Granulomas associated with renal neoplasms: A multi-institutional clinicopathological study of 111 cases.

AIMS: Formal depiction of granulomatous inflammation associated with renal neoplasms has mainly consisted of case reports. Herein, we investigate the clinicopathological features and potential significance of granulomas associated with renal tumours from a large multi-institutional cohort. METHODS AND RESULTS: One hundred and eleven study cases were collected from 22 institutions, including 57 partial nephrectomies and 54 radical nephrectomies. Patient ages ranged from 27 to 85 years (average = 60.1 years; male = 61%). Renal neoplasms included clear cell renal cell carcinoma (RCC; 86%), papillary RCC (8%), chromophobe RCC (3%), clear cell papillary RCC (1%), mixed epithelial stromal tumour (1%) and oncocytoma (1%). Granulomas were peritumoral in 36%, intratumoral in 24% and both in 40% of cases. Total granuloma count per case ranged from one to 300 (median = 15) with sizes ranging from 0.15 to 15 mm (mean = 1.9 mm). Necrotising granulomas were seen in 14% of cases. Histochemical stains for organisms were performed on 45% of cases (all negative). Sixteen cases (14%) had a prior biopsy/procedure performed, and eight patients had neoadjuvant immunotherapy or chemotherapy. Eleven patients (10%) had a confirmed diagnosis of sarcoidosis, including five in whom sarcoidosis was diagnosed after nephrectomy. CONCLUSION: Based on this largest case-series to date, peri-/intratumoral granulomas associated with renal neoplasms may be more common than initially perceived. The extent of granulomatous inflammation can vary widely and may or may not have necrosis with possible aetiologies, including prior procedure or immunotherapy/chemotherapy. Although a clinical association with sarcoidosis is infrequent it can still occur, and the presence of granulomas warrants mention in pathology reports.

Tissue-based multigene expression tests for pretreatment prostate cancer risk assessment: current status and future perspectives.

Prostate cancer is a highly prevalent disease with ample spectrum of aggressiveness and treatment options. Low-risk disease can be safely managed by nonintervention strategies, such as active surveillance; however, accurate risk assessment is warranted. Molecular tests have been developed and validated to complement standard clinicopathological parameters and help to improve risk stratification in prostate cancer. Herein, we review selected tissue-based assays, including genomic prostate score, cell cycle progression score and genomic classifier, with particular emphasis on their role in patient risk assessment in a pretreatment setting, in view of their current or potential utilization in active surveillance.

Does cumulative prostate cancer length (CCL) in prostate biopsies improve prediction of clinically insignificant cancer at radical prostatectomy in patients eligible for active surveillance?

OBJECTIVES: To evaluate if cumulative prostate cancer length (CCL) on prostate needle biopsy divided by the number of biopsy cores (CCL/core) could improve prediction of insignificant cancer on radical prostatectomy (RP) in patients with prostate cancer eligible for active surveillance (AS). PATIENTS AND METHODS: Patients diagnosed with prostate cancer on extended (≥10 cores) biopsy with an initial prostate-specific antigen (iPSA) level of <15 ng/mL, clinical stage (cT) ≤ 2a, and highest biopsy Gleason score 3 + 3 = 6 or 3 + 4 = 7 with <3 positive cores who underwent RP were included in the study. The CCL/core and presence of insignificant cancer (organ-confined, volume <0.5 mL, Gleason score at RP ≤6) were recorded. pT2 prostate cancer with RP Gleason score ≤3 + 4 = 7 and volume <0.5 mL were categorised as low-tumour-volume organ-confined disease (LV-OCD). RESULTS: In all, 221 patients met the inclusion criteria: the mean age was 59 years and the median iPSA level was 4.5 ng/mL. The clinical stage was cT1 in 86% of patients; biopsy Gleason score was 3 + 3 = 6 in 67% (group 1) and 3 + 4 = 7 in 33% of patients (group 2). The maximum percentage of biopsy core involvement was <50 in 85%; the median CCL/core was 0.15 mm. Insignificant cancer was found in 27% and LV-OCD in 44% of patients. Group 2 was associated with higher number of positive cores, maximum percentage core involvement, total prostate cancer length, and CCL/core. Group 1 was more likely to have insignificant cancer (39%) or LV-OCD (54%) than group 2 (3% and 23%, respectively). Group 2 had significantly higher RP Gleason score and pathological stage. Univariate analysis of group 1 showed that the iPSA level, maximum percentage core involvement, prostate cancer length, and CCL/core were all significantly associated with insignificant cancer and LV-OCD. For group 2, the number of positive cores (1 vs 2) was also significantly associated with LV-OCD. On multivariate logistic regression analysis, maximum percentage core involvement of <50, and number of positive cores (1 vs 2) were independent predictors of insignificant cancer in group 1; biopsy Gleason score, maximum percentage core involvement of <50 and prostate cancer length of <3 mm or CCL/core of <0.2 mm were all independent predictors of LV-OCD in the whole population. The maximum percentage of core involvement of <50 and prostate cancer length of <3 mm or CCL/core of <0.2 mm were also independent predictors of LV-OCD in group 1 patients. CONCLUSION: In patients eligible for AS, a CCL/core of <0.20 mm was significantly associated with insignificant cancer and LV-OCD. However, when parameters of cancer burden were considered, CCL/core did not independently add any additional value for predicting insignificant cancer in patients with biopsy Gleason score 6. The CCL/core was an independent predictor of LV-OCD in the whole population and in group 1 patients, although the model including prostate cancer length showed slightly higher area under the receiver operating characteristic curve.

Case report: A novel somatic SDHB variant in a patient with bladder paraganglioma.

Background: Paragangliomas (PGL) are rare neuroendocrine tumors derived from the autonomic nervous system paraganglia. Urinary bladder paragangliomas (UBPGL) originate from the sympathetic neurons of the urinary bladder wall and represent 0.7% of all paragangliomas and <0.05% of all bladder tumors. PGL and UBPGL can be associated with SDHB, SDHD, NF1, and VHL gene variants, with the most common germline alterations found in SDHB and VHL. Case report: We report a case of a 42-year-old woman who presented with menorrhagia/hematuria, uterine leiomyomas, as well as cardiac and bladder masses. The cardiac mass was favored to be a myxoma based on clinical findings, while the bladder mass was diagnosed as UBPGL. A novel SDHB mutation (c.642G>A, p Q214Q), detected in the UBPGL, was proven to be somatic. Although this variant was seemingly synonymous, it was predicted to have a loss of function due to the splice site effect, which was further supported by the immunohistochemical loss of SDHB. Conclusion: This case highlights the challenges of diagnosing an extremely rare entity, bladder paraganglioma, with an emphasis on the multidisciplinary approach to navigate various clinical and imaging findings that may initially be misleading. In addition, a novel loss of function SDHB variant that could have been overlooked as a synonymous variant is herein reported, while also illustrating the importance of both germline and somatic mutation testing.

Association of computed tomography scan-assessed body composition with immune and PI3K/AKT pathway proteins in distinct breast cancer tumor components.

This hypothesis-generating study aims to examine the extent to which computed tomography-assessed body composition phenotypes are associated with immune and PI3K/AKT signaling pathways in breast tumors. A total of 52 patients with newly diagnosed breast cancer were classified into four body composition types: adequate (lowest two tertiles of total adipose tissue [TAT]) and highest two tertiles of total skeletal muscle [TSM] areas); high adiposity (highest tertile of TAT and highest two tertiles of TSM); low muscle (lowest tertile of TSM and lowest two tertiles of TAT); and high adiposity with low muscle (highest tertile of TAT and lowest tertile of TSM). Immune and PI3K/AKT pathway proteins were profiled in tumor epithelium and the leukocyte-enriched stromal microenvironment using GeoMx (NanoString). Linear mixed models were used to compare log2-transformed protein levels. Compared with the normal type, the low muscle type was associated with higher expression of INPP4B (log2-fold change = 1.14, p = 0.0003, false discovery rate = 0.028). Other significant associations included low muscle type with increased CTLA4 and decreased pan-AKT expression in tumor epithelium, and high adiposity with increased CD3, CD8, CD20, and CD45RO expression in stroma (P<0.05; false discovery rate >0.2). With confirmation, body composition can be associated with signaling pathways in distinct components of breast tumors, highlighting the potential utility of body composition in informing tumor biology and therapy efficacies.

Analytical validation of the Oncotype DX prostate cancer assay - a clinical RT-PCR assay optimized for prostate needle biopsies.

BACKGROUND: The Oncotype DX Prostate Cancer Assay is a multi-gene RT-PCR expression assay that was developed for use with fixed paraffin-embedded (FPE) diagnostic prostate needle biopsies containing as little as 1 mm of prostate tumor in the greatest dimension. The assay measures expression of 12 cancer-related genes representing four biological pathways and 5 reference genes which are algorithmically combined to calculate the Genomic Prostate Score (GPS). This biopsy-based assay has been analytically and subsequently clinically validated as a predictor of aggressive prostate cancer. The aim of this study was to validate the analytical performance of the Oncotype DX Prostate Cancer Assay using predefined acceptance criteria. RESULTS: The lowest quartile of RNA yields from prostate needle biopsies (six 5 µm sections) was between 19 and 34 ng. Analytical validation of the process requiring as little as 5 ng of RNA met all pre-defined acceptance criteria. Amplification efficiencies, analytical sensitivity, and accuracy of gene assays were measured by serially diluting an RNA sample and analyzing features of the linear regression between RNA expression measured by the crossing point (Cp) versus the log2 of the RNA input per PCR assay well. Gene assays were shown to accurately measure expression over a wide range of inputs (from as low as 0.005 ng to 320 ng). Analytical accuracy was excellent with average biases at qPCR inputs representative of patient samples <9.7% across all assays while amplification efficiencies were within ±6% of the median. Assessments of reproducibility and precision were performed by testing 10 prostate cancer RNA samples over multiple instruments, reagent lots, operators, days (precision), and RNA input levels (reproducibility) using appropriately parameterized linear mixed models. The standard deviations for analytical precision and reproducibility were 1.86 and 2.11 GPS units (100-unit scale) respectively. CONCLUSIONS: The Oncotype DX Prostate Cancer Assay, a clinical RT-PCR assay specifically designed for use with prostate needle biopsies, has been analytically validated using very limited RNA inputs. The assay requirements and analytical performance will provide physicians with test results from a robust and reliable assay which will enable improved treatment decisions for men diagnosed with early-stage prostate cancer.

Prostate cancer patients older than 70 years treated by radical prostatectomy have higher biochemical recurrence rate than their matched younger counterpart.

BACKGROUND: Consensus on prostate cancer (PCA) treatment in older men is currently lacking. We evaluated clinicopathological and oncological outcomes in patients >70-year-old treated with radical prostatectomy (RP). METHODS: Clinicopathological and follow-up (FU) data for >70-year-old RP men (2000-2011) were recorded. Association between preoperative features, extraprostatic extension (EPE) and biochemical failure (bF), and postoperative features and bF, was explored. Patients >70-year-old were matched with younger (50- to 70-year-old) men with similar RP features to analyze the effect of age on bF. RESULTS: Two hundred eighteen RP patients were >70-year-old. Clinical stage (cT) was T1 in 74.1%. Biopsy (Bx) Gleason score (GS) was 6 (35.8%), 7 (45.9%), and ≥8 (18.3%); RP GS was 6 (10.1%), 7 (63.3%), and ≥8 (26.6%). Median PSAD was 0.14 (range: 0.01-1.12). Pathologic stage (pT) was pT3 in 45.9%. bF occurred in 14.0%. Best preoperative predictive model for pT3 disease included D'Amico risk, number of Bx positive cores, PSAD, maximum % of PCA per core (P < 0.0001); cT, PSAD and primary Bx Gleason pattern best predicted bF preoperatively (P = 0.0031). Among postoperative features, high RP GS, positive margins, and pT3 were significantly associated with bF. Margin status and pT best predicted bF. Patients >70-year-old had 85% higher odds of bF compared to younger men (P = 0.036). CONCLUSIONS: PCA detected in >70-year-old men shows adverse pathologic features. Failure rate is significantly higher in older than in matched younger patients.

Genomic, epigenomic, and transcriptomic signatures of prostate cancer between African American and European American patients.

Prostate cancer is the second most common cancer in men in the United States, and racial disparities are greatly observed in the disease. Specifically, African American (AA) patients have 60% higher incidence and mortality rates, in addition to higher grade and stage prostate tumors, than European American (EA) patients. In order to narrow the gap between clinical outcomes for these two populations, genetic and molecular signatures contributing to this disparity have been characterized. Over the past decade, profiles of prostate tumor samples from different ethnic groups have been developed using molecular and functional assays coupled with next generation sequencing or microarrays. Comparative genome-wide analyses of genomic, epigenomic, and transcriptomic profiles from prostate tumor samples have uncovered potential race-specific mutations, copy number alterations, DNA methylation, and gene expression patterns. In this study, we reviewed over 20 published studies that examined the aforementioned molecular contributions to racial disparities in AA and EA prostate cancer patients. The reviewed genomic studies revealed mutations, deletions, amplifications, duplications, or fusion genes differentially enriched in AA patients relative to EA patients. Commonly reported genomic alterations included mutations or copy number alterations of FOXA1, KMT2D, SPOP, MYC, PTEN, TP53, ZFHX3, and the TMPRSS2-ERG fusion. The reviewed epigenomic studies identified that CpG sites near the promoters of PMEPA1, RARB, SNRPN, and TIMP3 genes were differentially methylated between AA and EA patients. Lastly, the reviewed transcriptomic studies identified genes (e.g. CCL4, CHRM3, CRYBB2, CXCR4, GALR1, GSTM3, SPINK1) and signaling pathways dysregulated between AA and EA patients. The most frequently found dysregulated pathways were involved in immune and inflammatory responses and neuroactive ligand signaling. Overall, we observed that the genomic, epigenomic, and transcriptomic alterations evaluated between AA and EA prostate cancer patients varied between studies, highlighting the impact of using different methods and sample sizes. The reported genomic, epigenomic, and transcriptomic alterations do not only uncover molecular mechanisms of tumorigenesis but also provide researchers and clinicians valuable resources to identify novel biomarkers and treatment modalities to improve the disparity of clinical outcomes between AA and EA patients.

Micro-Ultrasound Guided Transperineal Prostate Biopsy: A Clinic-Based Procedure.

Prostate cancer is the most common solid malignancy in men and requires a biopsy for diagnosis. This manuscript describes a freehand micro-ultrasound guided transperineal technique performed under local anesthesia, which maintains accuracy, keeps patients comfortable, has low adverse events, and minimizes the need for disposables. Prior micro-ultrasound-guided transperineal techniques required general or spinal anesthesia. The key steps described in the protocol include (1) the placement of the local anesthesia, (2) micro-ultrasound imaging, (3) and the visualization of the anesthetic/biopsy needle while uncoupled from the insonation plane. A retrospective review of 100 patients undergoing this technique demonstrated a 68% clinically significant cancer detection rate. Pain scores were prospectively collected in a subset of patients (N = 20) and showed a median procedural pain score of 2 out of 10. The 30 day Grade III adverse event rate was 3%; one of these events was probably related to the prostate biopsy. Overall, we present a simple, accurate, and safe technique for performing a micro-ultrasound-guided transperineal prostate biopsy.

"Oncocytoid Renal Cell Carcinomas After Neuroblastoma" Represent TSC -mutated Eosinophilic Solid and Cystic Renal Cell Carcinomas : Association With Prior Childhood Malignancy and Multifocality With Therapeutic Implications.

The concept of oncocytoid renal cell carcinoma in patients who have survived neuroblastoma as a distinct biologic entity has been controversial since its original description in 1999. This is in part because similar oncocytoid renal cell carcinomas have been described in association with other pediatric cancers, and also because other renal cell carcinoma subtypes (such as MiT family translocation renal cell carcinoma) have been described in children who have survived neuroblastoma. We identified an index case of a child who survived medulloblastoma and developed multifocal bilateral oncocytoid renal cell carcinomas with morphology and immunophenotype compatible with eosinophilic solid and cystic renal cell carcinoma (ESC RCC) and demonstrated that both neoplasms harbored distinctive mutations in the TSC1/TSC2 genes. Remarkably, the child's remaining bilateral multifocal renal neoplasms completely responded to MTOR inhibitor therapy without need for further surgery. To confirm our hypothesis that oncocytoid renal cell carcinomas after childhood cancer represent ESC RCC, we obtained formalin-fixed paraffin-embedded tissue blocks from 2 previously published cases of oncocytoid renal cell carcinoma after neuroblastoma, confirmed that the morphology and immunophenotype was consistent with ESC RCC, and demonstrated that both cases harbored somatic TSC gene mutations. Both expressed markers previously associated with neoplasms harboring TSC gene mutations, glycoprotein nonmetastatic B, and cathepsin K. Of note, one of these patients had 2 ESC RCC which harbored distinctive TSC2 mutations, while the background kidney of the other patient had multiple small cysts lined by similar oncocytoid cells which showed loss of TSC2 protein. We then reviewed 3 of 4 cases from the original 1999 report of oncocytoid renal cell carcinomas after neuroblastoma, found that all 3 demonstrated morphology (including basophilic cytoplasmic stippling) that is characteristic of ESC RCC, showed that all 3 overexpressed glycoprotein nonmetastatic B, and showed that both cases with adequate material demonstrated loss of TSC2 protein and expressed cytokeratin 20 and cathepsin K by immunohistochemistry. In summary, "oncocytoid renal cell carcinomas after neuroblastoma" represent ESC RCC which are often multifocal in patients who have survived childhood cancer, likely representing an incompletely characterized tumor predisposition syndrome. MTOR-targeted therapy represents an effective therapeutic option for such patients to preserve functional nephrons.

Discrepancy in prostate cancer localization between biopsy and prostatectomy specimens in patients with unilateral positive biopsy: implications for focal therapy.

BACKGROUND: Unilateral ablative strategy success depends on reliable prediction of prostate cancer (PCA) location. We evaluated the discrepancy in PCA localization between unilateral positive biopsy (PBx) and radical prostatectomy (RP). METHODS: Between 2004 and 2008, 431 patients were diagnosed with unilateral PCA by 12-core PBx; 179 underwent RP and constituted our study cohort. Specimens were reviewed to map tumor outline and determine number of cancer foci, tumor volume, Gleason score (GS), zone of origin, localization, and pathologic stage. RESULTS: In 50 men, biopsy and prostatectomy findings correlated (unilateral tumor); in 129, PCA was detected in the contralateral side of the prostate. In 52 patients, 54 clinically significant tumors were missed by biopsy. When patients with true unilateral and missed contralateral disease at RP were compared with respect to prognostic parameters no significant differences were detected. Sixty-one of the 88 patients with preoperative low-risk disease had true unilateral (n = 21) or missed insignificant contralateral (n = 40) PCA; 27 had missed significant contralateral PCA at RP. PSA > 4 ng/ml predicted presence of significant bilateral disease in low-risk population (P = 0.004). Twenty-four of 27 patients with significant bilateral cancer had PSA > 4, although 33/61 with unilateral or bilateral insignificant cancer had similar elevated PSA values. CONCLUSIONS: Twelve-core biopsy is inadequate to identify candidates for organ-sparing therapy. Most men with unilateral positive biopsies have bilateral cancer at prostatectomy. Tumors missed by biopsy were clinically significant in 40% of patients, but no prognostic parameters could predict unilateral disease. Hemi-ablative treatment might fail to eradicate significant lesions in the contralateral side.

Ovotesticular Disorder Mimicking Acute Spermatic Cord Torsion.

Ovotesticular disorder is a rare form of sexual development in which a patient may have one ovary and one testis, or more commonly a gonad or gonads containing both ovarian and testicular tissue. Patients with this condition typically present in infancy with ambiguous genitalia. Delayed presentations of clinically symptomatic, older patients with normal external genitalia are extremely rare. We present a case of a 14-year-old male with normal external genitalia who presented with symptoms and signs consistent with spermatic cord torsion but found to have ovotesticular disorder on evaluation.

Associations of Computed Tomography Image-Assessed Adiposity and Skeletal Muscles with Triple-Negative Breast Cancer.

Obesity measured by anthropometrics is associated with increased risk of triple-negative breast cancer (TNBC). It is unclear to what extent specific adipose tissue components, aside from muscle, are associated with TNBC. This retrospective study included 350 breast cancer patients who received treatment between October 2011 and April 2020 with archived abdominal or pelvic computed tomography (CT) images. We measured the areas of adipose tissue and five-density levels of skeletal muscle on patients' third lumbar vertebra (L3) image. Logistic regression was performed to examine the associations of specific adiposity and skeletal muscles components and a four-category body composition phenotype with the TNBC subtype. Results showed that higher vs. lower areas (3rd vs. 1st tertiles) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were associated with increased odds of TNBC vs. non-TNBC after adjusting for age, race, stage, tumor grade, tumor size, and skeletal muscle areas (adjusted odds ratio [AOR], 11.25 [95% CI = 3.46-36.52]) and (AOR, 10.34 [95% CI = 2.90-36.90]) respectively. Higher areas of low density muscle was also associated with increased odds of TNBC (AOR, 3.15 [95% CI = 1.05-10.98]). Compared to normal body composition (low adipose tissue/high muscle), high adiposity/high muscle was associated with higher odds of TNBC (AOR, 5.54 [95% CI = 2.12-14.7]). These associations were mainly in premenopausal women and among patients with the CT performed after breast cancer surgery. Specific adipose tissue and low-density muscle can be associated with the TNBC subtype in breast cancer patients. The direction of association warrants confirmation by prospective studies.

Intraindividual Reliability of Opportunistic Computed Tomography-Assessed Adiposity and Skeletal Muscle Among Breast Cancer Patients.

BACKGROUND: Adiposity and skeletal muscle levels assessed on computed tomography (CT) scans are prognostic indicators for patients with breast cancer. However, the intraindividual reliability of temporal changes in body composition assessed on opportunistic CT scans is unclear. METHODS: This retrospective study included 50 patients newly diagnosed with breast cancer who had archived CT scans pre- and postsurgery for breast cancer. The third lumbar CT image was segmented for areas of 3 types of adipose tissues and 5 different densities of skeletal muscles. Mean and percent changes in areas pre- vs postsurgery were compared using Wilcoxon signed rank tests. Intraclass correlation coefficients (ICCs) with 95% confidence intervals were assessed. A 2-sided P less than .05 was considered statistically significant. RESULTS: Mean (SD) age at diagnosis was 58.3 (12.5) years, and the interval between CT scans was 590.6 (536.8) days. Areas for body composition components were unchanged except for intermuscular adipose tissue (mean change = 1.45 cm2, 6.74% increase, P = .008) and very high-density muscle (mean change = -0.37 cm2, 11.08% decrease, P = .01) during the interval. There was strong intraindividual reliability in adipose tissue and skeletal muscle areas on pre- vs postsurgery scans overall (ICC = 0.763-0.998) and for scans collected 3 or less years apart (ICC = 0.802-0.999; 42 patients). CONCLUSIONS: Although some body composition components may change after breast cancer surgery, CT scan assessments of body composition were reliable for a 3-year interval including the surgery. These findings inform measurement characteristics of body composition on opportunistic CT scans of patients undergoing surgery for breast cancer.

Single focus prostate cancer: pathological features and ERG fusion status.

PURPOSE: We evaluated the clinicopathological characteristics of single focus prostate cancer in radical prostatectomies, its clinical relevance and the occurrence of TMPRSS2-ERG rearrangement. MATERIALS AND METHODS: We reviewed the records of 1,100 radical prostatectomies and determined the tumor outline and number of cancer foci. When single focus prostate cancer was identified, we recorded pathological characteristics. We assessed ERG fusion status in a subset of cases. RESULTS: Single focus prostate cancer was identified in 106 radical prostatectomies. Median patient age was 59 years. Median prostate specific antigen was 5.1 ng/ml. Single focus cancer was unilateral in 81% of cases and 98% originated from the peripheral zone. Tumor volume was 0.1 to 3.9 cm(3) (median 0.5). Gleason score was 6 in 38% of patients, 7 in 40%, 8 or greater in 21% and undetermined in 2%. Extraprostatic extension and seminal vesicles invasion were detected in 30% and 2% of cases, respectively. Stage was pT2 in 62% of cases, pT2 with positive margin of resection in 7% and pT3 in 30%. ERG fusion was detected in 68% of tumors. Cases rearranged via deletion had significantly higher tumor volume. Three cases showed intratumor heterogeneity. CONCLUSIONS: Single focus prostate cancer accounted for 9.6% of tumors. In most cases it involved 1 lobe of the gland and originated from the peripheral zone. Despite a trend toward high grade disease 62% of single focus prostate cancers were organ confined. Only 3 fusion positive cases showed intratumor heterogeneity, suggesting that most single focus cancer may evolve from a single clone of malignant cells.

A MEST up classification? Review of the re-classification of mixed epithelial and stromal tumor and adult cystic nephroma for the abdominal radiologist.

Mixed epithelial and stromal tumor (MEST) and the tumor formerly known as adult cystic nephroma (ACN) are uncommon renal tumors that have historically been described as separate entities in terms of histologic and imaging findings. However, these entities share many epidemiologic, radiologic, and pathologic features. While recent surgical and pathological literature has supported classifying MEST and ACN within the same tumor family, most radiologists and radiology texts continue to describe MEST and ACN as separate entities.

ERG rearrangement is present in a subset of transition zone prostatic tumors.

A majority of prostate cancers exhibit a recurrent gene rearrangement involving chromosome 21. In approximately 90% of cases, the rearrangement is characterized by fusion of the androgen-regulated gene TMPRSS2 with the oncogene ERG. A recent study suggested that TMPRSS2-ERG gene fusion is lacking in cancers arising from the transition zone of the prostate. A dominant transition zone cancer was detected in 62/397 (16%) patients who underwent radical prostatectomy at our institution and were reviewed and mapped by a single pathologist. In 46/62 specimens, a secondary tumor was identified in the peripheral zone of the prostate. A tissue microarray containing both transition and peripheral zone tumors was constructed and evaluated for gene fusion analysis. TMPRSS2-ERG fusion status was determined using a multicolor interphase fluorescence in situ hybridization assay for ERG break-apart. The median age of the patients was 59 years. Prostatectomy Gleason score was 6 in 21, 7 in 34, and ≥8 in 7 cases. Median tumor volume was 200 mm(2). TMPRSS2-ERG gene fusion was present in 7/59 (12%) transition zone, and in 12/35 (34%) peripheral zone tumors. Transition zone fusion-positive cases were larger than their negative counterparts. No significant correlation was found between fusion status and Gleason score or pathologic stage. Gene fusion through deletion occurred in 4/7 transition zone and 7/12 peripheral zone tumors. Transition zone prostate cancers are considered biologically and genetically different from peripheral zone tumors. Although ERG rearrangement is more common in peripheral zone tumors, we have detected TMPRSS2-ERG fusion in a subset of transition zone cancers (12%). The lower frequency of gene fusion in transition zone prostate cancer may suggest distinct molecular alterations from peripheral zone tumors and the association with a high tumor volume may indicate a growth advantage for transition zone tumors harboring the gene fusion. Further studies are necessary to confirm this hypothesis.

Clinicopathologic features and outcomes of anterior-dominant prostate cancer: implications for diagnosis and treatment.

OBJECTIVE: This study aims to describe the pathological features and clinical outcomes in anterior-dominant prostate cancer (APCA) compared to posterior/posterolateral-dominant prostate cancer (PPCA) among men treated with radical prostatectomy for localized prostate cancer. METHODS: This is a single-institution, matched case-control analysis of short-term clinical outcomes stratified by pathologic tumor location at radical prostatectomy. Pathologic data extracted by expert genitourinary pathologists on tumor location was linked to clinical and oncologic outcomes data from a prospective institutional database for analysis. RESULTS: From 2005 to 2013, 1580 patients were identified for analysis with 150 (9.5%) having APCA. One-hundred and thirty two of these APCA men had complete clinical data and were matched to 353 men with PPCA (~1:3 ratio) by GrdGrp at surgery, margin status, and pathologic T stage. There were no racial/ethnic differences between APCA and PPCA (p = 0.13). Men with APCA demonstrated a higher median PSA at diagnosis (6.4 [4.6-9.1] ng/mL vs 5.6 [4.4-8.1] ng/mL; p = 0.04), a higher rate of GrdGrp 1 disease at diagnosis (57.7% vs. 40.0%, p = 0.003), and lower rates of abnormal digital rectal examination (DRE) (10.1% vs. 23.2%, p = 0.003) when compared to PPCA. The rate of surgical upgrading was higher among men with APCA vs. PPCA (55.3% vs 42.0%, p = 0.015). Freedom from biochemical failure (BF) at 5-years was 85.1% (95% CI 73.1-98.9) for APCA and 82.9% (95% CI 69.2-99.5) for men with PPCA (p = 0.70, log-rank test). CONCLUSIONS: The majority of anterior tumors were undetectable by DRE and were associated with higher PSA at diagnosis. Despite presenting mostly as low/intermediate grade cancers, more than half of the men with APCA had upgrading at surgery and slightly more than 40% had positive margins and/or extraprostatic disease. When matched to a cohort of posterior predominant tumors, no differences were seen in the rate of biochemical-failure after prostatectomy.

Microscopic bladder neck involvement by prostate carcinoma in radical prostatectomy specimens is not a significant independent prognostic factor.

The independent prognostic importance of microscopic bladder neck involvement by prostate cancer in radical prostatectomy is questionable. We studied a cohort of 1845 patients to determine the significance of microscopic bladder neck involvement. Bladder neck involvement was defined as prostate cancer present within the coned bladder neck. We further categorized the cases as 'true bladder neck involvement' and 'false bladder neck involvement.' True bladder neck involvement required prostate cancer within thick smooth muscle bundles without intermixed benign prostatic glands. False bladder neck involvement was characterized by prostate cancer intermixed with benign prostatic glands. Bladder neck involvement was analyzed in relation to preoperative serum prostate-specific antigen (PSA) level, extraprostatic extension, seminal vesicle involvement, positive surgical margin, lymph node involvement, radical prostatectomy Gleason score, and tumor volume. Of the 90 patients (4.9%) with microscopic bladder neck involvement, 63 were further classified as true bladder neck involvement and 27 as false bladder neck involvement. In univariate model, both types of bladder neck involvement (P<0.001), true (P<0.001), and false (P=0.040), were significantly associated with increased PSA-recurrence risk compared to bladder neck negative cases. In multivariate model the PSA-recurrence relative risk associated with bladder neck involvement (true or false) was not a significant independent prognostic factor. Extraprostatic extension, seminal vesicle involvement, positive surgical margin, lymph node involvement, PSA, and Gleason score were significant independent predictors of PSA recurrence. The time to biochemical recurrence in patients with bladder neck involvement was similar to that of pT2 with positive surgical margin or pT3a with negative surgical margin patients (Kaplan-Meier curves). Bladder neck involvement was associated with other adverse pathologic features, but was not an independent predictor of PSA recurrence. In view of the previous and current data, the staging system for bladder neck involvement should be revised and patients may be best categorized as having pT3a disease.

Carcinoma In Situ With Plasmacytoid Features: A Clinicopathologic Study of 23 Cases.

Although there are 5 well-described morphologic patterns of (nonglandular) urothelial carcinoma in situ (CIS), we have encountered a novel pattern of flat urothelial carcinoma with plasmacytoid features characterized by a triad of morphologic findings including abnormal architecture with cellular rounding, enlarged nuclei with eccentric nuclear localization, and dense globular eosinophilic cytoplasm. A total of 23 cases of plasmacytoid CIS (mean age: 74.1 y, range: 58 to 91 y) were collected and reviewed. We excluded cases in which the diagnostic biopsy had any of the following findings admixed in the same tissue biopsy sample as the plasmacytoid CIS: traditional patterns of CIS, noninvasive glandular CIS, papillary urothelial carcinoma, or invasive carcinoma. Immunostains for CK20, CD44, p53, and e-cadherin were performed on available blocks. History of prior urothelial neoplasia, prior treatment, and clinical follow-up were obtained from medical records and pathology re-review. Immunohistochemical analysis of plasmacytoid CIS showed diffuse/strong CK20 reactivity in 96% of cases (23/24), an abnormal p53 reactivity pattern (either overexpression or "null phenotype") in 37% of cases (7/19), absence of CD44 reactivity in the neoplastic cells in 63% of cases (15/24), and retained membranous e-cadherin expression in 100% of cases (18/18). Clinical follow-up (average follow-up time: 37.7 mo, range: 7 to 115 mo) showed recurrence/new occurrence in 52% of cases (12/23), including all 4 of the 23 patients who initially presented with de novo plasmacytoid CIS (ie, no prior or concomitant urothelial neoplasia). The histologic features, the immunophenotype, the association with other forms of urothelial neoplasia, and the risk of recurrence and progression in de novo lesions support that plasmacytoid CIS represents a novel pattern of flat urothelial carcinoma. These histologic features may be more subtle than in other more typical patterns of CIS and should be carefully distinguished from therapy-related/reactive changes.