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

Raab, Stephen S.; Isacson, Christina; Layfield, Lester J.; Lenel, Julia C.; Slagel, Daniel D.; Thomas, Patricia A.

doi:10.1093/ajcp/104.5.574

Cited by 90 publications

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“…The fourth cytopathologist (P.A.T) was a participant in several AGUS projects defining cytologic criteria for subclassification. 33 ' 34 This cytopathologist had made the original diagnosis in 7 cases but had not viewed these cases within 4 years. The cytopathologists were told that the study was designed to measure the interobserver variability of a diagnosis of AGUS, and they were not given any clinical history or follow-up information.…”

Section: Methodsmentioning

confidence: 99%

“…Two-way logistic regression analysis was used to determine the cytologic criteria that are important to individual cytopathologists in separating a clinically significant from a benign lesion. 34 To briefly summarize, variables to be entered into the logistic regression were identified through univariate analyses of association. These analyses were performed between the dependent variable (clinically significant lesion) and the presence or absence of each independent variable (cytologic criterion).…”

Section: Methodsmentioning

confidence: 99%

“…34 Follow-up studies show that a clinically significant lesion, ranging from squamous dysplasia to adenocarcinoma, is present in up to 83% of women with a diagnosis of AGUS. 33 " 41 Only 12% to 46% of these lesions are true glandular neoplasias, and up to 68% are high-grade squamous intraepithelial lesions (HSILs).…”

Section: The Interobserver Variability Of a Papanicolaou Smear Diagnomentioning

confidence: 99%

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Interobsenrer Variability of a Papanicolaou Smear Diagnosis of Atypical Glandular Cells of Undetermined Significance

et al. 1998

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A b s t r a c t The interobserver variability of a Papanicolaou smear diagnosis of atypical glandular cells of undetermined significance (AGUS) has not been measured. Four expert cytopathologists restrospectively reclassified 100 smears originally diagnosed as AGUSAlthough the Papanicolaou smear is one of the most effective screening tools in medicine, errors still occur. One source or error that has received a great deal of attention is diagnostic error, which is a leading cause of medical litigation.1-17 There has been considerably less study of interobserver diagnostic variability, including the relationship of variability to error and its impact on patient care. 4,18-31For Papanicolaou smear interpretation, most cytopathologists use the Bethesda System, which is composed of semiquantitative categories. 32 Interobserver diagnostic variability has been measured for only some of these categories. The diagnosis of atypical glandular cells of undetermined significance (AGUS) has been poorly characterized and has not been evaluated in terms of interobserver diagnostic variability. Follow-up studies show that a clinically significant lesion, ranging from squamous dysplasia to adenocarcinoma, is present in up to 83% of women with a diagnosis of AGUS. 33 " 41 Only 12% to 46% of these lesions are true glandular neoplasias, and up to 68% are high-grade squamous intraepithelial lesions (HSILs). 33^11 Thus, AGUS is a high-risk diagnosis. Assuming equal disease prevalence, if a laboratory has a low rate of making a diagnosis of AGUS, lesions that would be called AGUS by a second laboratory are either being classified in another clinically significant category or being missed. Such potential diagnostic discrepancies raise the possibility that some errors are simply manifestations of interobserver diagnostic variability.In this study, expert cytopathologists, including 3 cytopathology laboratory directors, retrospectively and independently reviewed 100 cases that originally were diagnosed as AGUS. Interobserver agreement, diagnostic accuracy, and

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: The Interobserver Variability Of a Papanicolaou Smear Diagnomentioning

confidence: 99%

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Interobsenrer Variability of a Papanicolaou Smear Diagnosis of Atypical Glandular Cells of Undetermined Significance

et al. 1998

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“…1 Before 2001, a spectrum of glandular cell abnormalities in cervical smears was grouped under atypical glandular cells of undetermined significance (AGUS) and defined as glandular cells exhibiting changes beyond reactive or reparative changes, but lacking unequivocal features of invasive adenocarcinoma. 2 The incidence and clinical significance of AGUS have been extensively reported, [3][4][5][6] however, studies reporting AGUS smears in pregnancy and postpartum period are very limited.…”

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Atypical Glandular Cells in Cervical Smear During Pregnancy and Postpartum Period

Tam¹

2005

Clinical Medicine & Research

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The 2001 Bethesda System defines atypical glandular cells (AGC) as glandular cell abnormalities that are distinct from adenocarcinoma or adenocarcinoma in situ. 1 Before 2001, a spectrum of glandular cell abnormalities in cervical smears was grouped under atypical glandular cells of undetermined significance (AGUS) and defined as glandular cells exhibiting changes beyond reactive or reparative changes, but lacking unequivocal features of invasive adenocarcinoma. 2 The incidence and clinical significance of AGUS have been extensively reported, 3-6 however, studies reporting AGUS smears in pregnancy and postpartum period are very limited.Chhieng and colleagues 7 have reported the largest number of AGUS smears in pregnancy and postpartum period (n=35). Among the 13,361 smears performed during the 3-year study period, this group reported a 0.26% incidence rate with a mean patient age of 29. Of the 35 patients with AGUS smears, 8 patients were lost to follow up, 17 were referred for colposcopy and biopsy, and 10 had repeated smears. For those who underwent colposcopy and biopsy, five patients had histologically proven cervical intraepithelial lesions. The others had benign pathologies including squamous cell metaplasia, endocervical or endometrial polyps, Arias-Stella reactions and microglandular hyperplasia. Two of the 10 patients had persistent abnormalities on repeated smears but their outcomes were not reported. The authors reported the incidence of significant pathology in this study as 29%. However, the incidence rate of significant pathology was calculated on the basis of the 17 cases referred for colposcopy and biopsy only, and did not include the patients being followed with repeated smears which would reduce the rate of significant pathology to less than 20%.Two other studies have been reported on pregnancy related AGUS, although these involved smaller numbers of patients. Michael and colleagues 8 reported 26 cases of AGUS during pregnancy or postpartum period, most of which were followed with repeated cervical smears after 3 to 6 months. Biopsies were performed in the postpartum period only if atypia persisted on repeat smears. Eight patients had colposcopy directed biopsies and only 2 patients were diagnosed with squamous cell intraepithelial lesions. Kim and colleagues 9 reported a large study of 326 patients: 21 were diagnosed with AGUS during pregnancy or within 8 weeks postpartum. Only one of the 21 patients had significant pathology showing carcinoma in situ, though the method of follow-up was not specified. From the studies described above, the incidence of

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“…[1][2][3][4][5][6][7][8] Surprisingly, histologic follow-up has shown that some of the clinically significant lesions are pure squamous dysplasias without glandular neoplasia.…”

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

et al. 1997

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Histologic follow-up of patients with the Bethesda system cervicalvaginal 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. (Key words: Cytology; Accuracy; Cervical-vaginal smear; Dysplasia; Probability; Carcinoma) Am J Clin Pathol 1997,107:299-307.The Bethesda system diagnostic category of atypical glandular cells of undetermined significance (AGUS) is important for two reasons: (1) AGUS has a relatively high incidence that reportedly ranges from 0.46% to 2.5% of all cervical-vaginal smears 1-3 ; and (2) a high percentage (42%-83%) of patients with an AGUS diagnosis have a clinically significant lesion. [1][2][3][4][5][6][7][8] Surprisingly, histologic follow-up has shown that some of the clinically significant lesions are pure squamous dysplasias without glandular neoplasia.Problems with the AGUS diagnosis are that its defining criteria are somewhat nebulous, and it is used as a wastebasket for lesions that cannot be definitely classified as reactive or neoplastic.9-11 The Bethesda system recommends subclassification of AGUS into the categories of "favor endocervical origin", "favor endometrial origin", and "not otherwise specified" (NOS); "favor endocervical origin" lesions are further classified into the categories of "favor neoplastic" and "favor reactive". [9][10][11] This classification scheme is supposed to aid in patient triage, which, given the AGUS incidence and the high rate of clinically significant lesions, is exceedingly important. However, subclassification of AGUS has yet to be proved clinically effective, and although the Bethesda Committee and many others have studied cytologic criteria important in subclassification, these criteria have not been tested rigorously. This has resulted in the AGUS category being confusing for the pathologist and the clinician.To more thoroughly investigate the utility of AGUS subclassification, our laboratory used a rigorous statistical technique known as logistic regression analysis to identify cytologic criteria important in differentiating a clinically significant AGUS lesion from a benign AGUS lesion.3 The presence of the crit...

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

Cited by 90 publications

References 0 publications

Interobsenrer Variability of a Papanicolaou Smear Diagnosis of Atypical Glandular Cells of Undetermined Significance

Interobsenrer Variability of a Papanicolaou Smear Diagnosis of Atypical Glandular Cells of Undetermined Significance

Atypical Glandular Cells in Cervical Smear During Pregnancy and Postpartum Period

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

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