Atypical basal cell hyperplasia of the prostate.

Basal cell hyperplasia classically has been described as having bland cytologic features. During the past 2 years, we have seen 12 cases (11 in consultation) with atypical features that were confused with adenocarcinoma of the prostate. Eleven of these 12 cases contained prominent nucleoli mimicking carcinoma; in the 12th case, nuclei were enlarged, hyperchromatic, and moderately pleomorphic. Immunohistochemistry with antibodies against high-molecular-weight cytokeratin (34 beta E12) was performed in nine of the cases, verifying their basal cell nature. Additional findings in these cases were necrotic intraluminal secretions (two cases), immature squamous metaplasia (two cases), peculiar hyaline cytoplasmic globules (two cases), adenosis (one case), markedly atypical nuclei of uncertain nature occurring elsewhere in the specimen (one case), and intraluminal blue mucin (two cases). We analyzed nine cases of typical basal cell hyperplasia, all of which showed classic features of basal cell hyperplasia with benign cytology. Both atypical and classical basal cell hyperplasia were frequently infiltrated by lymphocytes such that the cytologic changes could not be attributable to inflammation. Atypical basal cell hyperplasia must be differentiated from ordinary adenocarcinoma of the prostate, prostatic intraepithelial neoplasia, and basaloid carcinoma (adenoid cystic carcinoma) of the prostate.

Diffuse idiopathic pulmonary neuroendocrine cell proliferation presenting as interstitial lung disease.

Pulmonary neuroendocrine cell (PNEC) hyperplasia typically occurs as an adaptive response in persons living at high altitudes and as a reactive response in the setting of lung injury. However, previous studies suggest that PNEC hyperplasia can occur in the absence of preexisting lung disease and may even give rise to airway disease through the development of pulmonary tumorlets and airway fibrosis and perhaps the release of paracrine secretions. We describe a patient with diffuse PNEC proliferation of a probable hyperplastic nature developing in the absence of a chronic pulmonary disorder who presented clinically with an interstitial lung process. Open lung biopsy displayed a florid intraepithelial population of PNEC diffusely involving the distal airways and alveoli with desquamation and filling of alveolar spaces by nests of PNEC. The presence of alveolar thickening was attributable to the intraepithelial proliferation of PNEC associated with interstitial fibrosis and accounted for mild reductions in the pulmonary diffusing capacity. The neuroendocrine differentiation of this proliferation was evident by light microscopic and ultrastructural examination. The absence of airway fibrosis and pulmonary tumorlets was in agreement with the lack of clinical airway disease in this case. The intraepithelial growth and absence of parenchymal invasion in this lesion favor a diffuse, florid PNEC hyperplasia with mild dysplastic features over a pulmonary neuroendocrine neoplasm.

Clinical and pathobiological effects of neoadjuvant total androgen ablation therapy on clinically localized prostatic adenocarcinoma.

Neoadjuvant total androgen ablation therapy leads to involutional changes in prostatic carcinoma and may have the potential to downstage operable prostate cancers. We studied 27 clinically localized prostatic carcinomas after 3 months of combined treatment with a luteinizing hormone-releasing hormone agonist, goserelin acetate, and the antiandrogen flutamide, followed by radical retropubic prostatectomy, for changes in the serum prostate-specific antigen (PSA) level, changes in prostatic volume, therapy-induced histopathologic changes, DNA ploidy, and proliferative activity. Ten hormonally untreated, grade-matched prostatic adenocarcinomas served as controls. The mean pretherapy serum PSA level was 17.5 ng/ml, and posttherapy PSA levels were all < 4.0 ng/ml, with 18 men having undetectable levels. The mean reduction in prostatic volume following hormonal therapy was 37% (range 16-52%). Pathologic staging confirmed 20 pT2N0, six pT3N0, and one pT3N1. All prostates showed residual adenocarcinoma (extremely focal in seven cases [26%] with loss of glandular architecture, cytoplasmic vacuolization, and nuclear pyknosis. High-grade adenocarcinoma was nondiploid in 25% of hormonally treated prostates and 80% of 10 untreated controls. Immunostaining for proliferating cell nuclear antigen showed > 10% nuclear reactivity in 33% of treated carcinomas and 90% of untreated carcinomas. In conclusion, 3 months of neoadjuvant androgen ablation for localized prostatic carcinoma significantly lowers serum PSA and prostatic volume and produces involutional changes in residual carcinomas that mimic high-grade disease. However, pretreated carcinomas have predominantly a diploid DNA content and low proliferative activity as opposed to untreated carcinomas. Thus, grading of pretreated adenocarcinomas by conventional methods may be misleading. Preoperative total androgen ablation has a profound effect on a subset of prostatic carcinoma cells, possibly by facilitating programmed cell death.

Immunohistochemical detection of cathepsin D in T2N0M0 breast carcinoma.

Recent studies have reported significant but inconsistent correlations between tumor cathepsin D (CD) concentration and prognosis in breast carcinoma. To investigate the tissue distribution and a prognostic utility of CD in breast carcinoma, 159 cases of T2N0M0 breast carcinoma with a minimum of 10 years' follow-up were studied for CD expression by immunohistochemistry. This group of patients was chosen for study because of current interest in prognostic markers for stage I breast carcinoma and the likelihood that there would be sufficient recurrences in this group to detect significant differences. Seventy-two carcinomas (45%) showed prominent staining of cells composing the tumor. Neoplastic cell staining for CD correlated with well-differentiated architecture, and lack of neoplastic cell CD expression correlated with high nuclear grade and the medullary carcinoma category. Stromal cell (primarily histiocyte) staining in carcinomas was the major contributor to CD expression in 67 of the 159 cases (42%). Intense intratumoral stromal cell staining correlated with absence of estrogen receptors and the medullary carcinoma subtype. There was no significant correlation between disease-free or overall survival and (a) intensity of overall staining for CD, (b) staining of carcinoma cells alone, or (c) staining of nonneoplastic cells within the region of the carcinoma. These results show that a significant proportion of CD activity detected within a tumor by immunohistochemistry may be contributed by nonneoplastic cells, and there is no significant correlation between survival and immunohistochemical detection of CD in T2N0M0 breast cancer.

Segmental mediolytic arteritis involving hepatic arteries.

Segmental mediolytic arteritis is a rare, noninflammatory arteriopathy that involves the splanchnic arteries of adults with shock and the coronary arteries of neonates with hypoxemia. We report the first case (to our knowledge) of segmental mediolytic arteritis involving the hepatic arteries. The lesion begins with cytoplasmic vacuolar degeneration of the arterial smooth-muscle cells, which then progresses to coalescence of vacuoles, leading to disruption of the media, intramural hemorrhage, and periadventitial fibrin deposition. Segmental mediolysis results in arterial wall defects, which can lead to dissecting aneurysms or hemorrhage due to arterial rupture. The intima and internal elastica are spared from the lytic process, and there is minimal periadventitial inflammation. Segmental mediolytic arteritis is not a true arteritis; therefore, segmental mediolytic arteriopathy may be a preferable term. Morphological similarities exist between segmental mediolytic arteritis and arterial fibromuscular dysplasia. In our case, hepatic ischemia correlated with mediolysis involving the hepatic arterial branches. Segmental mediolytic arteritis is thought to be due to an inappropriate vasospastic response, developing in the setting of hypoperfusion and hypoxemia.

Loss of medullary dendritic cells in the thymus after cyclosporine and irradiation.

Cyclosporine (CsA) induces a paradoxical graft-vs-host-like disease (GVHD) in syngeneic rat chimeras, providing the rat has a thymus and receives mediastinal irradiation. Here we evaluate the effect of CsA and irradiation on the relative abundance of thymic dendritic cells (DC). DC were identified with an immunoperoxidase stain for ED1 and were quantified by computerized planimetry. Normal young rats have scattered DC in the cortex and numerous DC in the medulla with a concentration at the cortico-medullary junction. Short-term CsA induces a marked loss of medullary DC (798 +/- 126 cells/mm to 88 +/- 103, P less than 0.001) and a modest loss of cortical DC (543 +/- 55 to 330 +/- 130, P less than 0.01). While medullary DC normally recover promptly post-CsA, rats receiving mediastinal irradiation demonstrated minimal recovery post-CsA (P less than 0.0003). The prolonged deficiency of medullary DC could represent an essential early step for loss of self-tolerance and sGVHD.

Radical retropubic prostatectomy outcomes at a community hospital.

PURPOSE: We reviewed a 6-year experience performing radical retropubic prostatectomy at 2 community hospitals (for-profit and not-for-profit) to assess outcomes and to compare them to the published literature reflecting outcomes from major academic hospitals. MATERIALS AND METHODS: Charts of 116 patients who underwent radical retropubic prostatectomy (nerve sparing in select cases) between 1990 and 1996 were reviewed for clinical and pathological outcomes as well as hospital charges. Subjective patient reports of urinary continence, potency and satisfaction were evaluated postoperatively. RESULTS: Average patient age was 66.6 years and average preoperative prostate specific antigen level was 9.6 ng./ml. Of the patients 43% had T1c disease, 63% pT2 and 37% pT3. Positive margins were present in 17.2% of the specimens and 66% of the patients had Gleason scores of 5 and 6. No deaths occurred. Major complications occurred in 5.4% of patients and included deep venous thrombosis (1.8%), pulmonary embolism (1.8%), rectal injury requiring ileostomy (0.9%) and fascial dehiscence (0.9%). Mean blood loss was 872 cc and mean blood transfusion rate was 1.7 units (almost exclusively autologous blood). Hospital charges decreased at the not-for-profit hospital to $13,233 in 1996 from $17,743 in 1990 to 1995, whereas charges increased at the for-profit hospital to $25,979 in 1996 from $24,481 in 1990 to 1995. Mean length of stay decreased from 5 days in 1990 to 1995 to 3 days in 1996. Of the patients 80% were totally continent (pad-free), 12% wore a protective pad once per day for minimal incontinence and 8% wore 2 or more pads. Of the men who were potent preoperatively 18% retained potency and 46% remained sexually active postoperatively either spontaneously or with assistance. Of the patients 84% were satisfied with surgical outcomes, 11% were somewhat satisfied and 5% were dissatisfied. CONCLUSIONS: Radical retropubic prostatectomy can be performed safely and with acceptable clinical and pathological outcomes at a community hospital. Impotence continues to be one of the most bothersome morbidities, particularly in older men. Increasing cost awareness, coincident with the proliferation of managed care, has led to reductions in length of hospital stay and charges at certain hospitals.

Nuclear morphology of prostatic carcinoma: comparison of computerized image analysis (CAS 200) versus video planimetry (DynaCELL).

We compared mean nuclear size and mean nuclear shape (nuclear roundness) on Feulgen-stained smears from 113 cases of prostatic carcinoma analyzed by DynaCELL system at x 100 magnification versus CAS system at x 40 where DNA can be assessed simultaneously. Correlation coefficients were 0.67 for size and -0.07 for shape. A subgroup of cases were compared at x 40 versus x 100 on the CAS system by two observers: The correlation for size ranged 0.47 to 0.49, with correlations for shape ranging from -0.19 to 0.54. In this subgroup at x 100 magnification, the correlation between CAS and DynaCELL was 0.32 for size and 0.07 for shape. At x 100 magnification on the CAS system, intraobserver correlation was 0.58 for size and 0.37 for shape with interobserver correlations of 0.36 for size and -0.05 for shape. At x 40 on the CAS system, intraobserver correlation was 0.42 for size and 0.72 for shape, with interobserver correlations of 0.06 for size and 0.45 for shape. This study shows that in comparison to video planimetry of prostatic cancer nuclei, which has been shown to have a high inter- and intraobserver correlation, the CAS 200 system provided accurate measurements of size yet not shape. Intra- and interobserver correlations were suboptimal with CAS, showing better results at x 100 for size and x 40 for shape. These results in part reflect the relative narrow range of size and shape in prostate cancer in comparison to other tumors, and the use of Feulgen smears where nuclear RNA is not stained or measured by the CAS system, potentially leading to artifactually irregular shapes.

Effects of cyclosporin A on the splenic tissue of rats: a histomorphometric analysis.

Histological studies demonstrated that long-term cyclosporin A treatment of nonantigenically challenged (untransplanted and unimmunized) Lewis rats markedly reduces the total percentage of splenic white pulp when compared to untreated control spleens (mean = 24 vs 34%, P less than 0.001). Direct measurements of periarteriolar sheaths and marginal zones demonstrated a marked reduction in size of these compartments in cyclosporin A-treated rats compared to untreated controls (P less than 0.001). In addition, there was a striking reduction in cellular density of the periarteriolar sheaths (P less than 0.001) and a minimal reduction in cellular density of the marginal zones (P less than 0.1) in the cyclosporin A-treated group when compared to untreated controls. There was no significant difference in total splenic size between the cyclosporin A-treated and the control groups, as indicated by total cross section measurements (mean = 33.3 vs 35.0, P less than 0.4). Qualitative observations of methyl green-pyroninophilic cells within and surrounding the marginal zones of the cyclosporin A-treated spleens revealed a much greater proportion of large pyroninophilic lymphocytes, which suggests that they are B immunoblasts. We conclude that long-term cyclosporin A treatment depletes splenic periarteriolar sheaths and marginal zones, compartments known to contain primary T lymphocytes, and induces an immunoblastic cell proliferation within the marginal zones and red pulp as well.

Correlation of prostate cancer nuclear deoxyribonucleic acid, size, shape and Gleason grade with pathological stage at radical prostatectomy.

Using image cytometry and a video planimetry unit, various deoxyribonucleic acid (DNA) measurements, nuclear size and shape factors, and Gleason grade were correlated with capsular penetration, seminal vesicle invasion and lymph node involvement in 113 radical prostatectomy specimens. Percentage of nondiploid cells was the best DNA measurement and standard deviation of nuclear area was the best size measurement correlating with capsular penetration. However, stepwise regression analysis demonstrated that Gleason grade was the only independent predictor of capsular penetration. The only parameter that independently predicted seminal vesicle invasion in a stepwise regression analysis was percentage of tetraploid cells. The mode of optical density was the best DNA measurement for predicting lymph node involvement, although stepwise regression analysis found that Gleason grade was the only independent predictor. DNA ploidy was not as predictive of pathological stage. In summary, DNA measurements and nuclear morphometry performed on smears offered relatively little additional prediction of pathological stage over that of Gleason grade.