Faculty Bibliography

Large cell neuroendocrine carcinoma of the prostate (LCNEC), de novo in particular, is an extremely rare entity that has only been described in the literature in case reports. Historically, the majority of the cases of LCNEC reported in the literature represent typical prostatic adenocarcinomas that transformed after long standing androgen deprivation therapy (ADT). These cases were admixed with histological areas of usual adenocarcinoma and showed hybrid features of both neuroendocrine and usual adenocarcinoma. Here we present a case of an LCNEC without admixed areas of usual prostatic adenocarcinoma arising de novo in a patient without prior history of hormonal therapy. The tumor also shows morphologic evidence of neuroendocrine differentiation; composed of large sheets and nests of cells with moderate amphophilic cytoplasm with peripheral palisading, and vesicular clumpy chromatin with prominent nucleoli. The carcinoma's prostatic origin is indicated by positive immunohistochemical staining for PSA, PAP, PSMA, racemase, and Nkx3.1. Diffusely positive staining for chromogranin and synaptophysin, as well as the presence of secretory granules in the cytoplasm of the tumor cells demonstrated by electron microscopy supports the NE differentiation. NE prostate cancer usually does not express AR and is refractory to ADT therapy while AR and ERG are positive in this case. In summary, we report a de novo LCNEC of the prostate with review of literature, in particular, clinical implications.

Localized urinary tract amyloidosis (UTA) is a rare disease that mimics neoplasia clinically, cystoscopically, and radiologically. We report eleven cases of isolated UTA from the urinary bladder (n=7) and upper urinary tract including the ureter (n=2) and renal pelvis (n=2). All cases clinically presented as mass lesions prior to histologic examination and clinically suggested a neoplastic process. The amyloid composition in most cases was mixed Kappa and Lambda light chains. All cases were cured after surgical excision except one case which was diagnosed as plasmacytosis/plasmacytoma six months later. Localized amyloidosis of the urinary tract usually has a benign clinical course and simple resection is recommended after systemic disease is ruled out.

Prostatectomy or irradiation is the most common traditional treatments for localized prostate cancer. In the event of recurrence and/or metastasis, androgen ablation therapy has been the mainstay treatment for many years. Although initially effective, the cancer inevitably recurs as androgen-independent PCa, a disease with limited effective treatments. Enhanced predictive biomarkers are needed at the time of diagnosis to better tailor therapies for patients. MicroRNAs are short nucleotide sequences which can complementary bind to and control gene expression at the post-transcriptional level. Recent studies have demonstrated that many miRNAs are variably expressed in cancers vs. normal tissues, including PCa. In this review, we summarize PCa-specific miRNAs that show potential for their utilization as identifiers of aggressive disease and predictors for risk of recurrence. Additionally, we discuss their potential clinical applications as biomarkers and therapeutic targets.

BACKGROUND: Tumors of the kidney are uncommon in children and young adults. Accurate classification is crucial for both prognostication and therapeutic intervention. However, majority of the tumors in this age group have unusual morphology that renders classification challenging. Tubulopapillary architecture is one of the most common morphological patterns observed in renal tumors of children and young adults. METHODS: A patient with epithelial predominant Wilms tumor was reported. Differential diagnosis of renal tumors with tubulopapillary morphology was discussed with an emphasis on the histological and immunohistochemical features, and the literature was reviewed. RESULTS: A 25 year-old female patient presented with bilateral multilocular cystic masses. She underwent right radical nephrectomy and left partial nephrectomy. The pathological examination revealed a tumor with tubulopapillary architecture which was lined with low columnar epithelial cells. During the work-up of this case, several entities were considered and ruled out by careful gross, microscopic examination and prudent use of immunohistochemistry. The tumor cells were positive for WT-1, and variably positive for cytokeratin AE1/3, CD56, CD57, and negative for cytokeratin 7 and EMA. Fluorescent in-situ hybridization revealed no gain of chromosome 7 and 17. A diagnosis of epithelial predominant adult Wilms tumors was rendered for both kidneys. The patient received systemic chemotherapy and radiation to the remnant left kidney and was free of disease three years after the initial surgery. CONCLUSION: The differential diagnosis of renal tumors with tubulopapillary features in children and young adults include papillary renal cell carcinoma, metanephric adenoma, epithelial predominant Wilms tumor, translocation renal cell carcinoma and metastatic adenocarcinoma to the kidney. An accurate classification relies on careful examination of clinical and pathological features and immunohistochemical characteristics.

INTRODUCTION: To compare qualitative and quantitative imaging features from conventional and diffusion-weighted (DW) magnetic resonance imaging (MRI) in detection of metastatic pelvic lymph nodes in bladder cancer patients undergoing cystectomy. MATERIALS AND METHODS: Thirty-six patients who had undergone cystectomy for bladder cancer with preoperative MRI with DWI sequence prior to surgery were included. Imaging features on conventional and DW-MRI were compared with histopathology at cystectomy. RESULTS: Nodal features associated with metastatic lymphadenopathy were short axis (AUC = 0.85, p < 0.001; when SA > 5 mm: sensitivity = 88%, specificity = 75%), long axis (AUC = 0.80, p < 0.001; when LA > 6 mm: sensitivity = 88%, specificity = 71%), apparent diffusion coefficient (ADC) on DWI, normalized to muscle (AUC = 0.66, p = 0.113; when nADC < 1.35: sensitivity = 75%, specificity = 68%), and absence of fatty hilum on conventional imaging (AUC = 0.73, p = 0.012; when fatty hilum absent, sensitivity = 75%, specificity = 71%). ADC without normalization was not associated with metastasis (p = 0.303). CONCLUSIONS: Imaging findings from conventional MRI and DWI achieved reasonable accuracy for detecting metastatic lymph nodes in bladder cancer, although sensitivity was higher than specificity. A short axis greater than 5 mm on conventional MRI had the highest accuracy of any individual finding. When using DWI, normalization of ADC values to muscle ADC may improve diagnostic performance.

BACKGROUND: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. METHODS: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). RESULTS: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. CONCLUSIONS: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients.

INTRODUCTION: Tumor grade plays a critical role in the management of papillary non-invasive urothelial carcinoma (UC). Since grading of UC relies on morphologic criteria, variability in interpretation exists among pathologists. The objective of this study was to examine inter-observer variability in the grading of papillary non-invasive UC at a single academic medical center. MATERIALS AND METHODS: One general pathologist and two genitourinary pathologists were blinded to patient identity and graded 98 consecutive UC specimens using the 1973 and 2004 classification systems. Kappa statistics (kappa) were used to measure inter-observer reproducibility to account for agreement expected purely by chance. By convention, varkappa values from 0.21-0.4 represent "fair", from 0.41-0.6 represent "moderate", and > 0.6 represent "substantial" agreement. RESULTS: Raw percentage agreement among all three pathologists was only 26% using the 1973 system and 47% using the 2004 system. When measured by kappa, overall agreement was only "fair" for both systems and while higher for the 2004 system than the 1973, this was not significant (: 0.38 versus 0.26, respectively). There were no significant differences in agreement when comparing the specialists agreement between themselves with agreement between each specialist and the generalist (varkappa: 0.31-0.37 versus varkappa: 0.18-0.46). CONCLUSIONS: The current grading system continues to demonstrate challenges in reproducibility among general and specialized pathologists. The degree of variability has significant implications on management decisions for non-invasive UC. Our findings underscore the need to identify molecular markers that can provide a more objective and reliable risk stratification system to guide patient management.