The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma

Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed

Emergent Orthotopic Liver Transplantation for Hemorrhage from a Giant Cavernous Hepatic Hemangioma: Case Report and Review

IntroductionCavernous hemangiomas represent the most common benign primary hepatic neoplasm, often being incidentally detected. Although the majority of hepatic hemangiomas remain asymptomatic, symptomatic hepatic hemangiomas can present with abdominal pain, hemorrhage, biliary compression, or a consumptive coagulopathy. The optimal surgical management of symptomatic hepatic hemangiomas remains controversial, with resection, enucleation, and both deceased donor and living donor liver transplantation having been reported.Case reportWe report the case of a patient found to have a unique syndrome of multiorgan cavernous hemangiomatosis involving the liver, lung, omentum, and spleen without cutaneous involvement. Sixteen years following her initial diagnosis, the patient suffered from intra-abdominal hemorrhage due to her giant cavernous hepatic hemangioma. Evidence of continued bleeding, in the setting of Kasabach-Merritt Syndrome and worsening abdominal compartment syndrome, prompted MELD exemption listing. The patient subsequently underwent emergent liver transplantation without complication.ConclusionAlthough cavernous hemangiomas represent the most common benign primary hepatic neoplasm, hepatic hemangioma rupture remains a rare presentation in these patients. Management at a center with expertise in liver transplantation is warranted for those patients presenting with worsening DIC or hemorrhage, given the potential for rapid clinical decompensation

Factors associated with downgrading in patients with high grade prostate cancer

ObjectiveTo determine the factors associated with downgrading between biopsy and prostatectomy in the contemporary era using extended-template biopsy techniques.Materials and methodsThe UCSF Urologic Oncology Database was used to identify subjects diagnosed with high grade prostate cancer (primary pattern 4 or 5) in at least one core on extended-pattern biopsy. Multivariable logistic regression analysis was performed to identify independent factors associated with downgrading at radical prostatectomy, defined as a change from primary pattern 4 or 5 to primary pattern 3.ResultsDowngrading occurred in 68 (34%) of 202 subjects who met the study criteria. Fourteen (47%) of 30 subjects with ≤25% of cores that were high grade and 9 (43%) of 21 subjects with <10% of total tissue containing cancer were downgraded. In a multivariable model, patients with mixed grade cores had much higher odds of downgrading than those with all high grade cores (OR 3.0 95% 1.3-7.1), P < 0.01). The proportion (per 10% increment) of positive cores containing high grade cancer (OR 0.8 95% CI 0.7-0.9 P < 0.01) and the percent (per 10% increment) of total tissue containing cancer (OR 0.7 95% CI 0.6-0.9 P = 0.01) were significantly associated with lower odds of downgrading.ConclusionsDowngrading following radical prostatectomy is a common event. Biopsy over-grading may preclude men from active surveillance or lead to unnecessary lymphadenectomy, excess radiation, or prolonged hormone therapy. The proportion of positive biopsy cores that are high grade and the percent of total tissue containing cancer should be incorporated into decision making

Factors associated with downgrading in patients with high grade prostate cancer.

ObjectiveTo determine the factors associated with downgrading between biopsy and prostatectomy in the contemporary era using extended-template biopsy techniques.Materials and methodsThe UCSF Urologic Oncology Database was used to identify subjects diagnosed with high grade prostate cancer (primary pattern 4 or 5) in at least one core on extended-pattern biopsy. Multivariable logistic regression analysis was performed to identify independent factors associated with downgrading at radical prostatectomy, defined as a change from primary pattern 4 or 5 to primary pattern 3.ResultsDowngrading occurred in 68 (34%) of 202 subjects who met the study criteria. Fourteen (47%) of 30 subjects with ≤25% of cores that were high grade and 9 (43%) of 21 subjects with <10% of total tissue containing cancer were downgraded. In a multivariable model, patients with mixed grade cores had much higher odds of downgrading than those with all high grade cores (OR 3.0 95% 1.3-7.1), P < 0.01). The proportion (per 10% increment) of positive cores containing high grade cancer (OR 0.8 95% CI 0.7-0.9 P < 0.01) and the percent (per 10% increment) of total tissue containing cancer (OR 0.7 95% CI 0.6-0.9 P = 0.01) were significantly associated with lower odds of downgrading.ConclusionsDowngrading following radical prostatectomy is a common event. Biopsy over-grading may preclude men from active surveillance or lead to unnecessary lymphadenectomy, excess radiation, or prolonged hormone therapy. The proportion of positive biopsy cores that are high grade and the percent of total tissue containing cancer should be incorporated into decision making

Factors associated with downgrading in patients with high grade prostate cancer.

ObjectiveTo determine the factors associated with downgrading between biopsy and prostatectomy in the contemporary era using extended-template biopsy techniques.Materials and methodsThe UCSF Urologic Oncology Database was used to identify subjects diagnosed with high grade prostate cancer (primary pattern 4 or 5) in at least one core on extended-pattern biopsy. Multivariable logistic regression analysis was performed to identify independent factors associated with downgrading at radical prostatectomy, defined as a change from primary pattern 4 or 5 to primary pattern 3.ResultsDowngrading occurred in 68 (34%) of 202 subjects who met the study criteria. Fourteen (47%) of 30 subjects with ≤25% of cores that were high grade and 9 (43%) of 21 subjects with <10% of total tissue containing cancer were downgraded. In a multivariable model, patients with mixed grade cores had much higher odds of downgrading than those with all high grade cores (OR 3.0 95% 1.3-7.1), P < 0.01). The proportion (per 10% increment) of positive cores containing high grade cancer (OR 0.8 95% CI 0.7-0.9 P < 0.01) and the percent (per 10% increment) of total tissue containing cancer (OR 0.7 95% CI 0.6-0.9 P = 0.01) were significantly associated with lower odds of downgrading.ConclusionsDowngrading following radical prostatectomy is a common event. Biopsy over-grading may preclude men from active surveillance or lead to unnecessary lymphadenectomy, excess radiation, or prolonged hormone therapy. The proportion of positive biopsy cores that are high grade and the percent of total tissue containing cancer should be incorporated into decision making

The relationship between prostate specific antigen change and biopsy progression in patients on active surveillance for prostate cancer.

PurposeWe assessed whether an association exists between a change in prostate specific antigen and biopsy progression in men on active surveillance.Materials and methodsA cohort of patients undergoing active surveillance for prostate cancer was identified from the urological oncology database at our institution. Multivariate logistic regression was performed to determine whether prostate specific antigen velocity, defined as the change in ln(prostate specific antigen) per year, is associated with biopsy progression, defined as a Gleason upgrade or volume progression on repeat biopsy within 24 months of diagnosis.ResultsA total of 241 men with a mean ± SD age of 61 ± 7 years and mean prostate specific antigen 4.9 ± 2.2 ng/ml met study inclusion criteria. Median time to repeat biopsy was 10 months (IQR 6-13). Biopsy progression developed in 55 men (23%), including a Gleason score upgrade in 46 (19%), greater than 33% positive cores in 11 (5%) and greater than 50% maximum single core positive in 12 (5%). The median prostate specific antigen ratio per year was 1.0 (IQR 0.95-1.03), although 1 man had a ratio of greater than 1.26 (doubled over 3 years) and 7 had a ratio of less than 1/1.26 (halved over 3 years). On multivariate analysis prostate specific antigen doubling within 3 years was associated with a 1.4-fold increase in the odds of biopsy progression (OR 1.4, 95% CI 0.6-3.4, p = 0.46).ConclusionsThere is little change in prostate specific antigen during the first 24 months of surveillance in men with well staged, low risk prostate cancer. We believe that these findings highlight the importance of repeat biopsy during surveillance

The relationship between prostate specific antigen change and biopsy progression in patients on active surveillance for prostate cancer.

PurposeWe assessed whether an association exists between a change in prostate specific antigen and biopsy progression in men on active surveillance.Materials and methodsA cohort of patients undergoing active surveillance for prostate cancer was identified from the urological oncology database at our institution. Multivariate logistic regression was performed to determine whether prostate specific antigen velocity, defined as the change in ln(prostate specific antigen) per year, is associated with biopsy progression, defined as a Gleason upgrade or volume progression on repeat biopsy within 24 months of diagnosis.ResultsA total of 241 men with a mean ± SD age of 61 ± 7 years and mean prostate specific antigen 4.9 ± 2.2 ng/ml met study inclusion criteria. Median time to repeat biopsy was 10 months (IQR 6-13). Biopsy progression developed in 55 men (23%), including a Gleason score upgrade in 46 (19%), greater than 33% positive cores in 11 (5%) and greater than 50% maximum single core positive in 12 (5%). The median prostate specific antigen ratio per year was 1.0 (IQR 0.95-1.03), although 1 man had a ratio of greater than 1.26 (doubled over 3 years) and 7 had a ratio of less than 1/1.26 (halved over 3 years). On multivariate analysis prostate specific antigen doubling within 3 years was associated with a 1.4-fold increase in the odds of biopsy progression (OR 1.4, 95% CI 0.6-3.4, p = 0.46).ConclusionsThere is little change in prostate specific antigen during the first 24 months of surveillance in men with well staged, low risk prostate cancer. We believe that these findings highlight the importance of repeat biopsy during surveillance

Imaging, Diagnosis, Prognosis Bladder Cancer Outcome and Subtype Classification by Gene Expression

Model s of bl adder tumor progressionhave suggested that genetic al terations maydetermine both phenotype and cl inical course.We have appl ied expression microarray anal ysis to a divergent set of bl adder tumors to further el ucidate the course of disease progression and to cl assify tumors into more homogeneous and cl inical l relD ant subgroups. cDNA microarrays containing 10,368 humangene el ements wereused to characterize the gl obal gene expression patterns in 80bl adder tumors, 9 bl adder cancer cel l l ines, and 3 normal bl adder sampl es. Robust statistical approaches accounting for the mul tipl e testing probl em were used to identify differential l y expressed genes

Cancer Therapy: Preclinical Bladder Cancer Stage and Outcome by Array-Based Comparative

Purpose: adder carcinogenesis is bel ieved to fol l ow al ternative pathways of disease progression driven by an accumul ation of genetic al terations. The purpose of this study was to eval uate associations between measures of genomic instabil ity and bl adder cancer cl inical phenotype

Genome-wide host methylation profiling of anal and cervical carcinoma.

HPV infection results in changes in host gene methylation which, in turn, are thought to contribute to the neoplastic progression of HPV-associated cancers. The objective of this study was to identify joint and disease-specific genome-wide methylation changes in anal and cervical cancer as well as changes in high-grade pre-neoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) anal tissues (n = 143; 99% HPV+) and fresh frozen cervical tissues (n = 28; 100% HPV+) underwent microdissection, DNA extraction, HPV genotyping, bisulfite modification, DNA restoration (FFPE) and analysis by the Illumina HumanMethylation450 Array. Differentially methylated regions (DMR; t test q0.3) were compared between normal and cancer specimens in partial least squares (PLS) models and then used to classify anal or cervical intraepithelial neoplasia-3 (AIN3/CIN3). In AC, an 84-gene PLS signature (355 significant probes) differentiated normal anal mucosa (NM; n = 9) from AC (n = 121) while a 36-gene PLS signature (173 significant probes) differentiated normal cervical epithelium (n = 10) from CC (n = 9). The CC progression signature was validated using three independent publicly available datasets (n = 424 cases). The AC and CC progression PLS signatures were interchangeable in segregating normal, AIN3/CIN3 and AC and CC and were found to include 17 common overlapping hypermethylated genes. Moreover, these signatures segregated AIN3/CIN3 lesions similarly into cancer-like and normal-like categories. Distinct methylation changes occur across the genome during the progression of AC and CC with overall similar profiles and add to the evidence suggesting that HPV-driven oncogenesis may result in similar non-random methylomic events. Our findings may lead to identification of potential epigenetic drivers of HPV-associated cancers and also, of potential markers to identify higher risk pre-cancerous lesions