Faculty Bibliography

Accurate recognition of Gleason pattern (GP) 4 prostate carcinoma (PCa) on needle biopsy is critical for patient management and prognostication. "Poorly formed glands" are the most common GP4 subpattern. We studied the diagnostic reproducibility and the quantitative threshold of grading GP4 "poorly formed glands" and the criteria to distinguish them from tangentially sectioned GP3 glands. Seventeen urologic pathologists were first queried for the definition of "poorly formed glands" using cases representing a spectrum of PCa glandular differentiation. Cancer glands with no or rare lumens, elongated compressed glands, and elongated nests were considered "poorly formed glands" by consensus. Participants then graded a second set of 23 PCa cases that potentially contained "poorly formed glands" with a fair interobserver agreement (kappa=0.34). The consensus diagnoses, defined as agreement by >70% participants, were then correlated with the quantitative (10) and topographic features of poorly formed glands (clustered, immediately adjacent to, and intermixed with other well-formed PCa glands) in each case. Poorly formed glands immediately adjacent to other well-formed glands regardless of their number and small foci of 10 poorly formed glands that were not immediately adjacent to well-formed glands were graded as GP4. Grading "poorly formed glands" is challenging. Some morphologic features are, however, reproducible for and against a GP4 diagnosis. This study represents an important step in standardization of grading of "poorly formed glands" based on quantitative and topographic morphologic features.

Clear cell sarcoma of the penis is exceedingly rare with only one prior case involving the penis reported in the literature. We present the case of a 32 year old male who presented with an infiltrative neoplasm at the base of the penis as well as extensive metastatic disease to the lymph nodes and bone. Morphologic, immunohistochemical and cytogenetic findings established the diagnosis of clear cell sarcoma. Despite chemotherapy the patient's disease was rapidly progressive and the patient died of disease within 8 months of diagnosis.

Lymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor mediating Wnt signaling pathway. Our previous studies indicate that LEF1 is highly expressed in androgen-independent prostate cancer (PCa) and enhances invasion ability in androgen-independent PCa cells. However, the molecular mechanism of LEF1 effect on invasion remains largely unknown. Using microRNA profiling analysis comparing androgen-independent LNCaP-AI PCa cells with high levels of endogenous LEF1 to LNCaP-AI cells with LEF1 knockdown by LEF1shRNA, we found miR-181a to be increased 12.3-fold in LNCaP-AI cells. We confirmed a positive correlation between LEF1 and miR-181a expression across multiple PCa cell lines. Additionally, we showed that in PCa cells, overexpression of LEF1 increased miR-181a expression and subsequently induced EMT associated migration and invasion, whereas LEF1 knockdown decreased miR-181a expression and subsequently resulted in inhibition of EMT, migration and invasion. Mechanistically, we demonstrated by chromatin immunoprecipitation assays that LEF1 could enhance miR-181a expression via its binding to the promoter regions of hsa-miR-181a. Overall, this study identified a novel LEF1-miR-181a-EMT axis in regulation of PCa migration and invasion.

PURPOSE: To compare boundaries of prostate tumors on MRI and histologic assessment from radical prostatectomy (RP) using detailed software-assisted co-registration, in order to define an optimal treatment margin to achieve complete tumor destruction during image-guided focal ablation. METHODS: 33 patients who underwent 3T MRI before RP were included. A radiologist traced lesion borders on MRI and assigned a suspicion score (SS) from 2-5. 3D reconstructions were created from high-resolution digitalized slides from RP specimens and co-registered to MRI using advanced software. Tumors were compared between histology and MRI using the Hausdorff Distance (HD) and stratified by MRI-SS, Gleason Score (GS), and lesion diameter. Cylindrical volume estimates of treatment effects were used to define the optimal treatment margin. RESULTS: 46 histologically confirmed cancers underwent 3D software-based registration with MRI. MRI underestimated tumor sizes, with the maximal discrepancy between MRI and histologic boundaries for a given tumor averaging 1.99+/-3.1mm (18.5% of the MRI diameter). Boundary underestimation was larger for MRI-SS>/=4 lesions (+3.49+/-2.1mm; p<0.001) and GS>/=7 lesions (+2.48+/-2.8mm; p 0.035). On average, a simulated cylindrical treatment volume based on the MRI boundary missed 14.8% of the tumor volume compared with a simulated cylindrical volume based on the histologic boundary. A simulated treatment volume based on a 9mm treatment margin achieved complete histologic tumor destruction in 100% of patients. CONCLUSION: MRI underestimates histologically-determined tumor boundaries, especially for high MRI-SS and high GS lesions. A 9mm treatment margin around an MRI-visible lesion consistently ensures treatment of the entire histologic tumor volume during focal ablative therapy.

PURPOSE: The aim of this study was to determine the diagnostic accuracy of positron emission tomography (PET) in cancer patients undergoing adrenalectomy for presumed metastatic disease, utilizing the gold standard of histopathology. METHODS: We retrospectively reviewed all adrenalectomies for metastatic disease performed at our institution over the last 12 years. Preoperative PET scans were compared with final pathology reports. Statistical analyses were performed with Fisher's exact test for categorical variables and Student's t test for continuous variables. RESULTS: Forty-nine adrenalectomies were performed for metastatic disease. Thirty had preoperative PET imaging and were included in this analysis. Mean age was 65.5 +/- 13.6 years (29-91) and 54 % were male. Mean size was 3.8 cm (0.4-7.1). Primary tumor distribution was 61 % (n = 17) pulmonary; 11 % (n = 3) breast; 7 % (n = 2) gastric; 7 % (n = 2) renal; and 4 % (n = 1) each of brain, lymphoma, melanoma, and uterine. Mean standardized uptake value (SUV) was 11 +/- 7.3 (3.2-30.0). Final pathology revealed that 80 % (25/30) were positive for metastatic disease and 20 % (5/30) were negative. The positive predictive value of PET in correctly identifying adrenal metastatic disease was 83 % (24 true-positive cases and 5 false-positive cases); there was one false-negative PET. False-positive PET results were not correlated with sex (p = 0.35), age (p = 0.24), or maximum SUV units (p = 0.26). CONCLUSIONS: The 20 % false-positive rate for PET-positive adrenalectomies performed for metastatic disease should warrant its inclusion in preoperative counseling to the patient and interaction with the treating oncologist.