeted NGS analysis increased the sensitivity to 93% and maintained specificity at 100%. This study provides evidence for the utility of NGS molecular profiling of PCC specimens to increase the sensitivity of BDB cytology samples, although studies with larger cohorts are needed to verify these findings.

Introduction Although most patients with SCLC die within a few months of diagnosis, a subgroup of patients survive for many years. Factors determining long-term survivorship remain largely unknown. We present the first comprehensive comparative genomic and tumor microenvironment analyses of SCLC between patients with long-term survivorship and patients with the expected survivorship. Methods We compared surgically resected tumors of 23 long-term SCLC survivors (survival >4 years) and 18 SCLC survivors with the expected survival time (survival ≤2 years). There were no significant differences in clinical variables, including TNM staging and curative- versus non–curative-intent surgery between the groups. Gene expression profiling was performed by using microarrays, and tumor microenvironment analyses were performed by immunohistochemistry of prominent immune-related markers. Results Immune-related genes and pathways represented the majority of the differentially overexpressed genes in long-term survivorship compared with in expected survivorship. The differences in the immunological tumor microenvironment were confirmed by quantitative immunostaining. Increased numbers of tumor-infiltrating and associated lymphocytes were present throughout tumors of long-term survivors of SCLC. Several differentiating patterns of enhanced antitumor immunity were identified. Although some areas of the tumors of long-term survivors of SCLC also harbored higher numbers of suppressive immune cells (monocytes, regulatory lymphocytes, and macrophages), the ratios of these suppressive cells to CD3-positive lymphocytes were generally lower in the tumors of long-term survivors of SCLC, indicating a less tumor-suppressive microenvironment. Conclusions Our data demonstrate that long-term survivorship of patients with SCLC is strongly influenced by the presence of the immune cells in the tumor microenvironment. Characterization of the antitumor immune responses may identify opportunities for individualized immunotherapies for SCLC.

Biopsy site changes in mediastinal lymph nodes (LNs) attributable to prior endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been studied in a systematic manner. Twenty-four contributors from 14 institutions in 5 countries collaborated via social media (Twitter) to retrospectively review consecutive cases of resected mediastinal LNs from patients with prior EBUS-TBNA. Resected LNs were reexamined by submitting pathologists for changes attributable to EBUS-TBNA. Patients who received neoadjuvant therapy were excluded. Cases with suspected biopsy site changes underwent central review by 5 pathologists. A total of 297 mediastinal LN resection specimens from 297 patients (183 male/114 female, mean age: 65 y, range: 23 to 87) were reviewed. Biopsy site changes were most common in station 7 (10 cases) followed by 11R, 4R, and 10R, and were found in 34/297 (11.4%) cases, including displacement of tiny cartilage fragments into LN parenchyma in 26, intranodal or perinodal scars in 7, and hemosiderin in 1. Cartilage fragments ranged from 0.26 to 1.03 mm in length and 0.18 to 0.62 mm in width. The mean interval between EBUS-TBNA and LN resection was 38 days (range: 10 to 112) in cases with biopsy site changes. A control group of 40 cases without prior EBUS-TBNA, including 193 mediastinal LN stations, showed no evidence of biopsy site changes. Biopsy site changes are identified in a subset of resected mediastinal LNs previously sampled by EBUS-TBNA. The location of the abnormalities, temporal association with prior EBUS-TBNA, and the absence of such findings in cases without prior EBUS-TBNA support the contention that they are caused by EBUS-TBNA.

Background The emergence of less invasive procedures coupled with the growth of molecular testing have created a need for clinical laboratories to optimize workflows to enable tissue preservation and ancillary testing. In the preparation of formalin-fixed paraffin-embedded cell blocks (FFPE CBs), there is a cytocentrifugation step for cell pellet extraction that results in postcentrifugation supernatant fluid (SN). This SN, which in most routine workflows is discarded, has been suggested to contain adequate cellular material for molecular testing. In the current study, the authors describe the use of DNA and RNA extracted from SN for the detection of clinically relevant biomarkers by next-generation sequencing (NGS). Methods After cell pellet removal, cytocentrifugation SN from 30 endobronchial fine-needle aspiration rinses that were positive for malignancy on FFPE CB were collected. DNA and RNA were extracted from the SN and tested using an in-house NGS Solid Tumor Focus Assay. The NGS results were compared with findings from corresponding FFPE samples. Results Testing was successful in all 30 samples. There was 100% concordance between variants observed in the SN and corresponding FFPE specimens, which included 50 single-nucleotide variants, 9 copy number amplifications, 3 structural variants, and 2 indels. Furthermore, there was excellent correlation (correlation coefficient, 0.93) between the variant allele frequency of mutations observed in SN compared with that noted in corresponding FFPE CBs. Conclusions Cytocentrifugation SN is a valuable source for NGS, is comparable to FFPE that preserves tissue for other ancillary testing, and can reduce the failure rate of testing that may result from insufficient material being available in the CB.

Existing tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p p n = 648). The combination of Histotyping, grade group, and preoperative PSA outperformed Decipher (c-index = 0.75 vs. 0.70, n = 167). These results suggest that a prognostic classifier for prostate cancer based on digital images could serve as an alternative or complement to molecular-based companion diagnostic tests.

Background The presence of invasive cribriform adenocarcinoma (ICC), an expanse of cells containing punched-out lumina uninterrupted by stroma, in radical prostatectomy (RP) specimens has been associated with biochemical recurrence (BCR). However, ICC identification has only moderate inter-reviewer agreement. Objective To investigate quantitative machine-based assessment of the extent and prognostic utility of ICC, especially within individual Gleason grade groups. Design, setting, and participants A machine learning approach was developed for ICC segmentation using 70 RP patients and validated in a cohort of 749 patients from four sites whose median year of surgery was 2007 and with median follow-up of 28 mo. ICC was segmented on one representative hematoxylin and eosin RP slide per patient and the fraction of tumor area composed of ICC, the cribriform area index (CAI), was measured. Outcome measurements and statistical analysis The association between CAI and BCR was measured in terms of the concordance index (c index) and hazard ratio (HR). Results and limitations CAI was correlated with BCR (c index 0.62) in the validation set of 411 patients with ICC morphology, especially those with Gleason grade group 2 cancer (n = 192; c index 0.66), and was less prognostic when patients without ICC were included (c index 0.54). A doubling of CAI in the group with ICC morphology was prognostic after controlling for Gleason grade, surgical margin positivity, preoperative prostate-specific antigen level, pathological T stage, and age (HR 1.19, 95% confidence interval 1.03–1.38; p = 0.018). Conclusions Automated image analysis and machine learning could provide an objective, quantitative, reproducible, and high-throughput method of quantifying ICC area. The performance of CAI for grade group 2 cancer suggests that for patients with little Gleason 4 pattern, the ICC fraction has a strong prognostic role. Patient summary Machine-based measurement of a specific cell pattern (cribriform; sieve-like, with lots of spaces) in images of prostate specimens could improve risk stratification for patients with prostate cancer. In the future, this could help in expanding the criteria for active surveillance.

To explore the associations between T1 and T2 magnetic resonance fingerprinting (MRF) measurements and corresponding tissue compartment ratios (TCRs) on whole mount histopathology of prostate cancer (PCa) and prostatitis.A retrospective, IRB-approved, HIPAA-compliant cohort consisting of 14 PCa patients who underwent 3 T multiparametric MRI along with T1 and T2 MRF maps prior to radical prostatectomy was used. Correspondences between whole mount specimens and MRI and MRF were manually established. Prostatitis, PCa, and normal peripheral zone (PZ) regions of interest (ROIs) on pathology were segmented for TCRs of epithelium, lumen, and stroma using two U-net deep learning models. Corresponding ROIs were mapped to T2-weighted MRI (T2w), apparent diffusion coefficient (ADC), and T1 and T2 MRF maps. Their correlations with TCRs were computed using Pearson's correlation coefficient (R). Statistically significant differences in means were assessed using one-way ANOVA.Statistically significant differences (p 0.01) in means of TCRs and T1 and T2 MRF were observed between PCa, prostatitis, and normal PZ. A negative correlation was observed between T1 and T2 MRF and epithelium (R = - 0.38, - 0.44, p 0.05) of PCa. T1 MRF was correlated in opposite directions with stroma of PCa and prostatitis (R = 0.35, - 0.44, p 0.05). T2 MRF was positively correlated with lumen of PCa and prostatitis (R = 0.57, 0.46, p 0.01). Mean T2 MRF showed significant differences (p 0.01) between PCa and prostatitis across both transition zone (TZ) and PZ, while mean T1 MRF was significant (p = 0.02) in TZ.Significant associations between MRF (T1 in the TZ and T2 in the PZ) and tissue compartments on corresponding histopathology were observed.• Mean T2 MRF measurements and ADC within cancerous regions of interest dropped with increasing ISUP prognostic groups (IPG). • Mean T1 and T2 MRF measurements were significantly different (p 0.001) across IPGs, prostatitis, and normal peripheral zone (NPZ). • T2 MRF showed stronger correlations in the peripheral zone, while T1 MRF showed stronger correlations in the transition zone with histopathology for prostate cancer.

Context.— Social media sites are increasingly used for education, networking, and rapid dissemination of medical information, but their utility for facilitating research has remained largely untapped. Objective.— To describe in detail our experience using a social media platform (Twitter) for the successful initiation, coordination, and completion of an international, multi-institution pathology research study. Design.— Following a tweet describing a hitherto-unreported biopsy-related histologic finding in a mediastinal lymph node following endobronchial ultrasound–guided transbronchial needle aspiration, a tweet was posted to invite pathologists to participate in a validation study. Twitter's direct messaging feature was used to create a group to facilitate communication among participating pathologists. Contributing pathologists reviewed consecutive cases of mediastinal lymph node resection following endobronchial ultrasound–guided transbronchial needle aspiration and examined them specifically for biopsy site changes. Data spreadsheets containing deidentified data and digital photomicrographs of suspected biopsy site changes were submitted via an online file hosting service for central review by 5 pathologists from different institutions. Results.— A total of 24 pathologists from 14 institutions in 5 countries participated in the study within 143 days of study conception, and a total of 297 cases were collected and analyzed. The time interval between study conception and acceptance of the manuscript for publication was 346 days. Conclusions.— To our knowledge, this is the first time that a social media platform has been used to generate a research idea based on a tweet, recruit coinvestigators publicly, communicate with collaborating pathologists, and successfully complete a pathology study.

// Kaustubh Bhinge 1 , Lin Yang 2 , Simone Terra 6 , Aqsa Nasir 2 , Prasuna Muppa 6 , Marie Christine Aubry 6 , Joanne Yi 6 , Nafiseh Janaki 2 , Irina V. Kovtun 3 , Stephen J. Murphy 1 , Geoffrey Halling 1 , Hamed Rahi 1 , Aaron Mansfield 5 , Mariza de Andrade 4 , Ping Yang 4 , George Vasmatzis 1 , Tobias Peikert 7 , Farhad Kosari 1 1 Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA 2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA 3 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA 4 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA 5 Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA 6 Department of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA 7 Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA Correspondence to: Farhad Kosari, email: kosari.farhad@mayo.edu Keywords: ASCL1, RET, EGFR, lung cancer, neuroendocrine Received: April 10, 2016 Accepted: February 06, 2017 Published: February 24, 2017 ABSTRACT Achaete-scute homolog 1 (ASCL1) is a neuroendocrine transcription factor specifically expressed in 10-20% of lung adenocarcinomas (AD) with neuroendocrine (NE) differentiation (NED). ASCL1 functions as an upstream regulator of the RET oncogene in AD with high ASCL1 expression (A + AD). RET is a receptor tyrosine kinase with two main human isoforms; RET9 (short) and RET51 (long). We found that elevated expression of RET51 associated mRNA was highly predictive of poor survival in stage-1 A + AD (p=0.0057). Functional studies highlighted the role of RET in promoting invasive properties of A + AD cells. Further, A + AD cells demonstrated close to 10 fold more sensitivity to epidermal growth factor receptor (EGFR) inhibitors, including gefitinib, than AD cells with low ASCL1 expression. Treatment with EGF robustly induced phosphorylation of RET at Tyr-905 in A + AD cells with wild type EGFR. This phosphorylation was blocked by gefitinib and by siRNA-EGFR. Immunoprecipitation experiments found EGFR in a complex with RET in the presence of EGF and suggested that RET51 was the predominant RET isoform in the complex. In the microarray datasets of stage-1 and all stages of A + AD, high levels of EGFR and RET RNA were significantly associated with poor overall survival (p < 0.01 in both analyses). These results implicate EGFR as a key regulator of RET activation in A + AD and suggest that EGFR inhibitors may be therapeutic in patients with A + AD tumors even in the absence of an EGFR or RET mutation.

We report an individual with a compound heterozygosity for Hb D-Ibadan (HBB: c.263C>A) and Hb C (HBB: c.19G>A), a hemoglobin (Hb) combination not previously identified. The compound hemoglobinopathy was detected in a young woman during routine prenatal screening. Variant Hbs were identified and confirmed by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) followed by Sanger DNA sequencing. Hb D-Ibadan was present in significant excess over Hb C (70.3 to 24.4%). A complete blood count (CBC) revealed moderate microcytosis with slight anemia. The history suggests the Hb combination is clinically silent. The findings indicate the compound hemoglobinopathy demonstrates thalassemia minor-like red cell indices with an unequal distribution of the variant Hbs. Comparison with other Hb D-like heterozygous conditions is reviewed.

Multiparametric magnetic resonance imaging (mpMRI) is increasingly used in detection and surveillance of prostate cancer. However, the co-localization of lower grade lesions between mpMRI and histopathologic specimen has not been well established.We aim to determine the factors on final histopathological exam that correlate to tumor visibility for Grade I and II disease on mpMRI.Fifty-five patients who underwent radical prostatectomy from July 2014 to June 2016 were analyzed for the study. Of the sample of 55 patients, 18 were found to have Gleason score (GS) of 3 + 3 or 3 + 4 disease, and then were re-reviewed and annotated by a pathologist. Lesion diameter, area, and distance from the prostate capsule were measured. The annotated lesions were co-localized to the MRI report.Of the 184 lesions identified on the whole mount histopathologic slides, 106 (57.6%), 62 (33.7%), 14 (7.6%), and 2 (1.1%) of the lesions had a GS of 3 + 3, 3 + 4, 4 + 3, and 4 + 4, respectively. On analysis, 27.3% (24/88) of GS 6 ( 1.5 cm in size), and 88.9% (16/18) of GS 6 ( 1.5 cm in size) were identified (p 0.001). Additionally, when assessing lesion proximity to the prostatic capsule, 46.1% (41/89) of lesions closer (≤ 0.05 cm), and 30.5% (29/95) of lesions further ( 0.05 cm) from the capsule were visualized.Lesion diameter, area, and capsule proximity correlated with MRI visibility. Further studies are encouraged to validate the findings of our study.

Introduction: While most small cell lung cancer (SCLC) patients die within a few months, a sub-group of patients survive for many years. Factors determining long-term survivorship remain largely unknown. We present the first comprehensive comparative genomic and tumor microenvironment analyses of small cell lung cancer (SCLC) between patients with long term (LTS) and expected (EXS) survival times. Methods: We compared surgically resected tumors of 23 LTS (survival > 4 years) and 18 EXS (survival ≤ 2 years). There were no differences in clinical variables including TNM staging and curative versus non-curative intend surgery between the groups. Gene expression profiling was performed by microarrays and tumor microenvironment analyses were by IHC of prominent immune related markers. Results: Immune related genes and pathways represented the majority of the differentially overexpressed genes in LTS compared to the EXS. The differences in the immunological tumor-microenvironment were confirmed by quantitative immuno-staining. Increased numbers of tumor infiltrating and associated lymphocytes were present throughout tumors of LTS. Several differentiating patterns of enhanced anti-tumor immunity were identified. While some areas of LTS tumors also harbored higher numbers of suppressive immune cells (monocytes, regulatory lymphocytes, and macrophages), ratios of these suppressive cells to CD3+ lymphocytes were generally lower in LTS tumors indicating a more tumor suppressive microenvironment. Conclusions: Our data demonstrate that long-term survivorship of SCLC patients is strongly influenced by the presence of anti-tumor immune cells in the tumor microenvironment. Characterization of the anti-tumor immune responses may identify opportunities for individualized immunotherapies for SCLC. Citation Format: Farhad Kosari, Prasuna Muppa, Simone Terra, Anurag Sharma, Aaron Mansfield, Marie Christine Aubry, Nafiseh Janaki, Aqsa Nasir, Tobias Peikert. Anti-tumor immunity is a key determinant of small cell lung cancer survivorship [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4577.

5060 Background: Following a radical prostatectomy (RP) for prostate cancer, a patient may experience biochemical recurrence (BCR), defined as two consecutive prostate specific antigen (PSA) readings > 0.2 ng/mL. BCR is correlated with metastasis and disease specific survival. Extant molecular based companion diagnostic tests for predicting risk of BCR and disease progression tend to be expensive and tissue destructive. We sought to evaluate whether computer extracted features of glandular architecture from routine digitized H&E slides could predict post-RP BCR risk. Methods: RP specimens from 683 patients (184 with BCR, 499 without) with post-surgical PSA follow-up information were gathered from six sites. Median non-BCR follow-up was 3.2 years. A representative tumor area was annotated on the diagnostic H&E slide of each patient. 324 (131 BCR) patients from two sites formed the training set. The other 359 (53 BCR) patients formed the validation set. Glands were segmented by a deep learning model. 216 features describing gland arrangement, shape, and disorder were then extracted. An elastic net Cox proportional hazards model was constructed from the training set using the top 10 stable features identified via feature selection. Risk score thresholds were chosen on the training set to stratify patients into low-, medium-, or high-risk. Validation set results were evaluated by the log-rank test and hazard ratio. For the 172 (37 BCR) patients for whom Gleason grade and preoperative PSA values were available, risk classifications were compared using Cox proportional hazards regression. Results: Nine of the top features were gland shape features and one was a gland arrangement feature. The hazard ratio between the low- and high-risk groups on the validation set was 3.04 (p < 0.05). The histomorphometric classifier was predictive of BCR (p < 0.05, hazard ratio = 1.63) independent of Gleason grade group and preoperative PSA in multivariate testing. Conclusions: Computer extracted features of gland morphology can stratify post-RP patients by BCR risk. Our computerized histomorphometric model could serve as a prognostic tool in the post-RP setting.[Table: see text]

Clinical management decisions in prostate cancer are often based on risk determination with major uncertainty since limited tools are available to understand the risk of disease progression and guide the treatment decision process. Computer-aided quantitative histomorphometric analysis has emerged as a powerful computing tool to identify, characterize, and quantitate histologic features of tissues beyond human visual capabilities. Several quantitative features can be assessed, such as precise numeric measurements pertaining to the spatial arrangement and architecture of nuclei, shapes of nests and nuclei, and nuclear texture. This technology has proven to be useful for the detection of cancer in tissue sections and also for predicting tumor biology and clinical outcome in cancer patients. Utilizing a combination of synergistic strategy of quantitative histomorphometry and biomarker expression of NF-κB/p65 from prostate tissue specimens, we sought to fuse structural and functional information from morphological and molecular markers to better characterize disease progression improving prediction of biochemical recurrence (BCR). Here we utilized radical prostatectomy specimens (n=23) for feature extraction from 15 patients without BCR and 8 patients who experienced BCR (PSA > 0.2 ng/ml) within two years of surgery. Digitized H&E slides were annotated for a representative cancerous region, glands were automatically segmented, and 216 features of gland architecture, shape, and orientation disorder were extracted. Nuclei were automatically segmented from NF-κB/p65 stained slides. Based on digitally calculated stain optical density, every nuclei pixel was classified as either negative or weakly, moderately, or strongly positive for NF-κB/p65 staining. We first used the H&E features alone in leave-one-out cross validation with a naive Bayes classifier, using the top two features by t-test in every fold, to obtain a recurrence probability for each patient. We repeated that experiment with the NF-κB/p65 features. We then multiplied together patients' posterior class probabilities from each model for a final probability. In every fold a probability threshold was identified from the training set to classify patients as BCR or non-BCR. Our results demonstrate that the three most predictive H&E features were all gland orientation disorder features. The top NF-κB/p65 feature was percentage of nuclei pixels positive for staining. Accuracy predicted was 78% with H&E features alone, 74% with NF-κB/p65 features alone, and 87% in the aggregate model. Taken together, our results demonstrate that fusing nuclei NF-κB/p65 and gland morphology information allows for functional and morphologic characterization of prostate cancer, potentially allowing for improved risk characterization and prognosis prediction in prostate cancer patients. Citation Format: Patrick Leo, Eswar Shankar, Robin Elliott, Andrew Janowczyk, Nafiseh Janaki, Gregory T. MacLennan, Anant Madabhushi, Sanjay Gupta. Combination of quantitative histomorphometry with NFκB/p65 nuclear localization is better predictor of biochemical recurrence in prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-021.

e16559 Background: Prostate cancer (PCa) is 1.7 times more prevalent and 2.3 times more lethal in African American (AA) men than in Caucasian American (CA) men. Additionally there is a higher incidence (when controlling for relative population size) of more aggressive PCa in the AA compared to the CA population which has led a number of groups to investigate whether there are molecular differences in the disease phenotype between the two groups. In this work we investigate whether computer extracted features of glandular morphology from digitized pathology images of surgical specimens identified as predictive of biochemical recurrence are also differentially expressed between AA and CA patients. Methods: Two cohorts were gathered. Cohort 1 (C1) contained digitized whole mount Gleason 7 radical prostatectomy specimens (RPS) from 72 patients (46 CA, 26 AA). Cohort 2 (C2) comprising quarter and whole mount RPS from 145 patients (135 CA, 10 AA), who either had biochemical recurrence in 5 years (47) or did not (98). A pathologist annotated each image in both cohorts for a representative cancerous region. Glands were automatically segmented and 216 features describing gland arrangement, shape, and disorder were extracted from every image. Features were tested for significance by Wilcoxon rank sum test at p < .05. Results: 8 features of gland morphology were significantly different between AA and CA groups and also predictive of biochemical recurrence (Table). Conclusions: We identified 8 computer extracted features of gland morphology that were both differentially expressed between AA and CA men and predictive of biochemical recurrence, suggesting that there are histomorphometric differences in prostate cancer appearance between AA and CA men. [Table: see text]