Jennifer Merrimen

Is high grade prostatic intraepithelial neoplasia still a risk factor for adenocarcinoma in the era of extended biopsy sampling

Aims: There is controversy regarding the role of high grade prostatic intraepithelial neoplasia (HGPIN) on prostatic needle biopsy (PNB) as a risk factor for prostatic adenocarcinoma. We utilise a large Canadian database to determine whether HGPIN detected on extended PNB is a significant risk factor for prostatic adenocarcinoma. Methods: Pathological findings from PNBs from 12 304 men who underwent initial PNB during an 8 year period were analysed. Patients were included in the study if their initial diagnosis was HGPIN alone or a benign diagnosis, if at least one follow‐up PNB was performed, and if both the initial and follow‐up PNB contained at least 10 prostate cores. Results: In the benign group of 105 patients and the HGPIN group of 120 patients, 14.1% and 20.8% were diagnosed with prostatic adenocarcinoma, respectively. When the HGPIN group was further subdivided into unifocal (1 core) and multifocal (≥2 cores) groups, 9.4% and 29.9% developed prostatic adenocarcinoma, respectively (p < 0.0001). Cox regression analysis adjusting for age and prostate specific antigen (PSA) confirms the significance of HGPIN as a risk factor for prostatic adenocarcinoma (p = 0.0045). Conclusions: Patients with an initial diagnosis of multifocal HGPIN on extended PNB are at a greater risk for subsequent prostatic adenocarcinoma than those with unifocal HGPIN or benign diagnoses.

A Model to Predict Prostate Cancer After Atypical Findings in Initial Prostate Needle Biopsy

PURPOSE Atypical small acinar proliferation can occur alone or with high grade prostatic intraepithelial neoplasia in either a discontinuous or contiguous pattern in a prostate needle biopsy. We assessed whether different subgroups of atypical small acinar proliferation and high grade prostatic intraepithelial neoplasia denote a differing risk of detecting subsequent prostate cancer. MATERIALS AND METHODS We reviewed the pathological findings in 12,304 men who underwent initial prostatic needle biopsy during May 1999 to June 2007. Patients were included in the study if the initial diagnosis was atypical small acinar proliferation alone or combined with high grade prostatic intraepithelial neoplasia, or a benign diagnosis, and if followup prostatic needle biopsy was done. RESULTS Prostate cancer developed in 22%, 27% and 49% of patients in the benign, high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation groups, respectively (p <0.0005). In all subgroups there was a 35% to 57% rate of prostate cancer detection. The prostate cancer risk increased in the atypical small acinar proliferation subgroups according to the extent of high grade prostatic intraepithelial neoplasia in the initial sample, with atypical small acinar proliferation associated with multifocal high grade prostatic intraepithelial neoplasia carrying a 71% prostate cancer risk. CONCLUSIONS Atypical small acinar proliferation combined with high grade prostatic intraepithelial neoplasia, particularly when associated with multifocal high grade prostatic intraepithelial neoplasia, is associated with a significant risk of prostate cancer detection on followup biopsy.

Intraductal carcinoma of the prostate: Interobserver reproducibility survey of 39 urologic pathologists

The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.

Carboxypeptidase-D is elevated in prostate cancer and its anti-apoptotic activity is abolished by combined androgen and prolactin receptor targeting

Carboxypeptidase‐D (CPD) cleaves C‐terminal arginine for nitric oxide (NO) production. CPD and NO levels are upregulated by testosterone (T) and prolactin (PRL) to promote survival of prostate cancer (pCa) cells. This study evaluated CPD immunostaining and T/PRL regulation of CPD and NO levels in benign and malignant prostate tissues/cells to determine the role of CPD in pCa.

Prolactin- and testosterone-induced carboxypeptidase-D correlates with increased nitrotyrosines and Ki67 in prostate cancer

Carboxypeptidase‐D (CPD) cleaves C‐terminal arginine for conversion to nitric oxide (NO) by nitric oxide synthase (NOS). Prolactin (PRL) and androgens stimulate CPD gene transcription and expression, which increases intracellular production of NO to promote viability of prostate cancer (PCa) cells in vitro. The current study evaluated whether hormonal upregulation of CPD and NO promote PCa cell viabilty in vivo, by correlating changes in expression of CPD and nitrotyrosine residues (products of NO action) with proliferation marker Ki67 and associated proteins during PCa development and progression.

Renal cell carcinoma after neuroblastoma: A case study and review of the literature

We present a case of renal cell carcinoma (RCC) arising in a 26-year-old patient with a history of neuroblastoma. RCC after a previous diagnosis of neuroblastoma is very uncommon, and there have only been 23 reported cases. Using the results of our patient workup, we hoped to determine whether there was a genetic predisposition or iatrogenic cause for the RCC. There is no clear explanation why neuroblastoma survivors are prone to developing RCC. However, genetic predisposition and previous treatment likely play a role. Since there have been few cases described, and few investigations into the genetics of this subtype of RCC, it remains important for individual cases to be added to the literature of this recently described and rare entity.

A rare case of bladder chondroma

Soft tissue chondromas are benign tumours that arise commonly in the hands and feet of adults, but rarely in other locations. Only two prior cases of chondroma of the urinary bladder wall have been reported. We describe a third case and discuss similarities and differences between the three cases reported to date.

Metastatic renal cell carcinoma to the testis: A case report and review of the literature

This is a case of a 68-year-old male who presented with a chief compliant of a testicular mass, which was discovered to be a meta-static lesion of undiagnosed renal cell carcinoma. A computed tomography scan revealed a large right renal mass and multiple pulmonary metastasis. Shortly after diagnosis, the patient was initiated on systemic therapy and received a cytoreductive nephrectomy. We discuss the details of this case as well as a pertinent review of metastatic renal cell carcinoma to the testes.

Spermatocytic Tumor With Sarcoma: A Rare Testicular Neoplasm

Spermatocytic tumor, formerly known as spermatocytic seminoma, is an uncommon testicular neoplasm which is a distinct clinicopathologic entity from classic seminoma. These tumors are not associated with germ cell neoplasia in situ, other germ cell tumors, or isochromosome 12p. Although typically, these tumors have an excellent prognosis occasional cases are associated with sarcoma and have a very poor prognosis. We present a case of spermatocytic tumor with sarcoma showing a chondrosarcomatous component, discuss the pathologic findings and differential diagnosis and provide follow-up information.

Accuracy of kidney cancer diagnosis and histological subtype within Canadian cancer registry data

INTRODUCTION Provincial/territorial cancer registries (PTCRs) are the mainstay for Canadian population-based cancer statistics. Each jurisdiction captures this data in a population-based registry, including the Nova Scotia Cancer Registry (NSCR). The goal of this study was to describe data from the NSCR regarding renal cell carcinoma (RCC) pathology subtype and method of diagnosis and compare it to the actual pathology reports to determine the accuracy of diagnosis and histological subtype assignment. METHODS This retrospective analysis included patients diagnosed with RCC in the NSCR from 2006-2010 with an ICD-O-3 code C64.9 seen or treated in the largest NS health district. From the NSCR, method of diagnosis and pathological diagnosis was recorded. All diagnoses of non-clear-cell RCC (nonccRCC) from NSCR were compared to the actual pathology report for descriptive comparison and reasons for discordance. RESULTS 723 patients make up the study cohort. 81.3% of patients were diagnosed by nephrectomy, 11.1% radiography, 6.9 % biopsy, and 0.7% autopsy. By NSCR data, 52.8% had clear-cell (ccRCC), 20.5% RCC not otherwise specified (NOS), 12.7% papillary, 4% chromophobe, and the rest had other nonccRCC subtypes. By pathology reports, 69.5% had clear-cell, 15% papillary, 5% chromophobe, only 2.7% RCC NOS. There was a discordance rate of 15.4% between NSCR data and diagnosis from pathology report. Reasons for discordance were not enough information by the pathologist in 45.5%, misinterpretation of report by data coder in 22.2%, and true coding error in 32.3%. CONCLUSIONS When using PTCR for RCC incidence data, it is important to understand how the diagnosis is made, as not all are based on pathological confirmation; in this cohort 11% were based on radiology. One must also be aware that clear-cell and non-clear-cell subtypes may differ between the PTCR data and pathology reports. In this study, ccRCC made up 52.8% of the registry diagnoses, but increased to 69.6% on pathology report review. Use of synoptic reporting and ongoing education may improve accuracy of registry data.