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Biomedical subjects

I A Sesterhenn

Publications and source records attributed to I A Sesterhenn.

At least 19 recordsLinked to original sources
PubMed1995

Prostate-specific antigen values at the time of prostate cancer diagnosis in African-American men.

OBJECTIVE: To determine if African-American men with newly diagnosed prostate cancer (PC) have higher pretreatment serum prostate-specific antigen (PSA) values after adjustment for clinical stage, age, and tumor grade, and to determine if any difference detected is related to tumor volume difference. DESIGN: Consecutive case series of newly diagnosed PC patients between January 1990 and September 1994 and cohort analytic study of PC patients treated by radical prostatectomy (RP) and who had whole-mount pathologic tumor volume assessment between May 1993 December 1994. SETTING: Tertiary care military medical center. PATIENTS: A total of 541 evaluable newly diagnosed PC patients (408 white and 133 black) having pretreatment PSA assessment at one laboratory; 91 patients undergoing RP had whole-mount tumor volume analysis. INTERVENTIONS: Medical record review for pretreatment PSA value, race, tumor grade, clinical stage, and age, as well as whole-mount pathologic assessment of RP specimen and measurement of tumor volume. MAIN OUTCOME MEASURES: The PSA differences between black and white PC patients with adjustments for age, biopsy tumor grade (Gleason score), and clinical stage (TNM stage); PSA differences between black and white PC patients undergoing RP with adjustment for age, RP grade, clinical stage, and tumor volume. RESULTS: The mean (geometric) PSA value for 133 black men was 14.00 ng/mL compared with 8.29 ng/mL for 408 white men (P < .001). The black patients had higher PSA values across all stage, grade, and age categories. The racial difference in PSA levels remained statistically significant when stage, grade, and age were simultaneously controlled for (P < .001). Multivariable odds ratio testing revealed that even after adjustment for stage, grade, and age, black patients were 2.2 times as likely as white patients to have a PSA value greater than 10.0 ng/mL (95% confidence interval, 1.3 to 3.6). Tumor volume (geometric mean) was 5.42 cm3 and 2.10 cm3 for black and white RP patients, respectively (P = .002). Across all clinical stages (T1a to T3), black men had tumor volumes 1.3 to 2.5 times greater than those of white men. Multivariable analysis of covariance revealed that tumor volume and stage of disease were important predictors of PSA level, but race, grade, and age were not. (The percentage of white and black patients whose cancer was detected by screening [75.4% vs 70.4%] or who had symptoms [37.7% vs 29.6%] was not significantly different.) CONCLUSIONS: As a group, African-American men with newly diagnosed PC have higher PSA values at initial diagnosis than white men. This PSA difference appears to be due to larger tumor volumes within clinical (TNM) stage categories among black patients. Elevated PSA value was a surrogate for larger tumor volume in this cohort of black men. This stage-for-stage tumor volume disparity even in an equal-access health care environment should prompt further study of screening behavior and/or biological differences of PC in the black population.

Age Distribution↗
PubMed1995

Pathology review in an early prostate cancer detection program: results from the American Cancer Society-National Prostate Cancer Detection Project.

Biopsy materials obtained in the American Cancer Society National Prostate Cancer Detection Project were reviewed at the Central Pathology Laboratory at the Armed Forces Institute of Pathology. Of 265 cases submitted, 177 were diagnosed as prostatic carcinoma, 7 as prostatic intraepithelial neoplasia (PIN), 13 as atypical glands or atypical hyperplasia, and the remaining 68 were benign hyperplasias. Irrespective of the means of detectin or the grading system used (Gleason or WHO-Mostofi), a large majority of the cancers were detected as low-grade tumors. Of 27 cases of PIN reported, 20 were associated with cancer, leaving 7 cases with the sole diagnosis of PIN. These data may indicate the increased use of prostate-specific antigen (PSA), digital rectal examination (DRE), and transrectal ultrasound (TRUS) in the United States is shifting the spectrum of prostate cancer pathology toward early low-grade tumors.

Biopsy↗
PubMed1995

Renal medullary carcinoma. The seventh sickle cell nephropathy.

Over the last 22 years, we have encountered 34 examples of a highly aggressive neoplasm with a microscopic morphology that is highly predictive of finding sickled erythrocytes in the tissue. With the exception of one patient, all are believed to have had sickle cell trait or, in one case, hemoglobin SC disease. These 33 patients are the subject of this report and, where their race was known, they were all blacks between the ages of 11 and 39 years. Between the ages of 11 and 24 years, males predominated by 3 to 1. Beyond age 24, however, the tumors occurred equally in men and women. The dominant tumor mass was in the medulla and ranged from 4 to 12 cm in diameter. Mean size was 7 cm; median, 6 cm. Peripheral satellites in the renal cortex and pelvic soft tissues, as well as venous and lymphatic invasion, were usually present. The lesions exhibited a reticular, yolk sac-like, or adenoid cystic appearance, often with poorly differentiated areas in a highly desmoplastic stroma admixed with neutrophils and usually marginated by lymphocytes. The tumors had usually metastasized when first discovered, and none was confined to the kidney at the time of nephrectomy. The mean duration of life after surgery was 15 weeks. These tumors probably arise in the calyceal epithelium in or near the renal papillae, the same site that produces the more familiar picture of unilateral hematuria in patients with sickle cell trait. We have concluded that renal medullary carcinoma represents another example of renal disease associated with sickle cell disorders. The other six are unilateral hematuria, papillary necrosis, nephrotic syndrome, renal infarction, inability to concentrate urine, and pyelonephritis.

Adolescent↗
PubMed1995

Interobserver reproducibility in the diagnosis of prostatic intraepithelial neoplasia.

To assess interobserver reproducibility in the categorization of prostatic intraepithelial neoplasia (PIN) seven pathologists reviewed 25 lesions. Rather than classic or consecutive examples of PIN, cases were selected to represent the full spectrum of diagnostic issues in this field. Lesions were classified into one of six categories: (a) benign prostate tissue, (b) PIN1, (c) PIN2, (d) PIN3, (e) PIN3 cannot rule out associated cancer, and (f) PIN3 plus cancer. Following evaluation of the slides, data were also analyzed by combining several of the groups into three categories: (a) benign/PIN1; (b) PIN2/PIN3/PIN cannot rule out cancer; and (c) PIN plus cancer. The level of agreement was fair (Kappa = 0.33) for the six categories and substantial (Kappa = 0.61) for the three groups. In no case was there a uniform diagnosis of PIN1; in all cases at least some pathologists considered the biopsies to be normal. This finding provides support for not commenting on PIN1 in biopsy material. In general, there was good distinction between low-grade PIN (PIN1) and high-grade PIN (PIN2-3). Among the seven cases for which there was a consensus that the lesion represented high-grade PIN, there was no case in which there was uniform agreement as to whether the lesion represented PIN2 or PIN3. This finding supports combining PIN2 and PIN3 into high-grade PIN. Cases classified as low-grade PIN by some and as high-grade PIN by others were those with pleomorphism but without prominent nucleoli. Difficulties in distinguishing "high-grade PIN" from "high grade PIN cannot rule out cancer" were those with cribriform glands, glands with necrosis, and where high-grade PIN was associated with only a few adjacent small atypical glands. These same histologies caused the participating pathologists difficulty in distinguishing "high-grade PIN cannot rule cancer" from "high grade PIN plus cancer."

Biopsy, Needle↗
PubMed1995

Metanephric adenoma. Clinicopathological study of fifty patients.

We report 50 examples of an uncommon type of renal adenoma from the files of the Armed Forces Institute of Pathology. They appear to be benign tumors with no malignant potential, and their chief importance is related to the fact that they are most often misinterpreted as renal cell carcinoma or epithelial Wilms' tumor. They predominated in females by well over 2:1. The mean age of the patients was 41 years, with a range of 5 to 83 years, and the mean size was 5.5 cm, with a range of 0.3 to 15.0 cm. Presenting signs and symptoms included pain in 11, hematuria in five, and palpable mass in five. In 20 patients the tumors were found incidentally during evaluation for other problems, and in six the other problem was polycythemia. This finding establishes a higher incidence of polycythemia in renal adenoma than in other previously reported renal diseases. Also of preoperative importance is the fact that these tumors are more commonly calcified than other renal neoplasms. Microscopically, these tumors consist of very small epithelial cells that form very small acini in an acellular stroma. Less often, they form tubular, glomeruloid, or polypoid and papillary formations. Most also show evidence of regression in the form of scarring and calcification. These lesions seem histogenetically related to epithelial Wilms' tumor, and, in fact, the two may occur together. They are histologically very similar to the metanephric hamartomatous element of nephroblastomatosis.

Adenoma↗
PubMed1995

Alteration of the tumor suppressor gene p53 in a high fraction of hormone refractory prostate cancer.

PURPOSE: We studied the role of p53 tumor suppressor gene alteration in prostate cancer progression by demonstrating a difference in abnormal p53 findings between early and hormone refractory disease. MATERIALS AND METHODS: The study included p53 immunohistochemistry of 26 archival transurethral resection specimens from patients with radiation recurrent and hormone refractory disease, 27 untreated primary tumors and 8 untreated metastatic lesions. p53 mutation analysis of tumor deoxyribonucleic acid (DNA) from microdissected specimens was done by cold single strand conformational polymorphism and DNA sequencing. RESULTS: Elevated p53 protein was present in 16 of 17 hormone refractory specimens (94%), 4 of 8 untreated metastatic tumors (50%) and 6 of 27 primary untreated tumors (22%). DNA analysis of representative specimens with elevated p53 confirmed p53 gene alterations in 9 of 11 cases (82%). CONCLUSIONS: Our study revealed a clear progression of increased p53 alteration from untreated primary to hormone refractory disease (p < 0.00005).

Base Sequence↗
PubMed1995

Increased p53 protein does not correlate to p53 gene mutations in microdissected human testicular germ cell tumors.

PURPOSE: To determine if primary testicular germ cell tumors that overexpress p53 tumor suppressor gene protein have p53 gene mutations. MATERIALS AND METHODS: We examined 30 primary testicular tissues from 26 patients representing two groups. Group one consisted of eleven cases (6 nonseminomatous germ cell tumors and 5 seminomas) in which tissue samples for DNA analysis were microdissected from paraffin block regions with elevated immunohistochemical staining for p53 protein. Group two consisted of 19 testis tumor tissues which had been fresh frozen and were chosen to correspond to archival tissue specimens exhibiting elevated levels of p53 protein. The DNA was extracted from these tissues and subjected to exon specific amplification by polymerase chain reaction (PCR) and cold single-strand conformation polymorphism (Cold SSCP) analysis. RESULTS: In these cases with elevated p53 protein, no p53 gene exon 5-8 mutations were detected except 1 seminoma with a codon 140 silent mutation (no protein alteration). CONCLUSIONS: Testicular tumors appear to exhibit elevated levels of wild-type p53 protein, the significance of which is yet to be elucidated.

Base Sequence↗
PubMed1993

A pathologist's view of prostatic carcinoma.

In this article, the pathologic findings of carcinoma of the prostate were reviewed. Criteria were discussed for the pathologic diagnosis of prostatic carcinoma (PC), premalignant lesions, lesions that simulate PC, immunopathologic findings, special types of PC, effects of therapy on the prostate, and recent efforts to improve diagnostic and prognostic capabilities. The possible role of the study of nucleolar organizing regions was reported. A new method for demonstrating chromosomes in formaldehyde-fixed paraffin-embedded tissue was mentioned. The need for research in all aspects of the pathology of prostatic cancer was emphasized.

Acid Phosphatase↗
PubMed1992

Pathology of carcinoma of the prostate.

In this presentation the authors review the pathology of prostatic carcinoma (PCa), and discuss criteria for pathologic diagnosis, premalignant lesions, lesions that simulate PCa, immunopathology, special types of PCa, effects of therapy on the prostate, and recent efforts to improve diagnostic and prognostic capabilities. The possible role of study of nucleolar organizing regions is reported. A new method for demonstration of chromosome in formalin-fixed, paraffin-embedded tissue is presented. The need for research in all aspects of pathology is emphasized.

Acid Phosphatase↗
PubMed1992

Prediction of prognosis in untreated stage A2 prostatic carcinoma.

Carcinoma is found unexpectedly in approximately 10% or more of the 400,000 prostatectomies performed annually in the United States. Patients with Stage A2 carcinoma die of their disease in only 35% of the cases. To alter the course of disease in these patients, 65% of Stage A2 patients may be treated unnecessarily by radical prostatectomy, radiation therapy, or hormonal therapy. An accurate method to predict the outcome of patients with Stage A2 carcinoma is needed. Histologic sections from 18 patients with Stage A2 prostatic carcinoma followed without further treatment until progression, or followed without progression, were evaluated by several investigators who did not have knowledge of patient outcomes and who employed standard pathologic grading systems as well as morphometric, cytophotometric, flow cytometric, and immunohistochemical techniques. Outcome was predicted correctly by random sampled absolute (17 of 18 cases) and relative (16 of 18) nuclear roundness factor (NRF), tumor volume expressed as percent of specimen (13 of 16), primary (13 of 18), secondary (14 of 18), sum (15 of 18), and worse (14 of 18) Gleason grades and prostate-specific antigen immunohistochemical findings (13 of 18) that produced statistically significant separation of the two groups. Significant separation was not obtained with Mostofi's pattern, nuclear, sum, and worse grades, Johns Hopkins' grade, absolute tumor volume, nuclear DNA content measured by image cytophotometric study of Feulgen-stained histologic sections and flow cytometric study of propidium iodide-labeled suspensions of nuclei obtained from paraffin blocks, nonrandom sampled NRF of worse and most prevalent neoplastic areas, and prostatic acid phosphatase and peanut agglutinin immunohistochemical study. NRF measured by a random technique best predicted outcome in these patients with A2 prostatic carcinoma and should be evaluated prospectively as a means for selecting patients who require therapy.

Adenocarcinoma↗
PubMed1992

Preliminary results of three-dimensional reconstruction of previously imaged prostates.

In patients with biopsy proven prostate cancer, preoperative transrectal magnetic resonance imaging (MRI) and ultrasound were performed, followed by total prostatectomy. Generally, the findings with MRI correlated well with the histopathologic findings, including infiltration of and extension through the capsule into periprostatic tissue and the seminal vesicles. False negative results with MRI included centrally located tumors and small tumors. False positive results with MRI included lobular atrophy, cystic hyperplasia, cystic atrophy, florid glandular hyperplasia and scars with chronic inflammation.

Humans↗
PubMed1992

Prostatic intraepithelial neoplasia (PIN): morphological clinical significance.

Premalignant lesions of the prostate fall into two categories. The first category includes formation of new, usually small, glands which are either abnormally distributed or show minimal nuclear atypia or both. Morphologically, this lesion presents the differential diagnostic alternatives of micro-acinar hyperplasia on the one hand and a low grade micro-acinar cancer on the other. If the presence or absence of nuclear anaplasia or acinar dispersion (i.e., stromal invasion) raises any degree of doubt, atypical glands are diagnosed. This is the category that is considered by some to be the precursor of well differentiated prostate cancer. The second category is prostatic intraepithelial neoplasia (PIN). We have defined PIN as an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. We consider PIN as essentially carcinoma in situ. The lesion designated by some as PIN 1 is classified by us as atypical hyperplasia.

Biomarkers↗
PubMed1992

Prostatic carcinoma: problems in the interpretation of prostatic biopsies.

We have endeavored to identify problems the pathologist may face in dealing with prostatic carcinoma (PCa). We have covered criteria for diagnosis and have discussed lesions that simulate PCa and the distinguishing features, treatment effects, and specific types of PCa. In many of these areas there is a need for developing objective, reproducible, and measurable criteria. The need for research is obvious.

Biopsy↗
PubMed1992

Prognosis and other clinical correlates of pathologic review in stage I and II testicular carcinoma: a report from the Testicular Cancer Intergroup Study.

PURPOSE: The Testicular Cancer Intergroup Study (TCIS) was undertaken to evaluate the pathologic findings in early-stage testicular cancer as determined by central pathology review, to compare these findings with the interpretation by the contributing pathologists, and to make correlations with various clinical parameters and outcomes. PATIENTS AND METHODS: The prospective study of non-seminomatous germ cell testicular cancer staged surgically involved 459 eligible patients with stage I (node-negative) or stage II (node-positive) disease. Pathologic materials from both the orchiectomy and lymphadenectomy specimens were submitted to a central laboratory for evaluation. RESULTS: Central and local pathologists differed significantly in their identification of certain cellular histologies (primarily yolk sac tumors [YST]) and recognition of invasion into vascular structures. In contrast to our prior findings with local pathologic assessment, venous/lymphatic invasion as determined by central review predicted relapse in both stages. In pathologic stage I disease, the relapse rate was 19.4% (12 of 62 cases) for those with invasion versus 6.0% (10 of 168 cases) for those without invasion. In pathologic stage II disease, the respective relapse rates were 63.5% (40 of 63 cases) and 24.0% (six of 25 cases). Vascular invasion was jointly predictive with nodal stage for risk of relapse. The percentage of embryonal carcinoma (EC) in the primary tumor was predictive of nodal stage and relapse in a univariate, but not a multivariate, analysis. In a large substudy, immunohistochemical staining identified a correlation between stain intensity in YST and serum alpha-fetoprotein (AFP) levels. In a similar fashion human chorionic gonadotropin (HCG) staining reactivity occurred exclusively in patients with syncytiotrophoblasts and correlated with serum levels of beta-HCG. CONCLUSIONS: A number of tumor histology correlates with clinical parameters have been identified or confirmed. Careful pathologic scrutiny of the primary testicular tumor, especially for vascular invasion, provides important prognostic information.

Adolescent↗
PubMed1992

Carcinoma of the male and female urethra.

About 600 cases of urethral carcinoma have been reported. Such tumors may arise from the surface epithelium or any of the glands, and four histologic patterns--squamous, transitional, glandular, and undifferentiated--have been recognized. Metastases from other sites are possible, as are melanomas and various types of sarcoma.

Carcinoma↗
PubMed1990

Tumor markers of epithelial ovarian neoplasms.

Ninety-three formalin-fixed, paraffin-embedded surgical specimens from 69 ovarian tumors representing all five epithelial cell types were studied by immunohistochemistry, peanut and ulex lectin binding, and carbohydrate histochemistry. Carcinoembryonic antigen (CEA) was mostly noticeable in mucinous tumors (21 of 26). Glycogen was highly prevalent in clear cell (8 of 9) and endometrioid (4 of 6) carcinomas, in contrast to serous carcinomas (3 of 6), where it was only focally distributed, and was completely absent in all mucinous tumors. Among the different types of malignant tumors examined, mucinous carcinomas most frequently contained neutral mucins (6 of 8). In mucinous tumors, an increase in CEA content and a decrease in the total mucin secretion, particularly the strongly acidic sulfated group, were found to parallel the increased malignant potential of the tumor. Peanut and/or ulex lectin binding was a feature common to almost all epithelial neoplasms. Although peanut lectin showed a slightly higher affinity to serous and clear cell tumors, while ulex lectin was bound more to mucinous and endometrioid neoplasms, distribution of D-galactose and L-fucose does not have a diagnostic utility in these tumors. Placental lactogen was detected in 3 of 17 benign tumors and one of 19 tumors of low malignant potential (LMP). The beta subunit of hCG was found in one of 17 benign tumors, in 2 of 19 LMP tumors, and in 3 of 31 carcinomas.

Biomarkers, Tumor↗