13-cis-Retinoic acid: inhibition of bladder carcinogenesis induced in rats by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Transitional cell carcinoma was induced in the bladders of male Fischer rats by 12 oral doses of the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Feeding of 13-cis-retinoic acid after completion of carcinogen treatment diminished the number and severity of cancers and other proliferative lesions of the bladder.

Morphological and clinical observations of patients with early bladder cancer treated with total cystectomy.

In 21 cases, early bladder cancer was detected by urine cytology, although not by cystoscopy, and was treated by total cystectomy. The neoplasms, all transitional cell carcinomas of moderate to high degrees of anaplasia, were entirely in situ in 17 of the 21 patients; in 4, although mainly in situ, the tumors showed additional minimal microinvasion. Widespread mucosal involvement was demonstrated in every case by step-sectioning, and extension into the prostatic ducts occurred in 7 of the 19 male patients and into the mucosa of one or both distal ureters in 12 patients. Premalignant atypia of the mucosa was also widespread and direct intramucosal spread of cancer cells was a significant factor, particularly along the prostatic ducts and ureters. The duration of significant symptoms (follow-up for 9 years before cystectomy in several cases and for 8 years in 1 histologically proved case) suggests that the evolution of these tumors may be considerably longer than previously documented.

Clinical observations on sixty-nine cases of in situ carcinoma of the urinary bladder.

In the course of screening 35,000 urological outpatients with urine cytological examinations, cytological indication of cancer was found in 106 patients in the absence of a cystoscopically visible bladder tumor. Sixty-nine of the 106 patients have biopsy-proven in situ carcinoma of the bladder, all transitional in type and anaplastic. Follow-up data on effects of therapy are available on 58 patients treated by various means, including total cystectomy, partial cystectomy, transurethral fulguration, intravesical thiotepa, and external radiation. The duration of symptoms before diagnosis was remarkably long, and the prolonged course of the in situ lesion was also noteworthy. Differences in the observed behavior of in situ bladder carcinoma may be due, in addition to differences in host resistance, to the existence of two pathogenetic forms of bladder cancer, one arising in an extensive field of abnormal epithelium and the other developing in a focal area of abnormality.

Radiotherapy as initial treatment for bulky stage II testicular seminomas.

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.

Carcinoma in Situ of the Bladder.

Central to the earlier detection and effective treatment of bladder cancer is the understanding of the basic principle that in situ cancer, evolving from epithelial atypia or hyperplasia, is the early phase in the development of invasive bladder cancer. While it may be asymptomatic, irritative bladder symptoms such as frequency, urgency, and dysuria irrespective of bacteriuria are usually evident and should be evaluated with exfoliative urinary cytology to detect the presence of this cancer. Properly collected and skillfully interpreted cytologic examination of the urine is probably the most accurate screening test for this and other important varieties of bladder cancer. Improved technologic features of cystoscopy have aided in the identification of in situ cancer, particularly when multiple random cold biopsy specimens of all quadrants, including the trigone, of the bladder and of the prostatic urethra are employed. Such investigative methods recognize that in situ cancer is a generalized urothelial malignancy that very often involves ureteral, prostatic as well as all bladder mucosa. Despite the pathologic observation that this cancer shows an intense cellular activity, the temporal aspect of its transition from a superficial cancer to an invasive one remains unpredictable, although clearly finite. Treatment is controversial. Radical cystectomy should effect cure if recommended early and before it becomes clinically apparent that the disease is already invasive in some urothelial locations. If the cancer appears to be localized to a relatively small (5 cm) area of the bladder and the patient's symptoms are not excessive, intravesical chemotherapy using such preparations as Thio-tepa, mitomycin, Adriamycin, or epodyl may result in a temporary, sometimes complete, remission.

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.

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.

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.

Elevated levels of the eosinophil granule major basic protein in the sputum of patients with bronchial asthma.

The eosinophil granule major basic protein (MBP) is toxic to parasites and mammalian cells. Because eosinophilia is characteristic of asthma, we tested the effect of MBP on bronchi and assayed sputa for this protein. We found that MBP damaged bronchial epithelium in vitro and produced changes that mimicked those in asthma. Radioimmunoassay of sputa from 100 consecutive patients with respiratory diseases revealed MBP levels above 0.1 mug/ml in 13 patients, and 11 of these had asthma. In 15 patient hospitalized for asthma, MBP levels of sputum were markedly elevated. Treatment with bronchodilators and glucocorticoids caused an increase peak expiratory flow rate, a reduction in blood eosinophils, and a decrease in the serum and sputum levels of MBP. The results indicate that eosinophil granule constituents are released into the bronchi in asthma and that measurement of sputum MBP may be useful in identifying asthma. The possibility that the eosinophil damages bronchial epithelium in asthma is discussed.

Stage D1 prostatic adenocarcinoma: significance of nuclear DNA ploidy patterns studied by flow cytometry.

Flow cytometric analysis of nuclear DNA ploidy pattern was performed on 91 samples of prostatic adenocarcinoma from patients with stage D1 disease (metastatic deposits in pelvic lymph nodes). All patients had undergone radical retropubic prostatectomy and bilateral pelvic lymphadenectomy. Clinical follow-up ranged from 5 to 19 years. Nuclei were extracted from paraffin-embedded archival material. Isolated nuclei were stained with propidium iodide. The DNA ploidy pattern was diploid (normal) in 42% of tumors, tetraploid in 45%, and distinctly aneuploid in 13%. Only 15% of DNA diploid tumors progressed locally or systemically, whereas 75% of tumors with an abnormal DNA ploidy pattern (tetraploid or aneuploid) subsequently progressed (P less than 0.0001). Among low-grade tumors, ploidy analysis detected a subgroup associated with a poor prognosis; among high-grade tumors, a subgroup associated with a favorable prognosis was detected. None of the patients with a DNA diploid tumor died of prostatic cancer during the period of observation. In contrast, 43% of patients with DNA tetraploid tumors and 44% of those with DNA aneuploid tumors had died of prostatic cancer 10 years after surgical treatment (P less than 0.001). Determination of nuclear DNA ploidy pattern by flow cytometry provides objective, highly significant, prognostic information for patients with stage D1 prostatic carcinoma.

Detection and localization of In situ carcinoma of the bladder with hematoporphyrin derivative.

The extent and localization of in situ carcinoma of the urinary bladder are frequently difficult to assess. We have studied this problem by employing intravenous hematoporphyrin derivative, an endoscopic detection device, and complete pathologic bladder mapping. These preliminary investigations indicate that hematoporphyrin derivative localizes in dysplastic and neoplastic transitional cell epithelium and that these abnormal areas can be detected during a cytoscopic examination with the use of our detection device.

Directed intravascular precipitation of bisantrene for pelvic malignant lesions: preclinical studies.

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/m2) 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/m2) 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.

Stage C prostatic adenocarcinoma: flow cytometric nuclear DNA ploidy analysis.

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.

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.

Malignant germ cell tumors of the mediastinum.

A review of 56 cases of primary malignant germ cell tumors of the mediastinum revealed that, as with benign teratomas, the tumors occurred in young adults (mean age 29 years) but that the sex distribution differed (86% male and 14% female). A single germ cell element was found in 37 (66%) of the tumors, and various combinations were present in the remaining 19 (34%). The tumors were classified among five recognized types of germ cell tissues. There were 24 seminomas (22 pure and two with mature teratomas), 17 embryonal carcinomas (nine pure and eight with mixtures), five teratomas, seven choriocarcinomas (three pure and four with mixtures), and three pure yolk sac tumors. Most (86%) of the patients were symptomatic at the initial examination, with chest pain, cough, and loss of weight being the most frequent presenting symptoms. The standard posteroanterior and lateral roentgenograms were the most helpful diagnostic tool, showing evidence of an anterior mediastinal mass in 53 patients. The diagnosis was established by surgical exploration of the mediastinum or by biopsy of a lymph node in 55 patients. Of the 55, 24 (43.6%) had complete resection of the tumor and 31 (56.4%) had incomplete resection or biopsy alone. The overall prognosis for mediastinal germ cell tumors is poor, partly because the tumors are far advanced at the time of diagnosis but also because some of the tumors that contain embryonal cell carcinoma, choriocarcinoma, and yolk sac elements are very aggressive. Factors that were prognostic in patients with seminoma--such as age, presence of the superior vena caval syndrome, lymphadenopathy, evidence of hilar disease on the chest roentgenogram, and resectability--were not predictive in patients with other types of malignant germ cell tumors. Although aggressive combination chemotherapy may represent a significant treatment modality for nonseminomatous mediastinal tumors, the present study spanned many years in which no chemotherapy was available. Patients in the later years of the study received combination chemotherapy with various treatment regimens. No conclusions concerning specific chemotherapy, therefore, can be derived from this study.

Benign teratomas of the mediastinum.

Approximately 8% of all mediastinal tumors are benign teratomas. We reviewed 86 cases of benign teratoma seen at the Mayo Clinic from 1930 through 1981. The mean age of the patients was 28 years and the sex distribution was approximately equal. The most common symptoms were chest, back, or shoulder pain, dyspnea, and cough, but 36% were asymptomatic at the time of presentation. Chest roentgenograms showed a well-circumscribed anterior mediastinal mass which often protruded into one lung field. Detectable calcification was observed in 22 patients: a calcified tumor wall in seven, bone or teeth in the mediastinum of seven, and nonspecific calcifications in eight. Surgical excision remains the best means of diagnosing and treating this benign tumor. Though the tumors are histologically benign, they may present difficult surgical problems because of the vital structures involved. Since 1952 there has been a change in the clinical presentation of patients with this entity: More patients are asymptomatic and have smaller tumors and fewer complications than prior to 1952.

Primary orbital hemangiopericytoma. An aggressive and potentially malignant neoplasm.

The aggressive behavior and potentially lethal nature of some hemangiopericytomas primary in the orbit are generally unknown in the field of ophthalmology. The neoplasm is not common in the orbit, and reports in the ophthalmic literature usually describe single-case examples of the neoplasm with short-term periods of observation. Two in our series of 11 patients died of metastasis 35 years after the onset of symptoms. Another patient died of local orbital recurrence with secondary invasion of the intracranial vault, which was possibly related to heavy radiotherapy. In the orbit, those neoplasms frequently are circumscribed in their growth. Complete and intact removal is recommended. If the tumors are incompletely excised, recurrences are frequent but may not be manifest as long as ten years after surgery.

Testicular yolk sac and embryonal carcinomas in pediatric patients: comparative immunohistochemical and clinicopathologic study.

Twelve Mayo Clinic patients less than 17 years of age were identified who had yolk sac tumors of the testis. Seven additional pediatric patients were identified who had embryonal carcinoma of the testis. These 19 patients form the basis for this study correlating histopathology and immunocytochemical patterns with clinical outcome. Immunoperoxidase studies were done with antibodies to alpha-fetoprotein, beta-subunit of human chorionic gonadotropin, alpha-1-antitrypsin, and human albumin. The immunocytochemical staining pattern in these neoplasms did not appear to correlate with prognosis.

Adrenocortical carcinoma: nuclear deoxyribonucleic acid ploidy studied by flow cytometry.

Nuclear deoxyribonucleic acid (DNA) ploidy studies with use of paraffin-embedded specimens were performed by flow cytometry on 52 adrenocortical carcinomas. Specimens were prepared by the combined techniques of Hedley and Vindeløv. Clinical course was obtained by chart review and follow-up examination. Nine (17%) tumors had a normal (diploid) DNA pattern, 13 (25%) were DNA tetraploid, and 30 (58%) were DNA aneuploid. The DNA aneuploid group was subdivided: 18 tumors with one stemline and 12 tumors with two stemlines of abnormal DNA cells. For tumors that were resected for cure, the 5-year Kaplan-Meier disease-free survival rates of the five patients with DNA diploid tumors and of the six patients with DNA tetraploid tumors were 80% and 33%, respectively. For 21 patients of whom 12 had one-stemline and nine had two-stemline DNA aneuploid tumors, the survival was 67% and 0%, respectively. Following palliative resection, the 4-year survival rates of the four patients with DNA diploid, seven with DNA tetraploid, five (omitting one with short follow-up) with one-stemline DNA aneuploid, and three with two-stemline DNA aneuploid tumors were 0%, 0%, 0%, and 33%, respectively. Although adrenocortical carcinoma is in general markedly aggressive, the addition of nuclear DNA ploidy studies may help to identify certain groups of patients who have a relatively favorable prognosis.

Pheochromocytoma: nuclear deoxyribonucleic acid patterns studied by flow cytometry.

Nuclear deoxyribonucleic acid (DNA) ploidy studies with paraffin-embedded archival tumor specimen blocks were performed by flow cytometry on extracted nuclei from 75 pheochromocytomas. Clinical details, specifically including histologic findings, biochemical studies, and ultimate fate, were investigated. Preparation of paraffin-embedded tissue specimens was carried out by the technique of Hedley et al. and stained with propidium iodide according to the method of Vindeløv et al. Twenty-three tumors showed a normal DNA histogram, 31 showed significant increase in the 4C (DNA tetraploid) peak, and 21 exhibited a DNA aneuploid peak. To define a subset of patients who had either died as a result of pheochromocytoma or had been followed for a minimum of 10 years, 13 patients were excluded. Of the remaining 62 patients, all of the 18 patients with a normal DNA histogram followed a benign clinical course, including normal fractionated urinary catecholamines. However, eight (31%) of the 26 patients classified DNA tetraploid/polyploid and seven (39%) of the 18 patients exhibiting a DNA aneuploid peak had evidence of malignancy; these two groups had significantly more malignant tumors (p less than 0.05 and p less than 0.02, respectively) than the normal DNA group. Flow cytometric DNA ploidy measurements of isolated nuclei seem to provide useful prognostic information for patients with pheochromocytoma.