Glandular Cells Of Undetermined Significance Research Articles

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.

Pregnancy-related changes: a retrospective review of 278 cervical smears.

Pregnancy-related physiologic changes are well recognized. However, the normal range of changes as reflected in the cervical smear have not been adequately described. Review of 278 abnormal cervical smears from 153 pregnant/preabortal and 125 postpartum/ abortal patients revealed the following: 21 high-grade squamous intraepithelial lesion (HGSIL) cases, 46 low-grade squamous intraepithelial lesion (LGSIL) cases, 185 atypical squamous cells of undetermined significance (ASCUS) cases, and 26 atypical glandular cells of undetermined significance (AGUS) cases. Surgical correlation (excluding 18 products of conception and 153 placentas) was available in 98 (35%) of the cases. Dysplasia was confirmed on biopsy of 11 cases cytologically diagnosed as HGSIL (7 CINII/III and 4 CIN I), 19 cases cytologically diagnosed as LGSIL (6 CIN II/III and 13 CIN I), 35 cases of ASCUS (4 CIN II/III and 31 CIN I), and 2 cases of AGUS (1 CIN III and 1 CIN I). Decidualization was present in six cervical and three endometrial biopsies. The remaining 180 cases revealed pregnancy-related changes in most of the atypical groups and a few in the dysplasia groups. With pregnancy, both cervical glands and stroma undergo physiologic changes. These result in squamous metaplasia due to ectropion and cells with hypervacuolated cytoplasm and atypical nuclei reflecting endocervical gland hyperplasia and/or Arias-Stella reaction. The decidual cells are large, with variably staining cytoplasm and a large nucleus. Degenerated decidual or trophoblastic cells can also shed from the endometrium and mimic HGSIL. Despite the caution required in this population, dysplastic changes should not be underestimated.

Cytologic features of neoplastic lesions in endocervical glands.

Cytologic criteria for classifying atypical endocervical cells on Pap smears are poorly defined. In this study we evaluated cytologic parameters that are useful in predicting the presence of neoplastic lesions (NL) and those that help distinguish squamous intraepithelial lesion (SIL) from glandular neoplastic lesions. The recently proposed Bethesda System (TBS) terminology for reporting atypical glandular cells of undetermined significance (AGUS) was also evaluated for its significance on patient management. Sixteen cases of biopsy-proven endocervical glandular NL that had cytologic smears available for review were included. Thirty-five smears with atypical endocervical cells and follow-up biopsies showing benign/reactive change (n = 22) and SIL involving glands (n = 13) were reviewed for comparison. Our results show that squamous NL often coexist with glandular NL. The presence of rosettes, hyperchromasia and increased N/C ratio is useful in distinguishing NL from benign/reactive conditions. Architectural features are helpful in distinguishing SIL from glandular NL. While a haphazard arrangement is more often seen with SIL, glandular NL are more likely to maintain polarity and to show glandular rosettes. Using TBS criteria, a conservative management seems justified in patients with AGUS-favor reactive and AGUS diagnosis on Pap smear, and colposcopy is indicated for patients with AGUS-favor NL.

Neoplasia Associated with Atypical Glandular Cells of Undetermined Significance on Cervical Cytology

The clinical importance of atypical glandular cells of undetermined significance (AGUS) on cervicovaginal smear has not been well defined. Between January 1990 and April 1996, 127 smears were reported as showing AGUS changes by the cytopathology division at the University of Massachusetts Medical Center. The medical records of these women were reviewed: 17 women were excluded because of previous hysterectomy or gynecologic cancer, 85 were biopsied, 16 were followed by repeat smears, and 9 were lost to follow-up. Forty-four women had negative biopsies or cervicitis. There were 15 endometrial lesions: 10 hyperplasias (2 with atypia) and 5 adenocarcinomas. Twenty-five women had cervix lesions including 3 endocervical atypias, 12 low-grade cervical intraepithelial neoplasia (CIN), 6 high-grade CIN, one adenocarcinomain situ,and 3 invasive adenocarcinomas. One patient had ovarian cancer. Two of the 16 women followed by repeat pap smear eventually had a cancer diagnosis: one with cervix cancer and one with colon cancer. We were unable to identify a subgroup of women with AGUS who were at increased risk for serious pathology when we compared multiple demographic variables, symptoms, or the presence of coexistent squamous abnormalities on cervical cytology. The mean age of the 15 women with endometrial lesions was 59.9 years, which was significantly older than those patients with cervix lesions who had a mean age of 38.9 years. The presence of AGUS on cervical cytology is a marker for significant gynecologic neoplasia and should be investigated with colposcopically directed biopsies, endocervical curettage, and, in older women, endometrial biopsy.

Papanicolaou smears showing atypical glandular cells of undetermined significance: a case series.

The authors' objective was to determine retrospectively the methods used to follow up atypical glandular cells of undetermined significance (AGUS) on Papanicolaou smears and to evaluate the effectiveness of those methods. The charts of all patients with AGUS smears obtained between February 1993 and April 1996 were reviewed retrospectively, and information was extracted. A computer database was used to identify the patients and review the method of evaluation. The findings from histological sampling also are reported and analyzed. All findings are reported descriptively. Seventy-nine AGUS smears were evaluated. Of these, it was found that six patients had no follow-up. Of the 62 with histological followup, most (74%) underwent colposcopy, endometrial biopsy (63%), or endocervical curettage (50%). Cervical or vaginal biopsy, cervical conization, hysteroscopy, and hysterectomy also were performed. Twenty-seven patients underwent more than one procedure for tissue sampling. Of the 62 patients from whom histological samples were taken, 18 (29%) were found to have clinically significant lesions, 11 of which were carcinomas. In our clinic, AGUS smears are a result of a significant number of high-grade neoplastic findings. Histological evaluation is necessary in most cases for accurate diagnosis because of the multiple, varied potential etiologies of AGUS smears.

Results of the Clinical Evaluation of Atypical Glandular Cells of Undetermined Significance (AGUS) Detected on Cervical Cytology Screening

Results of the Clinical Evaluation of Atypical Glandular Cells of Undetermined Significance (AGUS) Detected on Cervical Cytology Screening

Results of the Clinical Evaluation of Atypical Glandular Cells of Undetermined Significance (AGCUS) Detected on Cervical Cytology Screening

Kennedy, Alexander W.; Salmieri, Stephen S.; Wirth, Susan L.; Biscotti, Charles V.; Tuason, Laurie J.; Travarca, Mary Jane Author Information

Atypical Glandular Cells of Undetermined Significance: Diagnostic Accuracy and Interobserver Variability Using Select Cytologic Criteria

Histologic follow-up of patients with the Bethesda system cervical-vaginal diagnosis of atypical glandular cells of undetermined significance (AGUS), "favor endocervical origin", or "not otherwise specified" (NOS) shows a high percentage of clinically significant (neoplastic or preneoplastic) lesions. Using the criteria of atypical single cells, irregular nuclear membranes, and decreased cytoplasm, eight observers retrospectively reclassified 88 AGUS, "favor endocervical", or NOS smears using a probabilistic scheme. Follow-up showed 46 clinically significant and 42 benign lesions. The mean accuracy for all observers and the experienced observers was 65% and 72%, respectively. For the experienced observers, the mean specificity of a "favor clinically significant" category was 72%; the mean sensitivity of a "favor benign" category was 90%. For the less experienced observers, subclassification had poor predictive value. We conclude that experienced observers may use specific criteria to correctly subclassify AGUS lesions, and this may aid in patient management.

Significance of Atypical Glandular Cells of Undetermined Significance in Papanicolaou Smears

Significance of Atypical Glandular Cells of Undetermined Significance in Papanicolaou Smears

Results of the Clinical Evaluation of Atypical Glandular Cells of Undetermined Significance (AGCUS) Detected on Cervical Cytology Screening

Objective: To determine the clinical significance of and underlying pathology among patients with atypical glandular cells of undetermined significance (AGCUS) identified on cervical Pap smear screening. Methods: The computerized files of the Cleveland Clinic Foundation cytology laboratory were searched from 1990 to 1994 to identify all patients with AGCUS. Patients with other significant cytologic diagnoses were considered separately from patients whose only significant finding was reported to be AGCUS. Retrospective chart review was completed to identify associated conditions and to record the results of the clinical evaluations of these patients. Results: One hundred thirty-six patients were identified among the 68,368 (0.2%) specimens from this 5-year period in contrast to 3078 (4.5%) patients with atypical squamous cells (ASCUS). Mean patient age was 43.7 years (range 20–78). Among 77 patients without other significant cytologic findings in addition to AGCUS, without prior gynecologic cancer and who had a recorded gynecologic evaluation, 13 patients (17%) were diagnosed with the following lesions: two (3%) invasive cervical adenocarcinomas, three cervical adenocarcinomasin situ(4%), three grade 1 cervical intraepithelial neoplasms (CIN) (4%), four grade 2–3 CIN (5%), and one (1%) endometrial adenocarcinoma. Additionally, in subsequent follow-up examinations two patients were diagnosed with cervical adenocarcinomain situ,one with invasive adenocarcinoma of the cervix and one with diffusely metastatic pancreatic cancer. Conclusions: AGCUS on cervical cytologic screening, even in the absence of other associated cytologic findings, is associated with substantial underlying uterine pathology including at least 4% (95% confidence interval (CI) 0.8%, 11.0%) invasive cancers and 13% (95% CI 6.4%, 22.6%) precancerous lesions. Cervical colposcopy, endocervical curettage, and endometrial biopsy are recommended for the complete evaluation of AGCUS.

Cytomorphologic characteristics of thermal injury related to endocervical brushing following loop electrosurgical excision procedure (LEEP).

Loop electrosurgical excision procedure (LEEP) is gaining popularity in the United States as an alternative to other ablative and cone methods of treatment for preneoplastic conditions of the uterine cervix. The major advantage is that it is an outpatient procedure using local anesthesia. Post-LEEP evaluation of the endocervical canal can be accomplished by either endocervical curettage or cytobrush. We reviewed the immediate post-LEEP cytobrushes from 33 patients. Artifact related to the procedure was seen in all cases and included: 1) elongated endocervical cells with cytoplasmic "tails" and streaming nuclei ("taffy pulled"); 2) loose cellular aggregates with coalesced cytoplasm and "hockey stick" nuclei; 3) sheets of cells with frothy cytoplasm and shrunken thumbprinted nuclei; 4) nuclear enlargement; and 5) smudgy nuclear chromatin. The background ranged from bloody coagulum to watery proteinaceous material. Original diagnoses were negative in 25 cases. Eleven (44%) were considered abnormal on review. Of these, four were interpreted as having squamous intraepithelial lesions (SIL), one was atypical squamous cells of undetermined significance (ASCUS), and six had atypical glandular cells of undetermined significance (AGUS). It was not always possible to grade the degree of dysplasia. There was review agreement with 14 negatives, one SIL, one ASCUS, and one unsatisfactory specimen. Three AGUS were upgraded to SIL, and one unsatisfactory specimen was considered atypical on review. In conclusion it is possible to separate artifact from actual pathology on post-LEEP cytobrush specimens. Recognition of the characteristic changes seen on cytologic specimens obtained immediately following diathermy loop treatment will allow accurate identification of true abnormalities.

Cytomorphologic characteristics of thermal injury related to endocervical brushing following loop electrosurgical excision procedure (LEEP)

Loop electrosurgical excision procedure (LEEP) is gaining popularity in the United States as an alternative to other ablative and cone methods of treatment for preneoplastic conditions of the uterine cervix The major advantage is that it is an outpatient procedure using local anesthesia. Post-LEEP evaluation of the endocervical canal can be accomplished by either endocervical curettage or cytobrush. We reviewed the immediate post-LEEP cytobrushes from 33 patients. Artifact related to the procedure was seen in all cases and included: 1) elongated endocervical cells with cytoplasmic “tails” and streaming nuclei (“taffy pulled”); 2) loose cellular aggregates with coalesced cytoplasm and “hockey stick” nuclei; 3) sheets of cells with frothy cytoplasm and shrunken thumbprinted nuclei; 4) nuclear enlargement; and 5) smudgy nuclear chromatin. The background ranged from bloody coagulum to watery proteinaceous material. Original diagnoses were negative in 25 cases. Eleven (44%) were considered abnormal on review. Of these, four were interpreted as having squamous intraepithelial lesions (SIL), one was atypical squamous cells of undetermined significance (ASCUS), and six had atypical glandular cells of undetermined significance (AGUS). It was not always possible to grade the degree of dysplasia. There was review agreement with 14 negatives, one SIL, one ASCUS, and one unsatisfactory specimen. Three AGUS were upgraded to SIL, and one unsatisfactory specimen was considered atypical on review. In conclusion, it is possible to separate artifact from actual pathology on post-LEEP cytobrush specimens. Recognition of the characteristic changes seen on cytologic specimens obtained immediately following diathermy loop treatment will allow accurate identification of true abnormalities. Diagn Cytopathol 1996;14:212–215. © 1996 Wiley-Liss, Inc.

Atypical Glandular Cells of Undetermined Significance:Cytologic Criteria to Separate Clinically Significant From Benign Lesions

Histologic follow-up of the cervical-vaginal smear diagnosis of atypical glandular cells of undetermined significance (AGUS) shows a broad spectrum of clinically significant (preneoplastic or neoplastic) and benign lesions. There are few statistical studies that have attempted to separate these AGUS categories based on select cytologic criteria. The authors retrospectively reviewed 116 AGUS without concurrent squamous dysplasia smears (66 clinically significant and 50 benign lesions), and used logistic regression analysis to identify the cytologic criteria of irregular nuclear membranes, atypical single cells, and decreased cytoplasm as useful in separating clinically significant from benign lesions. Using contingency tables, these criteria in combination had a sensitivity 29% and a specificity of 94% in the diagnosis of clinically significant lesions. If any single criterion was present, the sensitivity and specificity were 100% and 28%, respectively. In conclusion, by using key cytologic criteria, a percentage of benign AGUS lesions can be separated from clinically significant AGUS lesions.