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.

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.

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.

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.

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.

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.

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.

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.

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.

The utility of epithelial membrane antigen and vimentin in the diagnosis of chromophobe renal cell carcinoma.

We evaluated the immunohistochemical expression of epithelial membrane antigen (EMA) and vimentin (VMT) in chromophobe renal cell carcinoma (CHRCC). We also studied the utility of EMA and VMT immunostains in helping differentiate CHRCC from renal oncocytoma and conventional (clear cell) renal cell carcinoma with granular morphology (GCRCC). Immunohistochemical staining for EMA and VMT was performed on 21 cases of CHRCC, 16 cases of renal oncocytoma, and 28 cases of GCRCC. The diagnosis in all cases was by concurrence of all pathologists involved in the study and was based entirely on examination of routinely stained slides. All cases were classic examples of these tumor types and presented no diagnostic difficulties. The intensity of immunohistochemical staining was graded on a scale of 0 to 3 (0 = no staining; 1 = equivocal; 2 = unequivocal, moderate intensity; and 3 = unequivocal, high intensity). Positive immunohistochemical staining was defined as unequivocal staining of at least 20% of the neoplastic cells. All cases of CHRCC were positive for EMA and negative for VMT. The same immunophenotype was observed in 75% of renal oncocytoma and 21% of GCRCC. In summary, all CHRCC cases in our study demonstrated immunohistochemical staining for EMA and not VMT. However, we also found that the same immunophenotype is observed in 75% of renal oncocytoma and in 21% of GCRCC, precluding its utility for positive identification of CHRCC. Nevertheless, the lack of such an immunophenotype is a reliable indication that a neoplasm under consideration is not CHRCC.

Adenocarcinoma of the small bowel: a study of 37 cases with emphasis on histologic prognostic factors.

PURPOSE: Primary small-bowel adenocarcinoma is uncommon. There are few large studies that have evaluated the prognostic impact of clinical and pathologic parameters. The purpose of this study was to perform a comprehensive analysis of the Cleveland Clinic experience with small-bowel adenocarcinoma, with emphasis on histopathologic parameters as prognostic indicators. METHODS: Thirty-seven cases of primary small-bowel adenocarcinomas resected at the Cleveland Clinic between 1978 and 1999 were retrospectively studied. Metastatic tumors and those arising from the biliary system were excluded from analysis. Clinical and pathologic data were recorded and their impact on prognosis was evaluated by either Kaplan-Meier or Cox proportional hazards analysis. RESULTS: The cohort included 25 males, and the age range was 24 to 82 (mean, 56) years. Tumor location was duodenum (18), jejunum (10), ileum (2), and site not specified (7). Patients most frequently presented with abdominal pain (48 percent), anemia (39 percent) and small-bowel obstruction (33 percent). Underlying conditions included Crohn's disease (4) and familial adenomatous polyposis (2). Overall survival was 52 and 47 percent at 5 and 10 years, respectively, with a mean follow-up of 50.5 (range, 0.5-184) months for all patients. Features found to be negative prognostic factors for survival were positive surgical margins (P < 0.001), extramural venous spread (P < 0.001), lymph node metastases (P = 0.038), poor tumor differentiation (P = 0.015), depth of tumor invasion (P = 0.023), and history of Crohn's disease (P < 0.001). Age, gender, tumor size, growth pattern, lymphocytic host response, and adjuvant therapy did not affect survival. CONCLUSIONS: Pathologic features, including positive surgical margins, extramural venous spread, positive lymph nodes, poor tumor differentiation, depth of tumor invasion, and history of Crohn's disease, are of major prognostic significance in small-bowel adenocarcinoma. Although many of these prognostic features are similar to the ones used for colorectal adenocarcinoma, they are easily applicable and reproducible for small-bowel adenocarcinomas. This is important considering the often dismal prognosis of small-bowel adenocarcinoma.

Pulmonary hemangiomas of infancy and childhood: report of two cases and review of the literature.

Pulmonary hemangiomas are exceptionally rare in childhood and more so in infancy. They may involve the airways or the parenchyma, and may be localized or multifocal. We present two cases of pulmonary capillary hemangiomas. The first case is a localized form of capillary hemangioma that was resected from an 8-week-old infant with signs of respiratory distress. A computed tomography scan showed a cystic mass initially thought to be an intrapulmonary bronchogenic cyst. A segmental resection was performed and examination revealed a localized capillary hemangioma without cystic or cavernous features. The second case is an example of a multifocal capillary hemangioma from a 9-year-old child who presented clinically with clubbing of fingers and toes and radiologically had multiple discrete nodules localized to the right lung. The clinical and pathological features of the cases are discussed together with a review of the literature. The distinction from other vascular neoplasms of childhood is briefly described. Although rare, pulmonary hemangiomas should be entertained in the diagnosis of both solid and cystic intrapulmonary lesions of childhood and infancy.