Search PubMedSearch

Biomedical subjects

D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 19 recordsLinked to original sources

Overexpression of the wild type p73 gene in human bladder cancer.

p73, a first p53 relative, was recently identified and shown to be monoallelically expressed in a number of different human tissues. To determine the potential role of this gene in human bladder cancer, we investigated p73 expression levels, allelic expression patterns, and analysed p73 mutations in 23 unselected primary invasive bladder cancers with matched normal tissues and in seven bladder cancer cell lines. In a comparison between normal and tumor tissues using quantitative RT-PCR analysis, we found that p73 was overexpressed in 22/23 bladder cancers, sometimes as great as 20-fold. Allelic expression analysis using a C/T polymorphism in exon 2 and a newly identified T/C polymorphism in exon 5 revealed that p73 was biallelically expressed in both normal bladder and cancer tissues, suggesting that p73 is not imprinted in bladder tissue. Mutation screening of the p73 gene in bladder cancer DNAs using denaturing high-performance liquid chromatography analysis and DNA sequencing revealed no tumor-specific mutations in any coding exons of the p73 gene. These data suggest that the p73 is unlikely to be a tumor suppressor gene, but that overexpression of p73 may contribute to tumorigenesis in bladder cancer.

Alleles

Cystic renal cell carcinoma is cured by resection: a study of 24 cases with long-term followup.

PURPOSE: The true incidence and biological behavior of cystic renal cell carcinoma are not known. To our knowledge we present the largest series of patients with cystic renal cell carcinoma with long-term followup. MATERIALS AND METHODS: We reviewed the Mayo Clinic surgical pathology files of renal cell cancer cases with a cystic component resected from 1969 to 1997, and arbitrarily chose 75% tumor involvement by cysts as a cutoff for inclusion in the study. RESULTS: We identified 24 cases of clear cell renal cell carcinoma with 75% or greater involvement by cysts comprising 0.79% of 3,047 renal cell cancer cases resected at our institution between 1969 and 1997. Mean patient age was 62.7 years (range 40 to 83). A total of 11 patients (46%) underwent radical nephrectomy, 4 (17%) simple nephrectomy, 3 (12%) partial nephrectomy and 6 (25%) tumor enucleation. Mean tumor involvement by cysts was 84% (range 75 to 95) and in 11 cases (46%) involvement was 90% or greater. Cancer stage was T1 in 20 patients (83%), T2 in 1 (4.4%) and T3a in 4 (12.5%). Cancers were diploid in all but 1 case. Mean followup was 77.6 months (range 8 to 428, median 51). A total of 22 patients (92%) had no evidence of cancer and 2 died of intercurrent disease. CONCLUSIONS: Our results indicate that cystic renal cell carcinoma is uncommon and usually cured by resection, regardless of size, stage or number of cysts. These patients may benefit from nephron sparing surgery, such as partial nephrectomy.

Adult

Subepithelial pelvic hematoma of the kidney clinically mimicking cancer: report of six cases and review of the literature.

OBJECTIVES: Renal pelvic subepithelial hematoma is a rare but significant clinical mimic of neoplasm. Investigation and treatment of this diagnostic problem are uncertain. METHODS: We add 6 patients with this entity to the 15 previously published cases. All 6 were clinically suspected of having cancer, and 5 underwent nephrectomy. RESULTS: The most common clinical findings are gross hematuria (19 of 21 cases) and acute onset of flank pain (13 of 21 cases). Intravenous urogram usually reveals a filling defect at the ureteropelvic junction. Pathologic findings include massive subepithelial and peripelvic hemorrhage, hydronephrosis, cortical infarcts, and renomegaly. Two of our patients have previously undescribed clinical associations, including one who was 2 weeks postpartum and another with ureteropelvic junction obstruction. In addition, our patient with obstruction is the first with subepithelial hematoma to be treated successfully with pyeloplasty. CONCLUSIONS: Subepithelial pelvic hematoma may be effectively treated with pyeloplasty or partial nephrectomy if distinguished from cancer preoperatively. Awareness of this rare entity may allow preoperative identification, but this has not been possible to date.

Adult

Clinically unsuspected and undetected (clinical stage t0) prostate cancer diagnosed on random needle biopsy.

OBJECTIVES: To describe the findings in 4 patients who underwent radical prostatectomy for clinically undetected and unsuspected prostate cancer detected on random needle biopsy. METHODS: We reviewed the Mayo Clinic Radical Prostatectomy Prostate Cancer Database of 5793 prostatectomies from 1987 to 1997, and identified 4 patients who had prostate cancer detected on random needle biopsy of the prostate with serum prostate-specific antigen (PSA) less than 4 ng/mL and normal digital rectal examination. Each had requested biopsy despite the absence of clinical suspicion of cancer; 3 had normal transrectal ultrasound, and the fourth had a benign hypoechoic lesion contralateral to the cancer. RESULTS: Mean patient age at diagnosis was 65.5 years (range 61 to 67). Mean PSA was 2.4 ng/mL (range 2 to 2.9). Mean tumor volume was 3 cc (range 0.04 to 11.2). Mean Gleason grade at prostatectomy was 5.75 (range 5 to 7). Prostate cancer was Stage T2a in 1 patient (25%), T2c in 2 (50%), and T3a (25%) in 1. Three tumors were DNA diploid, and one was aneuploid. All patients were alive without evidence of cancer at a mean follow-up of 43 months (range 25 to 53) with undetectable serum PSA concentration. CONCLUSIONS: Our findings indicate that clinically unsuspected and undetected (clinical Stage T0) prostate cancer may be clinically significant. Patient insistence on biopsy reflects increasing concern among the public about prostate cancer. Current clinical thresholds for biopsy detection will fail for some patients with clinically significant prostate cancer.

Aged

Prostatic central zone volume, lower urinary tract symptom severity and peak urinary flow rates in community dwelling men.

PURPOSE: Previous studies have suggested that central zone prostatic volume may be more strongly correlated with lower urinary tract symptom severity and peak urinary flow rates than total prostatic volume. We determine whether prostatic central zone volume and central zone index volume correlate better with these measures than total prostate volume in an age stratified, community based random sample of healthy white men. MATERIALS AND METHODS: A cohort of 474 men were randomly selected from the 2,115 community dwelling men, 40 to 79 years old, who participated in the Olmsted County study of urinary symptoms and health status among men. All men had undergone transrectal ultrasound of the prostate. The total prostate and hypoechoic central zone volumes were caliper measured by 1 operator on static ultrasounds from baseline. Volumes were calculated with the prolate ellipsoid formula. The operator was blinded to clinical information and outcome. The associations between total prostate volume and central zone index (central zone volume/total volume), and American Urological Association (AUA) symptom index and peak urinary flow rates, respectively, were quantified with the Spearman rank correlation coefficient and least squares regression models. RESULTS: There was a moderately strong correlation between patient age and central zone volume (rs 0.54, p <0.001), total prostate volume (rs 0.45, p <0.001) and central zone index (rs 0.38, p <0.001). The AUA symptom index and peak flow rates correlated less strongly with central zone volume (rs 0.17, p = 0.001 and rs -0.20, p <0.001, respectively) and total volume (rs 0.16, p <0.001 and rs -0.16, p <0.001, respectively). Central zone index weakly correlated with AUA symptom index (rs 0.08, p = 0.103) and peak urinary flow rate (rs -0.08, p = 0.0823). In regression models predicting AUA symptom index and peak flow rates central zone volume added little information after accounting for age and total prostatic volume in predicting AUA symptom index (p = 0.55) and peak flow rate (p = 0.84). CONCLUSIONS: Central zone volume measured from static images optimized for total prostate volume no more closely correlated with lower urinary tract symptom severity or peak urinary flow rates than total prostate volume. Thus, the potentially greater imprecision in measuring central zone volume may not be offset by gains in strength of association with lower urinary tract symptom severity or peak urinary flow rates.

Adult

Androgen receptor expression in prostatic intraepithelial neoplasia and cancer.

PURPOSE: Androgen receptors are present in virtually all epithelial cells of the prostate, including benign epithelium, high grade prostatic intraepithelial neoplasia and cancer. However, there have been variable results regarding the clinical significance of cells expressing androgen receptors in prostate cancer. We evaluated the predictive accuracy of androgen receptor expression in prostatic intraepithelial neoplasia and cancer for clinical progression and survival in patients with organ confined prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: The study consisted of 172 previously untreated patients who underwent radical prostatectomy at our clinic between 1987 and 1991 with intermediate to high grade (Gleason score 6 to 9), pathological stage T2 cancer and negative surgical margins. Mean followup was 7.4 years (range 1.2 to 10.1). Mouse monoclonal anti-human androgen receptor antibody was used for immunohistochemical studies on select tissue sections from each case. We counted 100 nuclei from 3 separate areas of benign epithelium, prostatic intraepithelial neoplasia and cancer (total 300 nuclei for each diagnostic category) for each case. Mean nuclear androgen receptor expression was determined from the mean of the individual cases for each diagnostic category. Intensity was also evaluated using a subjective scale from 0 (no staining) to 3 (strong staining). We determined the correlation of clinical progression and the number of androgen receptor immunoreactive prostatic intraepithelial neoplasia or cancer nuclei, and then performed multivariate analysis which included deoxyribonucleic acid ploidy, radical prostatectomy Gleason score and preoperative serum prostate specific antigen using the Cox proportional hazards model. Progression was defined as a positive biopsy, positive bone scan or biochemical progression (postoperative serum prostate specific antigen greater than 0.2 ng./ml.). RESULTS: Nuclear immunoreactivity for androgen receptors was observed in all cases. Mean percent of immunoreactive nuclei was higher in benign epithelium than in prostatic intraepithelial neoplasia and cancer (56.3, 46.1 and 53.6%, respectively, pairwise comparisons p <0.05 for each pair). With rare exceptions, basal cells in benign epithelium and prostatic intraepithelial neoplasia were negative. The most intense nuclear staining was observed in benign epithelium. Immunoreactivity was also faint but detectable in the cytoplasm in prostatic intraepithelial neoplasia but not in benign epithelium or cancer. Mean number of androgen receptor immunoreactive nuclei in prostatic intraepithelial neoplasia and cancer was not a significant univariate or multivariate predictor of clinical and/or biochemical progression, or all cause survival (all p >0.05). CONCLUSIONS: Androgen receptor expression was present in all cases of benign epithelium, prostatic intraepithelial neoplasia and cancer. The greatest extent and intensity of expression were observed in benign epithelium, with about half of the nuclei showing intense immunoreactivity. The number of androgen receptor immunoreactive nuclei in prostatic intraepithelial neoplasia and cancer in patients with organ confined prostate cancer treated with radical prostatectomy was not predictive of progression or survival.

Adenocarcinoma

Androgen receptor expression in prostate cancer lymph node metastases is predictive of outcome after surgery.

PURPOSE: Androgens mediate the growth of prostate cancer cells. The predictive value of androgen receptor immunostaining in patient outcome is controversial. We studied the expression of androgen receptors in a large series of patients with node positive cancer, and correlated the results with clinical progression and survival. MATERIALS AND METHODS: We evaluated 197 patients with a mean age of 65.5 years who had node positive adenocarcinoma, and who underwent bilateral pelvic lymphadenectomy and/or radical prostatectomy at our clinic between 1987 and 1992. Mean followup was 6.3 years. Immunohistochemical studies were performed using an antihuman androgen receptor monoclonal antibody. In each case 100 nuclei were counted from 3 separate areas (total 300 nuclei per diagnostic category) of benign epithelium, cancer and lymph node metastases. Mean androgen receptor expression was determined from the mean of the individual cases. The intensity of immunoreactivity was evaluated on a scale of 0-no staining to 3-strong staining. We assessed the correlation of androgen receptor immunoreactivity, deoxyribonucleic acid ploidy, Gleason score and preoperative serum prostate specific antigen (PSA) with clinical progression, all cause survival and cancer specific survival using the Cox proportional hazards model. Clinical progression was defined as a positive bone scan. RESULTS: There was heterogeneous staining in the majority of cells in benign and malignant prostatic epithelium. The mean number of immunoreactive nuclei was similar in all groups (56, 53 and 56% of benign epithelium, cancer and lymph node metastases, respectively). Pairwise comparisons revealed that the only significant difference was between benign epithelium and cancer (p = 0.001) with greater immunoreactivity in benign epithelium. Intensity was lower in benign epithelium than in cancer and lymph nodes (p <0.05). Androgen receptor expression in lymph node metastases was associated with all cause and cancer specific survival on univariate analysis (p = 0.03 and 0.04, respectively). The 7-year cause specific survival was 98, 94 and 86% in patients with 51 to 69, less than 50 and greater than 70% androgen receptor expression in lymph node metastases, respectively (p <0.05). The association of androgen receptor expression in lymph node metastases was significant on multivariate analysis for cancer specific survival (p = 0.021) but not all cause survival (p = 0.16) after controlling for Gleason score, deoxyribonucleic acid ploidy and preoperative PSA. Androgen receptor immunoreactivity in lymph nodes was not a significant univariate or multivariate predictor of clinical progression, while androgen receptor expression in the primary cancer was not predictive of clinical progression or survival (p >0.05). CONCLUSIONS: Androgen receptor expression was similar in benign epithelium, primary cancer and lymph node metastases with approximately half of the epithelial cell nuclei staining. Androgen receptor immunoreactivity in lymph node metastases was predictive of cancer specific but not all cause survival in univariate and multivariate models. Gleason score was the strongest predictor of all cause survival in this cohort of patients. Our results indicate that it may be clinically useful to determine lymph node androgen receptor expression in men with advanced prostate cancer when combined with Gleason score and PSA.

Adenocarcinoma

Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans.

Prostate cancer (PCA), the most commonly diagnosed cancer in males in the United States, is the second leading cause of cancer-related deaths of males in this country. Because of the poor success rate in the treatment of PCA, an intervention at an early stage may reduce the progression of small carcinoma to large metastatic lesion, thereby reducing PCA-related deaths. Concerted efforts are needed to establish mechanism-based approaches to develop: (a) the markers for early detection of the disease as well as toward monitoring the efficacy of treatment(s); and (b) novel chemopreventive strategies against PCA. Using unique samples of pair-matched benign and cancer tissue obtained from the same PCA patient, we showed that ornithine decarboxylase (ODC) activity is significantly (P < 0.001) elevated in PCA (1142 +/- 100; mean +/- SE) than in paired benign tissue (427 +/- 51; mean +/- SE). The immunoblot analysis also showed a significant elevation in the protein expression of ODC in the PCA tissues as compared with the paired benign tissue. Furthermore, our data showed that the ODC activity in the prostatic fluid obtained by a digital rectal massage from the patients with PCA (3847 +/- 162; mean +/- SE) was significantly higher than in the patients with benign prostatic hyperplasia (2742 +/- 167; mean +/- SE) or normal individuals (1244 +/- 67; mean +/- SE). This observation might be of significance because the prostatic fluid could be obtained noninvasively by digital rectal massage. We suggest that ODC could serve as a target for early detection of human PCA as well as for monitoring the efficacy of treatment(s). The development of ODC as a target for novel chemopreventive strategies against PCA is an intriguing possibility.

Biomarkers

Steam heat with an EDTA buffer and protease digestion optimizes immunohistochemical expression of basal cell-specific antikeratin 34betaE12 to discriminate cancer in prostatic epithelium.

In select cases of prostatic carcinoma, antikeratin 34betaE12 immunohistochemical analysis is diagnostically useful for specific labeling of basal cells. This antibody, however, is prone to variability in staining, and the optimal conditions were not, to our knowledge, previously defined. We combined steam heat with EDTA buffer (steam-EDTA) and protease digestion (steam-EDTA + protease) to optimize epitope retrieval of antikeratin 34betaE12 in 42 cases of prostatic cancer. Results were judged by the percentage of cells staining and by staining intensity. In benign epithelium, steam-EDTA + protease significantly increased the percentage of immunoreactive cells (from 74 to 93%) and the intensity of staining (from 2.1 to 3.0 on a scale of 0-3+) by comparison with protease alone (all P<.001). In high-grade prostatic intraepithelial neoplasia, the percentage of cells staining increased from 55 to 73% and intensity increased from 1.7 to 2.8 (both P<.001). Steam-EDTA + protease also minimized variability in results between cases, with essentially no background stromal staining. Cancer was negative in all of our cases by both methods. We conclude that steam-EDTA + protease significantly enhances basal cell immunoreactivity compared with protease treatment alone in noncancerous prostatic epithelium. This helps to prevent misinterpretation of histologic mimics of cancer, such as atrophic acini and high-grade prostatic intraepithelial neoplasia, that result from false-negative staining.

Antibodies, Monoclonal

Prostate cancer microvessels: a novel method for three-dimensional reconstruction and analysis.

BACKGROUND: Studies of prostate cancer microvessels to date have relied on routine two-dimensional images from histologic tissue sections, and there have been no previous reports of three-dimensional (3D) reconstruction and analysis of prostatic microvessels in benign or malignant specimens. Knowledge about the 3D architecture of microvessels would be useful for determining the utility and limitations of two-dimensional (2D) measures, as well as for determining the usefulness of 3D measures to predict pathologic stage and patient outcome in prostate cancer. However, the ability to study microvessels in 3D must first be demonstrated. METHODS: We developed a novel method to visualize and analyze prostate microvessels in three dimensions from serially-sectioned prostate specimens, including tissue preparation, reconstruction of serial histologic sections into 3D volumes, extraction of vessels from this data set, and calculation of geometric characteristics. Eleven regions of benign and cancer tissue were studied and compared in an effort to validate our methodology. RESULTS: Microvessels and glandular elements from benign and malignant tissue were visualized together in three dimensions. In the 3D visualizations, microvessels associated with cancer were seen to have more arbitrary pathways, increased tortuosity, and a more casual relationship with glandular elements than microvessels associated with benign tissue. A quantitative measure, the volume length density, discriminated between benign tissue and cancer better than simple microvessel density in this exploratory study. CONCLUSIONS: Microvessels in prostate cancer have a more homogeneous distribution and greater tortuosity than those in benign tissue. Volume length density of microvessels shows promise as a 3D marker in prostate cancer.

Adenocarcinoma

Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen.

BACKGROUND: Current statistics indicate that prostate carcinoma is the most common form of cancer diagnosed in American men, resulting in the second highest cancer death rate. Early diagnosis and accurate staging are imperative given that there is little effective treatment for metastatic disease, especially after androgen deprivation therapy fails. Identification of new biochemical markers for disease progression will provide important tools for diagnosis and monitoring. One such potential marker is prostate specific membrane antigen (PSMA). METHODS: A review was conducted to identify reports concerning evaluation of diagnostic applications of PSMA. RESULTS: PSMA is a membrane-bound glycoprotein that is highly restricted to the prostate. Immunohistochemical findings indicate that PSMA is a marker of epithelial cells of the prostate. This expression is increased in association with prostate carcinoma, particularly in hormone-refractory disease. Given its membrane-bound character, PSMA has been exploited as a marker for tumor detection by immunoscintiscanning with the 111In-labeled anti-PSMA monoclonal antibody 7E11.C5. Increased concentrations of 7E11.C5-reactive antigen are present in the serum of prostate carcinoma patients compared with healthy individuals; also, hematogenous circulating prostate carcinoma cells are detectable with reverse transcriptase-polymerase chain reaction analysis with primers specific for PSMA. New monoclonal antibodies specific for extracellular portions of the PSMA molecule currently are being utilized in applied studies. CONCLUSIONS: PSMA is a widely used marker for prostate epithelial cells. Its up-regulation in association with cancer, particularly in advanced cancer, is ideal for application as a prognostic marker. A variety of promising clinical applications utilizing PSMA have been or are being developed. In the future, these promise to have an important impact on cancer diagnosis and patient treatment.

Antigens, Surface

Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy.

BACKGROUND: Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy. METHODS: The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996. The mean interval from radiation therapy to biopsy-proven recurrence was 3.7 years (range, 6 months to 17 years). Patient age at surgery ranged from 51 to 78 years (median, 66 years). The mean follow-up after surgery was 5.8 years (range, 1.0-15.2 years). Cox proportional hazards models were used to identify clinical and pathologic factors associated with distant metastasis free survival and cancer specific survival. RESULTS: Actuarial distant metastasis free survival, cancer specific survival, and overall survival were 83%, 91%, and 85% at 5 years and 69%, 64%, and 54% at 10 years, respectively. In multivariate analysis, radical prostatectomy Gleason score and DNA ploidy were independent predictors of distant metastasis free survival and cancer specific survival. CONCLUSIONS: Postirradiation Gleason score and DNA ploidy were highly predictive of the clinical outcomes of patients treated by salvage radical prostatectomy after radiation therapy.

Aged

Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma.

BACKGROUND: Prostate carcinoma usually is heterogeneous and multifocal, with diverse clinical and morphologic manifestations. Understanding of the molecular basis for this heterogeneity is limited, particularly for the putative precursor, high grade prostatic intraepithelial neoplasia (PIN). In this study, the authors attempted to determine the genetic relation between multiple foci of PIN and matched foci of carcinoma, and whether they are independent in origin. METHODS: The distribution and prevalence of allelic imbalance at 6 microsatellite polymorphic markers on chromosomes 7q, 8p, 8q, and 18q were examined in 84 microscopically excised PIN foci (mean, 1.6 foci/case) and 95 foci of prostate carcinoma (mean, 1.8 foci/case) from 52 completely embedded, mapped whole mount prostates. RESULTS: PIN contained a lower overall proportion of allelic imbalance than matched prostate carcinoma foci for the 6 polymorphic microsatellite markers (65% vs. 82%), but this difference was not significant. The rate of allelic imbalance in PIN was similar to that in prostate carcinoma at 5 of 6 loci studied; the exception, D18S34 (18q12.2-12.3), had a significantly lower rate of allelic imbalance in PIN than in prostate carcinoma (19% vs. 52%), suggesting that genetic alterations in this chromosomal region may be important in carcinogenesis. Of 22 cases with allelic imbalance in at least 1 focus of PIN and 1 focus of prostate carcinoma, 21 informative cases (95%) showed a similar pattern of allelic imbalance at > or = 1 markers in the matched PIN and prostate carcinoma foci. Significant genetic heterogeneity was observed in both PIN and prostate carcinoma. Allelic imbalance was observed in at least 1 focus in 11 of 25 cases with multiple foci of PIN (44%) and 20 of 25 cases with multiple foci of prostate carcinoma (80%). There was no significant correlation between allelic imbalance and pathologic stage or tumor grade. CONCLUSIONS: Our findings indicate that multiple foci of PIN arise independently within the same prostate. This observation suggests that a field effect underlies prostatic neoplasia. Multiple foci of prostate carcinoma also often arise independently, lending additional support for this hypothesis. The strong genetic similarities between PIN and prostate carcinoma strongly suggest that evolution and clonal expansion of PIN may account for the multifocal etiology of carcinomas.

Aged

Malignant lymphoma involving the prostate: report of 62 cases.

BACKGROUND: Malignant lymphoma involving the prostate is rare, and to the authors' knowledge the factors determining patient outcome have not been studied in a large series. METHODS: The authors evaluated the clinical and pathologic findings in 60 cases of non-Hodgkin's lymphoma and 2 cases of Hodgkin's lymphoma involving the prostate. A variety of clinical and histologic findings were considered as factors predictive of patient outcome. RESULTS: Lymphoma tended to occur in elderly men, with a mean age at diagnosis of 62 years (range, 5-89 years), although 6 patients were age < 40 years (ages 5, 19, 30, 32, 38, and 38 years, respectively). Clinical signs and symptoms were due to lower urinary tract obstruction. Twenty-two patients (35%) presented with primary extranodal lymphoma of the prostate with a variety of histologic subtypes, including small lymphocytic (4 patients); follicular center cell, diffuse, small cell (2 patients); follicular center cell, Grade 1 (according to the revised European-American classification (small cleaved) (1 patient); Grade 2 (mixed) (1 patient); diffuse large B-cell (12 patients); and high grade B-cell lymphoma, Burkitt-like (2 patients). At the time of presentation, none of these patients had hepatosplenomegaly, inguinal lymphadenopathy, or an abnormal complete blood count. Thirty other patients (48%) with previously documented lymphoma at other sites developed prostatic involvement; these secondary prostatic lymphomas displayed a variety of subtypes, including small lymphocytic (8 patients, all with concomitant leukemia); follicular center cell lymphoma, diffuse, small cell (2 patients); follicular center, Grade 1 (small cell) (1 patient); follicular center, Grade 2 (1 patient); diffuse large B-cell (11 patients); peripheral T-cell lymphoma (2 patients); high grade B-cell lymphoma, Burkitt-like (1 patient); Burkitt's lymphoma (1 patient); Hodgkin's lymphoma (nodular sclerosing [1 patient] and mixed cellularity [1 patient]); and unknown (1 patient). Ten cases were not classifiable as primary or secondary lymphomas. Twenty-five patients died of malignant lymphoma, 14 died of unknown or other causes, 18 patients were alive 12-20 months after diagnosis (8 primary and 10 secondary tumors; 3 had persistent lymphoma; all treated since 1981), and 5 were lost to follow-up. Lymphoma specific survival was 64% at 1 year (95% confidence interval [CI], 51-80%), 50% at 2 years (95% CI, 36-68%), 33% at 5 years, 33% at 10 years, and 16% at 15 years. There was no difference in median survival after diagnosis of prostatic involvement between primary and secondary lymphoma (23 months vs. 28 months, respectively) or among histologic types. CONCLUSIONS: Although malignant lymphoma involving the prostate is rare, it should be considered in the differential diagnosis of lower urinary tract obstruction, particularly in patients with a previous history of lymphoma.

Adult

High grade prostatic intraepithelial neoplasia in military working dogs with and without prostate cancer.

BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer and is commonly found in men undergoing prostatic needle biopsy for suspected cancer. Recent work has demonstrated that pet dogs, like humans, develop PIN spontaneously and in association with prostate cancer. Pet dogs are the most domesticated animal, sharing the habitat and oftentimes the diet of their owners. If PIN and prostate cancer are strongly related to environmental factors, then the prevalence of these findings might differ in a population of dogs such as military working dogs which is not exposed to the habitat and diet of humans. In this study, we determined the prevalence of PIN in prostates of aged military working dogs with and without prostatic adenocarcinoma. METHODS: Cases were selected from the military working dog slide and tissue archive at the Armed Forces Institute of Pathology, Washington, DC. The most recent 329 necropsies (1991 to 1996) were examined histologically by multiple reviewers; of these, 199 dogs (60%) were found to have evaluable prostatic tissue. In addition, the most recent 50 necropsies (1958 to 1996) with the diagnosis of prostatic cancer were examined, of which 25 cases (50%) were found to have evaluable prostatic adenocarcinoma. In most cases, a single large transverse section of prostatic tissue was available for review. Medical records for each dog were reviewed independently, and age, clinical history, indications for euthanasia, and other health problems were recorded. RESULTS: High grade PIN was identified in 3% of dogs (6 of 199 dogs) without prostate cancer. A total of 50.8% of dogs in this study group (101 of 199 dogs) were known to be sexually intact, 26.7% of dogs (53 of 199 dogs) were castrated, and the status of the remaining 22.6% of dogs (45 of 199 dogs) was unknown. High grade PIN was present in 18 of 25 dogs (72%) with prostatic adenocarcinoma. Of these cases, 11 dogs (44%) were castrated, 4 dogs (16%) were intact, and the status of 10 dogs (40%) dogs was unknown. Gleason scores ranged from 6 to 10, with a mean of 8.4 and a median of 8. CONCLUSIONS: High grade PIN is present in a small but substantial number (3%) of military working dogs. Of military working dogs with prostatic adenocarcinoma, 72% had high grade PIN. The true prevalence in each of these cohorts is likely to be higher given the sampling variation inherent in evaluating a single random histologic section. Aged male dogs seem to have substantial clinical utility as an animal model for prostatic carcinogenesis. We recommend that serial sectioning and total embedding of the prostate should be used to more thoroughly characterize premalignant and malignant diseases in aged military working dogs. This method will provide important data to determine whether a model of spontaneous PIN in elderly dogs may have clinical utility in developing strategies directed toward preventing and treating prostate.

Adenocarcinoma