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Jonathan I Epstein

Publications and source records attributed to Jonathan I Epstein.

At least 91 records · Page 5Linked to original sources
PubMed2004

Urinary bladder biopsy with denuded mucosa: denuding cystitis-cytopathologic correlates.

Denuding cystitis is often encountered in tissue biopsies of bladder mucosa performed by either cold-cup forceps or wire loop electrocautery to evaluate hematuria or to rule out recurrent urothelial carcinoma. Lack of urothelium in these biopsies is often a frustrating experience, leading to a nonspecific interpretation. In this study, 151 cases of denuding cystitis were retrieved from the surgical pathology files of The Johns Hopkins Hospital over a 4-year period (1996-1999). Patients under the age of 40 years and outside consultation material were excluded. Of the 151 cases of denuding cystitis, 48 patients were identified who had concurrent urinary cytologic studies. Of these patients, 35 were male (73%) and 13 were female (27%). Patient ages ranged from 43 to 85 years (mean, 67). Twenty-six of these 48 patients (54%) had at least one concurrently positive urinary cytology, which was histologically confirmed. All except three cases were high-grade urothelial carcinoma with the following histologic subtypes: flat carcinoma in situ (n = 11), noninvasive papillary (n = 9), and invasive urothelial carcinoma (n = 3). We conclude that urinary cytology is a sensitive modality that detects exfoliated carcinoma cells in patients with a histologic diagnosis of denuding cystitis. An inconclusive diagnosis of denuding cystitis on tissue might be related to biopsy method and technique, small sample size, or biopsy of cystoscopically abnormal urothelium that is denuded. A cytologic diagnosis of high-grade urothelial carcinoma in these cases leads to a timely clinical intervention for optimal patient management.

Adult↗
PubMed2004

Negative 34betaE12 staining in a small focus of atypical glands on prostate needle biopsy: a follow-up study of 332 cases.

Atypical glands on prostate needle biopsy with a negative 34betaE12 (cytokeratin 903; CK903) immunostain, indicating a lack of a basal cell layer, are typically diagnostic of prostate cancer. However, in certain cases a negative 34betaE12 immunostain in a small focus of atypical glands is still not convincing enough to make the diagnosis of cancer. This study is the first report to evaluate the incidence of prostate cancer on follow-up biopsy in individuals with this diagnosis. A total of 543 men who had prostate core biopsy specimens diagnosed as a small focus of atypical-appearing glands with a negative 34betaE12 immunostain between January 1, 1997 and December 31, 2000 were selected for study. Some 61% of these 543 individuals (n = 332) had undergone at least one follow-up biopsy procedure. Of these, 43% of repeat biopsy cases (n = 142) were diagnostic of prostate cancer. A total of 46 individuals had at least 2 follow-up biopsy procedures, with 48% of these (n = 22) being diagnosed as cancer. The Gleason grades of the detected carcinomas were broken down as follows: Gleason grade 3 + 2 = 5, 6%; grade 3 + 3 = 6, 86%; grade 3 + 4 = 7, 1%; grade 4 + 3 = 7, 4%; and grade 4 + 4 = 8, 3%. The median amount of time to the first follow-up biopsy was 79 days, with 52% of follow-up biopsies performed within 90 days. A negative 34betaE12 immunohistochemical stain in a small focus of atypical glands is not associated with an increased prediction of prostate cancer on follow-up biopsy (43%), compared with previously published data for "small focus of atypical glands" alone (approximately 45%). Because 48% of men with an initial negative biopsy and multiple follow-up biopsy procedures were found to have cancer, more than one repeat biopsy session or more extensive sampling on the first repeat biopsy procedure may be necessary to maximize the identification of cancer. This finding is similar to that found in men with atypical diagnoses in general, without a negative 34betaE12 immunohistochemical stain. Only half of all individuals with a diagnosis of 34betaE12-negative focus of atypical glands underwent repeat biopsy within 3 months. Urologists need to be educated as to the significance of an atypical diagnosis and the need for repeat biopsy. In a small focus of atypical glands on prostate biopsy, negative staining for 34betaE12 should not necessarily lead to a definitive malignant diagnosis in all cases, because almost half of these biopsies on follow-up sampling are benign.

Adenocarcinoma↗
PubMed2004

Use of interphase fluorescence in situ hybridization in prostate needle biopsy specimens with isolated high-grade prostatic intraepithelial neoplasia as a predictor of prostate adenocarcinoma on follow-up biopsy.

Isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on needle biopsy confers an increased risk of prostate carcinoma (CaP) on follow-up biopsy. The aim of this study is to determine whether paraffin-section fluorescence in situ hybridization (FISH) of specific chromosome/oncogene copy number abnormalities (CNAs) in biopsy specimens with isolated HGPIN increases the predictive value for CaP on repeat biopsy. Cases were divided into 3 groups: controls (n=8) and sextant biopsy specimens with isolated HGPIN without CaP (group A; n=11) and with CaP (group B; n=14) on follow-up biopsy. Dual-color FISH assessing c-myc, HER-2/neu, chromosome region 7q31 (D7S486), and corresponding chromosome centromeres was performed. An amplification ratio (AR) for each marker centromere was derived for each biopsy specimen, with AR ranges designated as no/low, low-intermediate, and high. Also calculated for each marker were the percentage of cells with marker amplification, hyperdiploidy, and monosomy. A composite score for each biopsy specimen was calculated based on these parameters, with a possible range of 0 to 15. The specific chromosomal oncogene CNAs were as follows: for chromosome 7/7q31, 2 of 11 (18%) in group A and 6 of 14 (43%) in group B; for chromosome 8/c-myc, 4 of 11 (36%) in group A and 9 of 13 (69%) in group B; and for chromosome 17/HER-2/neu, 10 of 10 (100%) in group A and 13 of 14 (93%) in group B. The mean composite score was 0 for controls, 2.5 for group A, and 4.7 for group B. Composite scores > or =4 for the 3 groups were 0 of 9 (0%) for controls, 1 of 11 (12%) for group A, and 8 of 14 (57%) for group B. These differences were statistically significant (P=0.015). One group A patient with a high composite score (6) had atypical small glands on follow-up biopsy at <1 year. Chromosome/oncogene CNAs are uncommon in control patients, occurring with increasing frequency and magnitude in patients with isolated HGPIN without and with follow-up CaP. Chromosome/oncogene CNAs in HGPIN are mostly of the low to intermediate level and display intercellular heterogeneity. HER-2/neu amplification is common in HGPIN with and without follow-up CaP. Chromosome 7 and 8 aneusomy and 7q31 and c-myc amplification are greater in HGPIN with follow-up CaP. Patients with isolated HGPIN and high composite score without follow-up CaP are uncommon; these patients may have a small, unsampled CaP. Although patients with HGPIN without CaP are more likely to have a low composite score, a subset of patients with follow-up CaP have low composite score, suggesting (1) mutational pathways independent of chromosomes 7, 8, and 17 and HER-2/neu, c-myc, and chromosome region 7q31 CNAs; (2) CaP derived from an independent, unsampled focus of HGPIN; or (3) CaP not derived from HGPIN.

Adenocarcinoma↗
PubMed2004

Utility of immunohistochemistry for alpha-methylacyl-CoA racemase in distinguishing atrophic prostate cancer from benign atrophy.

Small atrophic prostate cancers on needle biopsy are rare and difficult to distinguish from benign atrophy on needle biopsy. We report on a study of 23 needle biopsy specimens with small foci of atrophic prostate cancer from the consult service of one of the authors. In 19 cancer cases the atrophic component was pure; in 4 cases it was dominant with a minor (<5%) nonatrophic cancer component. These atrophic cancers and 16 cases of florid benign atrophy on needle biopsy were examined by immunohistochemistry for alpha-methylacyl-CoA-racemase (AMACR). All cases of cancer and atrophy were verified immunohistochemically with antibodies to basal cells (34betaE12 and p63). AMACR staining were scored as 1+ (5% to 25% of glands expressing AMACR), 2+ (26% to 50% of glands expressing AMACR), or 3+ (>50% of glands expressing AMACR). Positive staining was defined as staining above that of surrounding benign glands. AMACR was expressed in 69.6% of atrophic prostate cancers (3+, 11 cases; 2+, 3 cases; 1+, 2 cases); 30.4% (7 cases) of atrophic prostate cancer exhibited no AMACR expression. In the 4 cases with a few glands of ordinary (nonatrophic) prostate cancer, the nonatrophic cancer demonstrated more intense and a greater extent of AMACR staining. Fourteen cases (87.5%) of benign atrophy showed no AMACR expression. In 2 cases (12.5%) of benign atrophy, background immunostaining made it difficult to assess AMACR expression. We conclude that AMACR immunostaining alone is not sufficiently discriminatory in the differential diagnosis of atrophic prostate cancer versus benign atrophy. Atrophic prostate cancers are not as frequently or as strongly positive as ordinary prostate cancer. Using a panel of immunostains including AMACR, 34betaE12 and p63 (positive AMACR immunostaining along with negative basal cell markers) is recommended in the differentiation of atrophic prostate cancer and benign atrophy.

Adenocarcinoma↗
PubMed2004

Immunohistochemical analysis of tumor polyamines discriminates high-risk patients undergoing nephrectomy for renal cell carcinoma.

Renal cell carcinoma (RCC) is known to display a wide variation in biological behavior and clinical outcome. Although usual bioclinical prognostic parameters (eg, nuclear grade, tumor stage) are to a certain extent useful in predicting the outcome of RCC after radical nephrectomy, they now appear to be insufficient. The polyamines (spermidine, spermine, and putrescine) are ubiquitous polycations that are essential for cell proliferation. To support their excessive proliferation, cancer cells have high rates of polyamine metabolism. Indeed, malignant cells typically have higher polyamine levels than their normal counterparts. Before this report, antipolyamine antibodies that are potentially valuable tools for the in situ observation of polyamines had not been exploited in clinical conditions. In the present study, tumor tissues obtained from radical nephrectomy performed for RCC (n = 73) were immunostained with the anti-spermine monoclonal antibody Spm8-2, and the immunoreactivity was evaluated as a prognostic tool. RCC cells displayed various reactivity to the antibody Spm8-2 that translated into a heterogeneous cytoplasmic staining. The prognostic value of the labeling index (LI) on clinical outcome was correlated with the usual clinicopathologic parameters, and the cell proliferation rate was evaluated using Ki-67 labeling. Multiple correspondence analysis and ascending hierarchical classification were performed to determine significant prognostic factors. Univariate statistical survival analysis demonstrated that tumor size (P < .001), nuclear grade (P < .01), necrosis (P < .007), tumor stage (P < .004), metastasis (P < .001), Ki-67 LI (P < .0003), and Spm8-2 immunoreactivity (P < .0001) were predictors of tumor-related death. A positive correlation was found between Ki-67 LI and Spm8-2 immunoreactivity (r' = .53). Multivariate analysis revealed that only Ki-67 LI and Spm8-2 immunoreactivity were significant independent factors in patients with metastases (P < .04 and <.001, respectively) and in patients without metastases (P < .006 and <.001, respectively). Moreover, 100% of the patients with Spm8-2 immunoreactivity <10% were alive at the end of the follow-up. In terms of predictive values, Spm8-2 immunoreactivity had the highest predictive values (sensitivity, 89; specificity, 75; risk ratio, 11) of all clinicopathologic parameters. This study demonstrates that the anti-spermine monoclonal antibody Spm8-2 may be used at the time of radical nephrectomy as a reliable prognostic marker for defining RCC patients at high risk for progression.

Adult↗
PubMed2004

Atypia in inverted urothelial papillomas: pathology and prognostic significance.

Inverted papillomas of the bladder are considered benign urothelial neoplasms, based on their histology and clinical course. There are scant data on inverted papillomas with atypical features. Whether to designate them as inverted papillomas with atypia or low-grade transitional cell carcinomas with inverted features is controversial. In the present study, 11 cases of inverted papillomas with atypia and 10 controls of classic inverted papillomas without atypia were collected from 2 institutions. The inverted papillomas with atypia had the typical architectural features of inverted papillomas consisting of thin anastomosing trabeculae of urothelium growing downward into the stroma without an exophytic papillary component. The atypical areas in the current series were focal, with other areas exhibiting the benign cytology of classic inverted papillomas. Cases with atypia were subdivided into the following groups: (1) 5 cases notable for areas containing prominent nucleoli, (2) 2 cases with foci with atypical squamous features, (3) 2 cases with areas of dysplasia, approaching the level of carcinoma in situ, (4) 1 case with degenerative-appearing multinucleated giant cells, and (5) 1 case notable for nests of atypical squamous cells associated with large, atypical squamoid cells with a pagetoid appearance in addition to degenerative-appearing multinucleated giant cells. Ki67 was slightly increased in 1 case, with focal dysplasia approaching carcinoma in situ and in 1 case with prominent nucleoli (increased Ki67 in both the atypical and non-atypical areas) and in the case with atypical squamous, pagetoid, and giant cells (no increased Ki67 in the atypical components). Two of the atypical inverted papilloma cases with prominent nucleoli demonstrated an increase in p53 staining throughout the lesions. Cytokeratin (CK) 20 staining was negative in all cases of inverted papillomas. No significant increase in Ki67 staining was found in any of the 10 control cases; increased p53 staining was seen in 1 control case. CK20 staining was negative in the 10 control cases. In the 11 cases with atypia, clinical follow-up revealed no history of prior or subsequent bladder neoplasms. In the cases reviewed, most inverted papillomas with atypia did not demonstrate significantly increased cellular proliferation in comparison with inverted papillomas without atypical features. To date, there has been no association with urothelial carcinoma in the individuals diagnosed with atypical inverted papillomas. These findings suggest that these lesions are currently best classified as inverted papillomas with atypia, not as low-grade transitional carcinomas, and that they merit continued evaluation as a distinct group.

Adult↗
PubMed2004

Biopsy indication--a predictor of pathologic stage among men with preoperative serum PSA levels of 4.0 ng/mL or less and T1c disease.

OBJECTIVES: To determine the indications for biopsy among men with a prostate-specific antigen (PSA) level of 4 ng/mL or less and T1c disease and whether the reason for biopsy correlated with the final pathologic stage. It is not uncommon for men to undergo radical prostatectomy (RP) with a prostate-specific antigen (PSA) level of 4 ng/mL or less and T1c disease. METHODS: We examined the percentage of men with T1c disease and PSA level of 4.0 ng/mL or less undergoing RP over time. We identified 874 men with T1c prostate adenocarcinoma and PSA levels of 4 ng/mL or less who were treated with RP between 1994 and 2003. We excluded 72 patients who had received preoperative hormonal therapy and 86 patients for whom the reason for biopsy was unclear. The pathologic outcomes were compared between the various biopsy indication groups using analysis of variance. RESULTS: The percentage of men with T1c disease and a PSA level of 4.0 ng/mL or less has steadily increased from 0% before 1990 to 19% in 2003. Among men treated between 1994 and 2003, the most common indication for biopsy was a spike in the PSA level to greater than their reference level before biopsy (n = 471, 66%), although in all patients, the PSA level returned to 4 ng/mL or less before surgery. In 163 patients (35%), the PSA level remained elevated above the reference range and in the remaining 308 patients (65%), the PSA declined to a value below the reference range before surgery. The second most common indication for biopsy was an abnormal digital rectal examination by the referring/primary physician that, when repeated by the attending surgeon, was believed to be normal (n = 155, 22%). Abnormal PSA velocity accounted for biopsy in 68 patients (10%). Among patients with the three most common indications for biopsy, no statistically significant differences in the pathologic tumor characteristics between the groups were noted on the basis of the biopsy indication. CONCLUSIONS: One in five men undergoing RP at our institution today has T1c disease and a PSA value of 4.0 ng/mL or less. The most common indication for biopsy was an elevated PSA level above their reference range, although in most, the PSA had returned to a normal value before surgery. Regardless of the indication for biopsy, these men had favorable findings at RP. That 22% of patients underwent biopsy because of what was perceived to be an abnormal digital rectal examination underscores the need to continue to perform digital rectal examination along with PSA determination as a part of routine prostate cancer screening.

Biopsy↗
PubMed2004

Positive proximal (bladder neck) margin at radical prostatectomy confers greater risk of biochemical progression.

OBJECTIVES: To identify the prognostic significance of positive bladder neck margin as the sole positive margin after radical retropubic prostatectomy for treatment of prostate cancer. METHODS: We retrospectively analyzed the data from patients who underwent radical retropubic prostatectomy at Johns Hopkins Hospital between 1984 and 2001. Of 164 patients with positive margins, 38 had a positive margin only at the bladder neck margin and 126 had a positive margin at one or more locations separate from the bladder neck margin. RESULTS: Kaplan-Meier analyses showed that patients with a positive bladder neck margin had a greater biochemical progression risk than patients with positive margins at one or more locations other than the bladder neck margin. The 5-year actuarial risk of progression in men with positive and negative bladder neck margins was 69.8% and 33.0%, respectively. A positive bladder neck margin was statistically an independently significant predictor of progression (P = 0.001), along with the prostatectomy Gleason score (P = 0.0001) in the multivariate analysis. The hazard ratio for predicting progression for postoperative Gleason score and bladder neck positivity was 2.1 and 2.5, respectively. Serum prostate-specific antigen values, clinical stage, age, and the percentage of tumor at the bladder neck margin were not predictors of progression in either univariate or multivariate analysis. CONCLUSIONS: Patients with a positive bladder neck margin as the sole positive margin at radical retropubic prostatectomy have a greater risk of biochemical progression than patients with one or more positive margins at other locations, although not as adverse as the risk reported for those with Stage T4 disease.

Adenocarcinoma↗
PubMed2004

Characterization of minute adenocarcinomas of prostate at radical prostatectomy.

OBJECTIVES: To characterize minute prostate cancer seen at radical prostatectomy. With aggressive screening and more extensive biopsy sampling, we have increasingly seen these cancers at radical prostatectomy. METHODS: We examined radical prostatectomy specimens submitted in total for minute cancer. RESULTS: During the past 1.5 years, 78 prostates (5.2%) had either no cancer (2 cases) or contained between one and six foci of organ-confined carcinoma (76 cases) measuring 6 mm or less, with a Gleason score of 6 or less. The mean prebiopsy serum prostate-specific antigen level was 5.8 ng/mL, and 84.6% of the patients had undergone biopsy because of an elevated prostate-specific antigen level. Of these patients, 40% had had either benign or atypical diagnoses on prior biopsies, and 43% had only minute (0.5 mm or less) foci of carcinoma on biopsy. The radical prostatectomy specimens had a mean of two cancer foci measuring, on average, 3 mm in the greatest dimension. In 85% of the cases, the side of the positive biopsy matched the side of the carcinoma found at radical prostatectomy; 81.5% of cases had high-grade prostatic intraepithelial neoplasia immediately adjacent to the cancer. CONCLUSIONS: The incidence of minute carcinoma of the prostate has increased from 0.5% in 1988 to 5.2% in the current study. The patients often had moderately increased prostate-specific antigen levels and minute foci of carcinoma on biopsy. These small tumors at radical prostatectomy are usually discovered by fortuitous biopsy that is often preceded by other biopsies with noncancerous diagnoses. Patients with the above clinical and biopsy findings should be counseled about the possibility of finding only minute foci of carcinoma at radical prostatectomy and may want to consider watchful waiting.

Adenocarcinoma↗
PubMed2004

Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy.

The diagnosis of limited adenocarcinoma of the prostate is one of the more difficult challenges in surgical pathology. This paper highlights the methodological approach to diagnosing limited cancer, based on a constellation of features more commonly present in adenocarcinoma than benign glands. In assessing small foci of atypical glands on needle biopsy, one looks for differences between the benign glands and the atypical glands in terms of nuclear features, cytoplasmic features, and intraluminal contents. Only a few features, such as glomerulations, mucinous fibroplasia (collagenous micronodules), and perineural invasion are diagnostic in and of themselves for prostate cancer. Immunohistochemistry may be a useful adjunct in the diagnosis of limited adenocarcinoma of the prostate, although as with any immunohistochemical studies, there are problems with both sensitivity and specificity. Basal cell markers, such as high molecular weight cytokeratin and more recently, p63, highlight basal cells found in benign glands, yet are absent in adenocarcinoma of the prostate. However, not all benign glands label uniformly with basal cell markers. Certain mimickers of adenocarcinoma of the prostate are even less frequently labeled uniformly with these stains. Consequently, negative staining in a small focus of atypical glands for basal cell markers is not diagnostic of adenocarcinoma of the prostate. More recently, a marker has been identified that relatively selectively labels adenocarcinoma of the prostate. AMACR will label the cytoplasm of approximately 80% of limited adenocarcinoma of the prostate cases on needle biopsy. In positive cases, not all of the glands will be positive and those that are positive are often not intensely positive. Certain variants of adenocarcinoma of the prostate that are a little more difficult to recognize, such as foamy glands adenocarcinoma, pseudohyperplastic adenocarcinoma, and atrophic adenocarcinoma, are labeled with AMACR in only approximately 60-70% of cases. In addition to problems with sensitivity, AMACR is not entirely specific for adenocarcinoma, and will label almost all cases of high-grade prostatic intraepithelial neoplasia, some foci of adenosis, and even some entirely benign glands. Finally, this paper will briefly cover the significance of atypical or suspicious prostate needle biopsies, and how to report the key diagnostic and prognostic information on needle biopsy.

Adenocarcinoma↗
PubMed2004

Paraganglioma of the urinary bladder: a lesion that may be misdiagnosed as urothelial carcinoma in transurethral resection specimens.

Paraganglioma of the urinary bladder is a rare tumor with characteristic histologic and immunohistochemical features. However, in our experience, it may be misdiagnosed as urothelial cancer because of 1) its frequent involvement of the muscularis propria; 2) morphology that may suggest urothelial cancer in transurethral resection specimens, particularly if there are artifactual changes induced by that procedure; 3) failure of pathologists to include it in their differential diagnosis when evaluating a bladder tumor; and 4) only a minority of the cases are associated with symptoms that might prompt consideration of the diagnosis. Distinction between paraganglioma and urothelial cancer is important because of likely different therapeutic options. In this report, we describe our experience with the histopathology of paragangliomas of the urinary bladder with emphasis on the histologic features that have led to their being misdiagnosed as conventional urothelial cancer and, most importantly, those that will help pathologists recognize this rare tumor of the bladder. Fifteen cases of paraganglioma of the urinary bladder were studied, 11 of them consult cases. They affected patients (8 male, 7 female) with a mean age of 49.5 years; only two had symptoms suggestive of the diagnosis, including hypertension during cystoscopy and episodic headache. Three consult cases were submitted with a diagnosis of "transitional cell carcinoma" and 4 with a diagnosis only of "bladder tumor." Histologically, "zellballen" and diffuse patterns were present in 12 (80%) and 3 (20%) of the cases. A delicate fibrovascular stroma was obvious in 14 (93%) cases. Other patterns included irregular nests and pseudorosette formation. Tumor necrosis, significant cautery artifact, and muscularis propria invasion were present in 1 (7%), 3 (20%) cases, and 10 (67%) cases, respectively. All 15 tumors were composed of large polygonal cells with abundant granular cytoplasm. Focal clear cells were present in 3 (20%). The nuclei were mostly uniform, although occasional pleomorphic nuclei were seen in 6 (40%) cases, and 2 (13%) had frequent pleomorphic nuclei. Mitoses were rare overall, and no abnormal mitotic figures were found. The major histologic features that led to misdiagnosis included a diffuse growth pattern, focal clear cells, necrosis, and muscularis propria invasion, with significant cautery artifact compounding the diagnostic problems. Immunohistochemically, 2 of 2 tumors were positive for neuron-specific enolase, 9 of 10 tumors for chromogranin, and 2 of 3 tumors for synaptophysin; 3 of 3 tumors were negative for cytokeratin and 1 of 1 tumor negative for HMB-45. Paraganglioma of the urinary bladder may be misdiagnosed as urothelial cancer, but a careful search for the characteristic histologic features and, if necessary, supportive immunohistochemical studies, should lead to a correct diagnosis.

Adolescent↗
PubMed2004

How often does alpha-methylacyl-CoA-racemase contribute to resolving an atypical diagnosis on prostate needle biopsy beyond that provided by basal cell markers?

BACKGROUND: Alpha-methylacyl-CoA-racemase (AMACR), a recently discovered tumor marker for prostate cancer, is being used increasingly in conjunction with hematoxylin and eosin (H&E) histology and basal cell markers in the workup of difficult prostate needle biopsies. However, it is not known how often a positive AMACR staining is used merely to support a malignant diagnosis that could otherwise be established based on routine H&E histology and negative basal cell staining. METHODS: This study included 307 prostate needle biopsies that were sent to us for consultation diagnosed as "atypical" by contributing pathologists. Immunohistochemistry for AMACR, high molecular weight cytokeratin, and p63 was performed. AMACR staining intensity was graded as negative, weak, moderate, and strong. Only staining that was significantly stronger than that of background benign glands was considered positive. An "expert review" diagnosis was first rendered as benign, atypical, or cancer based on the H&E-stained section and basal cell marker stains without the knowledge of AMACR expression. The AMACR stains were then reviewed and a final diagnosis was rendered. RESULTS: A total of 215 cases had a final diagnosis of cancer following evaluation of the H&E-stained section, basal cell markers, and AMACR. Of these 215 cases, 176 (81.9%) were positive and 39 (18.1%) were negative for AMACR staining. Of 81 cases with a final diagnosis of atypical following review of all material, 42 (51.9%) were positive and 39 (48.1%) were negative for AMACR staining. When AMACR staining was negative, in no case was the initial cancer, atypical, or benign diagnosis (based on routine histology and negative basal cell markers) changed based on AMACR stain results. Of 115 cases called atypical after expert review, 76 were positive for AMACR; of these 76 cases, 34 (44.7%) were changed to a final diagnosis of cancer. AMACR expression was positive, with moderate and strong staining in 30 of the 34 cases (88.2%), for which the immunohistochemical result converted the expert review atypical diagnosis to a final cancer diagnosis. Of these 34 cases, 11 underwent radical prostatectomy, and cancer was found in all cases. Three additional patients underwent repeat biopsy, and cancer was present in the repeat biopsy in 2 patients. The cases whose diagnosis was changed from "atypical" on expert review to cancer were all highly suspicious for cancer based on H&E histology and negative basal cell markers, yet a definitive cancer diagnosis could not be established because of small size, insufficient cytologic atypia, or biopsy artifact. CONCLUSION: Interpretation and use of AMACR staining should be executed with caution. A negative AMACR stain can be seen in approximately 18% of cases considered to be cancer based on H&E stain combined with negative basal cell markers. A positive AMACR staining converted an atypical diagnosis, based on suspicious histology and negative basal cell marker stains, to cancer in approximately 10% (34 of 307) of cases thought to be atypical by contributing pathologists and in approximately 50% (34 of 76) of cases thought be atypical on expert review by a specialist in genitourinary pathology.

Biomarkers↗
PubMed2004

The prognostic significance of tertiary Gleason pattern 5 in radical prostatectomy specimens.

In the Gleason grading system for prostatic cancer only the two most prevalent patterns are reported, although a third (tertiary) pattern grade may be present. We compared the pathologic stage of 227 radical prostatectomies with tertiary pattern 5 to the pathologic stage of 604 radical prostatectomies lacking a tertiary component. Gleason score 3 + 4 tumors with a tertiary pattern of 5 were more likely to present with higher stage disease than those Gleason score 3 + 4 tumors without a tertiary component (P = 0.012) and at a stage similar to Gleason score 3 + 5 tumors. Gleason score 4 + 3 tumors with a tertiary pattern of 5 were less likely to be organ-confined than Gleason score 4 + 3 tumors (P = 0.02) and less likely to have lymph node metastases than Gleason score 4 + 4 tumors (P = 0.027). However, Gleason score 4 + 4 with a tertiary pattern of 5 were indistinguishable from Gleason score 4 + 4 tumors. The relative effects of a tertiary pattern of 5 were greatest when the primary and secondary stages were low but become obscured by the already aggressive nature of advanced primary and secondary patterns. Therefore, except for very high-grade tumors, tertiary scoring of prostatic adenocarcinoma at radical prostatectomy should be reported as it has prognostic significance.

Adenocarcinoma↗
PubMed2004

High-grade prostatic intraepithelial neoplasia on needle biopsy: risk of cancer on repeat biopsy related to number of involved cores and morphologic pattern.

The importance of isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on needle biopsy is its association with synchronous invasive carcinoma. The relevance of this relationship has been called into question in recent years. In our study, we examined whether the histologic subtype of HGPIN (ie, tufting, micropapillary, cribriform, flat) and/or the number of core biopsies involved by HGPIN was predictive of a subset of men who were at higher risk of having invasive carcinoma on follow-up biopsies. We examined 200 sets of needle biopsies with a diagnosis of isolated HGPIN. Patient age ranged from 46 to 90 years (mean 66.4 years). The breakdown of the histologic subtypes of HGPIN is as follows: tufting 59%, micropapillary 34.3%, cribriform 6.2%, and flat 0.5%. A total of 132 patients (66%) had follow-up biopsies. Prostatic adenocarcinoma was identified in 28.8% of patients with 89.5% of cancers identified on the first two follow-up biopsies. For men that had two or more cores with HGPIN on the initial biopsy, 35.9% eventually had cancer on follow-up whereas men with only single core involvement had cancer in 22% of cases. Men with tufting/flat HGPIN on the initial biopsy had cancer on follow-up in 31.9% of cases, whereas the micropapillary/cribriform subtype was associated with cancer in 22% of follow-up biopsies. The histologic findings on the first repeat biopsy can be quite informative as to the risk of synchronous invasive carcinoma. Of the men with HGPIN on the first repeat biopsy, 32% eventually had cancer on follow-up. Additionally, if multiple cores were involved by HGPIN on the first repeat biopsy, the risk of finding cancer was 50%, regardless of single or multiple core involvement on the initial biopsy. Men with a benign diagnosis on the first repeat biopsy had a 14% risk of having cancer on follow-up. These data indicate that the multiple core involvement by HGPIN, both on initial and first repeat biopsy, defines a subset of men that are at increased risk of harboring synchronous invasive carcinoma. The histologic subtype of PIN does not appear to be as informative.

Adenocarcinoma↗
PubMed2004

Radiation or chemotherapy cystitis with "pseudocarcinomatous" features.

BACKGROUND: The features of radiation or chemotherapy cystitis mimicking invasive urothelial cancer are not widely known. DESIGN: A search of the consultation files from our institution between January 1996 and September 2003 identified 20 patients with bladder biopsies showing cystitis mimicking invasive urothelial cancer. RESULTS: The mean age at diagnosis was 69 years (range, 40-85 years); 80% were males. Complete history was not available in 1 patient. Seventeen patients had a history of pelvic irradiation (15 prostate cancer and 2 endometrial cancer). Two patients had systemic chemotherapy (1 metastatic colon cancer and 1 mixed connective tissue disease). All patients presented with hematuria. The mean time from radiation and/or chemotherapy to presentation was 27 months (range, 0-84 months). All cases showed epithelial proliferation that mimicked invasive cancer within the lamina propria, with marked proliferation seen in 45% of cases. Mild to moderate nuclear pleomorphism was seen in all cases. A characteristic feature was the presence of pseudoinvasive urothelial nests wrapping around the vessels associated with fibrin deposition. Most cases did not show any mitoses (75%). Ulceration was seen in 39% of cases. All cases showed some degree of hemorrhage, fibrin deposition and fibrin thrombi, fibrosis, and acute and chronic inflammation, with hemosiderin identified in 60% of cases. Edema and vascular congestion were common features (95% and 80%, respectively). Thickened vessels and vascular changes associated with radiation injury were identified in 75% of cases. Seventeen patients were followed for a mean of 9 months (range, 0.25-37 months), and none developed bladder cancer. CONCLUSIONS: Radiation or chemotherapy cystitis can show epithelial proliferations that may be confused with invasive urothelial carcinomas. Other findings characteristic of radiation or chemotherapy cystitis, such as hemorrhage, fibrin, and vascular changes, are often seen in association with the epithelial proliferations and are helpful in distinguishing it from invasive cancer. Pathologists must be aware that these changes may be seen with a remote radiation or chemotherapy history, where this information may not be provided or known at the time of the biopsy evaluation.

Adult↗
PubMed2004

ALK-1 expression in inflammatory myofibroblastic tumor of the urinary bladder.

Inflammatory myofibroblastic tumor (IMT) of the bladder is an uncommon myofibroblastic spindle cell proliferation. Because of its cytologic features and infiltrative nature, it may be difficult to distinguish histologically from sarcomatous proliferations such as sarcomatoid urothelial carcinoma, leiomyosarcoma, and embryonal rhabdomyosarcoma. Recently, anaplastic lymphoma kinase (ALK) gene translocations or ALK protein expression in IMT has been reported, especially in patients of relatively young ages. However, there are only a few reports mentioning IMT of the bladder. We sought to determine the frequency of ALK expression among IMTs of the urinary bladder. We examined 16 cases of IMTof the bladder in 14 patients to elucidate the incidence of ALK-1 expression by immunohistochemistry and its diagnostic usefulness. The age of patients with IMT ranged from 18 to 76 years, with an average age of 42.8 years. The tumors from 10 of 14 patients (12 of 16 cases) were positive for ALK-1. ALK-1-positive cases ranged in age from 18 to 73 years (mean, 39.2 years; median, 38 years) and ALK-1-negative cases from 41 to 76 years (mean, 41.5 years; median, 44.5 years). Two locally recurrent cases were positive for ALK-1 in both the primary and recurrent lesion. ALK-1 immunostaining was detected only in the cytoplasm, with granular or subplasmalemmal linear features, suggesting ALK gene translocation. ALK-1 immunostaining was also performed in 8 sarcomatoid urothelial carcinomas, 5 genitourinary leiomyosarcomas, and 2 stromal tumors of uncertain malignant potential of the prostate, all of which were negative. These results support that ALK-1 immunostaining is useful to differentiate IMT from other malignant spindle cell neoplasms of the bladder. There were no histologic differences between ALK-1 positive and negative IMTs.

Activin Receptors, Type I↗
PubMed2004

Urothelial papilloma of the bladder: a review of 34 de novo cases.

BACKGROUND: Urothelial papilloma of the bladder is an uncommon entity when using restrictive diagnostic criteria. DESIGN: We retrospectively studied 34 patients who were diagnosed with urothelial papilloma of the bladder using the criteria of the 1998 WHO/ISUP classification system. Six cases were in-house and the remaining 28 were referred from other institutions as consults to one of the authors. In all cases, the diagnosis of papilloma was the first manifestation of urothelial neoplasia. RESULTS: The mean age of the patients at diagnosis was 57.8 years (range, 23-87 years). The male-to-female ratio was 2.4:1 (24 males and 10 females). The tumor size averaged 3.3 mm (range, 1-20 mm; median, 2 mm). Simple papillary fronds were seen in all cases; in 5 cases the additional finding of secondary budding off of small fronds from larger ones was also seen. In all cases, the fronds had a round morphology; yet in 4 cases elongated fronds were also noted. In 5 cases, dilated lymphatics within the fibrovascular fronds were apparent. One case had foamy histiocytes within the fibrovascular stalks. In all cases, the lining consisted of normal-appearing urothelium without hyperplasia, dysplasia, and/or mitotic figures. Some of the distinctive histologic features seen were changes in the umbrella cells: vacuolization (n = 4), prominence with cytologic atypia (n = 2), eosinophilic syncytial morphology (n = 1), apocrine-like morphology (n = 1), and mucinous metaplasia (n = 1). Follow-up was available in 26 cases with a mean follow-up for those without evidence of progression of 28.9 months (range, 3-127 months). Three patients (8.8%) developed recurrent papilloma 4, 15, and 18 months after the initial diagnosis of papilloma; 1 of these patients also showed progression to noninvasive low-grade urothelial carcinoma at the time of recurrence (15 months). Three patients (8.8%) progressed to higher-grade disease: 2 to noninvasive low grade urothelial carcinoma (11 and 15 months after the original diagnosis) and 1 to a papillary urothelial neoplasm of low malignant potential at 104 months and a noninvasive low-grade urothelial carcinoma at 141 months from the initial diagnosis of papilloma. None of the patients demonstrated progression to either lamina propria (T1) or muscularis propria (T2) invasion. Two patients died of unrelated causes. None of the patients died of bladder cancer. CONCLUSION: Patients with urothelial papillomas have a low incidence of recurrence and rarely progress to develop urothelial carcinoma. It seems reasonable to avoid labeling these patients as having cancer. It remains to be studied whether and when patients with papillomas who have no evidence of recurrence or progression no longer need to be followed.

Adult↗