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Biomedical subjects

D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 253 records · Page 14Linked to original sources
PubMed1995

The pathology of incidental carcinoma.

"Incidental" cancer refers to predominantly well differentiated cancer that arises in the transition zone and is found by chance in TURP chips. These tumours are frequently small and may be completely resected by TURP, although a significant number have an additional tumour that is unreachable with a resectoscope. These tumours often co-exist with benign prostatic hyperplasia. Putative precursors of incidental carcinoma include high grade PIN and AAH, and these lesions are frequently found in the transition zone in prostatectomies for cancer. The single most significant question in treating incidental adenocarcinoma is how to separate tumours that will progress from those that will not progress during the expected lifetime of the patient. The 1992 revision of the TNM staging system separated non-aggressive (T1a) and aggressive (T1b) incidental cancer according to the number of foci of cancer, using more than three foci as the cutpoint to identify more aggressive cancer. However, 8-37% of patients with T1 a cancer will develop cancer progression within 10 years if untreated, with the risk of progression increasing with additional years of follow-up. Important prognostic factors include the patient's age, tumour location (peripheral zone v. transition zone), tumour grade, tumour volume, serum PSA concentrations and morphometric factors such as nuclear roundness. Studies directed at early detection allow discovery of increasingly smaller cancers.

Humans↗
PubMed1995

The volume of prostate cancer in the biopsy specimen cannot reliably predict the quantity of cancer in the radical prostatectomy specimen on an individual basis.

Previous studies suggest that prostate cancer with a volume of 0.5 ml. or less and a Gleason score of less than 7 may be clinically insignificant and may be managed with watchful waiting. A proposed method of determining the volume of cancer in the prostate gland has been the grade and volume of cancer present in the transrectal needle biopsy specimen. Volume of cancer in the biopsy specimen as a predictor of volume of cancer in the prostate gland was studied in 130 men who underwent radical retropubic prostatectomy for adenocarcinoma. Of the men 46 (35%) had clinical stage T1c (nonpalpable) disease, while 84 (65%) had clinical stage T2 (palpable) disease. Each radical prostatectomy specimen was whole-mounted and step-sectioned for accurate cancer volume determination. Three parameters for measuring volume of cancer in the biopsy specimen (percentage of biopsy cores involved, millimeters of cancer per biopsy core and percentage of cancer in the biopsy specimen) were determined and compared by Spearman rank correlation analysis. The percentage of cancer in the biopsy specimen was marginally better than the percentage of cores involved and the millimeters of cancer per biopsy core as a predictor of cancer volume in the radical prostatectomy specimen. While regression analysis revealed a direct correlation between the volume of cancer in the biopsy and radical prostatectomy specimens (r = 0.51), there was significant variability in prostate cancer volume for a given percentage of cancer in the biopsy specimen since the standard error of the estimate was 6.1 ml. Of the 13 patients with 5% or less cancer volume and a Gleason score of less than 7 in the biopsy specimen 1 (8%) had a cancer smaller than 0.5 ml. in volume in the radical prostatectomy specimen. Therefore, the risk of removing clinically insignificant prostate cancer, even when the biopsy parameter indicates low volume disease, is less than 10%. Overall, only 3 study patients (2.3%) had a prostate cancer volume of less than 0.5 ml. With 97.7% of the men having a clinically significant cancer by a volume criterion, it is apparent that the majority of clinically insignificant prostate cancers remained undetected and untreated. Currently, transrectal needle biopsy does not provide adequate information for differentiating between clinically insignificant and life threatening prostate cancer on an individual basis.

Adenocarcinoma↗
PubMed1995

Collagenous micronodules in prostate cancer. A specific but infrequent diagnostic finding.

OBJECTIVE: Collagenous micronodules (CMs) are microscopic stromal fibrillar aggregates of uncertain histogenesis that arise in association with prostatic adenocarcinoma. We studied a large series of biopsies and matched radical prostatectomies to determine the frequency, specificity, and predictive value of CMs. DESIGN: Retrospective study of 308 needle biopsies and matched radical prostatectomies with prostate cancer. PATIENTS AND SETTING: Consecutive series of men with prostatic adenocarcinoma undergoing needle biopsy of the prostate and subsequent radical prostatectomy at a large tertiary-care academic medical center. MAIN OUTCOME MEASURES: Incidence and extent of CMs, and correlation of CMs with multiple prognostic factors. RESULTS: Collagenous micronodules were identified in 0.6% of needle biopsies and 12.7% of prostatectomies, with a median of 2.0 high-power microscopic (x 40) fields of CMs per positive prostatectomy; most cases were identified in association with mucin-producing glands. The number of fields of CMs was not related to clinical or pathologic stage, serum prostate specific antigen concentration, prostatic weight, volume of cancer, Gleason score, percent of poorly differentiated cancer, nuclear grade, or DNA ploidy content. There were no CMs in benign prostatic glands, benign prostatic hyperplasia, or prostatic intraepithelial neoplasia in any specimen. Histochemical and ultrastructural studies showed that CMs are composed chiefly of collagen; in one case, flocculent laminated calcospherites were present. CONCLUSIONS: Collagenous micronodules are a specific but infrequent diagnostic clue in prostatic adenocarcinoma, particularly in those with prominent mucin production, but are not associated with factors predictive of progression.

Adenocarcinoma↗
PubMed1995

Prospective analysis of multifocality in renal cell carcinoma: influence of histological pattern, grade, number, size, volume and deoxyribonucleic acid ploidy.

In an effort to characterize more fully multifocal renal cell carcinoma, 100 radical nephrectomy specimens with localized renal cell carcinoma were analyzed in a prospective fashion. Analysis of each specimen consisted of preoperative computerized tomography or magnetic resonance imaging, standard pathological examination with frozen section and 3 mm. step sectioning under magnification. Multifocal renal cell carcinoma was found in 16 specimens. Multifocal disease was suspected by preoperative imaging in 7 specimens (44%) and confirmed after standard pathological investigation in 10 (63%). Papillary and mixed histological patterns occurred at a significantly increased rate in specimens with multifocal disease (p = 0.011). Other parameters, such as stage, tumor size and volume, histological grade and deoxyribonucleic acid ploidy were evaluated and did not correlate with the presence or extent of multifocality. The number of secondary tumors per specimen varied from 1 to 50 (median 2) and were of higher grade in 3 (19%) and of lower grade in 2 (12%) when compared with the predominant tumor. In conclusion, information from preoperative and to some degree intraoperative tests (except histological pattern) cannot reliably predict multifocality. The true risk for unknown multifocality in a surgical setting seems to be 6%, which roughly corresponds to the incidence of locally recurrent disease in published large institutional series.

Adult↗
PubMed1995

Prostatic intraepithelial neoplasia and the origins of prostatic carcinoma.

The participants agreed that high grade prostatic intraepithelial neoplasia was the most likely precursor of prostate cancer. Consensus was reached regarding grading, suggesting that PIN be classified as low grade and high grade, noting that high grade PIN is the clinically significant end of the morphologic continuum. Grade 1 PIN is now considered low grade, and grades 2 and 3 are considered high grade. All participants agreed that urologists should be informed when high grade PIN is identified in isolation in tissue specimens, but consensus was not reached regarding the value of reporting low grade PIN. No therapy was recommended for patients with high grade PIN, although repeat biopsy and follow-up is of value. No consensus was reached regarding the biologic potential of the lesion known as atypical adenomatous hyperplasia. Further investigation is needed to determine the diagnostic utility of this finding in prostatic specimens.

Forecasting↗
PubMed1994

Potential markers of prostate cancer aggressiveness detected by fluorescence in situ hybridization in needle biopsies.

Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, 11, and 12 was used to evaluate multiple 18-gauge needle biopsy cores from 50 randomly selected radical prostatectomy specimens. FISH analysis detected 26 diploid (52%), 7 tetraploid (14%), and 17 aneuploid tumors (34%). The FISH results were concordant with flow cytometric (FCM) DNA content measurements of the corresponding prostatectomy specimens for 31 tumors. For the 19 FISH/FCM discordant tumors, FISH was more sensitive than FCM for detecting ploidy anomalies. Common numerical chromosome alterations were gains of chromosomes 7 and 8, which were found in 13 (76%) and 10 (59%) aneuploid tumors, respectively. Gain of chromosome 7 was strongly associated with higher Gleason score (> or = 8) (P < 0.0001) and with advanced tumor pathological stages (stages T3 + T4; P < 0.01). Gain of chromosome 8 also correlated with higher Gleason score (P < 0.01). FISH showed intratumoral ploidy heterogeneity in 3 of 41 (7%) studied tumors. Among 17 noncancerous adjacent tissue specimens, chromosome alterations were observed in one, which contained high-grade prostatic intraepithelial neoplasia. Combined FISH and fluorescent leukocyte common antigen staining showed that infiltrating leukocytes do not contribute to the observed gains of chromosomes 7 and 8 in prostate cancer tissue. These results demonstrate that (a) FISH analysis of prostate needle biopsy-sized specimens can be a practical, sensitive method for determination of nuclear ploidy and numerical chromosome alterations; and (b) gains of chromosomes 7 and 8 are common numerical alterations of prostate cancer cells and may be potential markers of tumor behavior and patient prognosis.

Biopsy, Needle↗
PubMed1994

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.

Adenocarcinoma↗
PubMed1994

Paneth cell-like change in prostatic adenocarcinoma represents neuroendocrine differentiation: report of 30 cases.

Paneth cell-like change (PCLC) of the prostatic epithelium is considered to be a distinct form of neuroendocrine differentiation characterized by isolated cells or small groups of cells with prominent eosinophilic cytoplasmic granules. We evaluated 300 serially sectioned radical prostatectomy specimens from patients with prostatic adenocarcinoma who had not received prior adjuvant therapy (pathologic stages T2NOMO [177 patients], T3NOMO [100 patients], and TxN1MO [23 patients]). Paneth cell-like change was identified in 30 cases (10%), ranging from 1 to 20 high-power fields/positive case (mean, 4.1 high-power fields/case). There was no correlation of PCLC with prostate volume, prostate weight, Gleason grade, nuclear grade, lymph node metastases, serum prostate-specific antigen levels, cancer volume, area or presence of capsular perforation, seminal vesicle invasion, or glandular mucin (all P > .05), although a positive correlation was seen with cribriform pattern (r = 0.50, P = .0015). Immunohistochemistry revealed cytoplasmic immunoreactivity within cells of PCLC for chromogranin (seven of seven cases), neuron-specific enolase (seven of seven cases), serotonin (six of seven cases), prostate-specific antigen (five of seven cases), and prostatic acid phosphatase (four of seven cases); lysozyme was negative (seven cases). Our findings indicate that PCLC is more common than previously reported, but that it is not associated with tumor grade, serum PSA levels, or pathologic stage. This study also shows that PCLC represents neuroendocrine differentiation, suggesting that the term "Paneth cell-like change" be deleted from the pathologist's lexicon in relation to prostatic adenocarcinoma; a more appropriate term might be "neuroendocrine cells with large eosinophilic granules."

Acid Phosphatase↗
PubMed1994

Eliminating the need for bilateral pelvic lymphadenectomy in select patients with prostate cancer.

To determine if the preoperative variables of serum prostate specific antigen (PSA), primary Gleason grade from the biopsy specimen and local clinical stage as determined from digital rectal examination can accurately predict the pelvic lymph node status in patients with clinically localized prostate cancer, we reviewed the medical records of 1,632 patients who underwent bilateral pelvic lymphadenectomy at our institution between January 1988 and December 1991. Using logistic regression analysis, serum PSA was found to be the best predictor of pelvic lymph node metastases (p < 0.0001). The predictive power of serum PSA could be enhanced considerably by taking into account the Gleason grade (p < 0.001) and local clinical stage (p < 0.001). A statistical model using all 3 variables was developed that allows the practicing urologist to estimate on an individual basis the probability of pelvic lymph node involvement. Using a conservative cutoff point of less than 3% as an acceptable false-negative rate, 61% of the patients with clinical stages T1a to T2b (A1 to B1) disease and 29% of those with clinical stages T1a to T2c (A1 to B2) prostate cancer may be spared an open or laparoscopic staging bilateral pelvic lymphadenectomy. As a result, patient morbidity can be decreased and a significant economic savings to the health care system can be realized. This observation has particular importance for prostate cancer patients being managed with radical perineal prostatectomy or definitive radiation therapy.

Adult↗
PubMed1994

Combining prostate specific antigen with cancer and gland volume to predict more reliably pathological stage: the influence of prostate specific antigen cancer density.

The serum prostate specific antigen (PSA) level was determined in 311 men with documented prostate cancer (stages T1cN0, T2N0 and T3N0) before bilateral pelvic lymphadenectomy and radical retropubic prostatectomy. The prostates were whole mounted, serially sectioned, and examined for cancer volume, capsular perforation, seminal vesicle invasion, lymph node involvement, Gleason grade, nuclear grade and nuclear deoxyribonucleic acid content. Median serum PSA level was significantly different between cancers that were organ confined, those that had capsular perforation or seminal vesicle invasion and those with positive lymph nodes (p < 0.001). Median serum PSA level was also significantly different between tumors with Gleason scores of less than 6 and those with higher Gleason scores (p < 0.001), and between tumors with greater than 30% of poorly differentiated cancer (Gleason primary grades 4 and 5) and those with 30% or less poorly differentiated cancer (p < 0.001). Bivariate analysis revealed that the strongest correlations of serum PSA level were with cancer volume (r = 0.56), per cent of poorly differentiated cancer (r = 0.42), positive surgical margins (r = 0.39) and pathological stage (r = 0.38), for all p < 0.001. Multivariate analysis showed that cancer volume was the major contributor to serum PSA level. The derivative, PSA-cancer density (serum PSA times cancer volume divided by prostate volume), accounted for the effects of prostate volume and cancer volume on serum PSA. PSA-cancer density showed a significant correlation with pathological stage (r = 0.56), Gleason score (r = 0.53) and per cent of poorly differentiated cancer (r = 0.49, for all p < 0.001), and these correlations were significantly stronger than serum PSA level alone or PSA density (serum PSA divided by prostate volume; volume determined from tissue specimens) for all variables. These results indicate that preoperative serum PSA level has significant predictive value in determining tumor burden and pathological stage, and this predictive value is increased by accounting for cancer and gland volume with PSA-cancer density.

Adenocarcinoma↗
PubMed1994

Decrease of prostatic intraepithelial neoplasia following androgen deprivation therapy in patients with stage T3 carcinoma treated by radical prostatectomy.

OBJECTIVES: Prostatic intraepithelial neoplasia (PIN) is considered the most likely precursor of prostatic adenocarcinoma. The effect of androgen deprivation therapy on the prevalence of PIN is unknown. METHODS: We undertook a case-control study of radical retropubic prostatectomies from 24 treated patients and a control group of 24 untreated patients matched for age and clinical stage (all T3). Androgen deprivation therapy included LHRH agonist leuprolide and flutamide (18 patients), diethylstilbestrol (DES) (2 patients), DES with leuprolide and flutamide (1 patients), and orchiectomy (3 patients). Prostatectomy specimens were evaluated for the presence and extent of high-grade PIN according to the number of high-power microscopic fields, and nuclear tumor grade (1 to 4 scale) and Gleason score were also determined. RESULTS: The prevalence of high-grade PIN in pretreatment transrectal needle biopsies was similar in the treated and untreated groups. The prevalence and extent of high-grade PIN were lower in cases treated with androgen deprivation therapy than controls. Nuclear tumor grade was also lower in treated patients, but there was a paradoxical increase in the Gleason score. The prevalence of aneuploidy in the cancers was similar in both groups. CONCLUSIONS: These findings suggest that androgen deprivation therapy decreases the prevalence and extent of high-grade PIN.

Adenocarcinoma↗
PubMed1994

Gleason grading of prostatic needle biopsies. Correlation with grade in 316 matched prostatectomies.

The automated spring-loaded 18-gauge gun recently introduced for prostatic needle biopsy provides less than half the tissue of the traditional 14-gauge biopsy, possibly influencing the accuracy and predictive ability of biopsy tumor grade. In order to determine the value of tumor grade in contemporary needle biopsy specimens, we compared grade in 316 biopsies with matched whole-mounted radical retropubic prostatectomy specimens according to Gleason primary pattern, Gleason secondary pattern, Gleason score, percent of Gleason patterns 4 and 5, and nuclear grade. Biopsy grading accuracy was correlated with rates of capsular perforation, seminal vesicle invasion, pelvic lymph node metastasis, serum prostate specific antigen level, prostatic volume, prostatic weight, cancer volume, perineural invasion, DNA ploidy, and pathologic stage. The greatest grading error was encountered with low-grade tumors; there was no correlation of grading error with clinical staging error or other pathologic factors. Significant differences were noted between biopsy and prostatectomy for Gleason primary pattern, secondary pattern, and score. The percent of poorly differentiated carcinoma (Gleason patterns 4 and 5) in biopsies and prostatectomies showed a moderate positive correlation. The results indicate that the accuracy of 18-gauge needle biopsy in predicting tumor grade in the prostatectomy is similar to that reported with 14-gauge biopsies. Based on these findings, we recommend that the Gleason score (sum of primary and secondary patterns) be employed in all needle biopsies, recognizing that the accuracy of grade is decreased in cases with low-grade cancer and small amounts of cancer.

Adenocarcinoma↗
PubMed1994

Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma.

Neuroendocrine cells are thought to have a regulatory role in prostatic epithelial growth and may be prognostically useful in prostatic adenocarcinoma. To determine the extent of neuroendocrine differentiation in high-grade prostatic intraepithelial neoplasia (PIN), a putative precursor of cancer, we studied the immunohistochemical expression of 10 markers in 26 radical prostatectomy specimens with PIN and adenocarcinoma. Expression was measured as mean percent of positive cases and positive high-power (x40) fields. The highest percentage of cases showed immunoreactivity for serotonin (73%, PIN; 54%, carcinoma), neuron-specific enolase (NSE) (67%, PIN; 46%, carcinoma), chromogranin (62%, PIN; 65%, carcinoma), and human chorionic gonadotropin (hCG) (30%, PIN; 22%, carcinoma); the remaining markers showed immunoreactivity in fewer than 5% of cases (somatostatin, calcitonin, corticotropin) or in no cases (thyrotropin, prolactin, and glucagon). At least one of the markers was present in 88% of cases of PIN and 92% of carcinoma. Non-neoplastic epithelial cells expressed serotonin, NSE, chromogranin, and hCG in every case, and the expression was significantly greater than in PIN and cancer. Stepwise regression analysis revealed the following positive correlations: chromogranin expression in PIN and patient age, NSE expression in cancer and number of lymph node metastases, and hCG expression in cancer and percentage of Gleason pattern 5; serotonin expression in PIN and cancer did not correlate with any of the clinical and pathologic factors. Neuroendocrine differentiation is downregulated in prostatic carcinogenesis, with intermediate levels of expression in PIN compared with normal cells and carcinoma.

Adenocarcinoma↗
PubMed1994

Prostate-specific antigen. Current role in diagnostic pathology of prostate cancer.

Prostate-specific antigen is the most important, accurate, and clinically useful biochemical marker in the prostate. It is manufactured by the secretory epithelial cells and drains into the ductal system, where it catalyzes the liquefaction of the seminal coagulum after ejaculation. Serum levels are normally less than 4 ng/mL (monoclonal) but vary according to patient age and race; any process that disrupts the normal architecture of the prostate allows diffusion of prostate-specific antigen into the stroma and microvasculature. Elevated serum prostate-specific antigen levels are seen with prostatitis, infarcts, hyperplasia, and transiently after biopsy, but the most clinically important increases are seen with prostatic adenocarcinoma. Cancer produces less prostate-specific antigen per cell than benign epithelium, but the greater number of malignant cells and the stromal disruption associated with cancer account for the increased serum prostate-specific antigen level. Serum prostate-specific antigen level correlates positively with clinical stage, tumor volume, histologic grade, and the presence of capsular perforation and seminal vesicle invasion; despite these strong correlations, its value is limited in predicting stage for individual patients. It may also predict the presence of lymph node metastases, bone metastases, and survival after androgen-deprivation therapy. The use of prostate-specific antigen has resulted in an increase in the early detection rate of cancer, and it is now advocated for annual routine use in men older than 40 years who are at increased risk and in all men older than 50 years. It is a test with high sensitivity and specificity that is rapid, inexpensive, minimally invasive, and acceptable to patients. In addition to serum prostate-specific antigen level, five derivatives of serum prostate-specific antigen were recently described that may increase the predictive value by accounting for confounding variables such as patient age, prostate volume, and cancer volume: age-specific reference ranges, prostate-specific antigen density, prostate-specific antigen velocity, prostate-specific antigen cancer density, and prostate-specific antigen doubling times. Serum prostate-specific antigen detects a heterogeneous group of cancers (clinical stage T1c) that are clinically important and potentially curable. Immunohistochemical expression of prostate-specific antigen in tissue sections allows determination of the prostatic origin of some metastatic adenocarcinomas, although extraprostatic expression of prostate-specific antigen has been reported in several tissues and tumors, including periurethral gland adenocarcinoma in women, rectal carcinoid, and extramammary Paget disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Forecasting↗