ASCUS, mature metaplastic type. Cytologic diagnosis and follow-up.

OBJECTIVE: To study the cytologic criteria for follow-up of mature metaplastic cells within the atypical squamous cells of undetermined significance (ASCUS) category. STUDY DESIGN: Squamous epithelial abnormalities between January 1994 and June 1997 at our institution totaled 2,632 and included squamous carcinoma (1), high grade squamous intraepithelial lesions (278), low grade squamous intraepithelial lesions (875) and ASCUS (1,478). From the ASCUS group, 134 (9.06%) were metaplastic; 89 were selected for review. Criteria for case selection were follow-up with tissue biopsy or at least two Pap smears and no previous epithelial abnormality. Patients ranged from 27 to 70 years of age. Parameters tabulated included number of abnormal cells per slide, their architecture, cell size, shape, cytoplasmic hue and texture, nuclear size and contour, chromatin pattern and nucleoli. Additionally, specimens were reviewed for hormonal status and inflammation. The findings were correlated with follow-up data. RESULTS: Cells generally appeared single or in loose, monolayered sheets of three to seven cells per group. The cells were well demarcated, polygonal or oval and ranged from 11 to 30 microns with cyanophilic or eosinophilic thickened cytoplasm. The round to oval nuclei with slight irregularity showed a minimally increased nuclear/cytoplasmic ratio with stippled chromatin. Upon review, 69 smears were confirmed as ASCUS-M. Follow-up revealed 42 with benign findings, 9 with persistent ASCUS/ASCUS-M and 18 with low grade squamous intraepithelial lesions. CONCLUSION: In mature metaplastic cells with minimal atypia in patients with no previous or concurrent dysplasia, the follow-up details were similar to those described for ASCUS-superficial/immediate squamous cells. These patients could be followed conservatively.

The challenge of quality improvement with the Papanicolaou smear.

Quality improvement measures must be inherent in the management of all cytopathology laboratories. They are essential for quality patient care, are mandated by the Clinical Laboratory Improvement Amendments of 1988, are of particular focus in the updated College of American Pathologists Laboratory Accreditation Program, section on Cytopathology, and are indispensable for risk management. Special areas of challenge include workload, Papanicolaou smear rescreening and review, and maintenance and use of laboratory statistics.

Candida-related changes and ASCUS: a potential trap!

Detection of potential pitfalls for the ASCUS interpretation is essential for appropriate patient management. Between 1991-1994, 50 cervicovaginal specimens with Candida spp. were submitted for pathologists' review because of a possible ASCUS diagnosis. None had been preceded by abnormal smears, and all were followed by one or more benign smears and/or biopsy. Candida-associated changes included nuclear enlargement with focal hyperchromasia and cytoplasmic changes of orangeophilia, vacuoles, and perinuclear rings. Initially, 16 cases had been interpreted as ASCUS and 34 as benign. Upon review, utilizing strict Bethesda System criteria for ASCUS and awareness of Candida-associated changes, 10 of the 16 ASCUS cases were reclassified as benign. Knowledge of Candida-associated changes which may mimic ASCUS can prevent overuse of the ASCUS term, providing optimal, cost-effective management.

Benign breast aspirates: two decades of experience.

OBJECTIVE: To evaluate the reliability of benign breast aspirates. DESIGN: A 20-year retrospective study of cytologically benign aspirates from palpable breast lesions followed by surgery and review of false negatives. RESULTS: Data encompassed 1518 benign aspirates followed by benign histology, and 99 by malignant histology. Of the latter, 89% underwent biopsy within 1 month. Review of 52 available false negatives revealed 10 (19%) with no change in the original diagnosis, 16 (31%) reviewed as unsatisfactory specimens, and 26 (50%) reviewed as specimens with focal cytologic atypia (dyshesion, nuclear enlargement, and contour irregularity). Cellularity (>20 epithelial groups per slide) was an important criterion in postmenopausal women. CONCLUSION: Our study confirms the reliability of benign breast aspirates interpreted in light of clinical and mammographic findings and demonstrates the importance of adequacy evaluation and focal atypia in preventing false negatives.

Atypical parakeratosis: a marker of dysplasia?

The Bethesda System categorizes atypical parakeratosis (APK) as "ASCUS or SIL depending on the degree of cellular abnormalities." APK, however, is not well-defined. We retrospectively reviewed 68 cervicovaginal specimens with follow-up material to identify specific criteria and clinical significance of APK. APK cells were small cells, 2-3 times the diameter of neutrophil, with dense, orangeophilic cytoplasm, high nuclear cytoplasmic ratio, dense, often uneven chromatin, and irregular nuclear contour. Of 62 cases with APK, 37 had accompanying dysplastic cells. Of 25 cases with APK alone, follow-up revealed 12 with squamous intraepithelial lesion (5 HSIL and 7 LSIL) and 13 with benign changes. A major diagnostic pitfall of APK was inflammation with degeneration. Abundant APK cells, minimal inflammation and degeneration, and previous history of dysplasia frequently were associated with follow-up SIL. The findings of this study identify APK as an important marker for dysplasia that warrants careful evaluation and follow-up.

Atypical squamous cells of undetermined significance. Current laboratory practices of participants in the College of American Pathologists Interlaboratory. Comparison Program in Cervicovaginal Cytology.

OBJECTIVE: To evaluate current laboratory practices and rates for atypical squamous cells of undetermined significance (ASCUS), a category of epithelial cell abnormality in the Bethesda System. DESIGN: Questionnaire surveys were mailed in December 1993 and March 1994. SETTING: Cytopathology laboratory participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP). RESULTS: Most responding laboratories (82.5%) limited the use of "atypia" terminology to abnormalities of undetermined significance. Nearly half of the laboratories employed only the term ASCUS for squamous epithelial changes in this category. The median rate of ASCUS in 1993 was 2.8%, with 10% of laboratories reporting rates greater than 9.0%. The median squamous intraepithelial lesion rate was 2.0%, with a median ASCUS-squamous intraepithelial lesion ratio of 1.3. The majority of laboratories qualified a portion of ASCUS cases and issued recommendations for follow-up when appropriate. Fifty-six percent of laboratories surveyed included patients diagnosed with ASCUS in follow-up programs. Laboratories estimated that about 20% (median response) of patients with ASCUS smears had a squamous intraepithelial lesion or equivalent diagnosis made within a year's follow-up. CONCLUSIONS: The ASCUS category is used by the majority of laboratories as recommended by the Bethesda System, but reporting rates vary. The results of this survey and associated surveys provide laboratories with useful benchmark figures for interlaboratory comparison of ASCUS practices.

Fine-needle aspiration biopsy of the breast.

Fine-needle aspiration biopsy is a quick, accurate, cost-effective office procedure that increases the diagnostic usefulness of breast examination. It is a technique best used at initial discovery of a lesion. Its sensitivity, ranging from 90 to 97 percent in large series, depends on two factors: biopsy performance and interpretation. To attain a high sensitivity for this procedure, a team approach that includes the physician, pathologist and radiologist is essential.

Interobserver variability of cervical smears with squamous-cell abnormalities: a Philadelphia study.

The reproducibility of reporting squamous lesions by the Bethesda System (TBS) was evaluated by distributing 20 slides to be classified among 5 panelists considered experts in the field of cytopathology. Four cases were chosen for their classic morphology and the remainder were foreseen to produce possible discrepancies within one diagnostic category. For 7/20 (35%) cases there was unanimous agreement. Participants disagreed within one category of magnitude for seven (35%) cases. In six (30%) cases there was a range of more than one category disagreement. However, additional written comments modifying TBS diagnoses often diminished the clinical significance of these discrepancies. We conclude that despite the important role of TBS in standardization of Pap smear reports, a great degree of subjectivity exists in classifying squamous abnormalities without "classic" morphology. The lack of reproducibility should be taken into account in cytology proficiency testing.

Atypical squamous cells of undetermined significance: interlaboratory comparison and quality assurance monitors.

The Bethesda System recognizes "Atypical Squamous Cells of Undetermined Significance" (ASCUS) as a category of epithelial cell abnormality. Neither the acceptable rate of ASCUS nor the clinical follow-up are well defined. This study focused on interlaboratory comparison and quality assurance methods for evaluating the rate and outcome of ASCUS. Data was collected from questionnaire surveys from the College of American Pathologists Interlaboratory PAP Program and the four authors' laboratories. Most PAP laboratories (82.5%) limit the use of "atypia" terminology to abnormalities of undetermined significance. According to PAP data, the median rate of ASCUS in 1992 was 2.9%, with 10% of laboratories reporting rates greater than 9.0%. The median squamous intraepithelial lesion (SIL) rate was 2.2%, with a median ASCUS/SIL ration of 1.3. The authors' laboratories (university, independent, and hospital) revealed ASCUS rates of 1.6-9.0%, while SIL rates were 2.1-9.0%. The ASCUS/SIL ratio was less variable, 0.8-2.7. Follow-up of ASCUS patients in the authors' laboratories showed 10.3-43% with SIL, but less than 6% with high grade SIL. The ratio ASCUS/SIL may serve as a useful laboratory monitor. Peer review and follow-up studies of ASCUS serve to validate laboratory criteria and consequent clinical follow-up. Communication with clinicians is vital in ensuring optimal patient care.

Abnormal endocervical cells. Really abnormal? Really endocervical?

With the increasing incidence of endocervical adenocarcinoma, cytopathologists must distinguish between benign dysplastic and malignant endocervical cells. For this reason, the authors began a retrospective review of 44 cytology specimens initially interpreted as "abnormal endocervical cells of uncertain significance" and of 10 endocervical carcinomas. Cytologic specimens were categorized according to tissue into three groups: reactive cells (9), abnormalities associated with squamous intraepithelial lesions (17 low grade, 18 high grade), and adenocarcinoma (10). Reactive cells were monolayered, with demarcated cytoplasm and bland nuclei. Abnormal cells from squamous intraepithelial lesions showed crowding and irregular nuclei with smudgy or granular chromatin. Cells from adenocarcinoma showed multilayering and nuclei with clumped chromatin and occasional mitoses. On reexamination, numerous cells were found to be of metaplastic rather than endocervical origin. Surprisingly, the presence of abnormal metaplastic or endocervical cells sometimes was the only indicator of associated squamous intraepithelial lesion.

Occult breast lesions and aspiration biopsy: the Lankenau experience.

With the increased use of screening mammography, many occult lesions are being identified. Despite the availability of ultrasonography and stereotaxis, their use in conjunction with fine-needle aspiration biopsy for further examination of these lesions, at the time when cost containment is a serious consideration, must be evaluated. Consequently, the role of cytopathologist becomes important in identifying lesions requiring timely follow-up and surgical treatment. To assist the clinicians in evaluating the best approach to occult lesions, we reviewed the results from ultrasonographic guided aspiration biopsies (100) and stereotactic guided aspiration biopsies (61) at our institution. Our findings and review of the literature suggest that the former should only be used sparingly. By contrast, stereotactic biopsies interpreted as a part of an interdisciplinary approach can provide critical information for decision-making.

Postmenopausal squamous-cell atypias: a diagnostic challenge.

Exfoliative cytologic studies directed toward atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) have been neglected in the rising postmenopausal population. This retrospective study from 60 cases, initially interpreted as ASCUS or LSIL, concentrates on these lesions and their associated diagnostic pitfalls. Cytologic reevaluation of the 60 patients revealed squamous-cell abnormalities in 45 (18 ASCUS and 27 LSIL) and cervicitis alone in 15 cases. Follow-up studies of the 18 ASCUS cases showed cervicitis in seven, persistent ASCUS in five, CIN I in five, and VAIN I-II in one. Follow-up of the 27 cases categorized as LSIL, showed ASCUS in two, CIN in 20 and VAIN in one, while four had cervicitis alone. Interestingly, two of these 45 patients had only vaginal dysplasia. By application of uniform diagnostic criteria, 15 of the 60 cases were reviewed as benign. Pitfalls included inflammatory and drying alterations, reactive metaplasia, and sampling problems. Thus, squamous-cell abnormalities in postmenopausal women can be significant when artifactual alterations are eliminated.

Specimen adequacy evaluation in gynecologic cytopathology: current laboratory practice in the College of American Pathologists Interlaboratory Comparison Program and tentative guidelines for future practice.

Routine specimen adequacy evaluation, as advocated by The Bethesda System (TBS), can play an important role in improving the sensitivity and accuracy of cervical cytopathology screening. The effectiveness of this measure, however, has been limited by the lack of uniform criteria for adequacy. Practice parameters are now emerging, through TBS development of tentative criteria and interlaboratory comparison of adequacy practices. This study reviews 1) nationwide responses to surveys of laboratory practices in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (CAP PAP); 2) the definitions of adequacy based on TBS; and 3) the results of implementation of these criteria in a private independent laboratory, university hospital laboratory, and private nonprofit hospital laboratory. In the initial CAP PAP survey in 1990, 35% of responding laboratories routinely reported specimen adequacy, increasing to 66% in 1991 and 85% in 1992. Interlaboratory variations in adequacy practices were observed, however, underscoring the need for consensus criteria. The experience in the authors' laboratories indicates that TBS criteria can serve as a sound guideline. Effective implementation of adequacy assessment in the individual laboratory requires careful attention to ensuring the quality of adequacy ratings, correlating clinical and prior laboratory information, issuing clear and concise reports, and giving recommendations judiciously. Through interlaboratory comparison and consistent intralaboratory emphasis on specimen adequacy, greater uniformity of adequacy assessment can be achieved, and adequacy evaluation can achieve its promise of improving the quality of cervical cytopathology.