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Biomedical subjects

D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 271 records · Page 15Linked to original sources
PubMed1994

Grading prostate cancer.

Histologic tumor grade is a strong predictor of outcome for men with prostate cancer. All existing grading systems successfully identify well-differentiated cancer, which progresses slowly, and poorly differentiated cancer, which progresses rapidly, but they are less successful in subdividing most moderately differentiated cancers, which have an intermediate malignant potential. The Gleason system, the de facto standard for grading, identifies histologic patterns by the degree of glandular differentiation without relying on morphogenetic or histogenetic models; it reflects tumor heterogeneity by combining primary and secondary patterns into a cancer score. Modifications that have been proposed for Gleason grading include morphometric nuclear grading, grouping of grades, estimating the amount of high-grade cancer (Gleason patterns 4 and 5), and including the cribriform pattern as Gleason pattern 4 rather than 3. Most variants of prostate cancer are high grade (Gleason patterns 4 and 5), including small cell undifferentiated carcinoma, signet ring cell carcinoma, sarcomatoid carcinoma, and carcinosarcoma. The Gleason system can be reproduced by most investigators, although there is a small but significant level of interobserver and intraobserver variability that is unavoidable. When compared with matched prostatectomy specimens, contemporary 18-gauge needle core biopsy underestimates tumor grade in 33% to 45% of cases and overestimates grade in 4% to 32% of cases, similar to results with traditional 14-gauge biopsies. Grading errors are common in biopsy specimens with small amounts of tumor and low-grade tumor, and are probably due to tissue sampling error and tumor heterogeneity. Upgrading of prostate cancer may occur after radiation therapy but is common after androgen-deprivation therapy. Univariate and multivariate analyses of prognosis in prostate cancer almost always identify cancer grade as one of the most significant predictors of patient outcome. The combination of cancer grade with other prognostic variables to create a multiple prognostic index should allow greater precision in predicting outcome for individual patients.

Biopsy, Needle↗
PubMed1994

The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials.

Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention trials to avoid the excessively long study periods and high costs associated with the use of cancer incidence reduction as an endpoint, particularly with relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be directly associated with the evolution of neoplasia, and develop with high frequency in abnormal cells of susceptible individuals. If SEBs can be modified by a particular intervention regimen in short-term studies, the rationale for carrying out long-term studies may be strengthened. The consensus panel identified a small and manageable group of biomarkers measured in tissue or serum as the most promising in prostate cancer chemoprevention, including (1) prostate specific antigen (PSA); (2) morphometric markers, such as nuclear size and roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) nuclear DNA content (ploidy); (5) oncogene c-erbB-2 (HER-2/neu) expression; (6) angiogenesis; and (7) high-grade prostatic intraepithelial neoplasia (PIN). Information regarding many of these and other biomarkers is limited, calling for further investigation. Also, these factors, chosen chiefly for their proven or proposed utility as prognostic factors, may be less useful as SEBs. It was agreed that concurrent study of numerous markers rather than single markers allows comparison of their relative utility, including assessment of ease of quantitation and the sensitivity, specificity, and positive and negative predictive value.

Anticarcinogenic Agents↗
PubMed1994

Target populations and strategies for chemoprevention trials of prostate cancer.

Chemoprevention trials usually target healthy populations and employ non-toxic chemicals in an effort to eliminate, reduce, or reverse premalignant lesions or early cancer. Recent efforts have been directed at short-term Phase II trials which rely on changes in surrogate endpoint biomarkers rather than cancer incidence reduction as an endpoint. Chemopreventive agents are chosen that are likely to produce a modulating effect on one or more biomarkers in prostate cancer, including extent and grade of morphometric, genetic, proliferative, differentiative, and regulatory biomarkers. Five target populations appear to have the greatest promise in chemoprevention trials for prostate cancer: (1) Patients with high-grade prostatic intraepithelial neoplasia, a microscopic lesion which is the likely precursor of some prostate cancers; (2) patients with early cancer treated by watchful waiting; (3) patients with cancer waiting for prostatectomy; (4) men at high risk of developing prostate cancer; and (5) men from the general population (normal risk of prostate cancer).

Anticarcinogenic Agents↗
PubMed1994

Establishment of the formalin-free surgical pathology laboratory. Utility of an alcohol-based fixative.

Concerns about the toxicity of formalin dictate the need for alternative methods of tissue fixation. Alcohol-based fixatives have been proposed as optimal for immunohistochemical and nucleic acid methods and may be useful for diagnostic light microscopy. We recently converted our surgical pathology laboratory from 10% neutral buffered formalin to an alcoholic fixative (56% ethanol and 20% polyethylene glycol) and compared 100 consecutive cases after conversion with 100 formalin-fixed cases prior to conversion. One representative slide from each case was reviewed independently by four pathologists without knowledge of the fixative employed. The quality of fixation of each case was graded (0, very poor; 1, below average; 2, average; and 3, above average) based on the subjective composite evaluation of seven morphological features: tissue architecture, cell borders, cytoplasm, nuclear contours, chromatin texture, red blood cell membranes, and uniformity of staining. No significant difference in the quality of fixation was observed, although the average score of the alcoholic fixative was slightly lower than that of the formalin (2.59 vs 2.74). Interobserver concordance was 74%. Advantages of the alcoholic fixative included elimination of carcinogenic vapors, more rapid fixation, greater stain avidity, elimination of enzyme predigestion in immunohistochemical studies, and simple and rapid disposal. Disadvantages included slightly increased viscosity, increased variability of tissue staining and nuclear shrinkage, artifactual pigment deposition in bloody specimens, and increased flammability risk. Alcohol-polyethylene glycol appears to be a satisfactory alternative to formalin in routine diagnostic surgical pathology.

Ethanol↗
PubMed1993

Cystosarcoma phyllodes of the seminal vesicle.

An unique case of high-grade phyllodes tumor (cystosarcoma phyllodes) arising in the seminal vesicle is reported. A 61-year-old man had symptoms of urinary obstruction, and ultrasonography and computed tomography showed a large mass posterior to the bladder. Using cystoprostatoseminovesiculectomy, a high-grade phyllodes tumor of the left seminal vesicle was found that did not involve the bladder or prostate. Histologically, the tumor consisted of benign irregular slit-like glands set in a mitotically active cellular sarcomatous stroma. The epithelium displayed intense cytoplasmic immunoreactivity with all keratin proteins (AE1/AE3, CAM 5.2, and high-molecular-weight keratin [clone 34 beta E12]). The stromal cells were strongly positive for vimentin, and approximately 30% were positive for muscle-specific actin and desmin. Four years after resection, a lung metastasis was removed, which was histologically and immunohistochemically identical to the seminal vesicle tumor. This case represents the malignant end of the range of phyllodes tumors (cystosarcoma phyllodes). Like similar tumors in the breast and prostate, phyllodes tumors of the seminal vesicle should be considered high-grade lesions (malignant) in which there is significant mitotic activity, stromal pleomorphism, and stromal overgrowth.

Genital Neoplasms, Male↗
PubMed1993

Architectural patterns of high-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (PIN) is characterized by cellular proliferations within pre-existing ducts and glands with cytologic changes mimicking adenocarcinoma, including prominent nucleoli, but lacking stromal invasion. To determine the architectural spectrum of high-grade PIN, 60 serially sectioned radical prostatectomy specimens with PIN and cancer were reviewed. Four common patterns of high-grade PIN were identified, usually with multiple patterns in each case: tufting (in 87% of cases), micropapillary (in 85% of cases), cribriform (in 32% of cases), and flat (in 28% of cases). Tumor grade was not significantly associated with any pattern of PIN. Luminal cytoplasmic apical blebs were found in all cases regardless of the pattern of PIN. A variety of associated architectural and cytologic features were observed with high-grade PIN: epithelial arches (in 60% of cases), cellular trabecular epithelial bars (in 22% of cases), "Roman" bridges (in 30% of cases), partial gland involvement (in 82% of cases), basal cell layer disruption with glandular budding (in 23% of cases), large cystic gland involvement (in 10% of cases), involvement by nodular hyperplasia (in 5% of cases), microcalcifications (in 8% of cases), proteinaceous luminal secretions (in 62% of cases), corpora amylacea (in 55% of cases), exfoliated cells of PIN (in 42% of cases), luminal crystalloids (in 3% of cases), and mucinous metaplasia (in 2% of cases). High-grade PIN exhibits a variety of architectural patterns while retaining the distinctive cytoplasmic apical blebs and diagnostic nuclear and nucleolar features. Identification of high-grade PIN warrants a further search for invasive carcinoma, but should not influence or dictate decisions regarding definitive therapy.

Adenocarcinoma↗
PubMed1993

Atypical adenomatous hyperplasia of the prostate: morphologic criteria for its distinction from well-differentiated carcinoma.

Atypical adenomatous hyperplasia (AAH) is a localized proliferation of small glands within the prostate that may be mistaken for carcinoma. To determine the diagnostic criteria for separating AAH from carcinoma, seven observers independently evaluated 54 selected lesions from 44 transurethral resection specimens. Three patterns of glandular proliferation were observed, all arising in association with nodular hyperplasia: AAH (38 foci), atypical small acinar proliferation of uncertain significance (eight foci), and well-differentiated carcinoma (eight foci). Of 24 architectural and cytologic features evaluated, the following were useful in separating these three patterns: variation in nuclear size (14%, 22%, and 25%, respectively), mean nucleolar diameter (0.69 micron, 1.43 microns, and 1.78 microns, respectively), largest nucleolar diameter (mean, 1.66 microns, 2.71 microns, and 2.81 microns, respectively), percentage of nucleoli greater than 1 micron in diameter (17.6%, 58.1%, and 77.5%, respectively), crystalloids within suspicious glands (16%, 13%, and 75%, respectively), luminal basophilic mucinous secretions, infiltrative borders, discontinuity of the basal cell layer in AAH (compared with complete absence in carcinoma; shown with basal cell-specific anti-keratin monoclonal antibody 34 beta E12 immunostaining), and intact basement membrane in AAH (compared with discontinuity in carcinoma; shown with type IV collagen immunostaining). Features that could not reliably separate AAH from carcinoma included lesion shape, circumscription, multifocality, average gland size, variation in gland size and shape, nuclear shape, chromatin pattern, and amount and tinctorial quality of cytoplasm. Although the biologic significance of AAH is uncertain, its light microscopic appearance and immunophenotype allow it to be distinguished from carcinoma in most cases.

Adenoma↗
PubMed1993

Staging of early prostate cancer: a proposed tumor volume-based prognostic index.

Current staging of early prostate cancer separates patients into two groups: those with palpable and non-palpable tumors. Such staging relies on digital rectal examination in making this separation, despite the low sensitivity, low specificity, and low positive predictive value of this method. As an alternative, tumor volume may be useful for staging because of its powerful prognostic ability and its potential to be assessed clinically due to recent advances in imaging techniques such as transrectal ultrasound. In this study, we evaluate the utility of tumor volume in predicting progression of early prostate cancer based on the composite published evidence from nine pathologic studies of serially-sectioned prostates. Logistic regression revealed that tumor volume was a good positive predictor of all measures of tumor progression. There was a 10 percent probability of capsular invasion in tumors measuring about 0.5 cm3; 10 percent probability of seminal vesicle invasion in tumors measuring about 4.0 cm3; and 10 percent probability of metastases in tumors measuring about 5.0 cm3. These composite results suggest that tumor volume is a significant predictor of cancer progression. A volume-based prognostic index is proposed as an adjunct to staging for early prostate cancer.

Humans↗
PubMed1993

Atypical basal cell hyperplasia of the prostate. Immunophenotypic profile and proposed classification of basal cell proliferations.

Prostatic basal cell proliferations range from focal basal cell hyperplasia (BCH) to florid adenoid basal cell tumor (ABCT). We reviewed 36 cases of basal cell proliferation to evaluate the architectural and cytologic spectrum of these lesions and identified four distinct patterns by light microscopy: BCH, 12 cases, including two cases with stromal sclerosis; atypical BCH with nucleolomegaly, eight cases; basal cell adenoma (BCA), nine cases; and ABCT, seven cases. Twenty-three cases were evaluated immunohistochemically, and all displayed cytoplasmic immunoreactivity in basal cells with basal-cell-specific high-molecular-weight keratin 34 beta E12 but with increased staining in BCH compared with that in BCA and ABCT. Prostate-specific antigen and prostatic acid phosphatase reactivity were seen at least focally in all cases except two cases each of BCA and ABCT. Chromogranin, S-100 protein, and neuron-specific enolase reactivity were rare or negative in all cases. Nucleolar diameter, measured in 18 of the 36 cases, was significantly greater in atypical BCH (mean, 1.96 microns) than in other forms of basal cell proliferation (mean, < 1.0 microns) (P < 0.05). These results indicate that on the basis of light microscopic, immunohistochemical, and morphometric findings, the spectrum of basal cell proliferations in the prostate can be separated into four distinct groups: BCH, atypical BCH, BCA, and ABCT.

Adenoma↗
PubMed1993

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.

Aged↗
PubMed1993

Diagnosis of hepatic allograft rejection: role of liver biopsy.

The role of the liver biopsy for establishing a diagnosis of liver allograft rejection was investigated by examining under code 151 liver biopsies from 32 recipients and correlating the results with the clinical diagnosis determined by chart review. One-hundred-and-four biopsies were obtained to evaluate the cause of liver dysfunction and 47 were performed on a weekly protocol basis independent of the clinical status. A diagnosis of "definite histologic rejection" was made if a biopsy contained portal triaditis, bile duct injury, and endothelialitis, while biopsies were said to be suspicious for rejection if portal triaditis and bile duct injury were evident. A diagnosis of rejection using clinical and biochemical findings and response to therapy was made in association with 37 biopsies, of which 16 had definite histologic rejection and 13 were suspicious for rejection. Of the 114 biopsies performed in patients without clinical rejection, 71 had histology suspicious for rejection. Thus, biopsy was sensitive for the detection of rejection (78%), but was not very specific (33%). The positive predictive value was low (28%), while the negative predictive value was high (83%). These results indicate that liver biopsy is useful to evaluate graft dysfunction, to exclude rejection, to confirm clinically suspected rejection, and to diagnose other problems that can affect allograft function. Protocol biopsies appear to have little value.

Adolescent↗
PubMed1993

PSA-detected (clinical stage T1c or B0) prostate cancer. Pathologically significant tumors.

With the rapidly spreading enthusiasm for early detection of prostate cancer and the increasing use of serum PSA to evaluate the gland, more cancers that are not palpable on digital rectal examination are being identified. These tumors have pathologic characteristics that are very similar to those of clinically localized, palpable prostate cancers identified on digital rectal examination. Thus, the tumors detected on the basis of an elevated serum PSA value should not be disregarded as insignificant. In fact, these tumors should be given the same therapeutic consideration as the clinically localized, palpable cancers. In the TNM staging system, "PSA-detected" cancers can be classified as stage T1c, and in the Whitmore-Jewett staging system, they can be referred to as stage B0. Long-term follow-up of these prostate cancers will be necessary to establish the prognosis.

Adult↗
PubMed1992

The association of benign prostatic hyperplasia and cancer of the prostate.

There are a number of similarities between benign prostatic hyperplasia (BPH) and cancer. Both display a parallel increase in prevalence with patient age according to autopsy studies (86.2% and 43.6%, respectively, by the ninth decade), although cancer lags by 15-20 years. Both require androgens for growth and development, and both respond to antiandrogen treatment regimens. Most cancers arise in prostates with concomitant BPH (83.3%), and cancer is found incidentally in a significant number of transurethral prostatectomy (TURP) specimens (10%). The clinical incidence of cancer arising in patients with surgically treated BPH is approximately 3%. BPH may be related to a subset of prostate cancer which arises in the transition zone, perhaps in association with atypical adenomatous hyperplasia (AAH). It is important to exclude cancer in patients presenting with symptoms of bladder outlet obstruction presumably due to BPH. For such patients, we recommend digital rectal examination (DRE) and, at least in high-risk patients, serum prostate specific antigen (PSA) determination. Transrectal ultrasound (TRUS) should be employed in patients with elevated PSA levels to determine the volume of the prostate, the relative contribution of BPH to volume, and the PSA density (ratio of PSA level to volume). Biopsy should be obtained from any area suspicious for cancer. Early detection and treatment of cancer when it is localized offers the greatest chance for cure.

Adult↗
PubMed1992

Prostatic intraepithelial neoplasia (PIN): current concepts.

Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts, ductules and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered to be a precursor to invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterized by basal cell layer disruption, basement membrane disruption, progressive loss of secretory differentiation markers, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognizing PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma.

Adult↗