A clinicopathologic analysis of urothelial carcinomas diagnosed on prostate needle biopsy.

No data exist on urothelial carcinoma diagnosed on prostatic needle biopsy. We reviewed 21 cases (19 consultations) of urothelial carcinoma diagnosed on prostate needle biopsy from 1991 to 1998. In 13 of 21 (62%) cases, urothelial carcinoma showed in situ urothelial carcinoma involving prostatic ducts and acini (DCIS) only; 6 of 21 (29%) cases showed both DCIS and invasive carcinoma and 2 of 21 (9%) cases showed widespread stromal invasion without DCIS. In contrast to prostatic adenocarcinoma, cases exhibited greater nuclear pleomorphism, variably prominent nucleoli, increased mitoses, and necrosis. Immunostains for PSA and PSAP were negative in all 18 cases studied. CK7 was positive in 14 of 16 cases, CK20 was positive in 13 of 16 cases, and 34betaE12 was positive in 11 of 17 cases. A total of 7 of 17 (41%) men had no prior or subsequent history of urothelial carcinoma outside the prostate, 6 of 17 (35%) had concurrent urothelial cell carcinomas of the bladder (1 with extensive carcinoma in situ [CIS] at cystoprostatectomy), 2 of 17 (12%) had a prior urothelial cell carcinoma, and 2 of 17 (12%) developed urothelial cell carcinomas outside the prostate subsequent to the needle biopsy diagnosis. A total of 14 of 18 (78%) men had an elevated prostate specific antigen (PSA), abnormal digital rectal examination, or abnormal ultrasound suggestive of prostatic adenocarcinoma. Follow-up information was available in 17 cases. Six of nine (67%) patients with DCIS eventually died of disease (DOD) (2 with prior urothelial cell carcinoma, 1 with no prior or subsequent history, 3 without information), and 3 of 9 (33%) patients with DCIS were alive with residual disease (AWD). Of the patients with invasive carcinomas, 4 of 8 (50%) were DOD, 2 of 8 (25%) were AWD, and 2 of 8 (25%) were alive without evidence of disease. All men who are alive were treated aggressively with surgery and often adjuvant chemotherapy-radiation. Overall, 10 of 17 (59%) men were DOD with a mean survival after diagnosis of 23.2 months (2-72 months). The diagnosis of urothelial carcinoma on prostate needle biopsy is difficult because it is rare and clinically can mimic prostatic adenocarcinoma; often there is no history of urothelial carcinoma elsewhere. Although the prognosis is poor even with only apparent DCIS, histologic recognition is essential because the only opportunity for improved outcome is early and aggressive treatment.

Infarct of the prostate gland: experience on needle biopsy specimens.

Prostatic infarcts are uncommon and in the past have only been reported on transurethral resections of the prostate. We reviewed 13 consults and 2 nonconsult cases of needle biopsies showing prostatic infarcts from two institutions. The incidence of infarcts on biopsy were 2 in 2958 (0.07%) and 1 in 108,586 (0.0009%) in our nonconsult cases. Men averaged 71 years of age (range, 57-84 yrs). No relationship was seen with histories of hypertension, diabetes, atherosclerotic coronary vascular disease, recent surgery, and steroid use. Four of 12 men with available information had acute urinary retention, with markedly enlarged prostates in three (90 cc, 92 cc, 94 cc); two of these men had hematuria. An additional two men also had large glands (84 cc, 150 cc), one also with hematuria. Of eight men without acute urinary retention, three had sudden prostate-specific antigen (PSA) rises (increases of 199 ng/mL, 219 ng/mL, 287 ng/mL). Infarcts were usually an isolated focus on one core and varied from 1 mm to 11 mm (mean, 6.3 mm). Six cases showed earlier-aged infarcts with coagulative necrosis and recent hemorrhage and six showed intermediate-aged infarcts with reactive stroma and epithelium without necrosis. In the remaining three cases, there were remote infarcts characterized by replacement of the stroma by dense fibrosis with metaplastic glands. Adjacent tissue revealed reactive nests of immature squamous metaplasia in 14 of 15 cases with visible nucleoli (12 cases), squamous atypia (7 cases), and mitoses ranging from 1-10 (7 cases). Pathologists sent in 10 of 13 consult cases (77%) for problems with interpretation of the infarcts; remaining consults had other pathology of concern. One case was misdiagnosed as urothelial cancer. Features helpful in recognizing infarcts' benign nature were cyst formation containing cellular debris with or without neutrophils (73%), corpora amylacea (20%), and rings of collagen around squamous islands (40%). Infarcts are typically, although not exclusively, found in large prostates and may result in sudden rises in serum PSA. Infarcts' distinctive histology must be recognized and distinguished from necrosis resulting from infection and prior cryotherapy, as we have seen such misdiagnoses. Pathologists' awareness of prostatic infarcts on needle biopsy and their potential for atypical histology can prevent the misdiagnosis of cancer.

Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy.

The diagnosis of prostate cancer on needle biopsy is based on a constellation of histologic features. There are, however, three histologic findings that are diagnostic of prostate carcinoma: perineural invasion (PNI), mucinous fibroplasia, and glomerulations. We prospectively identified core needle biopsies during a 5-month period in which one of these three entities was the key diagnostic feature of carcinoma within the biopsy specimen. Of 1480 consult cases reviewed, the following were key features to the diagnosis of very limited carcinoma: PNI (n = 9; 0.6%), mucinous fibroplasia (n = 2; 0.1%), and glomerulations (n = 0). To assess the incidence of PNI as the key feature, we also analyzed reports from Dianon during a 1-year period. Of approximately 16,300 Dianon needle biopsies with cancer, 12(0.07%) cases had PNI as the key diagnostic feature. Six of these 12 cases were also consult cases. Of the total of 15 cases with PNI, cancer was limited with 11 of the cases showing involvement of only one nerve. The median number of glands per nerve was five (range, 1-15). In addition to PNI, malignant cytologic features included amphophilic cytoplasm in 11 of 11 assessable cases and nuclear enlargement and hyperchromasia in 11 of 15 cases. Other malignant features were limited. Twelve cases showed rare to no visible nucleoli. Two cases had eosinophilic intraluminal debris. Blue mucin, crystalloids, and mitoses were absent in all cases. Nine of the 15 cases of PNI and the two cases of mucinous fibroplasia were verified as carcinoma with immunohistochemistry using high molecular weight cytokeratin. In rare cases, PNI is virtually the sole finding necessary to establish the diagnosis of carcinoma on needle biopsy. Although mucinous fibroplasia and glomerulations are also considered diagnostic of carcinoma, their occurrence alone without more conventional forms of carcinoma is even more rare.

Adenocarcinoma of the prostate in men younger than 40 years of age: diagnosis and treatment with emphasis on radical prostatectomy findings.

OBJECTIVES: Prostate cancer is rarely diagnosed in men younger than 40 years of age. It is thought, although not documented, that these tumors behave particularly aggressively. METHODS: We studied 87 men younger than 40 years old who underwent prostate needle biopsy and were from three populations: (a) 71 cases (63 benign, 7 cancer) from Dianon Systems; (b) 9 needle biopsies with cancer sent to one of us (J.I.E.) in consultation; and (c) 7 men with cancer who came to Johns Hopkins for consultation. RESULTS: The median age of men with a benign biopsy was 35 years (mean 33.9, range 22 to 39); the median age of men with cancer was 38 years (mean 35.9, range 22 to 39) (P = 0.004). The most common indications for biopsy were abnormal digital rectal examination (DRE) (n = 61); elevated prostate-specific antigen (PSA) (n = 14), and inflammatory symptoms (n = 12). Other reasons cited included hematuria, abnormal ultrasound, pain, ejaculatory problems, obstructive symptoms, and family history of prostate cancer. The median PSA was 2.6 ng/mL (mean 4.8, range 0.3 to 66) for all men, 1.2 ng/mL (mean 3.4, range 0.3 to 19.9) for benign cases, and 4.4 ng/mL (mean 8.7, range 2.1 to 66) for cancer (P = 0.0004). Abnormal DRE was not predictive of cancer. Of the 55 patients whose family history was known, 40 men had no family history of prostate cancer, and of those, only 6 (15%) had cancer. Of the 1 5 patients with a family history of cancer, 6 (40%) were found to have cancer on biopsy (P = 0.05). Of the 23 patients with cancer, 3 were lost to follow-up, 1 was treated with hormones, and 3 chose watchful waiting. The remaining 16 patients underwent radical prostatectomy and had diverse pathologic findings. Tumor volume ranged from 0.01 to 6.35 cc. Pathologic stage was pT2 in 9 cases and pT3 in 7 cases (2 with positive pelvic lymph nodes). In 14 men, serum PSA values were available: of 4 men with PSA greater than 10 ng/mL, all had Stage pT3, and of 10 men with PSA less than 10 ng/mL, 3 had Stage pT3. CONCLUSIONS: Young men who are candidates for radical prostatectomy have potentially curable disease, particularly if PSA at the time of diagnosis is less than 10 ng/mL.

Repeat biopsy strategies for men with atypical diagnoses on initial prostate needle biopsy.

OBJECTIVES: To evaluate trends in prostate sampling and the efficacy of different sampling methods to detect prostate cancer in subsequent biopsies after an initial "atypical" biopsy. METHODS: We searched Dianon Systems from March 1994 to June 1996 for cases with an initial atypical diagnosis on biopsy and that had repeat biopsies. The files of Dianon and Johns Hopkins Hospital (JHH) were also analyzed for cases with an initial atypical diagnosis on sextant biopsy and for repeat sextant biopsies showing cancer. RESULTS: Of the 1 24 Dianon cases in which we knew the site (sextant, left, right) of the initial and subsequent biopsies, 56 cases (45.2%) were cancer on repeat biopsy; in cases with repeat sextant biopsies, cancer was detected 59.3% of the time. There were 54 cases in which the initial biopsy was atypical and the repeat biopsy was cancer, where both sets of biopsies were sextants (44 Dianon, 10 JHH). Of the 46 cases with only one initial atypical site, the cancer was in the same sextant site as the previously atypical biopsy in 47.8% of cases; cancer was detected in 84.8% of the cases in either the same sextant, adjacent ipsilateral, or adjacent contralateral sites. CONCLUSIONS: Great variation exists in how urologists sample prostates both initially and after an atypical diagnosis. Of the 149 Dianon cases, only 32 were sextant to sextant biopsies, and another 32 were consistently left and right to left and right. Our study shows that in subsequent biopsies after an atypical biopsy, the chance of detecting cancer greatly increases with biopsy not only of the atypical site, but adjacent contralateral and adjacent ipsilateral areas as well. We advocate the precise labeling of the initial biopsies so that rebiopsy of atypical cases can be directed in a more concentrated fashion into the region of the initial atypical biopsy. Other sites should be biopsied as well, which urologists did not always do, because cancer may also be found away from the initial atypical site.

Accuracy of biopsy Gleason scores from a large uropathology laboratory: use of a diagnostic protocol to minimize observer variability.

OBJECTIVES: To examine the correlation of biopsy Gleason scores with radical prostatectomy specimens from a laboratory that uses protocols designed to minimize observer variability. This protocol mandates consensus case review of all nonbenign cases. METHODS: Between August 24, 1993 and June 26, 1997, 106 patients who underwent radical prostatectomy at Johns Hopkins Hospital, Baltimore, Maryland had their prostate cancer diagnosed and graded at one laboratory (DIANON Systems). We analyzed the Gleason scores from the biopsy and radical prostatectomy specimens. RESULTS: Exact correlation existed between biopsy and radical prostatectomy Gleason scores for 72 (68%) cases; 103 (97%) correlated within 1 grade, all cases correlated within 2 grades; 26 (25%) biopsies were undergraded and 8 (8%) were overgraded. Positive predictive values for biopsy Gleason scores 5, 6, and 7 were 66%, 67%, and 71%, respectively. Grouped Gleason scores (well differentiated [2 to 4], moderately differentiated [5, 6], moderately to poorly differentiated [7], and poorly differentiated [8 to 10]) correlated exactly for 74 (70%) cases and within 1 group for all cases. Patient age, digital rectal examination results, total number of positive cores, and maximum percentage of tumor on biopsy did not affect correlation, but prostate-specific antigen (PSA) levels did affect correlation (exact correlation 96% when the PSA level was less than 5 ng/mL; 50% when the PSA level was 11 ng/mL or greater, P <0.01). CONCLUSIONS: The combination of experience and the protocol described minimizes intra- and interobserver variability, thereby improving the predictive value of biopsy Gleason grading. Biopsy and radical prostatectomy Gleason scores correlate more poorly when the PSA level is high (11 ng/mL or greater) than when the PSA level is low (less than 5 ng/mL).

Granulomatous prostatitis on needle biopsy.

OBJECTIVE: To assess pathologic findings of granulomatous prostatitis (GP) on needle biopsy. DESIGN: Ninety-four cases of granulomatous prostatitis were culled from 25,852 (incidence 0.36%) consecutive men who underwent needle biopsy; clinical correlations were obtained for 75. Cases were categorized as nonspecific (NSGP, 77.7%), infectious (IGP, 18.1%), or indeterminate (4.3%) granulomatous prostatitis based on histologic and clinical criteria. SETTING: Consecutive cases from a large commercial laboratory and consultation cases. RESULTS: All cases of IGP had a history of prior bacillus Calmette-Guerin therapy for transitional cell carcinoma. Histologically, 57% of NSGP cases mimicked infection and 4% mimicked cancer. Caseating necrosis was identified in 76% of cases of IGP. Significant numbers of eosinophils were found in 68% of NSGP cases, but in only 12% of IGP cases. In no case was eosinophilia documented in peripheral blood. Multinucleated giant cells were absent or rare in 69% of NSGP cases. Significant numbers of neutrophils were found in 53% of NSGP cases, but in only 29% of IGP cases. At the time of biopsy, cancer was clinically suspected in 55% of cases categorized as NSGP and 73% categorized as IGP. Serum prostate-specific antigen ranged from less than 0.5 ng/mL to 114 ng/mL (mean 12.7 ng/mL) in NSGP and from 0.9 ng/mL to 9.7 ng/mL (mean 4.2 ng/mL) in IGP. Digital rectal exam was abnormal in 69% and 91% of NSGP and IGP cases, respectively. Transrectal ultrasound was abnormal in 77% and 100% of NSGP and IGP cases, respectively. There was no correlation between the extent of core involvement with either clinical impression, prostate-specific antigen levels, transrectal ultrasound, or digital rectal exam. Thirty additional granulomatous prostatitis cases on needle biopsy were obtained from the consultation files of one of the authors. The major difference in this group was a higher percentage of cases histologically mimicking cancer (20%); two cases were misdiagnosed by the referring pathologist as high-grade cancer. CONCLUSIONS: While NSGP is the most common granulomatous prostatitis seen on needle biopsy, bacillus Calmette-Guerin granulomas are not seen infrequently. Lesser known histologic features of NSGP were the frequent finding of neutrophils and eosinophils and infrequent multinucleated giant cells. Granulomatous prostatitis may be clinically indistinguishable from cancer, and NSGP may also histologically mimic carcinoma.

The significance of intraluminal crystalloids in benign prostatic glands on needle biopsy.

Based on data from autopsy, radical prostatectomy, and cystoprostatectomy specimens, it has been suggested that the finding of intraluminal crystalloids in benign glands on needle biopsy may indicate a concurrent carcinoma; therefore, repeat biopsy is recommended. We studied data from 56 consecutive needle biopsies from the Johns Hopkins Hospital and Dianon Systems in which the diagnosis of intraluminal crystalloids in benign glands was rendered and follow-up data were subsequently obtained. Cases in which crystalloids were present in glands suspicious for cancer, in glands of high-grade prostatic intraepithelial neoplasia, or in adenosis were excluded from the study. Follow-up data included repeat biopsy results and serum prostatic specific antigen levels. Of the 56 men, 31 (55%) had repeat biopsy (two underwent transurethral resection of the prostate [TURP]); the remaining men were either noncompliant or had medical conditions precluding subsequent biopsy. Of the 31 men who underwent repeat biopsies, 23 (74%) had benign diagnoses, one (3%) had high-grade prostatic intraepithelial neoplasia, and seven (23%) had adenocarcinoma. There was no difference in serum prostate-specific antigen values between those with and without cancer on repeat biopsy. In a control population of men with a benign first biopsy not showing crystalloids, the incidence of cancer on repeat biopsy was 16.2%, which was not statistically significantly different from the incidence found in our study group. We conclude that men with prostate biopsy results showing benign glands with crystalloids are at no significantly higher risk of having cancer on repeat biopsy than if crystalloids were not present.

Diagnosis of Cowper's glands on prostate needle biopsy.

The presence of normal anatomic structures may be a source of confusion to the pathologist examining prostatic needle biopsies. The morphologic features of Cowper's (bulbourethral) glands incidentally biopsied during transrectal sampling of the prostate have not been described. We reviewed seven cases of Cowper's glands found in prostatic core biopsy specimens. Sections containing Cowper's glands were stained with hematoxylin-eosin, mucicarmine, periodic acid-Schiff's-digest (PAS-D), and antibodies directed at high-molecular-weight cytokeratin (HMWCK), prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), Ulex europaeus agglutinin, and muscle-specific actin. Histologically, Cowper's glands resemble mucinous minor salivary glands entrapped within fascicles of muscle. Lobules of acini composed of cells distended with mucin (mucicarmine and PAS-D positive) were admixed with ducts and ductules composed of hybrid cells with both mucinous and ductular epithelial features. The HMWCK was strongly reactive with the ductular epithelium and demonstrated an attenuated cell lining at the periphery of lobules. The mucinous cytoplasm reacted with U. europaeus, whereas the ductal elements failed to stain. PSAP stains were negative, with PSA positive in most cases. Muscle-specific actin was positive in three cases. Cowper's glands occasionally may be sampled by transrectal needle biopsy. Recognition of this anatomic structure will allow discrimination from low-grade prostatic adenocarcinoma, foamy gland carcinoma, mucinous metaplasia of prostate glands, and atypical glands of undetermined significance.

Cell proliferation and apoptosis in prostate cancer--correlation with pathologic stage?

Gleason grade, especially at low and high ends of the spectrum, is a known predictor of pathologic stage. What are needed are predictors of stage with Gleason sum 5 to 7 tumors, which encompasses the majority of clinically organ-confined tumors. In this study, we analyzed whether cell proliferation and apoptosis (programmed cell death) were correlated with stage in men with clinically organ-confined Gleason sum 6 to 7 cancer. We studied 98 radical prostatectomies with the following pathologic stages: organ-confined disease (n = 28); capsular penetration (n = 28); seminal vesicle invasion (n = 21); and pelvic lymph node metastases (n = 21). Histological sections from the radical prostatectomies were stained for cell proliferation using MIBI antibody (Ki-67) and for apoptosis using the TUNEL technique. The extent of staining was recorded as the number of positive cells per 1000 cells. Overall daily growth (kp) was calculated as: kp = (ki/2) - (apoptosis/0.5), based on the time of prostate cancer to undergo mitosis and apoptosis per day. Using logistic regression analysis, pathologic stage did not correlate with cell proliferation, apoptosis, or overall daily growth. These parameters also did not distinguish between Gleason sum 6 and Gleason sum 7 tumors. We supplemented these cases with examples of Gleason sum < or = 4 and Gleason sum > or = 8 to study cell proliferation and cell death in the full spectrum of Gleason grades. There was a significant difference (P = 0.005) in cell proliferation between Gleason sum > or = 6 and Gleason sum < or = 4 tumors, but apoptosis and daily growth were not significant. We conclude that cell proliferation and apoptosis do not correlate with pathological stage in clinically organ-confined cancer with Gleason sum 6 or 7, but that cell proliferation can distinguish between high (Gleason sum > or = 6) and low (Gleason sum < or = 4) grade tumors.

Utilization of high molecular weight cytokeratin on prostate needle biopsies in an independent laboratory.

OBJECTIVES: Immunoperoxidase staining of prostate tissues with antibodies to high molecular weight cytokeratin, which selectively labels basal cells, has recently been shown to be useful in the diagnosis of prostate cancer in academic centers. A growing sector in pathology is large independent laboratories, where little is known regarding practice patterns. The following study evaluated the use of high molecular weight cytokeratin in an independent laboratory specializing in prostate needle biopsies. METHODS: In a 2-month period (July 1, 1994 to August 31, 1994), 4047 prostate needle biopsies were evaluated. RESULTS: Without the use of ancillary studies, 2710 (67%) were diagnosed as benign, 978 (24.1%) were diagnosed as cancer, and 23 (0.6%) were diagnosed as high-grade prostate intraepithelial neoplasia. The remaining 336 atypical cases (8.3%) were further evaluated with antibodies to higher molecular weight keratin. Of the 336 cases, 253 (6.2% of total) were resolved as diagnostic for cancer, 68 (1.7% of total) were diagnosed as benign, and 15 (0.4% of total) remained atypical. The cost of performing high molecular weight cytokeratin was approximately $5.00 per case, which was not passed on to the patient. CONCLUSIONS: The use of high molecular weight cytokeratin decreased the rate of an atypical prostate biopsy from 8.3% to 0.4% at a negligible cost to the pathologist and patient.