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D L Rosenthal

Publications and source records attributed to D L Rosenthal.

At least 19 recordsLinked to original sources

Telecytology: intraobserver and interobserver reproducibility in the diagnosis of cervical-vaginal smears.

Telecytologic diagnosis of cervical-vaginal smears is potentially useful because it could allow more efficient use of cytopathologist resources and expertise. A pathologist in one location could, in principle, review cytotechnologists' findings using a video display hundreds or thousands of miles away. Currently, bandwidth restrictions limit practical implementation of such a system to review of fields that had been selected for review by the cytotechnologist. The purpose of our investigation was to evaluate how well this type of review correlates with a review in which the entire slide is available for examination by the pathologist. We prospectively selected 100 consecutive cervical-vaginal smears over an 11-day period in August 1999. For each smear, 4 to 12 fields containing abnormal cells from each slide were digitally imaged. Each of 3 pathologists reviewed all digitized images and all glass slides. Diagnoses based on selected digitized images were compared with those based on conventional pathologist review. The kappa statistic, a measure of chance-corrected agreement (reproducibility), was calculated in each setting. Overall, intraobserver and interobserver reproducibility of cervical-vaginal smear diagnoses is fair to excellent. The use of remote digital images for pathologist review did not introduce large (2-step) diagnostic disagreements. The disagreement between a pathologist's glass slide and digital diagnoses is less than that for different pathologists reviewing glass slides, although interobserver differences were even greater in the interpretation of digital images.

Cytodiagnosis↗

Clinical significance of the qualification of atypical squamous cells of undetermined significance: An analysis on the basis of histologic diagnoses.

OBJECTIVE: This study was undertaken to evaluate the significance of further qualification of atypical squamous cells of undetermined significance in routine Papanicolaou smears. STUDY DESIGN: A retrospective medical records review was conducted on 316 women whose Papanicolaou smears yielded diagnoses of either atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion or atypical squamous cells of undetermined significance suggestive of a reactive process. RESULTS: The overall incidence of a squamous intraepithelial lesion (cervical intraepithelial neoplasia grades I, II, and III) was higher in the group with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion than in the group with results suggestive of a reactive process (41.1% vs 22.3%; P =.0344). Women with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion were 9.7 times more likely to have high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia III) develop than were women with atypical squamous cells of undetermined significance suggestive of a reactive process (95% confidence interval, 1.26-74.64). The incidence of high-grade squamous intraepithelial lesion was higher among women </=35 years old than among women >35 years old (17.8% vs 6.3%; P =.0378). CONCLUSION: Women with a diagnosis of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion are more likely to have intraepithelial lesions develop than are those with atypical squamous cells of undetermined significance suggestive of a reactive process. Aggressive evaluation of cases of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion with colposcopy and cervical biopsies may be appropriate. Age should be considered as an independent factor in the plan of management.

Adult↗

The accuracy of combined cytopathologic and flow cytometric analysis of fine-needle aspirates of lymph nodes.

We studied flow cytometry in 156 fine-needle aspirations (FNAs) of lymph nodes performed between June 1993 and September 1998. Information from flow cytometry was combined with cytomorphologic evaluation, and the diagnosis determined by using combined modalities was compared with tissue biopsy results or clinical follow-up. In 74 cases, a combined cytopathologic-flow cytometric diagnosis of lymphoma was made; histologic material was available for 52 patients; in no case was a benign process found. The lymphoma grade assigned agreed with histopathologic findings in 45 of 48 cases with a specific cytologic diagnosis. Treatment was initiated on the basis of the FNA alone for 17 of 52 patients with a history of lymphoma and in 22 additional patients with no follow-up biopsy. Among 71 cases in which the diagnosis using both modalities was benign, the only false-negative was 1 case of Hodgkin disease. Of the 156 cases, 11 were considered atypical or suggestive of lymphoma; biopsies from 8 of 10 patients revealed lymphoma. A combination of flow cytometry and cytomorphology of cells obtained by FNA of lymph nodes can distinguish between benign and malignant lymphoid infiltrates and support a diagnosis of lymphoma that permits definitive therapy in most cases.

Biopsy, Needle↗

Metastatic testicular Sertoli-cell tumor: cytopathologic findings on fine-needle aspiration.

Malignant Sertoli-cell tumors of the testis are exceedingly rare. We present cytopathologic findings in pelvic metastasis of such a tumor in a 45-year-old man, diagnosed on fine-needle aspiration, 2 months after radical orchiectomy. Ultrasound-guided aspirate showed tissue fragments and isolated discohesive tumor cells with characteristics of testicular Sertoli cells. Immunoperoxidase (IPOX) studies and histopathologic correlation with the primary testicular tumor are also presented. Cytopathologic features complimented by IPOX studies should allow an accurate diagnosis of this rare entity, when seen at metastatic sites.

Adult↗

Significant reduction in the rate of false-negative cervical smears with neural network-based technology (PAPNET Testing System).

False-negative cervical Pap smears may lead to disability or death from carcinoma of the uterine cervix. New computer technology has led to the development of an interactive, neural network-based vision instrument to increase the accuracy of cervical smear screening. The instrument belongs to a new class of medical devices designed to provide computer-aided diagnosis (CADx). To test the instrument's performance, 487 archival negative smears (index smears) from 228 women with biopsy-documented high-grade precancerous lesions or invasive cervical carcinoma (index women) were retrieved from the files of 10 participating laboratories that were using federally mandated quality assurance procedures. Samples of sequential negative smears (total 9,666) were retrieved as controls. The instrument was used to identify evidence of missed cytological abnormalities, including atypical squamous or glandular cells of undetermined significance (ASCUS, AGUS), low-grade or high-grade squamous intraepithelial lesions (LSIL, HSIL) and carcinoma. Using the instrument, 98 false-negative index smears were identified in 72 of the 228 index women (31.6%, 95% confidence interval [CI]: 25% to 38%). Disregarding the debatable categories of ASCUS or AGUS, there were 44 women whose false-negative smears disclosed squamous intraepithelial lesions (SIL) or carcinoma (19.3%; 95% CI: 14.2% to 24.4%). Unexpectedly, SILs were also identified in 127 of 9,666 control negative smears (1.3%; 95% CI: 1.1% to 1.5%). Compared with historical performance data from several participating laboratories, the instrument increased the detection rate of SILs in control smears by 25% and increased the yield of quality control rescreening 5.1 times (P < 0.0001). These data provide evidence that conventional screening and quality control rescreening of cervical smears fail to identify a substantial number of abnormalities. A significant improvement in performance of screening of cervical smears could be achieved with the use of the instrument described in this report.

Carcinoma in Situ↗

Computerized scanning devices for Pap smear screening: current status and critical review.

Automation of the Pap smear has taken almost half of a century. Two systems have recently received FDA approval for routine use as quality control (rescreening) devices. Technical triumphs are overshadowed by current conflicts among cytopathology professionals, clinicians, patients, and device manufacturers. The historic perspective of this potentially volatile situation provides the backdrop for possible solutions based on the scientific validity of this evolving technology.

Diagnosis, Computer-Assisted↗

Polymerase chain reaction-based K-ras mutation detection of pancreatic adenocarcinoma in routine cytology smears.

The cytologic diagnosis of pancreatic carcinoma is notoriously difficult, particularly in distinguishing benign atypia from well-differentiated adenocarcinoma. Mutation of codon 12 in the K-ras oncogene is frequently found with pancreatic cancers. Detection by polymerase chain reaction (PCR) followed by restriction endonuclease digestion can provide a powerful tool to improve and confirm diagnosis. The authors examined the utility of PCR-based detection in the diagnosis of pancreatic carcinoma using routinely obtained cytology smears that could be collected at most hospitals. Pancreatic cytology smears were collected retrospectively from 60 patients. DNA was extracted from the slides and amplified by PCR using mismatched primers that generated a Bst-N1 recognition site with the wild type codon 12 but not with the mutant allele. Results were compared with clinical follow-up. K-ras codon 12 mutations were observed in 44 of 46 (95.7%) cases of pancreatic cancer, but not in 12 benign cases nor in 2 cases of islet cell tumor. The amplification and digestion steps proved robust and sensitive, capable of detecting mutant K-ras alleles from cytology smears that contained only small foci of suspicious cells. Our results indicate that K-ras mutation analysis can be done reliably within 1 to 2 days from routine cytology slides without special handling, increasing the sensitivity of diagnosis in ambiguous cases while maintaining cost-effective and relatively noninvasive sampling strategy.

Adenocarcinoma↗

HPV DNA and the risk of squamous intraepithelial lesions of the uterine cervix in young women.

A population-based case-control study of college students was undertaken to estimate the effect of a positive clinical test for human papillomavirus (HPV) DNA (the Virapap test) on the rate of squamous intraepithelial lesions (SIL) of the uterine cervix. When age, multiple lifetime sexual partners, and oral contraceptive use were controlled by logistic regression, the adjusted odds ratio (OR) for a positive Virapap test was 7.3 (3.3, 17) for a cytologic diagnosis of SILs and 3.4 (1.4, 8.5) for a cytologic diagnosis of squamous intraepithelial lesions of undetermined significance (equivocal atypia). When case status was defined as patients whose Pap smears were confirmed histologically as high-grade SIL, the adjusted OR was 10.3 (3.3, 32), reflecting the high proportion of individuals with SILs who were harboring high-grade squamous intraepithelial lesions. These results confirm the many previous findings of a strong association between HPV DNA, and demonstrate that strength of the association persists when important confounding variables are controlled. This suggests a causal role for HPV in cervical neogenesis. Believing that HPV infection is a major causal agent for cervical cancer precursors suggests that in this time of rapidly increasing HPV prevalence, especially among young persons, the incidence of cervical neoplasia will rise. This underscores the importance of increasing the availability, usage, and perhaps the frequency of Pap smear screening.

Adolescent↗

A 35-year experience with the post-sophomore fellowship in pathology: analysis of its effectiveness as a recruitment resource.

Recent reports have indicated a shortage of pathologists coming out of training programs over the next few years. This is due, in part, to a decrease in the number of medical students entering pathology and an overall decline in the popularity of the field as a specialty choice. Medical students electing to spend a year in a post-sophomore fellowship in pathology would be expected to enter the field at a higher than average rate. In this study, the specialty choices of 140 former student fellows were analyzed. The students included in the study were enrolled in a year-long University of California, Los Angeles post-sophomore fellowship in pathology between 1953 and 1988. Twenty-seven of the 140 students (19.3%) ultimately chose pathology as a career. This represents a 9- to 10-fold increase over the average percentage of medical students entering pathology through the match (less than 2%) for any given year. Of all students from the University of California, Los Angeles who entered pathology, 75% did not elect to spend a year in fellowship. Eighty percent of the former fellows chose some other field, medicine and surgery being the most popular choices.

Cohort Studies↗

Role of percutaneous fine-needle aspiration biopsy in suspected intrathoracic malignancy.

Percutaneous fine-needle aspiration (PFNA) biopsy is an accepted technique for the diagnosis of suspected intrathoracic malignancy, but the appropriate indications for its use have not been clearly defined. To help establish guidelines, we performed a retrospective analysis of 188 patients who underwent PFNA biopsy for suspected intrathoracic malignancy. Biopsy led to a diagnosis in 72% (135/188) of the patients, but in 27% (50/188) samples were inadequate for cytological diagnosis, and in 2% (3/188) samples were adequate but failed to yield a diagnosis. Fifty-three patients underwent surgical intervention, thus allowing histological confirmation of the cytological diagnosis. In patients with a diagnosis from PFNA biopsy, operation confirmed malignancy in 97% (37/38) and a specific cell type in 79% (30/38). In patients without a diagnosis after biopsy, a malignancy was found in 73% (11/15) at the time of operation. This suggests a high rate of accuracy when PFNA biopsy provides a diagnosis. However, it also illustrates that a substantial percentage of PFNA biopsy attempts fail to yield a diagnosis in patients ultimately found to have malignancies. This implies that PFNA biopsy might best be reserved for patients who are not surgical candidates.

Adenocarcinoma↗

Sources of diagnostic error in fine needle aspiration of the thyroid.

Smears obtained from 795 patients with suspicious thyroid nodules by fine needle aspiration (FNA) of the thyroid gland were seen over a 5-year period at the UCLA Center for the Health Sciences. From 72 patients who underwent subsequent surgical excision of their nodules, inadequate or discrepant FNA diagnoses were noticed in 20 cases (27.8%). These errors could be attributed to inadequate material for diagnosis (n = 6), sampling errors (n = 2), and cytodiagnostic errors (n = 12). If the diagnosis of follicular neoplasm was treated as indeterminate for malignancy, the overall efficiency of FNA was 88.9%. All false-negative diagnoses were related to procedure (i.e., inadequate smears or missed sampling of the lesion). The frequency of inadequate smears, in turn, was strongly related to the type of physician performing the aspiration. The frequency was highest among community-based clinicians (32.4%) and lowest among hospital-based cytopathologists (6.4%). With adequate sampling, the finding of 100% sensitivity in the diagnosis of malignant neoplasms by FNA cytology reaffirms its role as the procedure of choice in the initial screening of thyroid nodules.

Adolescent↗

Canonical analysis of cells in normal and abnormal cervical smears.

Over 4,000 cells from 105 normal and 96 abnormal uterine cervical scrapes were prepared according to the UCLA monolayer procedure, stained by a routine Papanicolaou method and visually classified by two cytopathologists and a technologist into seven classes: parabasal, metaplastic, mild dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ and invasive carcinoma. Canonical analysis was used to correlate effects-coded class membership variables with 23 cell features derived from digital image analysis. In general, nuclear texture measures derived from linear combinations of run-length correlations along with features derived from a Markov transitional probability matrix provided the best predictors of cell class. After cells were divided into benign (moderate dysplasia or less) and malignant (severe dysplasia or worse) groups, discriminant analysis correctly classified 84% of the benign cells and 91% of the malignant cells.

Cell Nucleus↗

Multifactor analysis of intermediate cells from the uterine cervix. The importance of slide effects on variance components.

The ability to retrospectively examine cytologic material with digital image analysis is often desirable, particularly when long-term follow-up information is available for correlation with cell parameters. In an effort to characterize the magnitude of slide-age and staining-batch effects on cell parameters from digital image analysis, the cell features in 32 Papanicolaoustained cervical smears that varied in age from 10 to 16 years were analyzed. The slides were selected from eight patients sampled on four different occasions approximately one year apart. The findings indicate that the variance of cell features from an intermediate cell population within a slide is somewhat greater than is the variance among slides from the same woman or the variance among women. Aging effects were not detectable. The significant differences observed among replications of slides from the same woman as well as between women with no evidence of cervical disease should caution other researchers to account for this potential source of random error in their statistical models.

Cell Nucleus↗