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PubMed1996

Correlation of DNA ploidy and histologic diagnosis from prostate core-needle biopsies: is DNA ploidy more sensitive than histology for the diagnosis of carcinoma in small specimens?

DNA ploidy has been shown to have prognostic value in adenocarcinoma of the prostate. While occasional benign lesions of the prostate may be associated with a DNA aneuploid status, most aneuploid epithelial proliferations of the prostate are carcinomas. Because of the relationship between aneuploidy and malignancy, DNA ploidy analysis might improve detection of adenocarcinoma in small core-needle biopsy specimens. In this study, DNA ploidy analysis was performed on 186 fresh core biopsies from 32 patients who had undergone transrectal, ultrasonographically directed core-needle biopsies. Ploidy level was determined by Feulgen staining and image analysis with a CAS 200 image analyzer (Becton Dickinson-Cellular Imaging Systems, San Jose, CA). The resultant DNA ploidy levels were compared with the initial histologic diagnosis and subsequent clinical and pathologic follow-up. Nondiploid DNA patterns correlated with a diagnosis of carcinoma on core biopsy in 11 of 16 nondiploid cases and with a final diagnosis of malignancy in 13 of 16 nondiploid cases. Two patients with biopsy proven carcinoma had DNA diploid tumor patterns. Ploidy analysis had a sensitivity of 86.6% and a specificity of 73.7% in predicting the final diagnosis of malignancy. One case interpreted as DNA tetraploid by image analysis revealed seminal vesicle tissue on both the cytologic preparations and the core biopsy. Two DNA aneuploid specimen associated with cores initially read as benign or atypical demonstrated adenocarcinoma either on review of the original core biopsy or the prostatectomy specimen. The final DNA aneuploid specimen revealed acute prostatitis in the core biopsy. DNA ploidy analysis of core biopsy specimens appears to have relatively good specificity and sensitivity for the detection of prostatic carcinoma. Sampling errors appear to be the major cause of false negative results. Inappropriate measurement of seminal vesicle tissue and acute prostatitis can result in false positive results.

Adenocarcinoma↗
PubMed1998

Quantitative assessment of basement membranes in soft tissue tumours. Computerized image analysis of laminin and type IV collagen.

Basement membranes (BMs) in 201 soft tissue tumours were quantified using computerized image analysis of tissues immunostained for laminin and type IV collagen. The purpose of the study was to compare and quantify the extent of BM deposition in a large and varied group of benign and malignant tumours. Laminin and type IV collagen gave similar results. The difference between benign and malignant was statistically highly significant (P = 0.0001), with greater deposition in benign tumours. BM deposition was homogeneous in benign tumours and heterogeneous in sarcomas and appeared to correlate with the degree of differentiation. Some poorly differentiated sarcomas showed cytoplasmic laminin staining but little or no extracellular BM. Immunohistochemical evaluation of BM has some advantages over electron microscopy; specialized equipment is not needed and since large samples can be studied with little sampling error, heterogeneity can be studied more readily. Subjective visual assessment gives a good overall indication of the extent of BM deposition and in many situations is likely to be a suitable alternative to image analysis. Because of staining heterogeneity, BM immunohistochemistry is unlikely to be of significant value in the diagnosis of specific types of sarcoma.

Basement Membrane↗
PubMed2000

Granular cell tumor of the breast: definitive diagnosis by sonographically guided percutaneous biopsy.

Granular cell tumor is a rare, benign breast neoplasm that may mimic malignancy both clinically and radiologically. We present 2 cases in which granular cell tumor was initially diagnosed by sonographically guided percutaneous biopsies. Sonographic guidance confirmed needle placement during multiple passes and thereby decreased the likelihood of sampling error. A diagnosis of granular cell tumor prior to definitive resection enables optimal therapeutic planning and allows radical surgery to be avoided.

Adult↗
PubMed1998

The safety and efficacy of stereotactic biopsy for intracranial lesions.

BACKGROUND: Stereotactic brain biopsy is considered by many physicians to have significant morbidity and mortality rates with a high risk of sampling error resulting in misdiagnosis. The technical aspects necessary to perform the procedure safely and effectively are unfamiliar to most physicians. METHODS: After reporting his initial results with stereotactic brain biopsy, several modifications were implemented by the author to improve the morbidity, mortality, and diagnostic yield rates, including complex surgical planning with regard to patient selection, biopsy trajectory, imaging technique, target choice, and intraoperative pathologic review. The results of implementing these modifications were examined retrospectively in 134 consecutive brain biopsies. RESULTS: One hundred and thirty-four stereotactic brain biopsies were performed in 122 patients. Computed tomography guidance was used in 85 patients (63%) and magnetic resonance imaging was used in 49 patients (37%). Sixty-four lesions (48%) were located in the right hemisphere, 61 (45%) in the left, and 9 (7%) in the midline. The most common diagnoses included 62 malignant brain tumors (46%), 24 benign brain tumors (18%), 23 neurologic disorders (17%), and 20 infections (15%). Five biopsies (4%) did not demonstrate a pathologic process for an overall diagnostic yield of 96%. Reasons for diagnostic failure included lesion location adjacent to the ventricular system, inaccurate targeting, and the inability to penetrate the tumor. One patient sustained a neurologic deficit after the biopsy for a morbidity rate of 0.7% and one sustained a fatal hemorrhage during the biopsy of a vascular tumor for a mortality rate of 0.7%. These results are comparable to those reported in 7471 biopsies (current series included) in which the morbidity rate was 3.5%, the mortality rate was 0.7%, and the diagnostic yield was 91%. CONCLUSIONS: Stereotactic brain biopsy is an extremely safe and effective procedure for evaluating intracranial lesions. Complex surgical planning can decrease the risk of potential complications and the use of intraoperative pathologic examination can improve the diagnostic yield for this procedure.

Adolescent↗
PubMed1999

Ultrasound-guided fine-needle aspiration (FNA) of nonpalpable breast lesions: a review of 1885 FNA cases using the National Cancer Institute-supported recommendations on the uniform approach to breast FNA.

BACKGROUND: A probabilistic approach to the classification of fine-needle aspirates (FNAs) of the breast recently was recommended and received endorsement from the National Cancer Institute (NCI). In this system, FNAs are classified as benign, indeterminate/atypical, suspicious/probably malignant, and malignant, but to the authors' knowledge the use of these diagnostic categories has not been evaluated on a large scale. Furthermore, this classification scheme has not been applied to FNAs of nonpalpable lesions of the breast obtained under imaging guidance. Thus, the current study focused on whether the diagnostic categories could be applied usefully to ultrasound-guided FNAs (US-FNAs) of nonpalpable breast lesions. METHODS: Between 1988-1996, 1885 US-FNAs were performed on 1639 patients. The original FNA diagnoses were reclassified into the NCI-supported recommendations for diagnostic categories of breast FNAs. The cytologic findings were correlated with the tissue specimens, which were available in 851 cases, or with clinical follow-up of a minimum of 2 years in 127 of the 274 patients with benign solid lesions. RESULTS: The 1885 cases were categorized as follows: 1057 (56.1%) as benign, 86 (4.6%) as atypical, 79 (4.2%) as probably malignant, 502 (26.6%) as malignant, and 161 (8.5%) as unsatisfactory (defined as < 6 epithelial cell groups on all slides). The benign US-FNAs included 480 (45.4%) cysts and 577 (54.6%) solid lesions. Combined clinical and surgical follow-up showed that the frequency of malignancy was 3.7% in US-FNAs classified as benign, 52.9% in those designated as atypical, 75.8% in those designated as suspicious, and 98.9% in those classified as malignant. Based on combined histologic and clinical follow-up, a sensitivity of 97.1% and specificity of 99.1% were found for US-FNAs when definitive benign and malignant diagnoses were considered. A false-negative rate of 3.7% was attributed to sampling error. A false-positive rate of 0.68% was secondary to interpretative error of proliferative lesions. CONCLUSIONS: Application of the NCI-supported diagnostic categories to US-FNA of nonpalpable breast lesions is useful in stratifying aspirates based on the likelihood of underlying malignancy. The subcategories of US-FNAs diagnosed as atypical have similar probabilities of malignancy; this justifies their being grouped as a single category wherein tissue biopsy would be required to exclude carcinoma. Benign and inadequate FNA diagnoses must be correlated with the clinical and imaging findings and in noncorrelative cases the patient should undergo biopsy. US-FNA is a sensitive and specific means with which to diagnose nonpalpable breast lesions.

Biopsy, Needle↗
PubMed1997

Detection rates and false positive rates for Down's syndrome screening: how precisely can they be estimated and what factors influence their value?

Down's syndrome screening is currently carried out using a combination of biochemical markers measured in maternal serum samples; these include MSAFP, Total hCG, uE3 and Free beta-hCG. Recently a number of papers have compared the effectiveness of different combinations of these markers. Some recommend MSAFP, Total hCG and uE3 (triple test) while others advocate MSAFP and Free beta-hCG (double test). The cases put forward to support these tests rely on estimated detection and false positive rates for the proposed test. A recent paper by Wright used simulation techniques to estimate the effects of sampling error on such error rates. In prospective studies there are two methods commonly used for estimating these rates. We obtain formulae for the standard deviations of these estimates and show that one of them always gives a smaller standard error than the other. We also show that in such studies the accuracy of estimating detection rates and false positive rates depends not only upon the method of calculation but also on the age distribution of pregnant women and the parameters used to calculate patient specific risk. We show that these effects can result in estimation errors of such magnitude that many observed differences in detection rates could be of questionable significance, a conclusion also reached by Wright.

Adult↗
PubMed1997

Variation in baseline risk as an explanation of heterogeneity in meta-analysis.

A relationship of baseline risk to treatment effect size has been suggested as a possible explanation of between-study heterogeneity in meta-analyses. To address this question, we develop regression models to examine the relationship between the logits (or other response measure) in the intervention and control groups. A weighted least squares (WLS) approach is described that allows for the heterogeneous sampling variation in the two groups, together with a correction of the coefficients for sampling error. Two approximate maximum likelihood (ML) solutions are also obtained, with or without an assumption of equal variances between groups within studies. A closed form ML solution exists with the assumption of equal variances. Both methods appear preferable to a previously suggested regression model of the log odds ratio on the control event rate; the methods proposed here use the same scale of measurement for both study groups, and eliminate an artifactual correlation in the regression error structure. The ML approach may be preferable because of its symmetric treatment of study groups, but WLS is more easily implemented with standard software. The methods are illustrated with data from meta-analyses on pre-term delivery and on therapies to lower serum cholesterol.

Anticholesteremic Agents↗
PubMed1997

Use of fine-needle aspiration biopsy in the evaluation of splenic lesions in a cancer center.

Fine-needle aspiration biopsy (FNAB) of the spleen was performed on 50 patients, of whom 40 had had a previous diagnosis of malignancy (23 lymphoproliferative disorders, 13 carcinomas, 3 melanomas, and 1 sarcoma). The cytologic diagnoses included 22 cases positive for malignancy (10 lymphomas, 9 metastatic carcinomas, 2 metastatic melanomas, and 1 sarcoma), 18 cases negative for malignancy, 4 cases suspicious for malignancy, and 6 nondiagnostic specimens. No major complications were associated with the FNAB procedure, however, one patient did develop a pneumothorax that resolved spontaneously. Subsequent splenectomy was performed in 10 of the 50 cases. There were no false-positive diagnoses, and only one false-negative diagnosis, which was attributed to sampling error. The aspirate, showing only benign splenic parenchyma, was from a patient with splenomegaly and no previous diagnosis; subsequent splenectomy showed acute myelogenous leukemia. In our study, FNAB proved to be a safe and valuable diagnostic tool for evaluating splenic lesions in oncologic patients.

Adolescent↗
PubMed1997

Breast care consultation center: role of the pathologist in a multidisciplinary center.

The Breast Care Consultation Center (BCCC) is a multidisciplinary center providing, in a single setting, a complete outpatient facility for women who have been diagnosed with or suspected of having breast cancer. A team of specialists are available to provide comprehensive, diagnostic (radiologist, surgeon, and pathologist), therapeutic (surgeon, radiotherapist, and medical oncologist), and support options. The pathologist, as a member of the diagnostic team, evaluates the material obtained or received at the BCCC. These include fine-needle aspirations (FNAs) obtained on-site as well as previously prepared cytohistological specimens. The pathologist renders the diagnosis following examination of the material and consultation with the multidisciplinary team. Thus, this approach is conducive for appropriate and accurate diagnosis where all data are available. In addition, the pathologist discusses the findings of each patient in the multidisciplinary conference. One thousand four hundred eighteen patients were evaluated at Magee-Womens Hospital BCCC from February 1992 through December 1994, during which time 366 FNAs were performed. The accuracy for positive diagnosis was 100%. Six negative cases had cancer on histology; these were due to sampling error (the lesion was missed). A multidisciplinary team is ideal for the evaluation of breast lesions that are suspicious for malignancy as it provides one-stop shopping and same-day diagnosis and therapeutic decisions.

Aged↗
PubMed1999

Diagnostic accuracy of effusion cytology.

The aim of this investigation was to report on the diagnostic accuracy of conventional effusion cytology. Cytological diagnoses of 300 pleural effusions and 300 ascites were compared with clinical and/or histological follow-ups of the respective patients. Sensitivity of our cytological diagnoses on pleural effusions was 50.0%, specificity 97.0%, positive predictive value 95.7%, and negative predictive value 86.4%. Sensitivity in ascitic effusions was 62.4%, specificity 98.0%, positive predictive value 100.0%, and negative predictive value 88.3%; 5.8% of diagnoses for pleural and 4.4% for peritoneal effusions were suspicious or doubtful. The overall false-positive rate was 0.5%, while the false-negative rate was 31.5%. False-negative results were due to sampling errors in 71% of pleural and 73% of peritoneal effusions and to screening errors in 29% and 27%, respectively. Our data and those from the literature show that diagnostic accuracy of effusion cytology is still unsatisfactory and should be improved. Therefore, the use of different adjuvant methods is recommended.

Adolescent↗
PubMed2000

Fine-needle aspiration cytology of salivary gland: a review of 341 cases.

Three hundred and forty-one salivary gland fine-needle aspiration (FNA) cytology specimens taken over a 6-yr period were reviewed and correlated with clinical and/or histological findings. The aspirates were derived from parotid gland (212 cases), submandibular gland (124 cases), and minor salivary gland (5 cases). The major diagnostic categories were unsatisfactory (10 cases), normal (100 cases), sialadenitis (74 cases), cyst (34 cases), lipoma (5 cases), pleomorphic adenoma (55 cases), Warthin's tumor (36 cases), and malignancy (27 cases). The latter included 14 primary salivary neoplasms (4 lymphomas of mucosa-associated lymphoid tissue (MALT) type, 3 adenocarcinomas, 2 squamous carcinomas, 2 adenoid cystic cacinomas, and one case each of carcinoma ex pleomorphic adenoma, undifferentiated carcinoma, and high-grade mucoepidermoid carcinoma), and 13 metastases, 9 of which were derived from squamous carcinomas of head and neck origin. Clinicopathological review showed that 88 of 91 (97%) benign epithelial tumors and 27 of 31 (87%) malignant neoplasms with adequate FNA sampling were accurately diagnosed cytologically. False-negative results were caused by sampling error (7 cases), most notably in cystic tumors, or were due to misinterpretation of uncommon neoplasms (3 cases). The overall sensitivity, specificity, and accuracy were 92%, 100%, and 98%, respectively. FNA cytology provides accurate diagnosis of most salivary gland lesions and contributes to conservative management in many patients with nonneoplastic conditions.

Adenocarcinoma↗
PubMed1999

Impact of demographic distribution and population growth rate on haplotypic diversity linked to a disease gene and their consequences for the estimation of recombination rate: example of a French Canadian population.

A disease gene introduced into a rapidly growing population by a single individual remains in strong linkage disequilibrium with the surrounding molecular markers. Mapping strategies taking advantage of this phenomenon allow increased mapping resolution as compared to pedigree analysis. Demographic models underlying these strategies usually assume the population exponential growth approximated by Poisson distribution of the number of children per individual. Knowing the real demographic distribution in the studied French-Canadian population, we analyzed the validity of the Poisson approximation. We adapted the existing model of the Poisson branching process to the case of a rapidly growing population and to non-Poisson distributions. In consequence, we were able to apply maximum-likelihood methods to estimate the recombination rate under various demographic scenarios. Our analysis shows that the growth rate has a higher impact on the estimation of recombination rate than the shape of the demographic distribution. The choice of the demographic model (Poisson vs. non-Poisson) has little effect on the estimation of the recombination rate but affects the expected distribution of haplotype frequencies. This distribution, however, depends much more on the population growth rate. Finally, we also demonstrate the usefulness of the Luria-Delbrück method, which gives a correct estimation of the recombination rate in a growing population, provided the sampling error is taken into account in the confidence intervals.

Confidence Intervals↗
PubMed2001

Highly sensitive immunohistological study for detection of estrogen receptor in human breast cancer.

BACKGROUND: Immunohistological methods for the detection of estrogen receptor in human breast cancer using formalin-fixed, paraffin-embedded tissue not only have the advantages of being cheaper and requiring less tissue but also have several theoretical advantages. For example, such methods enable direct histological visualization of the assessed tissue and thereby reduce sampling error. Traditional immunohistological methods (traditional LSAB), however, show false-negative reactions more often than the enzyme-binding immunoassay method (EIA). METHODS: After determining 25 estrogen receptor-positive cases and 50 estrogen receptor-negative cases by EIA, we analyzed these same cases using a traditional LSAB method and a new highly sensitive immunohistological method for assaying formalin-fixed, paraffin-embedded tissue. RESULTS: Using this new method, we detected 10 instances of positive estrogen receptors among the 50 EIA receptor-negative cases. The 25 EIA-positive cases were positive for estrogen receptor antigen except 1case using the new method. CONCLUSIONS: This new method not only has the advantage of use in paraffin-embedded tissue but also is more sensitive than the EIA. We recommend this new method as a choice to decrease false-negatives.

Adult↗
PubMed1978

Hepatitis B antigen in black patients with hepatocellular carcinoma: correlation between orcein stained liver sections and serology.

Formalin-fixed paraffin-embedded autopsy tissue of liver and tumor from 50 male black mineworkers with hepatocellular carcinoma were examined by orcein stain for the presence of cytoplasmic hepatitis B surface antigen. The results were correlated with the serum hepatitis B antigen (HBAg). In 72% serum HBAg was positive. Orcein staining of nontumor liver cell cytoplasm was present in 18 (36%). Sixteen (89%) of these orcein-positive cases were serum HBAg positive. The two false negative serum HBAg results were obtained by immunodiffusion, immunoelectrophoresis and complement fixation. Serum HBAg, measured by radio-immunoassay and hemagglutination, was positive in 14 orcein-negative cases. Six other negative orcein results appeared to be due to sampling error. Orcein staining was noted in tumor cells of three serum HBAg positive patients. Provided the limitations of the technique are realized, orcein staining of liver tissue from hepatocellular carcinoma patients may prove useful for retrospective screening surveys to assess the prevalence of HBAg positivity in these patients.

Black People↗
PubMed1981

Electron microscopy in the diagnosis of malignant schwannoma.

Fifteen malignant schwannomas were examined by light and electron microscopy. Five tumors arose in patients with neurofibromatosis and five were contiguous with a peripheral nerve (Group I). Five tumors met neither of these generally accepted diagnostic criteria but were light microscopically seen as compatible with malignant schwannoma when examined under light microscope (Group II). In the better differentiated areas of Group I lesions, long, overlapping, tightly packed cytoplasmic processes were parallel to homogeneous flocculent material, occasionally assuming a linear appearance suggesting basal lamina. In Group II, similar cytoplasmic processes were present but the extracellular material was less extensive and had a less obvious relationship to the plasma membrane. In neither group were fine intracytoplasmic filaments prominent. Malignant schwann cells are seldom as ultrastructurally differentiated as their benign counterparts. Nevertheless, within the context of well-studied light microscopy and the sampling error inherent in ultrastructural examination, electron microscopy can support the diagnosis of malignant schwannoma.

Adult↗
PubMed1983

Tumor and urine catecholamines (CATs) in neurogenic tumors. Correlations with other prognostic factors and survival.

This study was undertaken to better define the relationship between catecholamine (CAT) metabolism within the malignant neuroblast and other factors known to influence clinical outcome in neuroblastoma (NB). Several CATs and their metabolites were measured in 32 tumors and 47 urines from 60 newly diagnosed children with neurogenic tumors. Absolute and relative CAT concentrations were correlated with age, clinical stage, histologic differentiation and survival duration. The major findings are: (1) urinary CAT excretion patterns often differ markedly from tumor CAT patterns in the same child, which may be explained by the continuous nature of tumor metabolism, hepatic and renal catabolism, and sampling errors; (2) definite patterns of biochemical maturation are apparent in tumors and urines, but standard light microscopy is insufficient to correlate this with degree of histologic differentiation; (3) more differentiated patterns of CAT metabolism, both in tumor and urine, are significantly associated with age less than 1 year at diagnosis, and with more favorable clinical Stage (I, II, IVS). Tumor NE was increased relative to DM and DA, and urine NMN and VMA were increased relative to DM and HVA, in these patients. (4) this more differentiated CAT pattern in infants and in less advanced stages was reflected in their better survival. Greater maturity of tumor enzyme systems is the probable reason for the better prognosis of NB in infants less than 1 year. Individual enzymes should be measured in fresh tumor tissues, and related to relative and absolute CAT concentrations in tumor and urine, to try to categorize patients on the basis of clearcut biological differences when planning new treatment strategies for NB.

Age Factors↗
PubMed1986

Flow cytometric analysis of deparaffinized nuclei in urinary bladder carcinoma. Comparison with cytogenetic analysis.

Both cytogenetic analysis and flow cytometry (FCM) have prognostic efficacy in the analysis of transitional cell carcinoma (TCC) of urinary bladder. To correlate results of the two methods, we studied a unique group of patients whose tumors had undergone prospective conventional cytogenetic analysis. Paraffin blocks of these tumors were processed for FMC, then analyzed for nuclear DNA content. Of the 34 tumors processed, 30 (88%) yielded interpretable DNA histograms. In 26 (87%) of these, there was good correlation between the two methods with respect to the presence or absence of a hyperdiploid cell line. Discrepancies may have resulted from sampling error or from interpretation of a tetraploid peak as a prominent G2M region. Retrospective FCM analysis of paraffinized TCC tissue correlates well with conventional, prospective cytogenetic analysis and is applicable to the majority of urinary bladder transitional cell carcinomas.

Adult↗
PubMed1989

The use of serum TA-4 in monitoring patients with malignant transformation of ovarian mature cystic teratoma.

The development of cancer in mature cystic teratomas of the ovary is rare and sometimes difficult to detect because of sampling errors. Six cases of squamous cell carcinoma arising in ovarian mature cystic teratomas were studied, five of which showed an elevated level of a squamous cell carcinoma-associated antigen, TA-4, in the sera obtained preoperatively; the preoperative determination was not performed in the sixth case. However, no elevated TA-4 level was detected in the sera of 28 patients with mature cystic teratomas of the ovary. Moreover, serial determination of the serum TA-4 level showed a good correlation between the clinical course and the serum TA-4 level. Interestingly, an abnormal TA-4 level preceded the clinical detection of recurrence by 2 months in two patients. Thus, determination of the serum TA-4 concentration may be useful for diagnosing and monitoring patients with squamous cell carcinoma arising in mature cystic teratomas of the ovary.

Adult↗