Leydig cell tumor of the testis: a clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors.

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.

Transitional cell carcinoma of the prostate: clinicopathologic study of 50 cases.

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.

Low-grade collecting duct carcinoma of the kidney: report of 13 cases of low-grade mucinous tubulocystic renal carcinoma of possible collecting duct origin.

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 beta E12 (8 of 13 cases), and Ulex Europeus antigen 1 (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.

Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic findings in 80 cases.

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.

Relationship between DNA ploidy and functional estrogen receptors in operable prostate cancer.

OBJECTIVE: To evaluate 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 between 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.

Carcinoid tumor of the rectum. DNA ploidy is not a prognostic factor.

PURPOSE: This study was designed to evaluate the clinical characteristics, surgical treatment, and outcome of carcinoid tumors of the rectum and to assess flow cytometry deoxyribonucleic acid (DNA) analysis as a potential prognostic factor for management of these tumors. METHODS: Medical records, tumor registry database, and pathology slides were retrospectively reviewed. Flow cytometry DNA analysis was performed on archived specimens. RESULTS: One hundred nine patients with rectal carcinoid tumors underwent surgery between 1962 and 1987. Follow-up was available in 86 patients for a mean period of 12 years. Of 100 patients with tumors less than 2 cm, only one with a 1.5 cm ulcerated tumor developed liver metastases. Of nine patients with a tumor more than or equal to 2 cm, three with known liver metastases underwent rectal biopsy only, and three had rectal biopsy and laparotomy with biopsy of liver metastases. Three patients underwent radical resection. Following abdominoperineal resection, one patient died with local recurrence after 5 years, and one developed hepatic recurrence after 5.5 years and died at 9 years. One patient with coloanal anastomosis developed local and hepatic metastases seven years after surgery and died at ten years. No patients developed carcinoid syndrome. DNA ploidy did not correlate with metastases at presentation or recurrence of carcinoid tumor. CONCLUSION: Radical resection of rectal carcinoids with ulceration or size greater than or equal to 2 cm is associated with a poor prognosis; however, survival may be long term, even in the presence of metastatic disease. DNA ploidy does not appear to be a useful prognostic factor for rectal carcinoid tumors.

Leiomyosarcoma of the prostate. Report of 23 cases.

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.

Chromophobe cell renal carcinoma: clinicopathological features of 50 cases.

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%) were discovered incidentally and most (86%) 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%) 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.

Carcinosarcoma of the prostate. Report of 21 cases.

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.

prostatic xanthoma: a mimic of prostatic adenocarcinoma.

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.

Renal cell carcinoma in autosomal dominant polycystic kidney disease.

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.

Clinical significance of nuclear DNA ploidy pattern in nonseminomatous germ cell testicular tumors.

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 cancer: role of conservative surgery.

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 of adulthood. Report of three cases.

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.

Use of fluorescent in situ hybridization for deoxyribonucleic acid ploidy analysis of prostatic adenocarcinoma.

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 (p < or = 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.

Flow cytometric DNA ploidy pattern for predicting metastasis of clinical stage I nonseminomatous germ cell testicular tumors.

The best treatment of patients with clinical Stage I nonseminomatous germ cell testicular tumors (NSGCTT) remains controversial. Archival formalin-fixed paraffin-embedded testicular tumor specimens from 23 patients diagnosed between 1977 and 1988 were available for analysis. All patients had clinical Stage I NSGCTT, and the specimens were prepared using Hedley's technique and propidium iodide staining prior to flow cytometric ploidy analysis. Tumors from 3 patients (13%) were classified as DNA diploid; the remaining 20 tumors had DNA aneuploid patterns. Eleven patients had retroperitoneal lymph node dissection (RPLND); 2 (18%) were upstaged to pathologic NSGCTT Stage IIA, and 1 had a subsequent relapse in the contralateral testicle. Among 12 patients in the surveillance protocols, 3 (25%) had tumor recurrence. All patients who were either upstaged to pathologic NSGCTT Stage IIA or had tumor recurrence while under surveillance had DNA aneuploid patterns. The 3 patients with DNA diploid tumor patterns had been in the surveillance protocols. To date, with fifteen months minimum follow-up, none has had tumor recurrence. Such data suggest that flow cytometric DNA ploidy analysis, when used as an adjuvant to more traditional prognostic parameters, may help to identify a group of patients with clinical Stage I NSGCTT at very low risk for recurrence and perhaps well-suited for surveillance management.

Human papillomavirus in penile squamous cell lesions. A comparison of an isotopic RNA and two commercial nonisotopic DNA in situ hybridization methods.

Sensitive isotopic in situ hybridization analysis of 34 paraffin-embedded penile squamous cell lesions for human papillomavirus (HPV) types 6, 11, 16, 18, and 31 revealed similar HPV detection rates, HPV-type specificity, and viral distribution patterns to those described in analogous cervical and vulvar lesions. Human papillomavirus was detected in six of six cases of condylomata acuminata (HPV type 6 [n = 4], HPV type 11 [n = 2]), in six of eight cases of squamous cell carcinoma in situ (HPV type 16 [n = 5], HPV type 31 [n = 1]), and in four of 10 cases of squamous cell carcinoma (all were HPV type 16). Interestingly, all 10 cases of penile verrucous carcinoma analyzed were HPV negative. Reevaluation of the HPV-positive penile lesions with two commercial nonisotopic HPV-typing in situ hybridization kits (Pathogene, Enzo, New York, NY; Viratype, Life Technologies, Gaithersburg, Md), revealed positive results for HPV type 6 and/or type 11 in all six cases of condylomata acuminata studied. However, only the Viratype assay detected HPV genome in the high-grade squamous cell lesions, with a relative sensitivity of 70% compared with that of the isotopic assay.

Clinical Stage B0 or T1c prostate cancer: nonpalpable disease identified by elevated serum prostate-specific antigen concentration.

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.