Angela Wu

Accuracy of Determining Small Renal Mass Management with Risk Stratified Biopsies: Confirmation by Final Pathology

PURPOSE We assess the accuracy of a biopsy directed treatment algorithm in correctly assigning active surveillance vs treatment in patients with small renal masses by comparing biopsy results with final surgical pathology. MATERIALS AND METHODS From 1999 to 2011, 151 patients with small renal masses 4 cm or smaller underwent biopsy and subsequent surgical excision. Biopsy revealed cell type and grade in 133 patients, allowing the hypothetical assignment of surveillance vs treatment using an algorithm incorporating small renal mass size and histological risk group. We compared the biopsy directed management recommendation with the ideal management as defined by final surgical pathology. RESULTS Biopsy called for surveillance of 36 small renal masses and treatment of 97 small renal masses. Final pathology showed 11 patients initially assigned to surveillance should have been assigned to treatment (8.3% of all patients, 31% of those recommended for surveillance), whereas no patients moved from treatment to surveillance. Agreement between biopsy and final pathology was 92%. Using management based on final pathology as the reference standard, biopsy had a negative predictive value of 0.69 and positive predictive value 1.0 for determining management. Of the 11 misclassified cases, 7 had a biopsy indicating grade 1 clear cell renal cancer which was upgraded to grade 2 (5) or grade 3 (2). After modifying the histological risk group assignment to account for undergrading of clear cell renal cancer, agreement improved to 97%, with a negative predictive value of 0.86 and a positive predictive value of 1.0. CONCLUSIONS Our results suggest that compared to final pathology, biopsy of small renal masses accurately informs an algorithm incorporating size and histological risk group that directs the management of small renal masses.

Neoadjuvant Docetaxel and Capecitabine in Patients with High Risk Prostate Cancer

PURPOSE Docetaxel is the most active cytotoxic agent in hormone refractory prostate cancer. Preclinically docetaxel increases expression of thymidine phosphorylase, an enzyme responsible for activation of capecitabine to 5-fluorouracil resulting in increased antitumor activity. We assessed activity and safety of neoadjuvant docetaxel and capecitabine in patients with high risk prostate cancer. MATERIALS AND METHODS Patients with either clinical stage greater than T2, prostate specific antigen 15 ng/ml or more, or Gleason sum 8 or greater received 3 to 6 cycles of docetaxel (36 mg/m2 intravenously on days 1, 8 and 15) and capecitabine (1,250 mg/m2 per day orally divided twice a day on days 5 to 18) every 28 days, followed by local therapy. The primary end point was rate of 50% or greater prostate specific antigen decrease. Correlative studies included qualitative changes in histology, tissue thymidine phosphorylase and survivin expression, and CK18Asp396 (serum apoptosis marker). RESULTS A total of 15 patients were treated, of whom 6 (40%) experienced a 50% or greater decrease in prostate specific antigen with infrequent diarrhea or hand-foot syndrome. Eleven patients underwent radical prostatectomy. There were no pathological complete responses and 4 patients demonstrated mild histological changes, including focal necrosis and vacuolated cytoplasm. While there was no discernable pattern of increased thymidine phosphorylase expression, 4 specimens showed decreased survivin expression, suggesting a possible mechanism for chemotherapy induced apoptosis. There was no correlation of prostate specific antigen response and survivin expression, and no increase in serum CK18Asp396. CONCLUSIONS Neoadjuvant docetaxel and capecitabine is well tolerated but is not associated with significant pathological and prostate specific antigen responses.

Independent surgical validation of the new prostate cancer grade-grouping system

To report the independent prognostic impact of the new prostate cancer grade‐grouping system in a large external validation cohort of patients treated with radical prostatectomy (RP).

Intraductal Carcinoma of the Prostate: Morphologic Features, Differential Diagnoses, Significance, and Reporting Practices.

The differential diagnosis for atypical cribriform lesions of the prostate has become increasingly complex and includes intraductal carcinoma of the prostate, high-grade prostatic intraepithelial neoplasia, and atypical intraductal proliferations. In this review, we summarize the morphologic and molecular features and significance of intraductal carcinoma of the prostate. We also summarize our institutions strategy for reporting and treatment recommendations for intraductal carcinoma of the prostate.

Papillary renal cell carcinoma revisited: a comprehensive histomorphologic study with outcome correlations.

Papillary renal cell carcinoma (P-RCC) is the second most common type of malignant renal epithelial tumor and can be subclassified into type 1, which demonstrates simple cuboidal low-grade epithelium and type 2, which demonstrates pseudostratified high-grade epithelium with abundant eosinophilic cytoplasm. Despite this clinically useful subclassification, P-RCCs exhibit considerable histomorphologic diversity, with many cases having features differing from classically described type 1 and type 2 tumors. To our knowledge, there has been no recent study that has methodically evaluated the histomorphologic features of a series of P-RCCs. To address this, we evaluated a cohort of P-RCCs diagnosed between 1997 and 2004 with long-term clinical follow-up data (n = 56). Histomorphologic features previously described in the spectrum of type 1 and type 2 P-RCCs were recorded for each tumor, including nuclear grade, complete tumor capsule, and cytoplasmic eosinophilia as well as several other features. The current TNM staging (American Joint Committee on Cancer, seventh edition) was assigned to all cases. Histomorphologic features were diverse, demonstrating classic type 1 P-RCC and classic type 2 P-RCC morphology and several tumors with nonclassic features. Four patients in this cohort had distant metastasis. The primary tumor was equally divided between type 1 (2 cases) and type 2 (2 cases) morphology in the cases with metastasis. All P-RCC cases with metastases demonstrated presence of high nuclear grade and high tumor stage in the primary tumor. Cluster analysis using staging parameters and histomorphologic features divided tumors into 2 primary clusters. All primary tumors associated with metastasis were in the same cluster.

Prostate Cancer With Aberrant Diffuse p63 Expression: Report of a Case and Review of the Literature and Morphologic Mimics

We report a case of a prostatic adenocarcinoma that showed diffuse aberrant p63 expression in the secretory cells and review the literature and differential diagnosis. p63-positive prostatic adenocarcinoma is rare and is typically encountered when working up an atypical focus with basal markers and α-methylacyl coenzyme A racemase. These carcinomas have unusual morphologic features such as atrophic cytoplasm and basaloid morphology. The differential diagnosis includes basal cell hyperplasia and basal cell carcinoma; morphologic features such as the presence of small, infiltrative acini with nuclear atypia, lack of high-molecular-weight cytokeratin expression, and positive α-methylacyl coenzyme A racemase and prostate-specific antigen expression can help distinguish a p63-positive prostatic adenocarcinoma from atypical basal cell proliferations. Current controversies regarding the grading, prognosis, and molecular profile of p63-positive prostatic adenocarcinomas are also discussed.

MP38-17 CLINICOPATHOLOGIC CHARACTERISTICS OF PATIENTS WITH VERY LOW-RISK (PI-RADS 1 OR 2) LESIONS BY MULTIPARAMETRIC PROSTATE MAGNETIC RESONANCE IMAGING

INTRODUCTION AND OBJECTIVES: Multiparametric prostate magnetic resonance imaging (mpMRI) utilizing the PI-RADS classification system attempts to identify clinically-significant [Gleason score (GS) 7 or higher] prostate cancer (PCa), with PI-RADS 1 or 2 typically corresponding to very low risk of clinically-significant PCa. In this study, we analyzed the clinicopathologic characteristics of patients undergoing prostate core biopsy (PBx) with PI-RADS 1 or 2 lesions. METHODS: All patients at a single large academic institution who had at most PI-RAD 1 or 2 lesions on mpMRI between 1/1/15 and 6/30/16 and underwent preor post-MRI PBx were retrospectively identified. All cases of clinically-significant PCa were re-reviewed by study pathologists to confirm pathologic findings; clinicopathologic data from all other cases was obtained from pathology reports and electronic medical records. RESULTS: 276 patients with PI-RADS 1 or 2 lesions were identified, of which 98 (35.5%) had either pre(60) or post-MRI (38) inhouse PBx. Six (6.1%) patients showed GS7 PCa (3 preand 3 postMRI), including 2 with GS4+31⁄47 tumors. For the remaining patients, the most recent PBx findings included: GS6 PCa (22 preand 13 post-MRI); atypical glands (3 preand 2 post-MRI); high-grade prostatic intraepithelial neoplasia (5 preand 4 post-MRI); or, benign (27 preand 16 post-MRI). For patients with GS7 PCa, the median number of involved cores was 1 (range 1⁄4 1-3), the median number of total cores was 20 (range 1⁄4 12-30), the median % involvement of a single core was 12.5 (range 1⁄4 5-25), and the median % Gleason pattern 4 was 30 (range 1⁄4 5-90); types of Gleason pattern 4 included: poorly-formed glands only (4), cribriform glands only (1), or poorly-formed and cribriform glands (1). One GS7 tumor occurred in the post-radiation (XRT) setting, and one showed aberrant p63 expression; follow-up for patients with GS7 PCa included primary XRT (1), salvage XRT (1), and active surveillance (AS; 4). Nearly all patients (>90%) with GS6 PCa opted for AS; one patient underwent radical prostatectomy (pT2a GS6 PCa), and one patient was lost to follow-up. CONCLUSIONS: The majority (58.2%) of patients with PIRADS 1 or 2 lesions by mpMRI do not have detectable PCa on core biopsy, however, a small subset (6.1%) harbor GS7 PCa. Although long-term follow-up data are needed, PCa patients with PI-RADS 1 or 2 lesions by mpMRI appear to represent a very low-risk cohort that may be amenable to AS in the majority of cases.

MP38-18 CLINICOPATHOLOGIC CHARACTERISTICS OF PATIENTS UNDERGOING PROSTATE CORE BIOPSY WITH HIGH-RISK (PI-RADS 5) LESIONS BY MULTIPARAMETRIC PROSTATE MAGNETIC RESONANCE IMAGING.

INTRODUCTION AND OBJECTIVES: Multiparametric prostate magnetic resonance imaging (mpMRI) utilizing the PI-RADS classification system attempts to identify clinically-significant [Gleason score (GS) 7 or higher] prostate cancer (PCa), with PI-RADS 1 or 2 typically corresponding to very low risk of clinically-significant PCa. In this study, we analyzed the clinicopathologic characteristics of patients undergoing prostate core biopsy (PBx) with PI-RADS 1 or 2 lesions. METHODS: All patients at a single large academic institution who had at most PI-RAD 1 or 2 lesions on mpMRI between 1/1/15 and 6/30/16 and underwent preor post-MRI PBx were retrospectively identified. All cases of clinically-significant PCa were re-reviewed by study pathologists to confirm pathologic findings; clinicopathologic data from all other cases was obtained from pathology reports and electronic medical records. RESULTS: 276 patients with PI-RADS 1 or 2 lesions were identified, of which 98 (35.5%) had either pre(60) or post-MRI (38) inhouse PBx. Six (6.1%) patients showed GS7 PCa (3 preand 3 postMRI), including 2 with GS4+31⁄47 tumors. For the remaining patients, the most recent PBx findings included: GS6 PCa (22 preand 13 post-MRI); atypical glands (3 preand 2 post-MRI); high-grade prostatic intraepithelial neoplasia (5 preand 4 post-MRI); or, benign (27 preand 16 post-MRI). For patients with GS7 PCa, the median number of involved cores was 1 (range 1⁄4 1-3), the median number of total cores was 20 (range 1⁄4 12-30), the median % involvement of a single core was 12.5 (range 1⁄4 5-25), and the median % Gleason pattern 4 was 30 (range 1⁄4 5-90); types of Gleason pattern 4 included: poorly-formed glands only (4), cribriform glands only (1), or poorly-formed and cribriform glands (1). One GS7 tumor occurred in the post-radiation (XRT) setting, and one showed aberrant p63 expression; follow-up for patients with GS7 PCa included primary XRT (1), salvage XRT (1), and active surveillance (AS; 4). Nearly all patients (>90%) with GS6 PCa opted for AS; one patient underwent radical prostatectomy (pT2a GS6 PCa), and one patient was lost to follow-up. CONCLUSIONS: The majority (58.2%) of patients with PIRADS 1 or 2 lesions by mpMRI do not have detectable PCa on core biopsy, however, a small subset (6.1%) harbor GS7 PCa. Although long-term follow-up data are needed, PCa patients with PI-RADS 1 or 2 lesions by mpMRI appear to represent a very low-risk cohort that may be amenable to AS in the majority of cases.

Surgical Pathology Reporting of Renal Cell Carcinomas

Given the importance of accurate surgical pathology reporting for kidney tumors, those factors necessary for a complete report (beyond grade, stage, and tumor type, which are treated elsewhere) are addressed in this chapter, with a survey of the data that support their inclusion.