Erratum: Challenging Cases in Urothelial Cancer.

[This corrects the article DOI: 10.3233/BLC-200004.].

Pyeloduodenal Fistula in Xanthogranulomatous Pyelonephritis: A Series of Two Cases.

Xanthogranulomatous inflammation, characterized by destruction and replacement of tissues with chronic inflammatory cells, including foamy histiocytes and hemosiderin-laden macrophages, is uncommon. In patients with xanthogranulomatous pyelonephritis, inflammation may extend from the kidney to the overlying duodenum, creating a pyeloduodenal fistula that further complicates medical and surgical management. We present two cases with recurrent kidney infections who each ultimately received a nephrectomy and repair of their duodenal fistula.

Morphologic characterization of preoperatively treated prostate cancer: toward a post-therapy histologic classification.

BACKGROUND: Preoperative treatment of prostate cancer (PCa) changes morphology of residual tumors so that the Gleason score is no longer valid. OBJECTIVE: To codify morphologic features of preoperatively treated PCa and identify potential classifiers predictive of outcome. DESIGN, SETTING, AND PARTICIPANTS: We performed a detailed morphologic evaluation of specimens obtained from 115 patients with high-risk PCa who had preoperative androgen ablation, alone or in combination with chemotherapy. MEASUREMENTS: Included hierarchical clustering analysis of morphologic characteristics, associations with other pathologic parameters, and univariate and multivariate analyses in search for associations with disease outcome. RESULTS AND LIMITATIONS: Based on hierarchical clustering analysis, we categorized pretreated prostate cancer in three morphologically distinct groups: group A, characterized by a predominance of cell clusters, cell cords, and isolated cells; group B tumors, by intact and fused small glands; and group C tumors by any degree of cribriform growth pattern or intraductal tumor spread. Univariate analysis identified associations between this grouping, pathologic tumor stage (p<0.01) and residual tumor volume (p<0.001). Presence of intraductal spread or cribriform pattern in biopsies was associated with group C tumors. The presence of cribriform or intraductal spread morphology and positive surgical margins were stronger predictors of biochemical relapse than pathologic stage on multivariate analysis. The number of specimens evaluated in this study was limited, and a prospective validation is warranted along with molecular studies to validate the proposed morphologic classifier. CONCLUSIONS: If validated, this classification will introduce uniformity in the selection of tissue samples for biomarker studies, facilitate the comparison of trials among different institutions, and may provide a new prognostic tool for preoperatively treated PCa.

Quantitative fluorescence imaging analysis for cancer biomarker discovery: application to beta-catenin in archived prostate specimens.

The surprising disparity between the number of protein-encoding genes ( approximately 30,000) in the human genome and the number of proteins ( approximately 300,000) in the human proteome has inspired the development of translational proteomics aimed at protein expression profiling of disease states. Translational proteomics, which offers the promise of early disease detection and individualized therapy, requires new methods for the analysis of clinical specimens. We have developed quantitative fluorescence imaging analysis (QFIA) for accurate, reproducible quantification of proteins in slide-mounted tissues. The method has been validated for the analysis of beta-catenin in archived prostate specimens fixed in formalin. QFIA takes advantage of the linearity of fluorescence antibody signaling for tissue epitope content, a feature validated for beta-catenin in methacarn-fixed prostate specimens analyzed by reverse-phase protein array analysis and QFIA (r = 0.97). QFIA of beta-catenin in formaldehyde-fixed tissues correlated directly with beta-catenin content (r = 0.86). Application of QFIA in a cross-sectional study of biopsies from 42 prostate cancer (PC) cases and 42 matched controls identified beta-catenin as a potential field marker for PC. Receiver operating characteristic plots revealed that beta-catenin expression in the normal-appearing acini of cancerous glands identified 42% (95% confidence intervals, 26-57%) of cancer cases, with 88% (95% confidence intervals, 80-96%) specificity. The marker may contribute to a PC biomarker panel. In conclusion, we report the development and validation of a new method for fluorescence quantification of proteins in archived tissues and its application to archived specimens for an evaluation of beta-catenin expression as a biomarker for PC.

Clinical significance of benign glands at surgical margins in robotic radical prostatectomy specimens.

OBJECTIVES: Completion of robotic radical prostatectomy compared with conventional open retropubic radical prostatectomy can result in different alterations in the prostatectomy specimens. One difference appears to be an increased incidence of benign glands at the margins, which has been associated with an increase in postoperative prostatic-specific antigen (PSA) levels. We compared the frequency and clinical significance of benign prostate glands at the surgical margins in radical prostatectomy specimens obtained by robotic versus open retropubic prostatectomy. METHODS: We reviewed 38 consecutive prostatectomy specimens from patients with biopsy-proven prostate cancer. Of these 38 specimens, 25 (65%) were obtained by robotic resection and 13 (35%) by open retropubic prostatectomy. Each case was analyzed for Gleason score, pathologic stage, including margin status, and the presence or absence of benign glands at the surgical margin. The study endpoint was the postoperative serum PSA level. RESULTS: A significantly greater incidence (P = 0.035) of benign glands at the surgical margins was found within the robotic group compared with the open retropubic prostatectomy group (54% versus 15%). With a median follow-up of 12.5 months for the robotic group and 24.5 months for the robotic prostatectomy group, only 2 patients, who also had had positive surgical margins, had a continued and persistent increase in the postoperative PSA level after an initial nadir. CONCLUSIONS: The early clinical follow-up data of our study have suggested that patients undergoing robotic radical prostatectomy with negative surgical margins achieve a PSA nadir of less than 0.1 ng/mL, irrespective of the presence or absence of benign prostatic tissue at the surgical margins.

Multilocular cystadenoma and cystadenocarcinoma of the prostate.

BACKGROUND: Multicystic prostatic tumors are rare, with only a few reported cases of prostatic cystadenoma and cystadenocarcinoma in the scientific literature. METHODS: A retrospective review of our tumor registry over the last 25 years identified 2 rare cystic tumors of the prostate: 1 multilocular cystadenoma and 1 multilocular cystadenocarcinoma. RESULTS: The first case illustrates the clinical and pathologic features of prostatic multilocular cystadenoma. A 42-year-old man presented with a 16-cm suprapubic mass causing displacement of adjacent visceral organs. Pathologic examination after prostatectomy confirmed it to be a multilocular cystadenoma of the prostate. The patient's postoperative course was uneventful, and his serum prostate-specific antigen level remained at < or =0.04 ng/ml throughout the course of his disease. In the second case, we present an 80-year-old male presenting with a 12-cm cystic mass of the prostate. His serum prostate-specific antigen level remained at > or =9.0 ng/ml throughout the course of his disease. The tumor had an aggressive local growth pattern, with invasion into perirectal adipose tissue. This patient underwent a pelvic exenteration, followed by adjuvant systemic chemotherapy and complete androgen blockade. Despite aggressive treatment, he had 3 recurrences over 4 months but remains alive with disease at 23-month follow-up. CONCLUSIONS: Cystadenocarcinoma of the prostate is locally aggressive and should be included in the differential diagnosis of cystic lesions of the prostate.

N-cadherin switching occurs in high Gleason grade prostate cancer.

BACKGROUND: The inappropriate expression of non-epithelial N-(neural) cadherin by epithelial cells, called cadherin switching, has been suggested to play a role in prostate cancer (PC) progression. We explored the role of N-cadherin as a biomarker in PC by correlating the expression with clinical parameters. METHODS: Two pathologists blinded to patients' history independently reviewed and scored the intensity and extent of staining of N-cadherin expression in 44 randomly selected radical prostatectomy specimens. The expression was correlated with total Gleason grade, individual Gleason patterns, tumor stage, and preoperative serum prostate specific antigen (PSA) levels and P-values < 0.05 were considered statistically significant. RESULTS: Of the 44 PC specimens, 14 (32%), 23 (52%), 7 (16%) consisted of Gleason grade 5-6, 7, and 8-10, respectively and 20/44 (45%) demonstrated N-cadherin expression. N-cadherin was expressed in 1/14 (7%) of Gleason 5-6 compared to 15/23 (65%) of Gleason grade 7, and 4/7 (57%) of Gleason grade 8-10, demonstrating a significant correlation between N-cadherin switching and higher Gleason grade (P = 0.001). While only about a third of primary or secondary Gleason pattern 3 demonstrated N-cadherin expression, a majority of Gleason patterns of > or = 4 expressed N-cadherin (P > 0.05), further suggesting that N-cadherin switching occurs with higher Gleason pattern. However, N-cadherin expression did not significantly correlate with preoperative serum PSA levels or tumor stage in our study cohort. CONCLUSIONS: We have demonstrated for the first time that N-cadherin switching occurs in higher grade PC and correlates significantly with increasing Gleason patterns. N-cadherin may be as a useful biomarker of aggressive PC.

The Internet for pathologists: a simple schema for evaluating pathology-related Web sites and a catalog of sites useful for practicing pathologists.

CONTEXT: With the increasing popularity of the Internet as a primary medical information source, it is critical for pathologists to be able to use and evaluate both general medical- and pathology-related Web sites. Several published models for evaluating Web sites prove cumbersome to use and often involve computer- or statistic-based algorithms. OBJECTIVES: To develop a simple group of scoring criteria to objectively evaluate medical Web sites and provide a list of the highest-scoring pathology-related sites that will be useful to the practicing pathologist. DESIGN: Using 11 commonly used Internet search engines, the top 50 "hits" retrieved from the search term websites for pathologists were scored using 5 criteria, including accuracy, ease of navigation, relevance, updates, and completeness. A possible 6 to 12 points per area were awarded, and the total score was summated. RESULTS: Scores obtained ranged from 12 to 21. Thirty-five Web sites, all scoring 15 or higher based on these criteria, were listed as most useful. CONCLUSION: A simple, easy-to-use, 5-category scoring system can prove useful in evaluating pathology- and medical-related Web sites.

Oncocytic renal neoplasms: diagnostic considerations.

Advances in our understanding of renal neoplasia have resulted in recognition of numerous tumors that are composed predominantly of cells with abundant eosinophilic cytoplasm. This article discusses the features of renal oncocytoma (including oncocytosis), chromophobe renal cell carcinoma (RCC), and clear cell RCC; explores the relationship between renal oncocytoma and chromophobe RCC; briefly discusses other tumors with abundant eosinophilic cytoplasm; and emphasizes the differential diagnosis of such tumors.

Evidence supporting preoperative chemotherapy for small cell carcinoma of the bladder: a retrospective review of the M. D. Anderson cancer experience.

PURPOSE: Neuroendocrine tumors of the bladder comprise a small subset of all bladder tumors. To improve our understanding of this tumor and define outcomes with current management, we performed a retrospective review of these cases. MATERIALS AND METHODS: We reviewed the records of 88 patients with small cell bladder carcinoma evaluated at our institution between 1985 and 2002. Of these patients 46 underwent cystectomy, including 25 who were treated with initial cystectomy and 21 who received preoperative chemotherapy. RESULTS: For patients treated with initial cystectomy median cancer specific survival (CSS) was 23 months, with 36% disease-free at 5 years. For patients receiving preoperative chemotherapy median CSS has not been reached (p = 0.026), although CSS at 5-years was 78% with no cancer related deaths observed beyond 2 years. Notably 7 of 25 patients treated with initial cystectomy received chemotherapy after surgery but their survival was no better than those treated with cystectomy alone. As others have observed, the pathological stage was higher than clinically appreciated for 56% of patients treated with initial cystectomy. Moreover, there were no cancer related deaths among patients with disease down staged to pT2 or less. CONCLUSIONS: Like other neuroendocrine tumors, small cell carcinoma of the bladder grows rapidly but is chemo-sensitive. Clinical under staging is the rule. Optimal results are achieved via integration of local and systemic treatment. Our results suggest that preoperative chemotherapy is the optimal strategy, even in the setting of clinically localized cancer. On the basis of these observations, we have initiated a trial in which 4 cycles of aggressive multiagent preoperative chemotherapy are followed by radical cystectomy.

Chromophobe renal cell carcinoma with sarcomatoid transformation.

We present a rare case of a chromophobe renal cell carcinoma that progressed to a high-grade spindle cell sarcoma. The tumor affected a 50-year-old man who had presented with right upper quadrant discomfort and hematuria and subsequently underwent a right radical nephrectomy. Microscopically, the tumor was composed of two distinct components, a chromophobe renal cell carcinoma and a sarcomatoid component. The sarcomatoid component had exhibited aggressive behavior by spreading to a regional lymph node. This case report shows that chromophobe carcinoma can develop a sarcomatoid transformation with a high propensity for invasive growth and metastasis.

Distinguishing atrophy and high-grade prostatic intraepithelial neoplasia from prostatic adenocarcinoma with and without previous adjuvant hormone therapy with the aid of cytokeratin 5/6.

We evaluated the sensitivity and specificity of cytokeratin (CK) 5/6 for distinguishing foci of atrophy from prostatic adenocarcinoma with and without previous hormonal adjuvant therapy and observed the intensity and pattern of staining in mimickers of prostatic adenocarcinoma (basal cell hyperplasia, atypical adenomatous hyperplasia, and tangentially cut high-grade prostatic intraepithelial neoplasia [PIN]). We reviewed 146 acinar proliferations in 81 specimens (radical prostatectomy, previously untreated, 41; radical prostatectomy, following androgen-deprivation therapy, 11; transurethral resection, previously untreated, 29). All benign acinar proliferations stained positively for CK5/6, with immunoreactivity restricted to basal cells. Untreated and androgen-deprived prostatic adenocarcinomas were invariably negative. The pattern of staining was continuous in 79% of the atrophy cases (15/19), and all foci stained with CK5/6. Characteristic double-layer staining in basal cell hyperplasia was observed in 93% of cases (13/14), and foci of high-grade PIN had a characteristic "checkerboard" staining with areas of discontinuity. Foci of atypical adenomatous hyperplasia showed continuous staining, including cauterized acini in 53% of cases (8/15), with a fragmented basal cell layer pattern in 47% of cases (7/15). CK5/6 staining of the basal cells in foci of atrophy is sensitive and specific for excluding prostatic adenocarcinoma with and without androgen-deprivation effect.

Prognostic importance of resection margin width after nephron-sparing surgery for renal cell carcinoma.

OBJECTIVES: To examine the relationship between the width of the resection margin and disease progression in renal cell carcinoma (RCC) after nephron-sparing surgery (NSS). During NSS for RCC, it is standard practice to excise the tumor along with a surrounding margin of normal parenchyma (margin of resection) to ensure complete resection of the neoplasm. However, no agreement has been reached on how wide the margin of resection should be. METHODS: We retrospectively reviewed the histopathologic sections and medical records of 69 patients with localized RCC who had undergone NSS between 1976 and 1988 to determine whether the resection margin, tumor size, TNM stage, and Fuhrman nuclear grade were associated with disease progression (defined as local tumor recurrence or metastasis). The mean postoperative follow-up interval was 8.5 years. RESULTS: No association was found between the width of the resection margin and disease progression (P = 0.98, log-rank test). Both TNM stage and Fuhrman nuclear grade correlated with disease progression. Patients with T1-T2 tumors had lower progression (P <0.001, log-rank test), and increased Fuhrman nuclear grade correlated with more disease progression (P <0.001, log-rank test). CONCLUSIONS: The width of the resection margin after NSS for RCC does not correlate with long-term disease progression. A histologic tumor-free margin of resection, irrespective of the width of the margin is sufficient to achieve complete local excision of RCC.