Neuroendocrine differentiation in the setting of prostatic carcinoma: contemporary assessment of a consecutive series.

AIM: Clinicopathologic characterisation of a contemporary series of neuroendocrine (NE) differentiation in the setting of prostatic carcinoma (PCa) was examined. METHODS AND RESULTS: We reviewed institutional databases for in-house cases with a history of PCa and histopathologic evidence of NE differentiation during the disease course. In all, 79 cases were identified: 32 primary and 47 metastases. Metastatic lesions were in liver (n = 15), lymph node (n = 9), bone (n = 6), lung (n = 3), brain (n = 1), and other sites (n = 13). In all, 63 of 76 (82%) cases with NE differentiation and available history were posttherapy: six postradiation therapy (RT), 24 post- androgen-deprivation therapy (ADT), and 33 post-RT + ADT. Morphologic assessment (n = 79): (i) 23 pure small-cell/high-grade NE carcinoma (HGNEC): 20/23 metastatic; (ii) 10 combined high-grade PCa and small-cell/HGNEC: 9/10 primary; (iii) 15 PCa with diffuse NE immunohistochemistry (IHC) marker positivity/differentiation, associated with nested to sheet-like growth of cells with abundant cytoplasm and prominent nucleoli, yet diffuse positivity for at least one prostatic and one NE IHC marker: all metastatic; (iv) 11 PCa with patchy NE differentiation, displaying more than single-cell positivity for NE IHC: five primary / six metastatic; (v) nine PCa with focal NE marker positive cells: four primary / five metastatic; (vi) 11 PCa with 'Paneth cell-like' change: all primary. CONCLUSIONS: In this contemporary series, the majority of NE differentiation in the setting of PCa was seen posttherapy. We highlight the tendencies of small-cell/HGNEC and PCa with diffuse NE differentiation by IHC to occur in metastatic settings, while morphologically combined high-grade PCa + small-cell/HGNEC and 'Paneth cell-like' change occur in primary disease.

Immunohistochemistry-based assessment of androgen receptor status and the AR-null phenotype in metastatic castrate resistant prostate cancer.

BACKGROUND: Molecular and immunohistochemistry-based profiling of prostatic adenocarcinoma has revealed frequent Androgen Receptor (AR) gene and protein alterations in metastatic disease. This includes an AR-null non-neuroendocrine phenotype of metastatic castrate resistant prostate cancer which may be less sensitive to androgen receptor signaling inhibitors. This AR-null non-neuroendocrine phenotype is thought to be associated with TP53 and RB1 alterations. Herein, we have correlated molecular profiling of metastatic castrate resistant prostate cancer with AR/P53/RB immunohistochemistry and relevant clinical correlates. DESIGN: Twenty-seven cases of metastatic castrate resistant prostate cancer were evaluated using histopathologic examination to rule out neuroendocrine differentiation. A combination of a hybridization exon-capture next-generation sequencing-based assay (n = 26), fluorescence in situ hybridization for AR copy number status (n = 16), and immunohistochemistry for AR (n = 27), P53 (n = 24) and RB (n = 25) was used to profile these cases. RESULTS: Of 27 metastatic castrate resistant prostate cancer cases, 17 had AR amplification and showed positive nuclear expression of AR by immunohistochemistry. Nine cases lacked AR copy number alterations using next-generation sequencing/fluorescence in situ hybridization. A subset of these metastatic castrate resistant prostate cancer cases demonstrated the AR-null phenotype by immunohistochemistry (five cases and one additional case where next-generation sequencing failed). Common co-alterations in these cases involved the TP53, RB1, and PTEN genes and all these patients received prior therapy with androgen receptor signaling inhibitors (abiraterone and/or enzalutamide). CONCLUSIONS: Our study suggests that AR immunohistochemistry may distinguish AR-null from AR-expressing cases in the metastatic setting. AR-null status informs clinical decision-making regarding continuation of therapy with androgen receptor signaling inhibitors and consideration of other treatment options. This might be a relevant and cost-effective diagnostic strategy when there is limited access and/or limited tumor material for molecular testing.

CT of renal cell carcinoma: assessment of collecting system invasion.

OBJECTIVE: Although renal collecting system invasion is not considered in the current TNM staging system, this finding may be relevant in terms of treatment planning and prognosis. The objective of this study was to investigate the frequency of collecting system invasion in renal cell carcinoma (RCC) and to assess the diagnostic performance of excretory phase CT for the assessment of collecting system invasion. MATERIALS AND METHODS: We conducted a retrospective study of 261 patients (171 men and 90 women; average age, 61 years; age range, 32-86 years) who underwent CT before nephrectomy for RCC between November 2008 and July 2011 at a single institution. On excretory phase contrast-enhanced CT images, two radiologists independently determined whether RCC components caused a filling defect within the collecting system and whether the RCC was in contact to the collecting system wall or separated from it. Histopathology served as the standard of reference. Interreader agreement and diagnostic performance tests for the detection of collecting system invasion were calculated. RESULTS: Histopathology identified collecting system invasion exclusively in clear cell RCC that showed a filling defect within the collecting system on excretory phase CT images (5.4%, 14/261). Tumors separated from or in contact with the collecting system on imaging (both readers; 94.6%, 247/261) did not show collecting system invasion on histopathology (sensitivity, 100%; specificity, 100%). Interreader agreement was excellent (κ, 0.965; 95% CI, 0.93-0.99). CONCLUSION: CT provides reliable assessment of collecting system invasion in patients with RCC, with excellent sensitivity and specificity.

Role of CT in the assessment of muscular venous branch invasion in patients with renal cell carcinoma.

OBJECTIVE: The purpose of this article is to determine whether the relationship between a renal cell carcinoma and the renal sinus fat on contrast-enhanced CT could predict muscular venous branch invasion and the type of surgery needed. MATERIALS AND METHODS: A total of 115 consecutive patients underwent pre-operative contrast-enhanced CT between August 2011 and December 2011. Without access to histopathologic information, on nephrographic phase contrast-enhanced CT images, two radiologists independently determined whether the renal tumor was in contact with the renal sinus fat or separated from the renal sinus fat. Interreader agreements and performance characteristics of imaging tests were calculated, and histopathologic analysis served as the standard of reference. RESULTS: Histopathologic analysis identified 115 renal tumors, 90% (103/115) of which were renal cell carcinomas. Thirty-nine percent (31/80) of renal cell carcinomas that abutted the renal sinus fat on CT displayed muscular venous branch invasion on histopathologic analysis. Patients with renal cell carcinomas separated from the renal sinus fat were more likely to undergo partial nephrectomies (96% [22/23]; p = 0.013). Sensitivity and specificity for the identification of muscular venous branch invasion on CT were 94% (95% CI, 80-99%) and 30% (20-42%), respectively. Interreader agreement of visual assessment was excellent (κ = 0.87; 95% CI, 0.81-0.92). CONCLUSION: If a renal cell carcinoma was separated from the renal sinus fat on CT, the likelihood of muscular venous branch invasion being identified by histopathologic analysis was significantly decreased, and the patient was more likely to undergo a partial nephrectomy.

Interobserver and intraobserver reproducibility in digital and routine microscopic assessment of prostate needle biopsies.

Advances in whole slide digital imaging in the past decade necessitate validation of these tools in each organ system in advance of clinical adoption. We assessed reproducibility in reporting prostate needle biopsy parameters among urologic pathologists using routine and digital microscopy in a consultation/second opinion-like setting. Four urologic pathologists evaluated a single core level from 50 diagnostically challenging needle biopsy specimens by routine microscopy and whole slide digital imaging. Interobserver and intraobserver agreement were calculated for primary and secondary Gleason grades, Gleason score, tumor quantitation (percentage and size in millimeters), and perineural invasion. Interobserver agreement for routine microscopy was excellent for primary Gleason grade (κ = 0.72) and good for all other parameters (κ ranging from 0.36 to 0.55). Whole slide digital imaging assessment yielded similar agreement for all parameters. Intraobserver agreement for primary Gleason grade and Gleason score was very good to excellent for all pathologists (all κ ≥ 0.65 and ≥ 0.73, respectively). Size of tumor in millimeters consistently displayed higher levels of agreement than percentage of tumor across media and pathologists. Digital assessment of routinely reported cancer parameters on prostatic needle biopsy for a given scanned core level is comparable to that of routine microscopy. These findings imply that histologic interpretation using dynamic whole slide images may accurately simulate routine microscopic evaluation in the consultation setting. Implementation of whole slide digital imaging in these scenarios may significantly reduce the workload of large referral centers in the near future and impact the manner in which pathologists seek second opinion consultation on challenging cases.