Isabelle Meiers

Immunohistochemical Analysis of Chromophobe Renal Cell Carcinoma, Renal Oncocytoma, and Clear Cell Carcinoma An Optimal and Practical Panel for Differential Diagnosis

CONTEXTnThe separation of chromophobe renal cell carcinoma, oncocytoma, and clear cell renal cell carcinoma using light microscopy remains problematic in some cases.nnnOBJECTIVEnTo determine a practical immunohistochemical panel for the differential diagnosis of chromophobe carcinoma.nnnDESIGNnVimentin, glutathione S-transferase alpha (GST-alpha), CD10, CD117, cytokeratin (CK) 7, and epithelial cell adhesion molecule (EpCAM) were investigated in 22 cases of chromophobe carcinoma, 17 cases of oncocytoma, and 45 cases of clear cell carcinoma.nnnRESULTSnVimentin and GST-alpha expression were exclusively observed in clear cell carcinoma. CD10 staining was more frequently detected in clear cell carcinoma (91%) than in chromophobe carcinoma (45%) and oncocytoma (29%). CD117 was strongly expressed in chromophobe carcinoma (82%) and oncocytoma (100%), whereas none of the cases of clear cell carcinomas were immunoreactive. Cytokeratin 7 was positive in 18 (86%) of 22 cases of chromophobe carcinoma, whereas all oncocytomas were negative for CK7. EpCAM protein was expressed in all 22 cases of chromophobe carcinoma in more than 90% of cells, whereas all EpCAM-positive oncocytomas (5/17; 29%) displayed positivity in single cells or small cell clusters.nnnCONCLUSIONSnUsing the combination of 3 markers (vimentin, GST-alpha, and EpCAM), we achieved 100% sensitivity and 100% specificity for the differential diagnosis of chromophobe carcinoma, oncocytoma, and clear cell carcinoma. The pattern of vimentin(-)/GST-alpha(-) effectively excluded clear cell carcinoma, and homogeneous EpCAM expression confirmed the diagnosis of chromophobe carcinoma rather than oncocytoma. CD117 and CK7 were also useful markers and could be used as second-line markers for the differential diagnosis, with high specificity (100%) and high sensitivity (90% and 86%, respectively).

Preoperative Prediction of Multifocal Prostate Cancer and Application of Focal Therapy: Review 2007

Prostate cancer is a leading malignancy among men. Early prostate cancer is most commonly treated with radical surgery and radiotherapy. In the era of prostate-specific antigen and newly emerging highly specific screening tests, a greater number of men are given a diagnosis earlier in life, and disease is more often confined. Less-invasive treatments, such as focal therapy, are becoming increasingly popular, yielding shorter hospital stays, faster recovery, and fewer complications. Potential drawbacks to focal therapy include the risk of incomplete treatment, which may result from missed cancer foci and inadequate ablation to target tissues. Furthermore, this approach is not universally applicable to all patients--for example, those who have periurethral and extraprostatic extension of the tumor may not benefit from focal treatment. This article reviews the importance of multifocal prostate cancer and the application of focal treatment.

Glutathione S-transferase pi (GSTP1) hypermethylation in prostate cancer: review 2007

Prostatic carcinoma is characterised by the silencing of the pi-class glutathione S-transferase gene (GSTP1), which encodes a detoxifying enzyme. The silencing of GSTP1 results from aberrant methylation at the CpG island in the promoter-5 and occurs in the vast majority of cases of high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancers. We review the potential novel role of GSTP1 and its related expression in prostate cancer. The loss of expression (silencing) of the GSTP1 gene is the most common (>90%) genetic alteration reported to date in prostate cancer. Quantitative methylation-specific PCR assays allow detection of GSTP1 methylation in prostate biopsies and may improve the sensitivity of cancer detection. Advances in the epigenetic characterisation of prostate cancer have enabled the development of DNA methylation assays that may soon be used in diagnostic testing of serum and tissue for prostate cancer. Inhibition of aberrant promoter methylation could theoretically prevent carcinogenesis.

Group Consensus Reports from the Consensus Conference on Focal Treatment of Prostatic Carcinoma, Celebration, Florida, February 24, 2006

( EPORT OF CONSENSUS GROUP 1: ATHOBIOLOGY OF PROSTATE CANCER: MPLICATIONS FOR FOCAL THERAPY ocal ablative therapy may be reasonable for some atients with prostate cancer; selection factors include variety of clinical and pathologic factors in combiation with informed patient choice. Our group evalated 4 specific pathologic features that may influence his treatment decision. We reviewed the published iterature for applicable studies regarding the natural istory of prostate cancer, multifocality, cancer volme, and accuracy of cancer detection by current ethods. Results were as follows:

Atypical small acinar proliferation in the prostate: clinical significance in 2006.

About 2% of contemporary prostate needle biopsy specimens contain collections of small acini that are suspicious for cancer but that fall below the diagnostic threshold and are reported as atypical small acinar proliferation suspicious for but not diagnostic of malignancy. Prostate cancer has been identified in specimens from subsequent biopsies in up to 60% of cases of atypical small acinar proliferation, indicating that this finding is a significant predictor of cancer. Identification of atypical small acinar proliferation warrants repeat biopsy for concurrent or subsequent invasive carcinoma.

Prostatic stromal hyperplasia with atypia: follow-up study of 18 cases.

CONTEXTnProstatic stromal hyperplasia with atypia is a rare lesion that can be mistaken for sarcoma because of the presence of atypical, bizarre, degenerative myocyte nuclei.nnnOBJECTIVEnTo determine the diagnostic criteria and clinical significance of prostatic stromal hyperplasia with atypia.nnnDESIGNnEighteen cases of prostatic stromal hyperplasia with atypia were reviewed from the consultation file of one of the authors (D.G.B.).nnnRESULTSnProstatic stromal hyperplasia with atypia consists of 1 or more ill-defined, uncircumscribed, hyperplastic stromal nodules, with variable numbers of atypical, bizarre giant cells, with vacuolated nuclei, smudged chromatin, and frequent multinucleation infiltrating around benign acini. There was a hypocellular, loose, myxoid stromal matrix, with ectatic hyalinized vessels and mild to moderate chronic inflammation. Stromal cells displayed intense immunoreactivity for androgen receptors and vimentin, but moderate reactivity for desmin and actin. There were 3 local recurrences, with a mean follow-up of 6.3 years (range, 0.5-14 years), but none developed evidence of sarcomatous transformation or malignancy.nnnCONCLUSIONSnProstatic stromal hyperplasia with atypia is a rare, benign lesion, composed of degenerative myocytes with atypia that is histologically and clinically reminiscent of benign counterparts in the myometrium, breast, vulva, vagina, and elsewhere. Recognition of this distinctive entity should allow separation from phyllodes tumor and sarcoma of the prostate. The phrase stromal tumor of uncertain malignant potential is inappropriate for this benign tumor, and its use is discouraged.

Diagnosis of Prostatic Carcinoma After Therapy

CONTEXTnProstate cancer is the most common cancer of men in the United States and is third only to lung and colon cancer as a cause of cancer death. In 2006, 27,350 Americans will die of prostate cancer, and 234,460 new cases will be diagnosed. Treatment changes in the benign and cancerous prostate create diagnostic challenges in pathologic interpretation, particularly in needle biopsy specimens and in evaluation of extraprostatic metastases.nnnOBJECTIVEnTo summarize therapy-related pathologic findings in the prostate with emphasis on recognition of treated adenocarcinoma.nnnDATA SOURCESnExtensive review of published literature and the authors experience.nnnCONCLUSIONSnFollowing therapy for prostate cancer, it is critical that the clinician provide the pertinent history of androgen deprivation or radiation therapy to assist the pathologist in rendering the correct diagnosis.

Improved filter method for urine sediment detection of urothelial carcinoma by fluorescence in situ hybridization.

CONTEXTnFluorescence in situ hybridization (FISH) of voided urine sediment is a sensitive and specific test for the detection of urothelial carcinoma. The time required for slide preparation using the conventional cytospin method is lengthy.nnnOBJECTIVEnTo present an alternative to the conventional cytospin method.nnnDESIGNnWe compared the results of an improved filter monolayer method with published results of the conventional cytospin method. A total of 624 patients with cytology and FISH analyses were followed with cystoscopy and/or bladder biopsy. Fluorescence in situ hybridization analysis was performed on 624 cases using fluorescence-labeled probes to the pericentromeric regions of chromosomes 3, 7, and 17 and band 9p21; cytology was also performed in all cases.nnnRESULTSnA total of 217 (34.7%) of 624 patients had follow-up bladder biopsies, and 170 of these (78.3%) had urothelial carcinoma. The sensitivity for cancer detection was higher for FISH than for urine cytology (92.9% [158/ 170] for FISH vs 72.9% [124/170] for urine cytology, P = <5%). The specificity was equivalent for FISH and urine cytology (97.5% [443/454] for FISH vs 92.2% [419/454] for cytology). The sensitivity for FISH was better (92.9% vs 81%), and there was no significant difference in specificity (97.5% vs 96%) between the filter method and the conventional cytospin method. Unlike the conventional cytospin method, the filter method did not require multiple centrifugation and decantation steps or investment in dedicated equipment.nnnCONCLUSIONSnThe improved filter method was faster, easier, and less expensive than published results with the conventional cytospin method with better sensitivity and equivalent specificity.

Prostatic leiomyoma with atypia: follow-up study of 10 cases

We studied the clinical and histologic features of 10 cases of prostatic leiomyoma with atypical bizarre nuclei. Immunohistochemical studies were undertaken in 6 cases. Patient follow-up was obtained in all cases. Patients ranged in age from 50 to 82 years (mean, 65 years) and presented with urinary obstructive symptoms in 7 cases, abnormal digital rectal examination in 3 cases. The histologic findings consisted of a solid circumscribed expansile stromal nodule with abundant smooth muscle and variable numbers of atypical bizarre giant cells. The cells of the tumor displayed intense immunoreactivity for desmin, actin, and androgen receptor and weak to moderate reactivity for vimentin. Four local recurrences were seen, with a follow-up for 3 to 16 years (mean, 7.4 years), but no evidence of sarcomatous transformation occurred. Despite worrisome histologic appearance, a benign clinical behavior was seen in all cases.

Prostate Cancer: Optimal Tissue Processing for Diagnosis and Prognosis

Optimal processing, handling, and sampling of prostatic biopsies and prostatectomy specimens ensure accurate diagnosis and staging. Prognostic factors derived from careful examination of tissue samples are critical for patient management, including cancer volume, extraprostatic extension, surgical margins, vascular/lymphatic invasion, and perineural invasion. This chapter addresses these important issues, including recent recommendations of a consensus panel of the International Society of Urological Pathology and the Union for International Cancer Control 2010 TNM Staging Committee.