Frozen section diagnosis of metastatic prostate adenocarcinoma in pelvic lymphadenectomy compared with nomogram prediction of metastasis.

OBJECTIVES: To compare the sensitivity and negative predictive values of frozen section analysis of pelvic lymphadenectomy in patients undergoing radical retropubic prostatectomy for prostate adenocarcinoma with the predictive power of published nomograms for metastasis to lymph nodes. METHODS: A retrospective review was performed on all patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for prostate adenocarcinoma between 1991 and early 1997. The sensitivity and negative predictive values were computed comparing frozen section analysis, and patients were grouped by risk stratification. Comparison was made using the McNemar text. RESULTS: The sensitivity for detecting lymph node metastasis on frozen section analysis for all risk groups was 33% (9 of 27). The sensitivity for identifying patients at high risk of having nodal metastasis by published nomograms alone was 67% (18 of 27) (P = 0.04). The overall negative predictive value for frozen section analysis was 96.5% (503 of 521). The negative predictive value for uninvolved lymph nodes, using low and intermediate-risk groups stratified by published nomograms, was 97.9% (436 of 445). CONCLUSIONS: Frozen section analysis of pelvic lymph nodes to detect metastatic prostate adenocarcinoma is less sensitive in determining which patients will have lymph nodes involved by metastatic adenocarcinoma than using risk stratification by published nomograms. The negative predictive value of frozen section analysis in all risk groups was very high, up to 97.9%.

Neuroendocrine stains and proliferative indices of prostatic adenocarcinomas in transurethral resection samples.

OBJECTIVE: To determine whether the quantification of certain neuroendocrine and proliferative markers would help in the prognostic evaluation of prostatic adenocarcinomas obtained during transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Samples from two groups of patients with prostate cancer were examined. One group comprised 23 patients, of whom 12 were stage IV and 11 stage III, all with Gleason scores of > or = 7; this group was designated as high-grade, high-stage (HGHS). The second group comprised 10 consecutive patients with stage T1a adenocarcinoma of the prostate with Gleason scores of < or = 6, designated as low-grade, low-stage (LGLS) tumours. Tumour tissue from each TURP was stained with MIB-1 (an indicator of cell proliferation), neuron-specific enolase (NSE), chromogranin A (ChA) and synaptophysin (Syn), and 1000 cells counted to determine the percentages of positive cells in both benign and malignant tissue. The percentage of MIB-1-positive cells was designated as the proliferative index (PI). Patients were clinically followed to evaluate tumour progression, documented by rising prostate-specific antigen (PSA) levels, X-ray evidence of recurrent or metastatic carcinoma, or tissue biopsy showing malignancy. RESULTS: The mean number of neuroendocrine cells (NEC) for each marker and the mean PI were greater in the HGHS tumours than in the LGLS tumours or surrounding benign tissue of either group (P < 0.01). The LGLS tumours were remarkable for a having mean PI of about twice that of the benign tissue (2.9 and 1.3, respectively, P < 0.01); the NEC in these cases were more frequent in the benign than in the malignant tissue. There was no significant difference between the mean PIs and the mean percentages of NEC in the 14 HGHS tumours that progressed and the nine HGHS tumours that did not (P values 0.37-0.96). CONCLUSIONS: Although the PI assessed by MIB-1 and the number of NEC-positive cells were much higher in HGHS than LGLS tumours, this finding did not appear to have independent prognostic significance. The significance of the higher PI in LGLS tumours than in corresponding benign tissue is uncertain; LGLS tumours had fewer NEC than the surrounding benign tissue. The quantification of any of these four markers (MIB-1, NSE, ChA, Syn) was not prognostically helpful in these groups of cancers present in TURP specimens.

Prostatic acid phosphatase levels (enzymatic method) from completely sectioned, clinically benign, whole prostates.

Clinically benign, whole untrimmed prostates were obtained from 104 patients at autopsy, completely sectioned, and examined microscopically. The histological and gross findings of the prostate were correlated with premortem prostatic acid phosphatase levels (PAP, enzymatic method, ACA, Dupont Co.) to determine how often carcinoma of the prostate (CAP) affected PAP levels and to identify other findings within the prostate associated with elevated PAP levels. Sixty (58%) prostates did not have CAP, 34 (33%) had CAP smaller than 1 ml in volume, and 10 (10%) had CAP larger than 1 ml in volume. PAP levels were elevated (greater than 1 U/L) in 8 of 60 (13%) prostates without CAP, in 2 of the 34 (6%) prostates with CAP smaller than 1 ml, and in 1 of the 10 (10%) prostates with CAP larger than 1 ml. These differences were not statistically significant. Likewise, a statistically significant correlation between PAP levels and patient age, patient race, severe inflammation, of high grade prostatic intraepithelial neoplasia (PIN) was not found. However, there was a statistically significant correlation between PAP levels and prostate weight (p < 0.0001). This study suggest that PAP cannot distinguish between patients with clinically undetected CAP and patients without CAP. Furthermore, elevated PAP levels are often not due to metastatic CAP and additional evidence should be present, even in patients with known CAP, before an elevated PAP level is considered to be conclusive evidence of metastatic CAP.

Neuroendocrine differentiation in prostatic adenocarcinoma and its relationship to tumor progression.

BACKGROUND: Neuroendocrine differentiation has been demonstrated by immunohistochemical preparations in many cases of acinar type prostatic adenocarcinoma (CAP). Some studies have suggested that this differentiation may indicate an adverse prognosis. METHODS: Tissue samples from 38 consecutive patients with clinical Stage II (AJCC) CAP who underwent radical retropubic prostatectomy (RRP) were studied after preparations were made with antichromogranin (ChA) and neuron-specific enolase (NSE). All patients were followed for at least 4 years post-RRP or until disease progression was documented by rising serum prostate specific antigen concentration, X-ray evidence of recurrence, or a positive tissue biopsy. RESULTS: Nine of the 38 RRP specimens (24%) were positive for NSE, and 11 (29%) were positive for ChA. Neither of these neuroendocrine markers showed a significant correlation with tumor progression. Neuroendocrine differentiation in needle biopsy specimens from these same patients (when available) did not correlate with tumor progression either. Of the patients with tumor progression, 9 of 11 (82%) had pathologic Stage III disease after RRP; of those with no progression of CAP, only 7 of 27 (26%) had pathologic Stage III disease. CONCLUSIONS: Neuroendocrine differentiation, as demonstrated by NSE and ChA preparations, was not helpful in predicting tumor progression of CAP.

Characteristics of prostatic infarcts and their effect on serum prostate-specific antigen and prostatic acid phosphatase.

OBJECTIVES: To determine how prostatic infarcts affect serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels. METHODS: Two hundred eighteen clinically benign, whole prostates were obtained at autopsy, completely sectioned, and examined histologically. PSA and PAP levels were determined from premortem serum. RESULTS: Six of the 218 (2.8%) prostates had infarcts. The infarcts were usually multiple and usually located in the central and/or middle concentric zones of the middle third of the prostate without a preference for a particular lobe. Serum PSA by immunoradiometric assay were elevated in all 6 cases. Serum PAP by both enzymatic assay (ACA), and immunoradiometric assay were available for 5 cases and were elevated by both methods in 2 cases, approached elevated levels by both methods in 1 case, and were normal by both methods in 2 cases. The PSA and PAP levels appeared to be affected more by the age than by the size of the infarct. CONCLUSIONS: Prostatic infarcts elevate PSA levels more frequently than PAP levels, and prostatic infarcts may be responsible for some unexplained elevations of serum PSA and PAP levels.

Pneumoscrotum: report of two cases and review of mechanisms of its development.

Scrotal emphysema and, less frequently, pneumatocele are uncommon signs of pneumoscrotum caused by a variety of pathogenic and iatrogenic disease processes. The finding of air in the scrotal sac may be an early sign of a life-threatening condition or may represent an incidental finding associated with more benign conditions. The three basic mechanisms by which air becomes localized to the scrotum are discussed, the literature is reviewed, and 2 new cases are presented.

Recurrent eosinophilic cystitis: a case responsive to steroids.

We report a case of eosinophilic cystitis that was responsive to prednisone but that recurred when the drug was withdrawn. The cause of eosinophilic cystitis remains an enigma but it probably represents a form of allergy. Investigation of etiology and therapeutic options are discussed.

Ultrasound detection of prostate cancer in postmortem specimens with histological correlation.

Transrectal ultrasound detection of prostatic adenocarcinoma was correlated to 63 histological whole mount step sectioned prostatic specimens harvested from 148 consecutive autopsies at our institutions. No patient had known or palpably suspected prostatic adenocarcinoma on premortem digital rectal examination. Prostate specific antigen (PSA) was assayed in each case from premortem serum samples. Of 19 cancers 6 (32%) were detected by transrectal ultrasound and all were hypoechoic. Of the 13 nondetected cancers 7 were isoechoic, 3 were mixed hypoisoechoic, 2 were hypoechoic and 1 was mixed hyperisoechoic. PSA greater than 4 ng./ml. would have aided in cancer detection by suggesting the need for biopsy or further biopsy in 5 cancers with significant volume, which were missed by transrectal ultrasound. The sensitivity (32%) and specificity (64%) of transrectal ultrasound appear too low for use in clinical screening for prostatic adenocarcinoma. PSA and transrectal ultrasound together appear more effective than sonography alone in prostatic adenocarcinoma detection in this series.

Cytogenetic abnormalities in renal oncocytic neoplasms.

We have performed cytogenetic studies on five renal oncocytic neoplasms (three grade 2 tumors and two grade 1 tumors) identified histologically by light microscopy. One grade 1 tumor failed to produce mitotic cells. The other four tumors exhibited both normal and abnormal cell lines. Numerical abnormalities were found in both the single grade 1 and two of the grade 2 tumors whereas structural abnormalities were limited to grade 2 tumors. Aneuploidy of chromosome 12 was observed in both grade 1 and 2 tumors. Grade 2 tumors showed more extensive numerical change than the grade 1 tumors. Abnormalities of chromosome 3 characteristic of renal cell carcinoma were not found in any tumor in this series. A combination of C-banding and HaeIII endonuclease banding was used to identify an ambiguous marker. In our four cases and in the cases previously reported, loss of a sex chromosome, abnormalities of chromosomes 1 and 22, and trisomy 12 are findings most often observed in renal oncocytoma.

Prostate-specific antigen levels from completely sectioned, clinically benign, whole prostates.

Clinically benign whole, untrimmed prostates and pelvic lymph nodes were obtained from 105 patients at autopsy. All 105 patients had premortem serum from which prostate-specific antigen (PSA) levels were obtained. Sixty-eight did not have carcinoma of the prostate (CAP), 28 had CAP less than 1 ml and 9 had CAP larger than 1 ml. Eleven untrimmed prostates weighed 80 g or more and eight had elevated PSA levels (more than 4.0 ng/ml): five of eight without CAP, two of two with CAP less than 1 ml, and one of one with CAP larger than 1 ml. Ninety-four whole untrimmed prostates weighed less than 80 g and 20 had elevated PSA levels: ten of 60 without CAP, two of 26 with CAP less than 1 ml, and eight of eight with CAP larger than 1 ml. This study suggests that PSA levels from patients with untrimmed prostates weighing 80 g or more (equivalent to a 60-g trimmed prostate) are usually elevated regardless whether CAP is present. However, CAP less than 1 ml, in untrimmed prostates less than 80 g, usually does not elevate PSA levels whereas CAP larger than 1 ml usually does (P less than 0.0001). The likelihood that elevated PSA levels, from patients with untrimmed prostates less than 80 g, are due to CAP larger than 1 ml increases as the PSA level increases.

Differential immunostaining of oncocytic renal tumors with an anti-renal cell carcinoma monoclonal antibody.

Formalin-fixed, paraffin embedded tissue sections from twenty three oncocytic renal neoplasms were stained with hematoxylin and eosin, retrospectively examined, and graded according to the criteria reported by Lieber and associates. Additional sections were stained by the avidin-biotin immunoperoxidase technique with anti-renal cell carcinoma monoclonal antibody 5F4. The results showed that cytological heterogeneity was the most prominent feature of the tumors. Four cases were composed predominantly of grade 1 cells, but also had foci of grade 2 cells. Seventeen cases were composed predominantly of grade 2 cells. Two cases were composed predominantly of grade 3 cells. Immunostaining with 5F4 showed differential reactivity between grade 1 and grades 2 and 3 cells. The antibody highlighted the foci of atypical cells which were difficult to detect by routine hematoxylin and eosin staining and thus could be useful in the differential diagnosis of oncocytic renal neoplasms.

Carcinoma of the prostate in the elderly.

A comprehensive practical approach to the diagnosis, staging, and treatment of carcinoma of the prostate is presented. Prostatic cancer in the elderly patient is not a benign clinical condition. The approach is designed to minimize the morbidity of the disease process and to allow the patient to live as normal a life as possible.

Experience with management of posterior urethral injury associated with pelvic fracture.

Review of records from 205 patients with pelvic fracture and hematuria revealed that 121 underwent urologic and radiographic evaluation. Of these patients 20 had severe posterior urethral injuries documented by urethrography of voiding cystourethrography: 9 underwent primary repair and 11 had delayed scrotal-inlay urethroplasty after initial cystostomy alone. Patients who underwent primary repair had a 77 per cent incidence of stricture, a 22 per cent incidence of incontinence and a 33 per cent incidence of impotency. Patients who underwent delayed closure had no incidence of stricture, incontinence or impotence. Patients in both groups had urinary tract infections. Simple cystostomy followed by delayed scrotal-inlay urethroplasty appears superior to primary realignment in the management of patients with posterior urethral injuries.