Search

Leydig cell tumors of the testis are rare and account for a small proportion of testicular neoplasms. The objective of this study was to identify clinical and morphologic features predictive of metastasis in a large series of Leydig cell tumors, and to determine whether ploidy or proliferative activity were predictive of malignancy. Thirty cases of Leydig cell tumor of the testis (23 tumors that had not metastasized and 7 that had metastasized) were studied. Clinical history and follow-up were collected in all cases. The morphologic features examined included tumor size, mitotic index (mitotic figures/10 high-power fields), necrosis, angiolymphatic invasion, cell type, tumor-testicle interface, presence of extension beyond the testicular parenchyma, and presence of lipochrome and Reinke crystals. Most patients (93%) had a testicular mass. Patients with Leydig cell tumors that metastasized were diagnosed at a mean age of 62 years (range, 39-70 years) compared with 48 years (range, 9-79 years) in patients with nonmetastasizing tumors (p = 0.25). Leydig cell tumors that metastasized were significantly larger than nonmetastasizing tumors (mean, 4.7 versus 2.6 cm, respectively; p = 0.008), and had a significantly higher mitotic index (mean, 13.9 versus 1.9, respectively; p < 0.0001). Metastasizing Leydig cell tumors were significantly associated with atypical mitotic figures (p < 0.0001), nuclear variation (p = 0.0025), necrosis (p < 0.0001), angiolymphatic invasion (p = 0.009), infiltrative margins (p < 0.0001), high grade (p = 0.0004), and invasion into rete testis, epididymis, or tunica (p = 0.001) when compared with nonmetastasizing tumors. There was no significant difference between metastasizing and nonmetastasizing tumors in regard to cell type, lipochrome content, presence of Reinke crystals, or nuclear inclusions. All Leydig cell tumors that metastasized and 7 of 18 (38.9%) nonmetastasizing tumors were DNA aneuploid by static image analysis (p = 0.02). Metastasizing Leydig cell tumors had a significantly higher mean MIB-1 activity of 18.6% (range, 5.8-33.6) compared with 1.2% (range, 0.04-8.2) in nonmetastasizing tumors (p = 0.001). In this study, the presence of cytologic atypia, necrosis, angiolymphatic invasion, increased mitotic activity, atypical mitotic figures, infiltrative margins, extension beyond the testicular parenchyma, DNA aneuploidy, and increased MIB-1 activity were significantly associated with metastatic behavior in Leydig cell tumors.

BACKGROUND This study was performed to identify clinical and histologic features most significant in predicting outcome in patients with transitional cell carcinoma (TCC) of the prostate without invasive bladder carcinoma. METHODS The histologic and clinical material from 50 patients with prostatic TCC without invasive bladder carcinoma were studied. The tumors were divided into the following locoregional categories: 1) TCC in situ (CIS) of the prostatic urethra; 2) CIS of the prostatic ducts and acini; 3) TCC with stromal invasion; 4) TCC with extraprostatic extension and/or seminal vesicle involvement; and 5) lymph node metastases. The Kaplan-Meier method was used to generate survival distributions for the locoregional categories, and comparison of survival curves was accomplished with the log rank test. RESULTS The 5-year disease specific survival rate was 52%. The 5-year disease specific survival rates for the locoregional categories were as follows: CIS of the prostatic urethra and prostatic ducts and acini (n = 19), 100%; TCC with stromal invasion (n = 21), 45%; TCC with extraprostatic extension and seminal vesicle involvement (n = 3), 0%; and lymph node metastases (n = 7), 30%. There was a significant difference in disease specific survival when patients with CIS were compared with patients with stromal invasion, extraprostatic extension and seminal vesicle involvement, and lymph node metastases (P = 0.0001). CONCLUSIONS This study demonstrates that patients with prostatic TCC involving prostatic stroma, extraprostatic tissues, seminal vesicles, and lymph nodes have a significantly poorer 5-year disease specific survival than patients with CIS. Cancer 1998;82:703-7. © 1998 American Cancer Society.

Objectives To assess the nature of a series of unusual low-grade mucin-producing tubulocystic renal cancers diagnosed at the Mayo Clinic since 1985. Methods We reviewed the clinical, radiologic, and pathologic features of 13 unusual low-grade renal carcinomas with features most suggestive of collecting duct origin. Results In 8 cases, the tumor was discovered incidentally. Presenting symptoms in the other 5 patients were similar to those of typical renal carcinoma. Imaging studies and angiography disclosed solid, cystic, or complex masses that were relatively avascular. Pathologic assessment revealed good circumscription, minimal hemorrhage and/or necrosis, minimal tendency to extend beyond the kidney, tubulocystic architecture, a fibrotic interface with adjacent normal renal parenchyma, low nuclear grade, and minimal mitotic activity. Mucin production was noted in all evaluable cases. All tumors expressed keratins AE1/AE3 and/or Cam 5.2. The tumors showed immunoreactivity to antibodies directed against keratin 34 β E12 (8 of 13 cases), and Ulex Europeus antigen I (6 of 10 cases). Follow-up ranged from 12 to 114 months (mean 62). No metastases occurred in 12 patients. One patient died of metastatic carcinoma morphologically identical to the primary renal neoplasm 46 months after his tumor had been misinterpreted as a benign condition. Conclusions We believe the tumors described in this article may be of collecting duct origin, representing the low-grade end of a spectrum of cancers arising in collecting duct epithelium.

Objective: To evalute the relationship between the nuclear DNA content and the tissue estrogen receptor (ER) level in patients with operable adenocarcinoma of the prostate. Method: Surgical specimens taken from 73 patients with clinically localized prostate cancer were studied. Tumor DNA ploidy pattern as measured by flow cytometry was correlated with the level of functional ER using the nuclear biopsy assay. Results: Forty-five percent of the tumors were DNA diploid, and 55% had an abnormal ploidy pattern (DNA tetraploid or DNA aneuploid). The ER level ranged from 0 to 6,475 fmol/mg DNA (mean 839 fmol/mg DNA). Twenty-two percent had no functional receptors. Marked association was noted beteen ER and nuclear DNA content. Seventy-five percent of the tumors with no ER had abnormal ploidy patterns. The mean receptor level for DNA diploid prostate cancer was 1,034 fmol/mg DNA versus 661 fmol/mg DNA for DNA nondiploid tumors (p< 0.008). An inverse correlation was found between ER values and histologic grade or pathologic stage. High-grade and high-stage tumors had lower levels of ER compared to low-grade and early-stage carcinomas. Conclusion: Our results demonstrate an association between ER values and variables that predict prognosis in prostate cancer. It is possible that this parameter may be helpful in identification of prognostic groups in patients with prostate cancer.

Renal oncocytoma has several features that overlap with other renal neoplasms with a preponderance of granular cytoplasm, such as chromophobe, granular, and papillary renal cell carcinomas. Lack of knowledge of this entire spectrum of eosinophilic renal cell neoplasms has led to several misconceptions in the literature regarding renal oncocytoma. These include the "grading of oncocytomas," "metastatic oncocytomas," and the impression that renal oncocytoma is usually low grade and lacks prominent nucleoli. In order to further characterize the histologic features and embelLish diagnostic criteria, we evaluated 93 tumors from 80 patients. Four tumors were bilateral and two were multifocal. The mean age was 67.2 years (32-89 years), men were more commonly affected (3.1:1), and 82.7% tumors were incidental findings. Grossly, the tumors were mahogany brown, lacked necrosis, and averaged 4.4 cm in size (range 0.6-15 cm). Histologically, renal oncocytoma was composed of an exclusive or predominant component of acidophilic cells with three architectural patterns of disposition: (a) The "classic" pattern (57.5%), composed of a characteristic nested or organoid arrangement of cells, each surrounded by a distinct reticulin framework; (b) a "tubulocystic pattern" (6.3%) with numerous closely packed cystically dilated tubular structures; and (c) "mixed pattern" (36.2%), which had both the organoid and tubulocystic patterns. A gross or microscopic scar was noted in 53.8% cases, and histologically a distinctive myxoid and/or hyalinized stroma separated nests of cells. Generally, the nuclei of renal oncocytoma were round with uniform nuclear contours. Nearly half of the tumors had prominent nucleoli (42.5% had prominent nucleoli equivalent to Fuhrman's grade III or IV). Pleomorphism was absent in 50% of cases but was conspicuous in 12.5% of cases including foci of bizarre cells. Other atypical features included perinephric fat involvement (11.3%), renal parenchymal invasion not associated with desmoplasia (10%), and hemorrhage (31.3%). Renal oncocytoma by definition lacks areas of clear cell carcinoma, significant lesional necrosis, or conspicuous papillary formations. Ancillary features noted included normal-appearing renal tubules within the lesion (15%), intranuclear holes (20%), psammoma bodies (7.5%), and foam cells (7.5%). 15% of tumors were locally excised, and 85% resulted in radical nephrectomy. Mean follow-up of 7.6 years (range 15-200 months) showed no evidence of recurrence, metastasis, or death due to tumor. In conclusion, renal oncocytoma, herein described, is a benign neoplasm and therefore does not merit a nuclear grading scheme. It has unique histologic features including an organoid and tubulocystic architecture, myxoid or hyalinized stroma, and occasionally some atypical findings including nuclear pleomorphism, prominent nucleoli, and adjacent renal parenchymal and perinephric fat involvement.

' Fundacion Puigvert (IVNA), Barcelona, Spain. Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland. Pathology Department, Northwest Hospital, Seattle, Washington. Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota. Department of Pathology, Mayo Clinic, Rochester, Minnesota. Department of Pathology, Mercy Hospital Medical Center, Des Moines, Iowa. ' UroCor Inc., Oklahoma City, Oklahoma. * Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Clinica Plato-Fundacio Privada, Barcelona, Spain.

Background. Leiomyosarcoma of the prostate is a rare neoplasm that accounts for less than 0.1% of prostate malignancies. Previous reports of this neoplasm consisted of single case studies or small series, often combined with cases of rhabdomyosarcoma. The relationship of prognosis with histologic and immunohistochemical findings has not, to the authors' knowledge, been described in a large series of cases, and the efficacy of various treatments is uncertain. Methods. The authors undertook a clinicopathologic study of all cases of prostate leiomyosarcoma observed at their institution from 1929 to 1994. Twenty-three cases were retrieved from the files of the Department of Pathology, Mayo Clinic (Rochester, MN), and clinical follow-up was available for 14. Immunohistochemical studies, including actin, desmin, S-100 protein, keratin, and vimentin were performed for 18 cases. Results. Patients ranged in age from 41 to 78 years, with a mean of 61 years. Presenting symptoms included urinary obstruction (100%), perineal pain (25%), burning on ejaculation (7%), and weight loss (7%). The neoplasms ranged from 3.3 to 21 cm (mean, 9 cm) in greatest dimension and were often associated with necrosis. Seven tumors were Grade 2, 10 Grade 3 and 6 Grade 4 (Broders' grading system; scale, 1–4). Mitotic figure counts varied from 2 to 24 per 10 high power fields. Fifteen of 15 (100%) cases were immunoreactive for vimentin, 10 of 16 (63%) were immunoreactive for actin, and 3 of 15 (20%) were weakly reactive for desmin. Keratin expression was observed in 4 of 15 cases (27%), and S-100 protein was negative in all cases. Treatment varied, and usually included a combination of radiation therapy, chemotherapy, and radical prostatectomy or cystoprostatecomy. Follow-up ranged from 2 to 72 months, with a mean of 19 months. Ten patients died from tumor 3 to 72 months (mean, 22 months) after diagnosis. Four patients were alive, including three with residual tumor and one without evidence of tumor at 2, 4, 30, and 4.5 months, respectively. Local recurrence occurred in 10 of 11 patients, including 5 who had gross residual tumor present after surgery. Metastases developed up to 40 months after surgery (mean, 10.3 months), and most frequently involved the lungs. Conclusions. These findings indicate that prostate leiomyosarcoma has a varied histologic appearance ranging from spindled cell neoplasm reminiscent of smooth muscle to pleomorphic sarcoma. Epithelioid features may be present. Most tumors are immunoreactive with antibodies to vimentin and actin, and reactivity with antikeratin antibodies does not exclude the diagnosis of leiomyosarcoma. Prostate leiomyosarcoma has a poor prognosis, although the length of survival is variable. Radical surgery was the treatment of choice in the current series, but complete excision was difficult in most cases and did not result in cure.

Background. Carcinosarcoma of the prostate is an unusual malignancy characterized by adenocarcinoma intimately admixed with sarcoma. Methods. The authors reviewed the clinical and pathologic findings of 21 cases of carcinosarcoma of the prostate from the files of the Mayo Clinic. Results. Patient age ranged from 50 to 89 years (mean, 68 years). Ten patients (48%) had a previous diagnosis of prostatic acinar adenocarcinoma 2–73 months (mean, 33 months) before the diagnosis of carcinosarcoma, 8 of whom had received androgen deprivation therapy and/ or radiation therapy in the interim. The Gleason score of adenocarcinoma ranged from 7 to 10 (mean, 9; median, 9). The sarcomas consisted of osteosarcoma (13), leiomyosarcoma (5), fibrosarcoma (1), malignant fibrous histiocytoma (1), and rhabdomyosarcoma (1), and the grade of the sarcoma component ranged from 2 to 4 (mean, 4; median, 4). Adenocarcinoma was the dominant histologic pattern in 7 cases and sarcoma in 14. Immunohistochemical staining revealed cytoplasmic reactivity for prostate specific antigen or keratin in 16 of 16 cases in the adenocarcinoma component. The sarcoma component was positive for vimentin in 16 of 16 cases, actin in 8 of 16 (focal in 2), S-100 protein in 2 of 16, and desmin in 1 of 16. At the time of diagnosis of carcinosarcoma, 11 patients had metastases, including 4 with metastatic adenocarcinoma before the diagnosis of carcinosarcoma. Treatment varied, and nonsurgical therapy was ineffective. Sites of metastases included lung (10 cases), bone (7), brain (4), liver (1), and peritoneum (1). Follow-up ranged from 1 to 107 months after the diagnosis of carcinosarcoma (mean, 34 months; median, 10 months). Mean time to tumor progression was 23 months (range, 1-96 months; median, 18 months). Eighteen patients died of carcinosarcoma from 2 to 107 months (mean, 34 months; median, 9.5 months) after diagnosis. Five-year survival was 41%, and 7-year survival was 14%. Progression and survival were not affected by histologic pattern. Conclusions. Carcinosarcoma of the prostate is an aggressive malignancy, regardless of histologic type. Cancer 1995;76:1035–42.

Purpose: We review the clinicopathological features of chromophobe cell renal carcinoma.Materials and Methods: Cases were identified by reviewing the histology of all renal neoplasms resected between 1977 and 1990. Clinical data were obtained by chart review.Results: Of 50 cases a majority (53 percent) were discovered incidentally and most (86 percent) were stage I. Typical pathological findings included the presence of 2 cell types (pale and eosinophilic), reactivity for Hale's colloidal iron, ultrastructural cytoplasmic vesicles and deoxyribonucleic acid aneuploidy. At last followup 47 patients (94 percent) were tumor-free or dead of unrelated causes. Survival was similar in patients with clear cell carcinoma of similar grade and stage.Conclusions: Chromophobe cell carcinoma is a morphologically distinctive neoplasm with a favorable prognosis. Distinction from renal oncocytoma is important.

The authors addressed the following question : Does DNA ploidy measurement provide additional unique prognostic information beyond the customary parameters of tumor stage and histologic grade for patients with prostate adenocarcinoma? They analyzed 494 patients treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic from 1967 to 1981, pathologic stages B (n = 258), C (n = 145), and D1 (n = 91). Clinical follow-up was a minimum of 10 years. Nuclear DNA ploidy patterns were measured with the archival paraffin embedded specimen blocks using the Hedley technique. Univariate analysis demonstrated that DNA ploidy, Gleason score, and pathologic stage are all highly important prognostic variables, each with a log-rank P value of

Objective. To evaluate the clinical significance of DNA ploidy pattern for patients with nonseminomatous germ cell testicular tumors who did not receive platinum-based chemotherapy. Methods. Flow cytometric nuclear DNA ploidy analysis of paraffin-embedded tissue blocks were used. Results. All patients underwent radical orchiectomy with or without retroperitoneal lymphadenectomy between 1960 and 1980. Mean follow-up time was eight years. Nineteen percent of the tumors were DNA diploid and 81 percent were DNA aneuploid. Signs of local tumor extension (spermatic cord involvement or vascular invasion) were found in 20 tumors, all were classified as DNA aneuploid (P < 0.04). After primary treatment 9 patients who were clinically cured experienced disease progression; only 1 of them had DNA diploid tumor; the rest were DNA aneuploid (P < 0.05). The ten-year survival rate was higher for patients having DNA diploid tumors compared with those with DNA aneuploid neoplasms (86% versus 53 percent, P < 0.02). Conclusions. The results of this retrospective study indicate that nuclear DNA content provide important information concerning the natural history and biology of nonseminomatous germ cell testicular tumor.

Urachal carcinoma is a rare neoplasm (0.22% of all bladder cancers) associated with a dismal prognosis. The obscure anatomic position of the tumor often minimizes early symptoms and precludes a timely diagnosis. The reported survival for urachal neoplasms has been inauspicious, and radical surgery (en bloc cystoprostatectomy and wide excision of the urachus and umbilicus) has been recommended as the primary treatment. To provide a rationale for the surgical management of this cancer, 38 patients with urachal carcinoma were reviewed, including 28 men and 10 women (2.8:1) (median age at diagnosis, 56 years; range, 28 to 88 years). The majority of the tumors were of high grade and stage at the time of diagnosis; they were exclusively DNA aneuploid in the 10 patients studied. Most patients had partial (segmental) cystectomy/umbilectomy (n = 30) or en bloc radical cystoprostatectomy/umbilectomy (n = 4) as their initial treatment; five-year overall survival of 43 percent and 50 percent revealed essentially comparable outcomes for the two surgical approaches. Thus, in the initial management of urachal carcinoma, umbilectomy with partial cystectomy may be considered in selected cases; this can enhance quality of life without necessarily influencing survival adversely. Rather, disease outcome seems more dependent on the adverse biologic potential of this usually DNA aneuploid tumor, necessitating the development of more innovative systemic treatment modalities.

Mesoblastic nephroma is an uncommon congenital tumor of infancy that rarely occurs in adults. We report three patients (two were female, one was male) who had mesoblastic nephroma of adulthood and who presented at 45, 64, and 66 years of age with hematuria, flank mass, and pain. All underwent nephrectomy without postoperative adjuvant therapy. The tumors were solitary yellow-tan masses with solid and cystic areas involving the renal cortex (three cases) with extension into the renal pelvis and calyces (two) and ureter (one). Microscopically, all consisted of uniform spindle cell proliferations with entrapped dilated renal tubules. Focal necrosis was present in two, but no atypia or mitoses were identified in any case. The spindle cells displayed cytoplasmic immunoreactivity for vimentin, desmin, panmuscle actin (HHF-35), and alpha-smooth-muscle actin, but were nonreactive for keratin (AE1/AE3), epithelial membrane antigen, and S-100 protein. Electron microscopy revealed the presence of smooth-muscle differentiation in two cases and undifferentiated mesenchyme in one. All tumors were DNA diploid by flow cytometry. The patients were free of recurrence 8 months-2 years postoperatively. Because surgical excision may be curative, mesoblastic nephroma in adult patients must be differentiated from spindle cell neoplasms of the kidney that require additional therapy.

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.

A retrospective study was performed to evaluate the clinical and pathologic characteristics of 60 patients with a palpably benign prostate gland, but with biopsy-proved prostate cancer. All patients underwent prostate biopsy because of elevated serum prostate-specific antigen (PSA) concentration, and subsequently underwent radical retropubic prostatectomy (RRP). Similar analysis was performed for a randomly selected group of 60 clinical Stage B1 prostate cancers from the same period (control cohort). Patients with nonpalpable prostate cancers had a higher preoperative PSA level as compared with the clinical Stage B1 group (median value: 12.3 ng/mL versus 4.6 ng/mL, p < 0.001). There was no significant difference between the two groups with regard to clinical parameters (voiding symptoms, hematuria, age). The nonpalpable prostate cancers exhibited a significant tumor volume (mean: 7.4 cc; range: 0.3-56 cc), and 18 (30%) demonstrated capsular perforation to involve the periprostatic tissues. Of these, three (5%) had seminal vesicle invasion, and one (2%) had pelvic lymph node involvement. There was no difference between these pathologic characteristics and those of the clinical Stage B1 prostate cancers. These findings suggest that nonpalpable prostate cancers identified by an elevated serum PSA level can be of clinical significance and warrant therapeutic consideration. Although nonpalpable, these cancers are peripherally located and were clinically suspected prior to biopsy. Therefore, we propose that these cancers be classified as clinical Stage B0 in the Whitmore-Jewett staging system; in the new TNM staging system, they are designated as clinical Stage T1c.

Renal oncocytomas are benign tumors whose morphologic features may sometimes be confused with those of certain low-grade malignant neoplasms of the kidney, e.g., chromophobe cell and granular cell variants of renal carcinoma. The presence of a specific genetic abnormality might help differentiate these tumors. Because very few cytogenetic studies of renal oncocytomas have been published, we investigated a consecutive series of six such tumors. We also performed chromosome analysis on a chromophobe cell carcinoma because cytogenetic analyses of this tumor have not been previously reported. Tumor cell metaphases were analyzed after mechanical and enzyme disaggregation, in situ culture, and robotic harvesting. Clonal abnormalities were present in five of the six oncocytomas, and loss of chromosome 1 with loss of the Y chromosome occurred in two. Review of the literature disclosed four other renal oncocytomas with the 44,X,-Y,-1 karyotype. In the chromophobe cell carcinoma, we noted an abnormal clone with a del(11)(p12p15.1); similar anomalies were not observed in the renal oncocytomas. We conclude that renal oncocytomas have clonal chromosome abnormalities and that a subgroup of these tumors may be specifically associated with loss of chromosomes 1 and Y. Because this is a small series, further investigation may help establish whether cytogenetic studies can provide diagnostic and pathogenic information about renal oncocytomas.

BACKGROUND Stage D1 disease is found in at least every sixth patient undergoing bilateral pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer (PC). Previous recommendations for monotherapy using surgery, radiation, or systemic therapy alone for Stage D1 disease have usually been associated with a poor outcome in regard to progression and survival. Unlike other pathologic stages, D1 disease treated with RRP is mainly related to DNA ploidy pattern in regard to all end points (progression and survival) and immediate adjuvant hormonal treatment (AHT) rather than to the usual pathologic variables, including the number of positive nodes. METHODS Complete DNA ploidy information was available in 370 patients with Stage D1 disease (age range, 40-77 years; mean, 64 years) undergoing RRP with or without AHT with a follow-up of up to 22 years (mean, 5 years). RESULTS Overall, 80% of all DNA ploidy classes (diploid, 37%; tetraploid, 46%; and aneuploid, 17%) had AHT that highly significantly delayed progression for diploid (P less than 0.0001) more than tetraploid (P less than 0.0001) and more than aneuploid (P less than 0.0001) tumors. Significant prolongation of the disease-free interval might have improved the quality of life for tetraploid and aneuploid patients. Survival (crude and cause-specific) was significantly (P = 0.02) improved only for diploid patients who received AHT but not for tetraploid and aneuploid patients. This was due to the significantly accelerated death rate after progression in those patients with early AHT for tetraploid and aneuploid (but not diploid) tumors. Delayed (on progression only) AHT resulted in high progression rates for all DNA ploidy classes (aneuploid greater than tetraploid greater than diploid); e.g., 21 of 30 diploid patients progressed and 6 patients died from disease at a median of 31.5 months in spite of immediate hormone treatment on progression. RRP and AHT for patients with Stage D1 disease resulted in a highly significant delay in overall progression (76% at 10 years) and excellent local control, depending on DNA ploidy pattern (diploid greater than tetraploid greater than aneuploid) compared with a treatment regimen without AHT (24% overall nonprogression); only 20% of all patients with AHT are projected to die of disease at 10 years. Disease in diploid patients (37%) treated with AHT rarely progressed and those patients are unlikely to die of disease in 10 years or less; delayed (on progression) hormone treatment for diploid patients seemed ineffective. Inclusion of values for prostate specific antigen led to a higher failure rate on progression, and this is dependent on DNA ploidy class (diploid greater than tetraploid greater than aneuploid). CONCLUSION Only patients with nondiploid tumors should be entered into prospective studies using innovative adjuvant treatment protocols to improve survival.

Flow cytometric nuclear DNA analysis was performed on paraffin-embedded tissue samples taken from 184 patients with pheochromocytoma and paraganglioma treated between 1960 and 1987. The Hedley technique was used for measurement of nuclear DNA content. Thirty-five percent of the tumors were DNA diploid, 33% showed a DNA tetraploid pattern, and 32% had DNA aneuploid pattern. Familial pheochromocytoma and associated endocrine or neoplastic disorders were more common among patients with DNA nondiploid tumors. Eighty-four percent of the tumors that invaded blood vessels and all patients with regional or distant metastases had tumors classified as DNA tetraploid or DNA aneuploid. Of 22 patients who had disease progression, 21 (95%) had tumors with abnormal DNA ploidy pattern (P less than 0.001). All 12 patients who died of cancer-related disease had abnormal DNA ploidy; none of the patients with DNA diploid tumor (n = 64) have died of pheochromocytoma (P less than 0.01). These results suggest that nuclear DNA ploidy pattern is an important and independent prognostic variable for patients with pheochromocytoma and paraganglioma.

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.

In the United States, nearly all cases of bladder cancer are of the transitional cell type, and epidemiological evidence indicates that among these, approximately 80% present initially as more or less well-differentiated, superficial papillary neoplasms with a tendency for multifocal or diffuse involvement of the urothelial surface and/or recurrent tumor episodes, but with limited potential for invasive growth or a lethal outcome. Bladder tumors with lethal potential generally begin as poorly differentiated, sessile growths that are usually invasive at first diagnosis. Carcinoma in situ is a change that must be elicited among intact surface cells before progressive proliferation results in a tumor mass. Evidence for such an association is both temporal and spatial. Since most transitional cell carcinomas begin as well-differentiated tumors, i.e., resembling normal urothelium, recognition of early neoplastic alteration before a papillary structure forms is unlikely and most of the evidence is spatial based upon urothelial changes adjacent to papillary tumors. The morphologic definition of carcinoma in situ is arbitrary and generally defined as a total replacement of the urothelial surface by cells which bear morphologic features of carcinoma, but which lack architectural alteration other than an increase in the number of cell layers, i.e., a flat lesion. The Union Internationále Contra Cancer/American Joint Committee on Cancer (UICC/AJCC) staging scheme for bladder cancer distinguishes non-invasive papillary growths as Ta and carcinoma in situ as Tis. Because detection of carcinoma in situ, either by cytology or biopsy, depends upon recognizable malignant morphologic characteristics, studies of the lesion tend to be limited to the higher grade or more anaplastic examples.(ABSTRACT TRUNCATED AT 250 WORDS)

A group of 41 young patients (age less than or equal to 40 years; mean, 35.7 years) and a group of 34 old patients (age greater than or equal to 80 years; mean, 82.4 years) who underwent operation for renal cell carcinoma between 1970 and 1986 were compared. Sex, grade, and DNA ploidy pattern distributions were similar between the groups. Granular cell and papillary cancers with lower stages at presentation were more common among the young. In patients with high-stage disease, 73 percent of the older group but none of the younger had DNA diploid tumors. Low-stage clear cell carcinoma caused cancer death only in the young. Stage I nondiploid clear cell carcinomas were associated with death (33%) only in the young. Overall, death rates seem similar for both groups but among the young most (63%) occurred with low-stage disease and a nondiploid pattern only; among the old, 88 percent occurred with high-stage disease and independent of DNA ploidy pattern.

We proposed a new classification of pheochromocytomas according to DNA ploidy patterns. Proliferation index (PI = S% + 4C%) might be an alternative to 4C% which was used as a critical marker of DNA nonaneuploid histograms. The follow-up survey revealed that DNA tetraploid with minimum increase of PI could not rule out the substantial possibility of malignancy and the comparison of DNA diploid histograms disclosed that 22 and 0% showed significant increase of the ratio of 4C% to S% under PI and 4C% criteria, respectively. In conclusion, 4C% was more effective and reliable than PI in order to classify DNA nonaneuploid pheochromocytomas.

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.

Cavernous hemangioma is a frequent tumor of the orbit in adults. Its complete removal results in dramatic relief of proptosis. The clinical course of an incompletely removed cavernous hemangioma is seldom recorded in the ophthalmic literature. The authors report the behavior of such a tumor that was observed during an 18-year period. Serial computed tomography (CT) documented a long period of slow growth, followed by a shorter interval of arrest, with eventual involution of tumor and relief of proptosis. No treatment was administered during observation.

We prospectively determined the accuracy of computerized tomography (CT) and needle biopsy of solid renal masses.A total of 100 patients with a solid renal mass who were scheduled for operation were prospectively evaluated. CT was performed before radical or partial nephrectomy. Biopsy of the surgical specimens was done twice through the tumor using an 18 gauge biopsy gun. Specimens were sent for permanent section and review by 2 pathologists blinded to each other and to the whole tissue specimens. Images were reviewed by 2 radiologists blinded to each other and to the results of pathological analysis. Results of CT and permanent biopsy were compared with the results of whole tissue specimen analysis.Specimens were obtained from 59 radical and 41 partial nephrectomies. Malignant neoplasms were present in 85 patients (85%). Overall accuracy was 77% and 72%, the nondiagnostic rate was 20% and 21%, sensitivity was 81% and 83%, and specificity was 60% and 33%. For the 2 radiologists overall accuracy was 60% and 66%, the nondiagnostic rate was 31% and 23%, sensitivity was 70% and 77%, and specificity was 20% and 20%, respectively.Overall permanent biopsy results were accurate in more than 72% of cases and CT was accurate in more than 60%. However, because the nondiagnostic rate for CT and needle biopsy was 20% and 31%, respectively, and specificity was low, we do not recommend routine preoperative CT and subsequent needle biopsy to guide treatment decision making. Rather, cases must be decided individually.

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.

Xanthoma is a localized collection of cholesterol-laden histiocytes that is usually idiopathic, but may be seen in patients with hyperlipidemia. We report seven cases of xanthoma involving the prostate, including one arising in a patient with mild hyperlipidemia. Prostatic xanthoma appeared as a solitary microscopic lesion in the peripheral zone (six cases) or transition zone (one case). One needle biopsy specimen with xanthoma was initially interpreted as well-differentiated adenocarcinoma with a clear cell (hypernephroid) pattern, but immunohistochemical studies revealed the histiocytic nature of the proliferation. Five cases (three needle biopsy specimens and two retropubic prostatectomy specimens) contained a solitary xanthoma adjacent to foci of adenocarcinoma. Another xanthoma was present in a transurethral resection specimen with nodular hyperplasia. Although unusual, xanthoma should be considered in the differential diagnosis of clear cell adenocarcinoma and other clear cell proliferations of the prostate, particularly in limited tissue samples, such as from needle biopsies and transurethral resections.

To provide information on the clinical presentation, diagnosis, pathology, and biologic behavior of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease (ADPKD), three cases seen at this institution between 1955 and 1992, as well as the cases reported in the literature, were reviewed in detail. No male predominance was observed (12 men, 13 women) in the 25 patients who met the inclusion criteria. The age of presentation was earlier than that seen in the general population (45 versus 61 yr). Fever, night sweats, and weight loss were prominent at presentation. Fever is a more common presenting symptom of renal cell carcinoma in ADPKD (32%) than in the general population (7%). Twenty percent of the patients had metastatic disease at presentation. Even with computed tomography and magnetic resonance, the diagnosis was difficult and often delayed, and the accumulation of 111In-labeled white blood cells can wrongly suggest a cyst infection. Renal cell carcinoma in ADPKD is more often concurrently bilateral (12 versus 1 to 5%), multicentric (28 versus 6%), and sarcomatoid in type (33 versus 1 to 5%) than in the general population. Because previous studies have failed to demonstrate a higher prevalence of renal cell carcinoma in ADPKD, this information suggests either a malignant potential restricted to a small subset of patients with this disease or an alteration in the biologic behavior of renal cell carcinoma when it develops in the setting of ADPKD.

Eighty-eight patients with pheochromocytoma and paraganglioma treated over a 28 year period (1960–1987) were studied. Based on clinical course, they were divided into three prognostic groups: benign (n = 57); multiple (n = 12); and metastatic (n = 19). Using clinical data, histopathologic findings, and tumor nuclear DNA content a prognostic profile for each group was constructed. The following variables were studied: age, familial pheochromocytoma, associated endocrine or neoplastic disorders, number and location of the lesion at diagnosis, size of the tumor, and the nuclear DNA ploidy pattern. Of these prognostic factors the most significant to predict a future malignant clinical course were large size and local tumor extension at time of surgery. Family history of pheochromocytoma, associated endocrine disorders, and young age at presentation predicted multiplicity. Old age, absence of familial pheochromocytoma or related endocrine disorders and DNA diploid tumors seem to be favorable findings. Using these variables in combination may be helpful for early identification of patients with malignant, multiple, or benign pheochromocytoma and paraganglioma. © 1992 Wiley-Liss, Inc.

Because small cell anaplastic carcinoma of the prostate is an uncommon tumor, it has remained a poorly defined entity. To elucidate further the clinical, pathological and immunohistochemical characteristics of this cancer the 27 patients who presented to the Mayo Clinic from 1960 to 1990 were reviewed. Of these patients 18 (67%) presented with pure small cell anaplastic carcinoma, and 9 (33%) were diagnosed with small cell anaplastic carcinoma and adenocarcinoma of the prostate. Twenty-six patients (96%) had either stage C or D disease at the time of diagnosis. Two patients presented with a paraneoplastic syndrome, including 1 man with inappropriate antidiuretic hormone secretion and 1 who suffered from thyroxine intoxication. Of 24 men with long-term followup 22 (92%) died of small cell anaplastic carcinoma of the prostate despite antiandrogen therapy and the remaining 2 are alive with active, progressive disease. The median survival time following diagnosis was 17.1 months (range 2 to 90 months). All tumors with tissue available for immunohistochemical staining reacted positive for neuron-specific enolase, indicating that small cell anaplastic carcinoma of the prostate is most likely a neuroendocrine neoplasm. No tumor stained positive for either prostatic acid phosphatase or prostate specific antigen. Pathologically, small cell anaplastic carcinoma of the prostate appears to be similar to oat cell carcinoma of the lung. This series of 27 patients emphasizes that small cell anaplastic carcinoma of the prostate is highly malignant, is frequently of advanced stage at presentation, responds poorly to antiandrogen therapy and has a poor prognosis.

Squamous cell carcinoma of the scrotum was diagnosed in 14 patients from 1945 to 1990. Patient age at diagnosis ranged from 40 to 73 years, with the mean age of 62 years. The most common presentation was a solitary skin lesion but inguinal adenopathy was noted in 5 patients (36%). The mean delay to diagnosis for all patients was 22 months, with a range of 2 months to 10 years. Predisposing factors included psoriasis treated with coal tar or arsenic, human papillomavirus infection and multiple cutaneous epitheliomas. The primary lesion was treated by local or wide local excision in all 14 patients. In addition, 4 patients underwent inguinal lymphadenectomy and 3 underwent radiotherapy to the pelvic and inguinal lymph nodes. Mean followup for all patients was 6 years. However, 11 patients were disease-free with a mean followup of 7 years. Improved prognosis was noted in patients with locally confined disease or carcinoma in situ only. There was no correlation between grade of tumor and survival. All patients with stages A1 and B disease treated with wide local excision and/or inguinal lymphadenectomy have done well on followup. Radiotherapy does not appear to impact on survival for patients with high stage disease.

Of 148 patients with clinical stage A1 (32) or A2 (116) disease who had radical prostatectomy only 63% and 62%, respectively, had pathological stage A disease. Although 25% of those with clinical stage A1 and 9% of those with clinical stage A2 disease had no cancer at radical prostatectomy, 12% and 29%, respectively, had pathological stage C disease or higher. Clinical Mayo grade 1 was never associated with extracapsular disease but 60% of those with grade 3 or higher tumor did have extracapsular disease. Over-all survival was comparable to the expected survival. Clinical stage A2 cancer was associated with a significantly higher progression rate (when prostate specific antigen values were considered, p = 0.0011) and cancer death rate (p less than 0.045) than stage A1 disease, whereas pathological stage was not significantly related to disease outcome, possibly because of the use of adjuvant treatment (hormonal or radiation) for some patients with pathological stage C or higher disease. The vagaries of clinical staging associated with stage A disease, as well as the previously documented progression on long-term followup (8 to 10 years) in younger (60 years old or less) patients with stage A1 prostate cancer make radical prostatectomy with its limited morbidity an acceptable treatment choice.

Of 3 patients with clinically localized adenocarcinoma of the prostate 2 were treated by radical prostatectomy and 1 was treated with radiation therapy. Serum prostate specific antigen (PSA) values were elevated before therapy. After treatment the PSA levels were decreased to zero. All 3 patients later had evidence of metastatic tumor spread to the liver with elevation of serum carcinoembryonic antigen but not PSA. Immunohistochemical staining of the 2 primary tumors from the prostatectomy specimens identified 2 cell clones, one immunoreactive to PSA and prostatic acid phosphatase (PAP) and nonimmunoreactive to carcinoembryonic antigen, and the other immunoreactive to carcinoembryonic antigen but not PSA or PAP. Biopsy of a hepatic metastasis in 2 patients confirmed anaplastic carcinoma of the carcinoembryonic antigen-producing cell type. Immunohistochemical staining of a lymph node metastasis identified the PSA-producing cell type only. Such results suggest selective metastatic spread of each cell type to its own organ tropic site. Occasional carcinoembryonic antigen-producing prostate cancers may metastasize to the liver. Serum carcinoembryonic antigen measurements occasionally may be useful in the management of certain prostate adenocarcinoma patients.

A total of 71 patients with prostate carcinoma who underwent radical retropubic prostatectomy had preoperative measurement of serum prostate specific antigen levels and subsequent nuclear deoxyribonucleic acid ploidy analysis of the resected tumors. Prostate specific antigen levels were determined by a commercially available prostate specific antigen radioimmunometric assay (normal range 0 to 4.0 ng./ml.). The paraffin-embedded blocks of the prostate specimens were analyzed by flow cytometry for nuclear deoxyribonucleic acid content using Hedley's technique and propidium iodide staining. A strong association was found between nuclear deoxyribonucleic acid ploidy patterns and preoperative prostate specific antigen values. All patients with tetraploid and aneuploid tumors had elevated preoperative prostate specific antigen values. By contrast, all patients with preoperative antigen values of less than 4 ng./ml. had diploid tumors (p less than 0.0034). Prostate specific antigen levels were proportional to the estimated volume of the primary tumor (p less than 0.0065). However, even after statistical adjustment for tumor volume the preoperative prostate specific antigen value was still significantly and independently correlated with deoxyribonucleic acid ploidy pattern (p less than 0.007). However, only 35% of the patients with diploid tumors had antigen levels within the normal range. Conversely, 65% of the patients with diploid neoplasms had abnormally high antigen levels preoperatively. These results suggest that patients with localized biopsy proved prostate carcinoma and normal preoperative prostate specific antigen values are most likely to have diploid tumors; based on a 95% confidence level, the true proportion of patients with normal prostate specific antigen values who also have a deoxyribonucleic acid diploid tumor is 85 to 100%. Since localized deoxyribonucleic acid diploid tumors are known to be associated with a favorable prognosis for patients with prostate carcinoma treated by radical prostatectomy, a preoperative serum prostate specific antigen level within the normal range may help to predict disease outcome.

Purpose: We prospectively determined the accuracy of computerized tomography (CT) and needle biopsy of solid renal masses.Materials and Methods: A total of 100 patients with a solid renal mass who were scheduled for operation were prospectively evaluated. CT was performed before radical or partial nephrectomy. Biopsy of the surgical specimens was done twice through the tumor using an 18 gauge biopsy gun. Specimens were sent for permanent section and review by 2 pathologists blinded to each other and to the whole tissue specimens. Images were reviewed by 2 radiologists blinded to each other and to the results of pathological analysis. Results of CT and permanent biopsy were compared with the results of whole tissue specimen analysis.Results: Specimens were obtained from 59 radical and 41 partial nephrectomies. Malignant neoplasms were present in 85 patients (85%). Overall accuracy was 77% and 72%, the nondiagnostic rate was 20% and 21%, sensitivity was 81% and 83%, and specificity was 60% and 33%. ...

• Over a 16-year period (1966 to 1981), 349 patients underwent radical retropubic prostatectomy for pathologic stage B adenocarcinoma of the prostate. Nuclear DNA content was measured by flow cytometry on available archival material of 283 patients. Two hundred sixty-one patients (92%) had high-quality histograms. The ploidy distribution was as follows: DNA diploid, 177 (68%); DNA tetraploid, 74 (28%); and DNA aneuploid, 10(4%) The average follow-up was 9.4 years. At the time of follow-up, 53 patients (20%) within the study group had developed tumor progression: 22 local, 23 systemic, and 8 both. The ploidy distribution of the population that developed tumor progression was 27 DNA diploid (51%), 16 DNA tetraploid (30%), and 10 DNA aneuploid (19%). This ploidy distribution is significantly different from that found for the nonprogression group with stage B disease. Overall, 31% of patients with DNA nondiploid tumors had tumors that progressed compared with 15% of patients with DNA diploid tumors. All (100%) DNA aneuploid tumors progressed. The DNA ploidy distribution of all pathologic stage B prostate cancers differs significantly from that found in more advanced stages (C and D1) previously reported for the same time interval. However, the ploidy distribution of stage B tumors that progressed closely resembles that of the stage C and D1 tumors. These results further support the working hypothesis that nuclear DNA content has marked prognostic significance for patients with adenocarcinoma of the prostate. It seems to us that analysis of ploidy by flow or static cytometry will become an essential tool for treating patients with localized prostate cancer. (Arch Surg. 1990;125:327-331)

Sixteen consecutive patients with bulky stage II seminoma were treated with primary radiotherapy from 1971 to 1982. Bulky stage II seminoma was defined as either Union Internationale Contre le Cancer (UICC) stage IIC (retroperitoneal metastases greater than 5 cm) or IID (palpable retroperitoneal metastases) with no evidence of visceral or supradiaphragmatic disease. The median age was 38 years (range, 26 to 52) and the median size of retroperitoneal disease was 11.5 cm (range, 5 to 25 cm). Patients were treated with generous radiation ports (such as wide hockey-stick or whole abdomen) often followed by boosts to the sites of bulky disease. Median tumor dose was 3,235 cGy (range, 2,700 to 5,668 cGy). Mediastinal (with or without supraclavicular) prophylactic radiation was administered to 15 of the 16 patients with a median dose of 2,590 cGy (range, 1,200 to 3,700 cGy). Treatment toxicity was mild. All 16 patients achieved a complete remission (CR) with radiotherapy. Median follow-up from the time of diagnosis was 60 months, and all patients are currently disease-free. Two patients recurred after therapy but were rendered disease-free with further radiation. These two relapsing patients have remained disease-free, following initial recurrence, for 8 years. The excellent results obtained with modern imaging and radiotherapeutic techniques justify radiotherapy as the initial treatment of choice for bulky stage II seminomas.

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.

Bisantrene, a clinically active anticancer drug with limited solubility at physiologic pH, was delivered by selective injection into the internal iliac artery of male calves. The percutaneous transfemoral angiographic techniques used in the calves were identical to those used in adult human patients. Directed intravascular precipitation of bisantrene at the maximal tolerable clinical dose for intravenous administration (260 mg/m 2 ) caused severe tissue damage in 5 of 10 animals that received these intra-arterial injections. (One calf in this study group died of unknown causes 10 days after the drug infusion.) A reduced intra-arterial dose (50 mg/m 2 ) was used in seven calves, and no local tissue damage was evident on gross or microscopic examination. Nevertheless, resultant concentrations of bisantrene deposited in the ipsilateral bladder wall were 10- to 100-fold those concentrations found after intravenous administration of a dose 5 times higher. These animal toxicology and pharmacology data support initiation of a phase I clinical trial of directed intravascular precipitation of bisantrene in humans. This clinical trial will be developed for patients with advanced refractory cancers of the anatomic true pelvis, such as those originating in the urinary bladder, prostate, rectum, and uterine cervix.

Voided-urine cytology as a screen for the early detection of urinary bladder cancer is analyzed to determine its potential in an asymptomatic population. Previous cost-effectiveness as sessments predict that screening will extend life-span at a cost-per-detected-case that is comparable to those of other cancer screening efforts. The focus here is on investigating screening from the perspective of the individual contemplating the screening decision. The analysis is based on a computerized model of bladder cancer which integrates a Markov representation of the induction and progression of the disease with algorithms representing diagnostic and therapeutic intervention strategies, intervention effectiveness, and cost. It is shown that the utilities, as well as the probabilities, of true-positive, false-positive, and false- negative screening outcomes are affected by the particular testing regimen employed and the age at which screening takes place. Screening at age 55 or age 65 was analyzed for individuals of normal risk. Analyses predict that the predisposition of cytology screening to identify the high-grade, aggressive form of the disease will result in gains in life expectancy of more than three years for the asymptomatic true-positive case. Results support the decision to screen, and by requiring a repeatedly positive test result, the probability of a false-positive outcome will not exceed that of a true-positive outcome at age 65. Except for the risk of a false-positive outcome, cytology screening compares favorably with what could theoretically be obtained if a 100% accurate screening test were available. Key words: cytology screening; decision analysis; disease modeling; bladder cancer. (Med Decis Making 8:110-119,1988)

Flow cytometric nuclear DNA ploidy analysis was used to study pathologic stage C prostatic adenocarcinoma (pT3, N0, M0) in 146 patients who underwent radical retropubic prostatectomy and bilateral pelvic lymphadenectomy between 1967 and 1981. Of these tumors, 46% had a DNA diploid pattern, 47% had a DNA tetraploid pattern, and 7% had a DNA aneuploid pattern. Abnormal ploidy patterns were associated more frequently with histologic high-grade tumors than with low-grade tumors. Considered alone, DNA ploidy pattern showed a strong association with subsequent prognosis. The median interval to progression for tumors with DNA tetraploid and DNA aneuploid patterns was 7.8 and 3.5 years, respectively. For the DNA diploid tumors, only 23% progressed within 18 years, the longest follow-up. At 10 years, only 10% of patients with DNA diploid tumors had died of prostatic cancer, in comparison with 28% of the DNA tetraploid and 36% of the DNA aneuploid groups (P less than 0.01). By analysis of a combination of histologic tumor grade and nuclear DNA ploidy pattern, an even stronger association with prognosis was demonstrated. For the 38 patients with histologic low-grade and DNA diploid tumors, progression-free survival was 92% at 10 years, in comparison with 57% for 23 patients with low-grade DNA nondiploid tumors. Patients with high-grade tumor had a poorer prognosis whether the DNA ploidy pattern was diploid or nondiploid. Nuclear DNA ploidy pattern is an important and independent prognostic variable for patients with pathologic stage C prostatic cancer treated by radical prostatectomy.

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.