A study of 10,296 pediatric and adolescent Papanicolaou smear diagnoses in northern New England.

OBJECTIVE: This study analyzes pediatric and adolescent Papanicolaou (Pap) smear diagnoses to determine the prevalence rates of squamous intraepithelial lesion (SIL) as well as infectious and reactive processes in this age group. DESIGN: A total of 10 296 Pap smear diagnoses from patients 10 to 19 years of age collected over a 1-year period and classified according to the Bethesda system were reviewed. This population was almost exclusively white, the majority residing in rural or suburban areas of Maine, New Hampshire, and Vermont. The percentage of abnormal smear results was then compared with data generated for older age subsets. RESULTS: The following diagnoses were made on 10 296 Pap smears from patients 10 to 19 years of age: 7208 (70.01%) normal; 1689 (16.4%) benign cellular change; 1004 (9.75%) atypical squamous cells of undetermined significance; 388 (3.77%) squamous intraepithelial lesion (SIL); and 7 (0.06%) atypical glandular cells of undetermined significance. A total of 1503 (14.6%) of smears showed infectious processes. Compared with the results of adult Pap smears collected over the same time period, the age 20 to 29 subset with 27 067 Pap smears and the age 30+ subset with 42 617 Pap smears showed 11.79% and 8.43% infectious processes and 3.49% and 1.27% SIL, respectively. Therefore, the highest rate of infectious processes and SIL was found in the subset of patients age 10 to 19 years. CONCLUSIONS: Because the development of SIL and hence cervical cancer is causally related to sexually transmitted human papilloma virus (HPV) infection, this high rate of abnormal Pap smear results of both an infectious and precancerous nature in this population may reflect a high level of sexual activity among adolescent girls. These data reinforce the importance of implementing early cervical Pap smear screening in the sexually active pediatric and adolescent population.

Performance optimization of the ThinPrep processor: effect of microscope slides.

Our objective was to evaluate the cellular adherence property of various microscope slides. Slide preparations were made using the ThinPrep 2000 System, in which cells are transferred from a filter to a slide. A total of eight slide types was selected for testing against the ThinPrep microscope slide: S/P MicroSlide, S/P Pusher, S/P Colorfrost, Menzel Superfrost, Sayag, Sail Brand, Fisher Plus, and Newcomer Poly-L-Lysine. Gynecologic samples from 4 different patients were utilized on the ThinPrep Processor. Multiple preparations were made from each sample using the different microscope slides. The slides were stained with a commercial Pap stain, and cellular material was quantified by scanning each preparation using a linear stage mounted on a Hitachi U-2000 spectrophotometer set at 580 nm. The data generated by this study show that ThinPrep microscope slides produce preparations with the highest level of cellular material. This study quantifies slide performance, examines a range of microscope slide types, and shows that ThinPrep microscope slides exhibit significantly increased cell adherence over the other slide types tested.

Evaluation of the ThinPrep Pap test in clinical practice. A seven-month, 16,314-case experience in northern Vermont.

OBJECTIVE: To compare the cytologic diagnoses and specimen adequacy of the ThinPrep Pap Test with historical data within a distinct patient population to assess test performance and its impact on clinical practice. STUDY DESIGN: A total of 16,314 ThinPrep Pap tests were processed and evaluated at Fletcher Allen Health Care over a seven-month period. A subset of 8,574 tests from a selected provider group (cohort) was compared to the historical conventional cervical cytologic smear data from the cohort population for both cytologic diagnoses and specimen adequacy. The cohort consisted of 12 practice groups, including 60 physicians and providers, utilizing the ThinPrep Pap Test as their primary cervical cancer screening sampling technique. Cytologic diagnoses and specimen adequacy were classified using the Bethesda system. RESULTS: Using a three-tiered diagnostic system similar to the Cytyc clinical trials (within normal limits [WNL], atypical squamous cells of undetermined significance [ASCUS]/atypical glandular cells of undetermined significance [AGUS] and low grade squamous intraepithelial lesion and higher [LSIL]+), the ThinPrep method increased the percentage of cases that could be definitively diagnosed as WNL by 1.71%, lowered the percentage of ambiguous or borderline cases diagnosed as ASCUS/AGUS by 26.59% and increased the percentage of cases diagnostic of LSIL+ by 52.15% in the cohort population. Further subdivision by the Bethesda classification showed that the identification of infectious agents increased 25.51% and the detection of high grade squamous intraepithelial lesion/carcinoma increased 55.14%. Concurrently, cases reported as benign cellular changes (reactive/reparative) decreased 23.1%, and the percentage of cases reported as unsatisfactory/"limited by ..." was reduced 52.71%. Histologic correlation of cases reported as squamous intraepithelial lesion revealed that the percentage of patients with subsequent benign biopsies was reduced by 31.7% utilizing the ThinPrep technique. Further, the percentage of ThinPrep patients with histologically confirmed cervical intraepithelial neoplasia (CIN) 1 and CIN 2/3 increased by 16.3% and 9.3%, respectively. CONCLUSION: Implementation of the ThinPrep Pap Test resulted in statistically significant improvements in both diagnostic yield and specimen adequacy, as seen by others in clinical trials. Comparison of results to historical data within a cohort population reinforced earlier data and lent further support to the claim that the ThinPrep Pap Test is "significantly more effective" than the conventional smear in clinical practice.

Evaluation of the ThinPrep processor for fine needle aspiration specimens.

OBJECTIVE: To test the ThinPrep Processor for fine needle aspiration. STUDY DESIGN: One hundred unfixed, surgically removed specimens were aspirated. One pass was directly smeared, fixed and stained with the Papanicolaou technique. The other pass was rinsed in a proprietary fixative, and a single ThinPrep slide was made. Smears were diagnosed without knowledge of the histologic diagnosis. RESULTS: Cellularity and architectural integrity of cell groups were superior on the conventional slides. Preservation and detail of both epithelial and stromal cells were superior with the ThinPrep Processor. Preservation of background material, such as mucus and colloid, was slightly superior on the ThinPrep slides. Diagnostic sensitivity and specificity for malignancy and unsatisfactory rates were all slightly better on the ThinPrep slides. CONCLUSION: The ThinPrep Processor offers an alternative to direct smears in situations in which expertise in slide preparation is not available.

Cell yield. ThinPrep vs. cytocentrifuge.

Cell yields on cytologic preparations made in the Cytospin II cytocentrifuge and the ThinPrep Processor were compared. Slides were prepared by each method using calibrated volumes (25 microliters) of cell suspensions from 13 nongynecologic specimens. Cell counts for each slide were calculated by counting cells in predetermined fields using a gridded reticle at 40 x magnification, then extrapolating to the total surface area of the preparation. The cell counts demonstrated that when processing equal amounts of cell suspension, the ThinPrep method retained three times as many cells as the cytocentrifuge method. The ThinPrep method, with a higher rate of cell recovery, may provide a valuable tool toward more accurate cytologic diagnosis, particularly for cytologic samples with small numbers of cells.

Flow cytometric DNA analysis versus cytology in the evaluation of peritoneal fluids.

The use of flow cytometric DNA analysis as an adjunct to cytology in peritoneal fluid evaluation was studied. One hundred ninety-five fluids from 193 gynecologic patients were subjected to both DNA analysis and cytologic examination. It was found that 117/195 (60%) had invasive malignancies (50 ovarian, 48 endometrial, 17 cervical, and 2 miscellaneous); 34/117 (28%) patients with malignancies were positive by cytology, and 10/117 (8.5%) were positive (aneuploid) by DNA analysis. Of 34 cytologically positive cases, 7 (21%) were DNA positive, 25 (74%) were DNA negative, and in 2 (6%) insufficient cells were obtained. Only 3 fluids (3%) from malignancies were positive by flow cytometry and negative by cytology (1 stage I ovarian cancer, 1 stage I endometrial cancer, and 1 stage III ovarian cancer). No false-positive cytology and one probable false-positive flow result was obtained. If only those patients with histologically documented peritoneal involvement are considered, 29/43 (65%) had positive cytology and 8/43 (19%) had a positive flow result. We conclude that: (1) the high false-negative rate of flow cytometry (79%) versus cytology in this study may be related to a high percentage of diploid cancers, specimen preparation, or histogram interpretation, and (2) flow cytometry rarely adds to cytologic evaluation and is probably best reserved for use only in selected cases.

Cytologic diagnosis of liver fluke infestation in a patient with subsequently documented cholangiocarcinoma.

In a 32-year-old Laotian immigrant who presented with a two-day history of vomiting, abdominal pain and jaundice, ultrasound examination revealed a posthepatic obstruction. Characteristic parasitic ova were present in bile fluid submitted for cytologic evaluation. Subsequent biopsy of the patient's bile duct lesion revealed a coexistent cholangiocarcinoma. The life cycles of Clonorchis sinensis and Ospisthorchis viverrini are reviewed along with the clinical and pathologic complications of infestation by these parasites in humans. The cytologic features of liver fluke infestation are characteristic and should be appreciated, as should the importance of its early diagnosis in the prevention of bile duct neoplasms.

Fine needle aspiration of the breast. Importance of the aspirator.

All 503 fine needle aspirations (FNAs) of the breast performed over a three-year period at the Medical Center Hospital of Vermont were analyzed. There were 93 aspirates diagnosed as "positive," all of which were from patients eventually shown to have cancer. However, there were 38 patients with primary carcinoma in which the FNA was not diagnosed as positive, for a diagnostic failure rate of 31.4%. In order to determine the possible effect of technique as practiced by an experienced aspirator in diminishing such diagnostic failures, we compared 190 aspirates obtained by a single individual with 193 aspirates obtained by 15 individuals in the same community. For the single experienced aspirator, the technical failure rate was 9.8% whereas in the group with many aspirators it was 45.9%. This finding confirms that, although fine needle aspiration of the breast is considered easy to perform, skill on the part of the aspirator is important for satisfactory results.

False-negative peritoneal cytology in metastatic ovarian carcinoma.

Seventy-nine laparotomies for disseminated intraperitoneal ovarian carcinoma were reviewed to determine the frequency and possible causes of false-negative peritoneal cytology. Negative peritoneal cytology (defined as any reading other than positive) was found in 16 of 79 cases (20%). False-negative cytology occurred more frequently with peritoneal washings (48%) than with ascites (6%; P less than .001); with second-look surgery (50%) than at primary surgery (12%; P = .004); with peritoneal metastasis less than 0.5 cm (50%) than with metastasis greater than 0.5 cm (16%; P = .02); and with bloody cytology specimens (25%) rather than specimens without blood (0%; P = .06). Volume of peritoneal specimen, architectural grade, cytologic grade, and stage of disease (III versus IV), did not affect the frequency of false-negative cytology. The high prevalence of negative cytology associated with peritoneal washings, small tumor size, and second-look surgery suggests that negative cytology is a result of poor distribution of peritoneal washings and infrequent exfoliation of malignant cells rather than misinterpretation of malignant cells present in cytology specimens.

The effect of cytoxan, adriamycin, and cis-platinum on cervical, vaginal cytology.

One hundred and thirty-four cervical and vaginal smears were obtained from 51 patients receiving cyclophosphamide, doxorubicin, and cis-platinum. These drugs do not appear to cause dysplasia or significant atypia. Additionally, the Pap smear was not useful for the diagnosis of unexpected persistent or recurrent carcinoma of the ovary.

Psammoma bodies in peritoneal washings.

Report is made of the first two cases in which psammoma bodies were detected in peritoneal washings. The significance of psammoma bodies in a cytologic specimen is reviewed. These case reports and review of the literature make it clear that the cytologic detection of psammoma bodies should be a stimulus for further investigation but that the diagnosis of malignancy cannot be based on their presence alone.

The perception and discrimination of arterial pulsations: implications for the behavioral treatment of hypertension.

The perception and discrimination of target visceral responses may be important for the development and control of physiological functions such as blood pressure. Despite this, biofeedback blood pressure studies have almost exclusively used auditory or visual feedback. The present experiment employed psychophysical scaling procedures to investigate subject's ability to perceive and discriminate pulsatile sensations associated with change in the intensity of arterial pulsations. The perceived intensity of these pulsations vary as a function of the relationship between arterial pressure and applied cuff pressure. The results indicated that maximum intensity pulsations were perceived when occluding cuff pressure equalled mean arterial pressure and that the perceived intensity of pulsations decreased monotonically as cuff pressure was varied relative to this point in either the systolic or diastolic direction. Furthermore, the function relating cuff pressure oscillation amplitude to applied cuff pressure was the same as that obtained for perceived pulsation amplitude. The finding that subjects could accurately discriminate different intensities of pulsating sensations suggests the possibility of their being employed as an effective discriminative stimulus in a blood pressure biofeedback procedure.

Fine-needle aspiration cytology in the management of gynecologic cancer.

The technique and application of fine-needle aspiration cytology in the management of gynecologic cancer are discussed. The authors report 90 cases that have been evaluated by means of fine-needle technique. The technique has been applied both for primary diagnosis and for follow-up evaluation. Among the 90 cases reported, there was two false negatives and one false positive and three cases in which the histologic findings were false negative.