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Fluorescent in situ hybridization using 2 chromosome specific centromere probes was evaluated as a method of ploidy analysis in touch preparations from 50 radical prostatectomy specimens. Tumors were classified as aneuploid by fluorescent in situ hybridization when nuclei had an abnormal copy number (aneusomic) for either chromosome centromere 8 or 12. Tetraploid tumors were defined as those with 4 copies (tetrasomic) of chromosome centromeres 8 and 12. The fluorescent in situ hybridization ploidy patterns were compared to the deoxyribonucleic acid (DNA) ploidy patterns subsequently obtained by flow cytometry on the same tissue following paraffin embedding. Concordant fluorescent in situ hybridization and flow cytometry ploidy classification was obtained in 82% of the cases (por = 0.0001). Of 7 aneuploid tumors 3 were identified by both methods. Trisomy 8 was detected by fluorescent in situ hybridization in 3 cases that were classified as DNA diploid (2 tumors) and DNA tetraploid (1 tumor). Conversely, flow cytometry detected aneuploidy (hypotetraploidy) in 1 tumor when the fluorescent in situ hybridization results were consistent with tetraploidy. Overall, fluorescent in situ hybridization was more sensitive in aneuploidy detection (6 of 7 cases) than flow cytometry (4 of 7). Of 19 tetraploid cases 5 had discordant fluorescent in situ hybridization and flow cytometry results. However, all 5 cases contained low levels of tetraploidy and the discrepant results were most likely due to the limits of precision of 1 or both methods. In conclusion, we demonstrated that fluorescent in situ hybridization ploidy analysis can be rapidly performed on fresh touch preparations of prostate tissue. This preliminary study demonstrates that the ploidy result determined by fluorescent in situ hybridization correlates well with that obtained by flow cytometry. More complete fluorescent in situ hybridization studies of prostate carcinoma will require additional probes for other chromosomes.

To determine if relative nuclear deoxyribonucleic acid (DNA) content is an important prognostic parameter for patients with clinically localized prostate carcinoma treated by external beam radiotherapy, we performed static DNA cytometry on archival paraffin embedded prostate needle biopsy specimens obtained before treatment. DNA content was measured with the Zeiss IBAS 2000 Image Analyzer and the Feulgen staining method. Tumor samples from 65 patients with clinically localized carcinoma of the prostate treated with at least 6,000 cGy. from 1974 to 1980 were studied. Patients and tumors were divided into 2 groups: group 1 - 31 patients with relative DNA content less than 1.5 times normal and group 2 - 34 patients with relative DNA content greater than 1.5 times normal. The prostate cancer nonprogression rate at 10 years was 64% for group 1 and 11% for group 2. Prostate cancer cause specific survival at 10 years was 73% for group 1 and 20% for group 2. These differences are highly significant (p less than 0.0001). By contrast, stratification and analysis according to tumor clinical stage, Mayo histological nuclear grade or Gleason score proved not to be as significant. Cox multivariate analysis also identified DNA content as the most important independent variable for cancer specific survival and progression. Nuclear DNA content measured by static cytometry appears useful in identifying those patients with clinically localized prostate carcinoma who may have a favorable probability of long-term disease control by external beam radiotherapy.

Purpose: We prospectively determined the accuracy of intraoperative needle biopsy of solid renal masses.Materials and Methods: A total of 103 patients diagnosed with a solid renal mass and scheduled for surgery were prospectively evaluated. Radical or partial nephrectomy was performed, and biopsy of the surgical specimen was done twice through the tumor using an 18 gauge biopsy gun. Biopsy specimens of 106 tumors were sent for frozen sectioning, stained with hematoxylin and eosin, and reviewed by 2 independent pathologists blinded to each other and whole tissue specimens. Biopsy results were compared to whole tissue specimens.Results: Specimens were obtained from 60 radical and 46 partial nephrectomy cases. Malignant neoplasms were present in 91 cases (86%). Overall, 15 cases (14%) were benign, of which 11 were oncocytomas. If lesions 4 cm. or less only were included in analysis, the incidence of benign lesions increased to 22%. Overall accuracy of the 2 pathologists was 76 and 80%. Nondiagnostic ...

Prostate-specific antigen (PSA) mRNA was detected by in situ hybridization utilizing a 428 base pair [35S]-labelled cDNA probe from the 3' noncoding region of the PSA gene. Thirty six fresh surgical specimens were collected from patients undergoing radical retropubic prostatectomy for carcinoma of the prostate. Quantitative analysis of the levels of PSA mRNA in both the benign and malignant tissues was performed using an IBAS 2000 Image Analysis System. The results of this study demonstrated that there is a significant decrease in the expression of PSA mRNA in the carcinoma tissue when compared to the benign epithelium. The average binding (number of silver grains/1 x 10(4) microns. 2) for 20 specimens of malignant epithelium was 475 +/- 161 and 586 +/- 140 for 16 specimens of benign epithelium (p less than 0.05). Eleven patients had both benign and malignant tissue from the same surgical specimen available for study. From these paired specimens, the PSA mRNA expression was also significantly reduced in the malignant epithelium when compared to the benign epithelium, 445 +/- 162 and 588 +/- 135 respectively (p less than 0.005). The PSA protein was detected using a monoclonal antibody to PSA with an immunohistochemical staining technique. The PSA protein expression paralleled the expression of the PSA mRNA in the majority of the tissue sections. Many of the tumor specimens showed a heterogeneous expression of PSA, whereas all of the benign epithelium had a uniform high level of PSA expression. In conclusion, PSA mRNA and protein are located only within the glandular epithelial tissue, the expression of PSA protein parallels that of the PSA mRNA, and both the PSA protein and PSA mRNA are significantly decreased in the malignant epithelium when compared to benign prostatic epithelium.

Flow cytometric nuclear deoxyribonucleic acid ploidy analysis was done successfully on 38 specimens of primary bladder adenocarcinoma treated between 1954 and 1985. Of the specimens 10 (26%) were deoxyribonucleic acid diploid, 8 (21%) were tetraploid and 20 (53%) were aneuploid. Distribution of ploidy patterns between the 14 histological low grade and 24 high grade tumors was similar. Of 38 tumors 35 (92%) showed muscle invasion. One tumor arose in a previously exstrophied bladder, 10 were of urachal origin and 27 arose in an anatomically normal bladder. Of the urachal origin tumors 80% were deoxyribonucleic acid aneuploid. At 5 and 10 years after diagnosis 80 and 70%, respectively, of the patients with diploid tumors were free of disease. By contrast, at 5 and 10 years after treatment only 20 and 12%, respectively, of the patients with nondiploid tumors have not had disease progression (p less than 0.001 log-rank test). None of the 6 patients with diploid, high grade, high stage, muscle invasive tumors had subsequent progression. In contrast, 16 of 17 patients (94%) with high grade, high stage, nondiploid tumors had either local or distant tumor recurrence (p less than 0.0005). Nuclear deoxyribonucleic acid ploidy pattern appears to be the most significant prognostic information currently available to stratify expected prognosis for patients with muscle invasive adenocarcinoma of the bladder. This test probably should be a standard tool in the clinical management of patients with this rare bladder malignancy.

From 1944 to 1987, 28 patients with squamous cell carcinoma of the upper urinary tract were treated and also had tumor specimens that were fully evaluable by flow cytometric nuclear deoxyribonucleic acid ploidy analysis: 22 had squamous cell carcinoma of the intrarenal collecting system, 4 had tumors of the ureter, and 2 had tumors of the renal pelvis and ureter. Eight patients (29%) had deoxyribonucleic acid diploid, 11 (39%) tetraploid and 9 (32%) aneuploid ploidy patterns. Ploidy pattern significantly correlated with histological grade and tumor stage. Almost all tumors were histologically of high grade; among the patients with high grade tumors ploidy analysis separated fair and poor prognosis groups. Pathological stage was the dominant clinical variable. A total of 14 patients (50%) had advanced stage disease and all died within 12 months of diagnosis. Nearly all of these patients showed abnormal ploidy patterns and ploidy analysis was not useful prognostically for this group. In contrast, all 3 patients with squamous cell carcinoma of the renal pelvis who were long-term survivors had deoxyribonucleic acid diploid tumors. However, there is no clear statistical evidence from this study that ploidy analysis provides important prognostic information independent of stage and grade for patients with squamous cell carcinoma of the renal pelvis.

We established the frequency of cancer multicentricity in kidneys removed for renal cell carcinoma by examining 100 intact, formalin preserved kidneys with a diameter of less than 80 mm. (1987 to 1989). The mean diameter of the predominant tumors was 51 mm. (range 15 to 80 mm). After the capsules were removed the kidneys were serially sectioned at 3 mm. intervals, and cortical and intraparenchymal nodules were removed for histological examination. A total of 3 kidneys had multiple tumors found previously on routine pathological examination. In addition, we discovered another 11 nodules in 10 other kidneys. Four nodules had histological features consistent with carcinoma. The size of the nodules ranged from 2 to 5 mm. The rest of the nodules consisted of 3 adenomas, 1 adrenal rest, 1 oncocytoma coexisting with an adenoma and 1 carcinoma permeating through the lymphatic vessels. The mean size of the predominant tumors in the kidneys bearing multiple nodules was 49 mm. Therefore, we observed a 13% incidence of small renal nodules and a 7% multicentricity of renal cell carcinoma in kidneys from patients who underwent nephrectomy.

We treated 11 patients with primary malignant lymphoma of the bladder. The typical patient is a woman more than 50 years old who presents with urgency and frequency of micturition, and occasionally gross hematuria. Hydronephrosis is present in half of the patients and cystoscopy usually reveals a solid tumor. Partial cystectomy, when feasible, with or without radiotherapy and chemotherapy is the usual treatment modality. When localized to the bladder, malignant lymphoma has an over-all favorable prognosis.

Flow cytometry was performed on 51 typical specimens of renal oncocytoma. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Of the 51 available tissue blocks 86 per cent were evaluable and 50 per cent of these samples showed a deoxyribonucleic acid (DNA) histogram that was approximately the same as normal renal parenchyma. Of the oncocytoma samples 39 per cent showed a marked increase (more than 10 per cent of the nuclei) in the tetraploid DNA peak, while 11 per cent showed a distinct DNA aneuploid peak. Among 21 evaluable grade 2 oncocytic renal tumors 33 per cent showed a normal DNA histogram, 43 per cent showed a marked increase in the DNA tetraploid peak and 24 per cent showed a DNA aneuploid peak. The common presence of polyploid nuclei containing double quantities of chromosomal DNA may correlate with the long-standing pathological observation that oncocytic tumors often contain a distinct population of large nuclei. Indeed, 86 per cent concurrence was seen between the detection of an abnormal DNA content by flow cytometry and the histopathological presence of large abnormal nuclei in these specimens. Since renal oncocytomas (grade 1 oncocytic tumors) rarely, if ever, metastasize and are relatively noninvasive locally, their markedly abnormal flow cytometry patterns are of considerable interest. Moreover, DNA polyploidy has not been identified previously in renal tumors. The biological significance and mechanism of DNA polyploidy, and the relationship of DNA polyploidy and DNA aneuploidy to the pathogenesis of oncocytic renal tumors require further laboratory investigation. The clinical use of flow cytometry to classify and to predict the behavior of renal tumors will be complicated, since renal oncocytomas commonly have polyploid and aneuploid DNA histograms.

A total of 23 men less than 60 years old with stage A adenocarcinoma of the prostate who were managed expectantly (that is untreated) and were at risk for 10 to 25 years form the basis of this study. The original amount of tissue obtained at transurethral resection, number of chips involved and examined, and tumor grade (Mayo grades 1 to 4) were recorded and compared in an in-depth analysis whereby the entire tissue removed was examined without knowledge of previous grading attempts. On the basis of volume estimation of the amount of cancer present 8 patients were reclassified as having stage A2 disease. Of these 8 patients 2 had disease progression and 1 died of metastatic adenocarcinoma of the prostate. At review 15 patients remained with stage A1 disease and 4 had disease progression (3 systemically and 1 locally) an average of 10.2 years after diagnosis. Because of longer life expectancy the young patient with stage A1 disease is at increased risk for local and/or systemic disease progression. Therefore, when incidental adenocarcinoma of the prostate is found in young patients consideration should be given to examination of all tissue resected, and to repeat transurethral resection and biopsy to ensure accurate staging. Lifelong careful followup is mandatory not only to detect local recurrence owing to heterogeneous adenocarcinoma of the prostate but also to detect a possible secondary clinical lesion.

Nuclear deoxyribonucleic acid ploidy studies with paraffin-embedded archival tumor specimens were performed by flow cytometry on extracted nuclei from 56 Wilms tumors. Before the era of chemotherapy 9 patients had a 33 per cent survival rate at 5 years. No significant correlation between deoxyribonucleic acid ploidy pattern and survival was seen in this early group of patients. Since 1960, 47 patients underwent radical nephrectomy and received chemotherapy. Deoxyribonucleic acid histograms in this group were normal in 13 tumors, while 23 tumors exhibited a tetraploid pattern (greater than 10 per cent nuclei in the G2 peak) and 11 showed an aneuploid pattern. Survival rates according to deoxyribonucleic acid ploidy pattern showed that 100 per cent of the patients with a normal or aneuploid histogram pattern were alive at 2 and 5 years. Patients with a deoxyribonucleic acid tetraploid pattern had a significantly worse survival of 74 and 69 per cent at 2 and 5 years (p less than 0.02 and less than 0.01), respectively. Tumors with a normal or aneuploid histogram pattern for all stages and a deoxyribonucleic acid tetraploid pattern for pathological stage I or II were associated with a 2 and 5-year survival rate of 100 and 97 per cent, respectively. However, patients with stages III and IV tumors with a deoxyribonucleic acid tetraploid pattern had a significantly worse survival of 25 per cent at 2 and 5 years (p less than 0.0001). Measurement of nuclear deoxyribonucleic acid ploidy identifies a patient group who are at high risk for treatment failure, that is stages III and IV tumors with a deoxyribonucleic acid tetraploid pattern.

The relationship of grade and local tumor extent to pelvic nodal involvement was assessed surgically in 469 patients who underwent pelvic lymphadenectomy and radical retropubic prostatectomy for adenocarcinoma of the prostate. Grade and local stage alone and combined score were associated in a linear fashion with nodal involvement. Gleason sum and Mayo grade alone were not predictive of nodal metastases. Some patients with a Gleason score of 4 had positive nodes and some with a score of 8 to 10 had negative nodes. Mayo sum (grade plus stage) consistently was related to negative nodal involvement.

Experience with 10 cases of malacoplakia of the urinary tract is reviewed. The bladder was affected in all 10 patients, in addition to both ureters in 1, possibly 1 ureter in 1 and the urethra in 1 patient. Symptoms were noted in 9 patients and intercurrent chronic liver disease was present in 3. Treatment of bladder lesions was by fulguration only in 1 patient, fulguration and short-term antimicrobial therapy in 5, fulguration and long-term therapy in 3 and thio-tepa instillation in addition to fulguration and long-term antimicrobial therapy in 1. A patient with ureteral involvement underwent temporary nephrostomy and the one with the urethral lesion healed after prolonged antimicrobial therapy. Recurrence has been rare in 3 patients who received long-term antimicrobial therapy with prolonged followup. We believe that fulguration and long-term antimicrobial therapy are therapies of choice for bladder lesions. Upper urinary tract lesions should be managed by long-term antimicrobial therapy and con...

Survival rates and various prognostic factors were studied in 89 patients between 20 and 40 years old who underwent nephrectomy for renal adenocarcinoma between 1950 and 1978. Although rare, renal carcinoma in young adults seems to follow a course similar to the disease seen in older patients. Among 18 suspected prognostic factors 2 are strongly and independently associated with survival. These are the pathologic stage of the tumor and preoperative weight loss. Several other prognostic variables show a statistically significant association with survival. These include the presence of preoperative fever, duration of symptoms, tumor cell type, microhematuria on admission to the hospital, tumor grade and sex. However, advanced statistical techniques demonstrate that the association of these variables with survival can be accounted for mostly by their close correlation with the stage of the tumor. Certain variables show no prognostic significance. These included the diameter of the tumor, age of the patient, presence or absence of gross hematuria, flank pain, palpable mass, arterial hypertension, sedimentation rate and side or site of the tumor.

From 1966 to 1980, 315 patients underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy without adjuvant treatment for clinically and pathologically localized adenocarcinoma of the prostate. Followup was 5 to 21 years, with a median of 8 years. The disease was pathological stage A in 24 patients (8%) and pathological stage B in 291 (92%). A total of 45 patients (14.2%) experienced progression. Over-all, 28 patients (8.9%) suffered local recurrence at a mean of 6.6 years postoperatively (median 5.5 years). Local recurrence was noted as late as 15 years postoperatively. Over-all, systemic progression was observed in 25 patients (8%) after a mean of 4.7 years (median 6 years). Eight patients (2.5%) experienced local and systemic failure. The projected local and systemic failure rates at 15 years were 22% and 15%, respectively. Disease-specific survival at 15 years was 93%, since only 11 patients (3.4%) died of prostate cancer. In an age-matched case control analysis, after all prognostic variables were analyzed (Mayo grade, Gleason score, capsule involvement, number of foci, volume of tumor and deoxyribonucleic acid tumor ploidy), progression was related to nondiploid deoxyribonucleic acid tumor ploidy (p less than 0.0004) as determined by flow cytometry in 63% of the patients who evidenced progression versus 8% of the nonrecurrent group.

The records of 108 patients presenting with leukoplakia of the urinary tract during the last 35 years were reviewed to define the natural history of this disease, with emphasis upon its association with urothelial cancer. Of the 108 patients 24 had upper urinary tract, 78 bladder and 10 urethral leukoplakia (1 with renal and bladder involvement, 3 with bladder and urethral involvement, and 1 with ureteral and renal involvement). Presenting complaints were primarily irritative. To date, 41 patients (37 per cent) have had associated carcinoma of the urothelium: 23 (21 per cent) presented with a concomitant or previous carcinoma and 18 of 85 (21 per cent) presenting without a concomitant or previous neoplasm have had documented progression to cancer. These figures support the concept that leukoplakia is a premalignant disease and that patients with this diagnosis deserve careful and frequent followup.

We reviewed the experience at this clinic from 1950 to 1980 with cases of grade 1 clear cell renal carcinoma. We wanted to determine whether patients with well differentiated clear cell renal tumors had the favorable clinical course that has been demonstrated for those with well differentiated oncocytic renal tumors. Of the 46 patients identified with pure grade 1 clear cell renal carcinoma two-thirds were discovered incidentally during diagnostic tests for unrelated complaints. These tumors generally were small, with 67 per cent being 6 cm. in diameter or smaller. Of all tumors 83 per cent were pathologic stage 1 (confined within the renal capsule). However, 10 patients have died of metastatic renal carcinoma and 3 are alive with disease. Actuarial survival curves show a significantly poorer prognosis for patients with grade 1 clear cell renal tumors compared to patients with grade 1 oncocytic renal tumors or to an age and sex-matched control group. We conclude that whereas well differentiated oncocytic renal tumors behave like benign renal tumors, well differentiated clear cell renal tumors can behave like aggressively malignant renal carcinomas and should be treated as such.

Flow cytometric analysis of nuclear deoxyribonucleic acid content was performed on 76 primary squamous cell bladder carcinomas treated between January 1970 and December 1975. Patients were followed for a median of 10.1 years. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Of the 76 tumors 73 were evaluable by flow cytometry providing high quality deoxyribonucleic acid histograms: 27 (37 per cent) showed a deoxyribonucleic acid diploid or normal pattern, 17 (23 per cent) exhibited a significant increase in the 4C peak (deoxyribonucleic acid tetraploid) and 29 (40 per cent) showed a distinct aneuploid peak. High grade (grades 3 and 4) and high stage (stages T2 to T4) tumors had a significantly higher incidence of abnormal (either tetraploid or aneuploid) deoxyribonucleic acid patterns than low grade (grades 1 and 2) and low stage (stages Tis/Ta/T1) tumors (p less than 0.005). The 5 and 10-year rate free of disease for patients with deoxyribonucleic acid diploid tumors was 67 per cent compared to 22 and 18 per cent, respectively, for patients with tumors showing abnormal ploidy patterns (p less than 0.0005). At 5 and 10 years after diagnosis an estimated 18 per cent of the patients with deoxyribonucleic acid diploid tumors will die of bladder cancer. In contrast, an estimated 53 per cent of the patients with tetraploid tumors and 82 per cent and 86 per cent of those with aneuploid tumors will die of squamous cell bladder carcinoma by 5 and 10 years after diagnosis (p less than 0.0001). These results demonstrate that nuclear deoxyribonucleic ploidy measured by flow cytometry is an important objective prognostic variable for patients with squamous cell carcinoma of the bladder.

Cytologic study of urine from 100 patients with transitional cell cancer of the upper urinary tract revealed that findings on the voided and catheterized specimens correlated well with grade and stage of the tumor. However, there was a significantly greater positive yield with urine specimens obtained by ureteral catheterization than by voiding. Consequently, because concomitant bladder tumors, diagnosed or not, can give questionable positive results ureteral catheterization specimens should be used for cytologic study.

Strict criteria were applied to 12 cases of carcinoma of the seminal vesicle in the Mayo Clinic tumor registry. Diagnosis was carcinoma of the seminal vesicle if the neoplasm was a papillary or anaplastic carcinoma localized primarily to the seminal vesicle and no other primary tumors were demonstrated. In addition, some degree of mucin production was required, especially when prostatic involvement was present. Only 2 of our cases and 35 cases reported previously were judged acceptable or probable cases of carcinoma of the seminal vesicle.Prognosis for patients with this tumor is poor. A combination of extirpative surgery and hormonal therapy appears to provide the best opportunity for extended survival, although this remains to be proved.

Adenocarcinomas that arise from primary or secondary prostatic ducts have distinctive histopathologic features. The age of patients, symptoms, findings on digital rectal examination and determinations of serum acid and alkaline phosphatase are similar to those of patients with acinic carcinomas. Carcinomas of secondary ducts may be less responsive to endocrine manipulation and of greater malignancy than carcinomas of primary ducts. The course and survival of patients with ductal carcinomas treated conservatively are poor.

We report on 2 men with multifocal papillary adenocarcinoma arising in the bulbous urethra proximal to a urethral stricture. Histologically, the tumors appeared similar to villous adenocarcinomas of the colon and rectum. Both patients were treated with segmental urethrectomy. Villous adenocarcinoma of the male urethra is a distinctive clinicopathologic entity. Although uncommon it should be added to squamous cell carcinoma and transitional cell carcinoma on the list of tumor types causing cancer of the male urethra.

Primary carcinoma in situ of the ureter or renal pelvis is rare. We describe 3 patients, each of whom had a different mode of presentation. When malignant cells in the urine from the upper urinary tract are associated with urographic evidence of an appropriate lesion, aggressive surgical therapy is indicated. In the absence of such a urographic abnormality patients with positive cytologic examinations should be followed closely because the exfoliated cells usually are from poorly differentiated neoplasms.

A 43-year-old man had clinically manifest prostatic involvement by a metastatic testicular seminoma. The signs, symptoms, diagnosis and treatment of this entity, as well as a hypothesis regarding its development, are discussed.

Primary, localized amyloidosis of the urethra is rare. The patient usually presents with hematuria and the appearance of urethral carcinoma. However, the disease is benign and it is treated effectively with local removal. We report our experience with 5 cases.

Sarcomas of the bladder occur rarely in adults. As a result, the natural history of these unusual tumors and the best methods of treatment are uncertain. We reviewed our experience with 13 patients presenting between 1970 and 1980 (5 had leiomyosarcoma, 5 had carcinosarcoma and 3 had rhabdomyosarcoma). Gross hematuria nearly always was the presenting symptom. Patients treated by partial cystectomy fared poorly, while 7 treated by radical cystectomy and supravesical urinary diversion had an excellent prognosis: 6 (86 per cent) have been free of disease for more than 1 year, including 4 who have survived more than 45 months without evidence of recurrence or metastasis.

We report a case of severe cystitis glandularis of the entire bladder, which caused a large retrovesical mass and bilateral hydronephrosis. Treatment included whole bladder neodymium:YAG laser therapy, a technique not previously reported for this extent of disease. The etiology, diagnosis, treatment and malignant potential of cystitis glandularis are discussed.