Endocervical glandular cell abnormalities in conventional cervical smears: evaluation of the performance of cytomorphological criteria and HPV testing in predicting neoplasia

Objective:  To analyse the correlation between cytomorphological criteria in smears with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) and human papillomavirus (HPV) reflex test results with different neoplastic histological diagnoses, particularly to distinguish between glandular and squamous neoplasia.
Methods:  A series of 155 women with glandular abnormalities in their conventional cervical smears was included: 106 with AGC, 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) and 14 with AIS. Two reviewers evaluated 35 cytomorphological criteria and hybrid capture II (HCII) was performed in all cases. Colposcopy was carried out in all cases and biopsy in 126/155. For statistical purposes, predictive values and odds ratio (OR) were calculated, followed by chi-square automatic interaction detection.
Results:  Histology detected 56 cases of squamous and 17 of glandular intraepithelial or invasive neoplasia. Predictive values of the papillary groups and feathering criteria for glandular neoplasia were, respectively, 80.0% and 73.3%. Feathering was the criterion with the highest OR for distinguishing glandular from squamous neoplasia and also for distinguishing between glandular and non-neoplastic diagnosis. Rosettes and pseudostratified strips did not perform as well. Multivariant Classification and Regression Trees analysis identified feathering as the best criterion for distinguishing between glandular, squamous and non-neoplastic diagnoses regardless of HPV status.
Conclusions:  Feathering was the best criterion for predicting glandular neoplasia.     

Clinical significance of atypical glandular cells of undetermined significance. A follow-up study from an academic medical center

OBJECTIVE: To determine the rate of atypical glandular cells of undetermined significance (AGUS) and the incidence of subsequent clinically significant lesions. STUDY DESIGN: A computer-based search of our cytology laboratory files was performed for cervicovaginal smears diagnosed as AGUS from January 1996 to December 1996. RESULTS: In 43,456 cervicovaginal smears examined during the 12-month period, AGUS was reported in 222 (0.5%) cases, with follow-up in 191 (86.0%) (133 [59.9%] biopsies and 58 [26.1%] repeat cervicovaginal smears). Among the patients with repeat cervicovaginal smears, 1 (1.7%) had a high grade squamous intraepithelial lesion, and 10 (17.2%) had persistent AGUS/atypical squamous cells of undetermined significance; the remainder were within normal limits. Thirty-three (24.8%) patients had preneoplastic or neoplastic, squamous or glandular lesions on biopsy (8 [6.0%] cervical intraepithelial neoplasia [CIN] 1, 18 [13.5%] CIN 2/3 and 7 [5.3%] endometrial adenocarcinomas). Half the patients with CIN 2/3 also had evidence of endocervical gland involvement. Squamous lesions were seen more commonly in premenopausal women, while glandular lesions were noted predominantly in postmenopausal women. Patients with a prior abnormal gynecologic history or a concomitant diagnosis of squamous intraepithelial lesion (SIL) had a higher incidence of significant lesions on subsequent biopsy. CONCLUSION: Our incidence of AGUS was 0.5%, similar to that in other published reports. AGUS is associated with a significant number of squamous or glandular, premalignant or malignant lesions. A majority of these lesions are high grade SIL, often with endocervical gland involvement. A small but significant number of patients had a glandular malignancy. Our results justify close and persistent follow-up for patients with a diagnosis of AGUS on cervicovaginal smears.     

Atypical glandular cells of undetermined significance. Cytologic predictive value for glandular involvement in high grade squamous intraepithelial lesions

OBJECTIVE: To verify the cytologic predictive value of a diagnosis of atypical glandular cells of undetermined significance (AGUS) in high grade squamous intraepithelial lesions (HSIL) cases. STUDY DESIGN: In a retrospective study, 98 cases of HSIL were reviewed. All patients were referred for colposcopy and directed biopsy to confirm the cytologic diagnoses. Loop excision of the transformation zone was performed to treat clinical lesions. Sensitivity, specificity, positive and negative predictive value were evaluated. Kappa statistics and logistic regression analysis were used to evaluate the findings statistically. RESULTS: By logistic regression analysis, we found that the chance of finding squamous intraepithelial lesions involving glands in AGUS smears was 5.32 times higher than in those with no AGUS. It was 5.74 times higher in cervical intraepithelial neoplasia (CIN) 3 lesions than in CIN 2. CONCLUSION: The cytologic predictive value for HSIL involving glands is statistically significant when specific and objective criteria are used for the AGUS diagnosis.     

Diverse glandular pathologies coexist with high-grade squamous intraepithelial lesion in cyto-histological review of atypical glandular cells on ThinPrep specimens

Objective: To identify in cytology, high‐grade squamous intraepithelial lesions with endocervical glandular extension in cases previously diagnosed as atypical glandular cells (AGC), analyse possible reasons for the diagnostic pitfall and document the frequency of glandular pathology coexisting with high‐grade cervical intraepithelial lesion in histology. Methods: Thirty‐nine ThinPrep® cervical smear (Pap) tests reported as AGC of undetermined significance and showing high‐grade lesions on histology [cervical intraepithelial neoplasia (CIN) 2 or 3, endometrial or extrauterine adenocarcinoma] were reviewed retrospectively to identify the cases of high‐grade squamous intraepithelial lesion with endocervical glandular extension, using the Bethesda 2001 system. Cyto‐histological correlation was performed. Results: A high frequency of diverse glandular pathologies coexisted with high‐grade cervical intraepithelial lesions on histology. This included endocervical glandular extension in 63%, benign glandular pathology in 33% and pre‐neoplastic or malignant glandular pathology (endocervical glandular dysplasia, adenocarcinoma in situ and metastatic breast carcinoma) in 17% cases. On cytology, the sensitivity was 40%, specificity was 80% and positive predictive value was 86% for endocervical gland extension in high‐grade squamous intraepithelial lesions. Conclusions: Special efforts to recognize endocervical glandular extension in high‐grade squamous intraepithelial lesions and glandular neoplasia coexisting with squamous intraepithelial lesions from the heterogeneous category of AGC can contribute to increasing the diagnostic accuracy. The identification of endocervical glandular extension on cervical cytology would alert the gynaecologist to perform a thorough assessment of the endocervix during colposcopy. This could also help to decide on the need to perform deeper conization rather than loop electrosurgical excision procedure to ensure negative margins when colposcopic biopsy shows CIN 2 or 3.     

Outcomes of pregnant patients with Pap smears classified as atypical glandular cells

J. Slama, P. Freitag, P. Dundr, J. Duskova, D. Fischerova, M. Zikan, I. Pinkavova and D. Cibula
Outcomes of pregnant patients with Pap smears classified as atypical glandular cells Objectives: The incidence of cervical cancers increases with age. Due to the trend of increasing age of first pregnancy, abnormal Pap smears including those classified as atypical glandular cells (AGC) are being found more often in early pregnancy. Once invasive cancer is excluded, conservative management of squamous intraepithelial lesions (SIL) in pregnancy is considered safe; however, optimal management of AGC is not well established. The aim of our study was to evaluate the outcome of patients with AGC diagnosed from smears during pregnancy. Methods: The study included 17 patients referred to us in early pregnancy with Pap smears reported as AGC: 11 not otherwise specified (AGC‐NOS), five favour neoplasia (AGC‐FN) and one adenocarcinoma in situ (AIS). Thirty‐one with high‐grade SIL (HSIL) Pap smears confirmed on punch biopsy in early pregnancy comprised a control group. Human papillomavirus (HPV) positivity was found in seven patients with persistent AGC‐NOS (including all four who had CIN3 postpartum). All the women were initially examined by expert colposcopy and those with AGC‐FN or AIS smears also by transrectal ultrasound to exclude invasive endocervical cancer. Follow‐up controls were carried out every 8–12 weeks and, if there were no signs of progression, revaluation was scheduled 6–8 weeks after delivery. Results: The mean age of the women was 31.4 years. Conization in one patient in the study group was performed in the 16th week of pregnancy due to colposcopic signs of microinvasive squamous cell cancer confirmed on histology. Progression to invasive cancer was not found in any of the other 16 patients in the study group or in the control group. Cervical intraepithelial neoplasia or AIS was confirmed postpartum by conization or punch biopsy in 47.1% (8/17) of patients in the study group and, in 77.4% (24/31) of patients in the control group. Conclusions: Conservative management of women with AGC in pregnancy is safe where invasive cancer is excluded. As histological verification of glandular pre‐cancerous lesions by punch biopsy is not reliable and the postpartum regression rate cannot be determined precisely, conization should be performed in all cases with AGC‐FN or AIS. Triage of persistent AGC‐NOS with HPV testing is useful in distinguishing significant underlying lesions.     

Atypical glandular cells in cervical smears: histological correlation and a suggested plan of management based on age of the patient in a low-resource setting

Objectives:  To perform an audit of all smears reported as atypical glandular cells (AGC) using the Bethesda system (TBS) 2001.
Methods:  A total of 18 376 cervical smears were screened from January 2005 to June 2007, of which 65 cases were reported as AGC. Follow-up histology was available in 31 cases (47.7%), in whom a detailed cytological/histological correlation was carried out.
Results:  AGC constituted 0.35% of all Pap smears. Follow-up histology was normal or benign in 20 cases, whereas a squamous or glandular abnormality was seen in 11 cases. Squamous abnormalities included one case each of cervical intraepithelial neoplasia (CIN)1, CIN2 and CIN3 and five cases of squamous cell carcinoma. All glandular epithelial abnormalities were endometrial in origin and included two endometrial adenocarcinomas and one uterine serous carcinoma. Neither in situ nor invasive adenocarcinoma of the endocervix was observed. Review of smears and reclassification as AGC, not otherwise specified and favour neoplasia revealed a higher proportion of abnormality in the latter group, reaffirming the utility of subtyping. The median age of women with AGC was 41 years. The outcome was analysed with respect to the median age. In women aged equal or more than 40 years, AGC reflected a high-grade squamous or glandular epithelial abnormality in 50% of cases compared with none in those less than 40 years old ( P  = 0.010).
Conclusion:  The age of the woman as well as the subtype of atypical glandular cells influences outcome and hence must be taken into consideration while formulating an acceptable management strategy in these women in a low-resource setting.     

Glandular lesions of the cervix—cytological and histological correlation

In this retrospective review we assessed the frequency with which atypical glandular cells in cervical smears predict cervical glandular lesions. Asymptomatic patients ( n =34) with one or more smears showing atypical glandular cells and subsequent histopathological assessment were studied. Independent cytological and histological review was undertaken. Cytological review confirmed atypical glandular cells in 29 cases, 17 of which had coexisting squamous dyskaryosis. Histological review of these 29 cases revealed glandular neoplasia in 13 (45%) and microglandular hyperplasia (MEH) in an additional four (14%). Initial reporting had underestimated the prevalence of glandular neoplasia.     

The role of cervical cytology and colposcopy in detecting cervical glandular neoplasia

Objective:  To determine the role of cervical cytology and colposcopy in the management of endocervical neoplasia.
Setting:  Colposcopy unit and cytology laboratory in a teaching hospital.
Sample:  Group 1 included 184 smears showing endocervical glandular neoplasia from 129 patients and group 2 included 101 patients with histology showing endocervical abnormalities in a 6-year period (1993–1998). Follow-up of 6–11 years to 2004 was available.
Methods:  Group 1 were identified from the cytology computer records. Group 2 were identified from histology records on the cytology database and a record of histology cases kept for audit purposes. The clinical records were examined retrospectively.
Results:  The positive predictive value (PPV) of abnormal endocervical cells in smears was 81.1% for significant glandular/squamous [cervical glandular intraepithelial neoplasia (CGIN)/cervical intraepithelial neoplasia grade2 (CIN2 or worse)] lesions. The PPV of colposcopy was 93.5% for significant glandular/squamous lesions of the cervix. The postcolposcopy probability of a significant lesion when colposcopy was normal was 87.5%. The sensitivity of colposcopy in detecting endocervical lesions was 9.8%. The sensitivity of cervical smears in detecting a significant endocervical abnormality (CGIN or worse) was 66.3%. The false negative rate for cytology of endocervical glandular lesions was 4.0%.
Conclusions:  Endocervical glandular neoplasia detected on cytology is predictive of significant cervical pathology even when colposcopy is normal, which supports excisional biopsy in the primary assessment of these smears. The high concomitant squamous abnormality rate justifies the use of colposcopy to direct biopsies from the ectocervix. Cervical cytology is the only current screening method for cervical glandular abnormalities but sensitivity is poor.     

Decrease in numbers of glandular cell groups in post-LLETZ liquid-based cytology preparations

Objective:  Large loop excision of the transformation zone (LLETZ) has become standard of care in the management of cervical squamous neoplasia and with cone biopsy glandular intraepithelial neoplasia. Controversy remains about the long-term effects of this traumatic procedure. The aim of this study was to count and compare the number of endocervical glandular cell groups in pre- and post-LLETZ cervical preparations using liquid-based cytology to establish a cyto-morphological correlate of destruction of the transformation zone.
Methods:  The cytology/histology correlation audit records of the Cytopathology Department of St Luke's Hospital in 2003 and early 2004 were used to select patients with a cytological diagnosis of high grade dyskaryosis followed by LLETZ. Only those cases with post-LLETZ cytological follow-up were selected. Cases using conventional smears were excluded. One hundred and twenty slides (60 pairs of slides) in total were retrieved. The cases underwent review and all groups of >3 glandular cells in each slide were counted by AM while blinded as to whether smears were pre- or post-LLETZ. Medians were compared using a Mann–Whitney U -test.
Results:  The median number of groups of endocervical glandular cells of the pre-treatment group was 5.5 and of the post-treatment group was 2.0. There were significantly fewer endocervical glandular cell groups in the post-LLETZ population ( P  = 0.03).
Conclusions:  The number of endocervical glandular groups in cervical cytological preparations decreases significantly following LLETZ procedure. This suggests that cytological follow-up may not be as useful in glandular neoplasia cases. Few or absent glandular cell groups in post-LLETZ preparations may have implications for adequacy assessment.     

Outcomes of cervical liquid-based cytology suggesting a glandular abnormality

Objective: To ascertain the positive predictive value of both ?glandular neoplasia (national standard code 6) and borderline change (national standard code 8) in glandular cells in liquid‐based cervical cytology specimens in Cardiff and Vale NHS Trust and to outline the histological outcomes of these cases. Method: Eighty‐nine liquid‐based (Surepath?) cervical cytology cases were retrospectively identified from a 2‐year period (January 2005 to December 2006) and correlated with histopathological diagnoses. Results: Initial punch biopsy histology revealed 18 cases (21%) of cervical glandular intraepithelial neoplasia (CGIN). A further nine cases (10%) of CGIN were identified following local excision or hysterectomy. Ten cases of invasive malignancy were identified: four endocervical adenocarcinomas (all node negative, TNM stage T1b1), five endometrial adenocarcinomas and one squamous cell carcinoma. There were 10 with high‐grade cervical intraepithelial neoplasia (CIN) alone. Women diagnosed with endometrial malignancy presented later with an average age of 64.6 years compared with 34.9 years for endocervical lesions. Taking high‐grade CIN or worse as a positive outcome, the overall positive predictive value (PPV) of glandular abnormalities on cytology (both code 6 and 8) was 58.1% [95% confidence interval (CI) 47.8, 68.4]. PPV for borderline change in glandular cells alone was 24.1% (95% CI 8.5, 39.6) and for ?glandular neoplasia alone 75.4% (95% CI 64.3, 86.5). Conclusion: With our interpretation of the classification, women with cytological diagnoses of glandular neoplasia of the cervix should initially be investigated by local resection rather than punch biopsy, and those with borderline change in glandular cells with repeat cytology.     

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions
This paper reports the cytological findings based on air-dried smears in a retrospective series of 143 cases of endocervical adenocarcinoma, combined adenocarcinoma-squamous carcinoma and adenosquamous carcinoma drawn from the files of the BC Cancer Registry. Cervical cytology smears were available before biopsy in 131 patients, but in 18 cases the cytology showed no abnormality. Malignant changes or high-grade atypia of glandular and/or squamous cells (defined as moderate or severe dyskaryosis) were detected in 103 cases. In 46 cases, only a high-grade squamous abnormality was detected. Low-grade glandular and/or squamous lesions were detected in nine cases and one showed atypical endometrial-type glands. The cervical smears of 64 cases were reviewed in detail to determine the important cytomorphological criteria of in situ and invasive adenocarcinoma in air-dried smears, the technique used for preparing PAP smears in British Columbia. Endocervical cells were absent in four cases. Numerous (>10) groups of glandular cells were present in 51 cases. Important clues to the diagnosis of adenocarcinoma included crowding of nuclei, stratification of nuclei, loss of polarity, syncytial balls and papillary groups of glandular cells, nuclear enlargement, nuclear pleomorphism, and the presence of free-lying atypical glandular cells. Nuclear hyperchromatism, chromatin pattern, nuclear borders, nuclear membranes, and numbers and morphology of nucleoli were not helpful criteria in our material. Criteria enabling reliable distinction between in situ and invasive adenocarcinoma and/or mixed adenocarcinoma-squamous carcinoma could not be established.     

Clinical significance of atypical glandular cells by the 2001 Bethesda System in cytohistologic correlation

OBJECTIVE: To evaluate incidence, cytology findings and pathology outcome of atypical glandular cells (AGC) in Pap smears according to the 2001 Bethesda criteria. STUDY DESIGN: From 103,073 consecutive Pap smears, 113 (0.1%) AGC cases were identified. Of these, 91 (80%) had adequate histologic evaluation included in this study. RESULTS: Abnormal histology findings were seen in 38 patients (42%). Final pathology results revealed 14 endometrial adenocarcinomas, 5 endocervical adenocarcinomas, 1 cervical squamous cell carcinoma, 1 endometrial stromal sarcoma, 6 other malignancies, 4 endocervical adenocarcinomas in situ, 4 cases ofendometrial complex byperplasia, 1 case of endocervical glandular dysplasia and 2 cases of cervical intraepithelial neoplasia 3 with glandular involvement. Women with AGC, favor neoplasia, were more likely to have significant pathology than those with AGC, not otherwise specified, 74% vs. 33% (p = 0.002). Some characteristic background cytologic findings were also noticed in most cases of endometrial, fallopian tube and endocervical adenocarcinoma. CONCLUSION: A diagnosis of AGC is more clinically significant by the 2001 Bethesda System, especially the "AGC, favor neoplastic" category. Some background cytologic features are important because they are indicators of malignancy.     

Glandular lesions of the cervix—cytological and histological correlation

In this retrospective review we assessed the frequency with which atypical glandular cells in cervical smears predict cervical glandular lesions. Asymptomatic patients (n=34) with one or more smears showing atypical glandular cells and subsequent histopathological assessment were studied. Independent cytological and histological review was undertaken. Cytological review confirmed atypical glandular cells in 29 cases, 17 of which had coexisting squamous dyskaryosis. Histological review of these 29 cases revealed glandular neoplasia in 13 (45%) and microglandular hyperplasia (MEH) in an additional four (14%). Initial reporting had underestimated the prevalence of glandular neoplasia.     

Cytological Changes Associated With Tubo-Endometrioid Metaplasia of the Uterine Cervix

Two women who had undergone previous cervical surgery for the treatment of glandular intraepithelial neoplasia (GIN) and cervical intraepithelial neoplasia (CIN), were found to have severely dyskaryotic cells of glandular and metaplastic type in follow-up cervical smears. A third patient was found to have similar abnormal cells in a routine screening smear. All of the patients were subjected to either hysterectomy or cervical conization and in all cases histological examination showed tubo-endometrioid glands in the endocervix, well away from the uterine isthmus, with no associated endometrial stromal tissue. All of the cervical smears were reviewed and cytological features that facilitate the distinction between tubo-endometrioid metaplasia and squamous or glandular dyskaryosis were identified. These features include the smaller size of affected cells, more marked nuclear hyperchromasia, inconspicuous nucleoli, the formation of glandular structures, the lack of discrete squamous dyskaryosis and the absence of the typical 'feathering' noted with GIN. the possibility of tubo-endometrioid metaplasia should be considered when atypical glandular or metaplastic cells are noted in cervical smears, particularly, but not exclusively, in women who have been treated for CIN or GIN. In the presence of these changes clinicians should rebiopsy the cervix before embarking on further unnecessary surgery which may adversely affect fertility and pregnancy, particularly in younger patients.     

Expression of p16INK4A in Pap smears containing atypical glandular cells from the uterine cervix

OBJECTIVE: To verify one of the diagnostic dilemmas concerning atypical glandular cells (AGC) by immunocytochemical detection of p16INK4A (p16) applied to routine Pap smears with correlation of follow-up biopsies for improvement of cytologic diagnoses. STUDY DESIGN: The study included 36 Pap smears in AGC diagnostic categories, all of which were correlated histologically. The cytologic diagnoses of AGC were further classified according to the 2001 Bethesda System. All Pap smears were decolorized and immunostained with the primary anti-p16 antibody, clone E6H4. Immunoreactivity for p16 was correlated with histologic sections in a semiblind fashion. RESULTS: Of the 36 smears containing AGC, 22 (61%) were reclassified as general AGC and 14 (39%) as AGC--favor neoplasia. Follow-up biopsies revealed that 15 (42%) cervixes had no obvious abnormalities and that 21 (58%) cases had different cervical lesions. More than half the cases (19/36, 53%) of follow-up biopsies concerning AGC-containing smears represented significant lesions. There was a much higher proportion of significant lesions (13/14, 93%) in AGC--favor neoplasia than those (6/22, 27%) in general AGC cases. Fifteen of 36 (36%) AGC-containing cases were actually squamous abnormalities on follow-up biopsies. p16 Immunocytochemical stain was reactive in 22 (61%) of 36 smears, either weakly/sporadically (2 cases, 6%) or strongly positively (20 cases, 55%). Conversely, 14 (39%) of the smears were negative for p16 and displayed predominantly reactive changes. However, there was 1 case of high grade squamous intraepithelial lesion showing negative immunostaining for p16. From the view-point of clinical significance, this analysis was highly sensitive (sensitivity, 95%) and specific (specificity, 88%) and had favorable positive (90%) and negative (94%) predictive values. CONCLUSION: On the basis of both morphologic and immunostaining patterns, there was a clear association between strong p16 immunostaining of atypical cells in smears and the presence of significant lesions in the cervix except in 1 patient. Similarly, there was a clear association between lack of p16 expression and absence of cervical lesions. p16 Immunocytochemical stain can be applied successfully to conventional Pap smears and may serve as a useful biomarker in diagnoses of AGC-containing smears. This may offer a more objective parameter to help clarify this ambiguous area of gynecologic cytopathology.     

Glandular and squamous atypia and intraepithelial lesions in atrophic cervicovaginal smears. One institution's experience

OBJECTIVE: To review the cytologic features and follow-up histologic findings in atrophic cervicovaginal smears with the diagnoses of glandular or squamous atypia or intraepithelial lesion. STUDY DESIGN: A total of 228 cases were included in the study. The selection criteria included: age > 48 years and a diagnosis of either atypical glandular cells (AGC) (51 cases), cellular changes suggestive of human papillomavirus (HPV) infection (S/O HPV, 97 cases), low grade squamous intraepithelial lesion (LSIL) (60 cases) or high grade squamous intraepithelial lesion (HSIL) (20 cases). Follow-up biopsy information was available for 103 cases (45%). RESULTS: From the AGC group, 35 (69%) cases had tissue studies; 14 (40%) cases showed glandular lesions; 5 (14%) showed squamous intraepithelial lesion (SIL) and atypical cells. Follow-up information was available for 32 (33%) cases classified as S/O HPV; significant lesions (glandular/squamous) were found in 11 (34%). In the LSIL category, 22 (37%) cases had follow-up; 16 (73%) showed SIL. In the HSIL category, 14 cases (70%) underwent biopsy, and all showed SIL (four LSIL and nine HSIL) or squamous cell carcinoma. CONCLUSION: Even though atrophy-related epithelial changes often pose diagnostic difficulties in the interpretation of postmenopausal smears, application of reproducible and established cytologic criteria in diagnosing SIL and/or glandular lesions can improve diagnostic accuracy and result in selection of patients for follow-up tissue studies.     

Endocervical glandular neoplasia and its mimics in ThinPrep Pap tests. A descriptive study.

OBJECTIVE: To document the cytologic features of endocervical adenocarcinoma in situ (AIS) and invasive endocervical adenocarcinoma as observed in ThinPrep slides and to compare these features with those that have been described for conventional smears. STUDY DESIGN: Six cases of endocervical AIS and three cases of invasive adenocarcinoma were evaluated with respect to 3 low-power and 14 high-power features. All cases were biopsy proven. Glandular "look-alikes" (tubal metaplasia, n = 3; florid repair, n = 3; sampling of lower uterine segment, n = 1) were also examined. RESULTS: All cases of AIS contained dark groups and sheets at screening power. At higher power, nuclear detail was extremely well visualized. All cases had crowding, continuous depth of focus, variability of nuclear size and shape within groups, irregular nuclear membranes, uniformly stippled chromatin and at least occasional single atypical cells. Only one case lacked nucleoli. Traditional features (strips, feathering, rosettes and mitoses) were observed about as frequently as in conventional smears. Invasive lesions had many of the same features, with relatively more inflammation and lysed blood. Nonneoplastic look-alikes could be distinguished from neoplasms using traditional criteria. CONCLUSION: In this small study, AIS and invasive endocervical adenocarcinoma maintained the features previously described for conventional smears. Improved visualization of nuclear detail may allow the application of additional criteria, such as irregular nuclear membranes and the more consistent presence of nucleoli, for distinguishing glandular neoplasms from their look-alikes.     

Atypical glandular cells of undetermined significance on cervical smears. A study with cytohistologic correlation.

OBJECTIVE: The incidence of endocervical adenocarcinoma has increased steadily over the past two decades. Since the Bethesda System was introduced, the diagnosis of atypical glandular cells of undetermined significance (AGUS) has also risen and now accounts for 0.46-1.83% of all cervical (Pap) smears. The purpose of this study was to evaluate the significance of a diagnosis of AGUS using cytohistologic correlation. STUDY DESIGN: A retrospective review of archival material from 1993 through 1996 identified 64 patients who had smears diagnosed as AGUS and had a subsequent surgical biopsy. The smears were reviewed and cytologic features analyzed and correlated with the histologic diagnosis. RESULTS: On biopsy, 3 (5%) of the 64 cases showed endocervical adenocarcinoma in situ (AIS) (1 case with invasive adenocarcinoma also), 14 (22%) had a benign glandular lesion (endocervical polyp, tubal metaplasia, microglandular hyperplasia, reactive changes), 35 (54%) had squamous intraepithelial lesion (SIL) (15 diagnosed on the original smear), and 12 (19%) had no abnormality. Among the cytologic criteria evaluated, feathering (P = .01), palisading (P < .001) and chromatin clearing (P = .002) were shown to have a significant association with the histopathologic diagnosis of AIS/adenocarcinoma. These features were also useful in distinguishing AIS/adenocarcinoma from SIL and benign glandular changes from AIS/adenocarcinoma but not benign/reactive glandular changes from SIL. CONCLUSION: A diagnosis of AGUS correlated with a clinically significant lesion in the majority of cases. Squamous dysplasia (SIL) was the most common lesion identified. The presence of feathering, nuclear palisading and chromatin clearing increased the likelihood of a histologic diagnosis of AIS/adenocarcinoma.     

Atypical glandular cells of undetermined significance in cervical smears after conization. Cytologic features differentiating them from adenocarcinoma in situ

OBJECTIVE: To evaluate the cytologic features of atypical glandular cells of undetermined significance (AGUS) smears following conization through a comparison with adenocarcinoma in situ (AIS) smears. STUDY DESIGN: Fifty cervical smears, diagnosed as AGUS based on groups of crowded glandular cells that raised the possibility of AIS, from 38 patients who had conization and 24 AIS smears, histologically confirmed, from 17 patients were reviewed. Subsequent follow-up biopsies or hysterectomies in 38 patients were evaluated. RESULTS: Nuclear atypia was a more reliable feature than architectural structure in differentiating postcone effect from AIS on cytology. The predominant cytologic features of the postcone smears were crowded glandular cells with a high nuclear/cytoplasmic ratio and relatively small, hyperchromatic nuclei with rather finely granular and uniformly dispersed chromatin, less distinct nuclear membranes, less frequent mitosis and presence of endometrial-type stromal cells in the background. The architecture of the crowded cells in the postcone smears was sometimes similar to that of AIS. No AIS or high grade squamous intraepithelial lesion histology was encountered in follow-up biopsies or hysterectomy specimens. CONCLUSION: The cytologic features distinguishing AGUS from AIS may be helpful in identifying the postcone effect. Since it is important to avoid miscalling the postcone effect as AIS, it is recommended that one check for a previous history of a cone biopsy.     

Glandular lesions of the cervix on thin-layer Pap tests. Validity of cytologic criteria used in identifying significant lesions

OBJECTIVE: To determine the cytologic features that are most helpful in characterizing significant glandular lesions of the cervix observed on the ThinPrep (TP) Pap test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) and to compare these features with those published for conventional smears. STUDY DESIGN: Thirty-nine TP preparations with cytologic evidence of glandular lesions of the cervix and histologic and/or clinical correlation were studied. These lesions included (1) 11 cases of benign/reactive conditions; (2) 10 cases of adenocarcinoma in situ (AIS), of which 1 had both AIS and carcinoma in situ; (3) 1 case of invasive adenocarcinoma; (4) 15 cases of squamous intraepithelial lesions and squamous cell carcinoma, including 4 with glandular involvement, and (5) 2 cases of adenosquamous cell carcinoma. These cases were reviewed by the first author without knowledge of the histologic diagnosis. Twenty-five previously published cytologic criteria were used to evaluate glandular cells on TP slides. Statistical analysis was performed using Fisher's exact test to determine the significance of the features studied. RESULTS: All glandular lesions had cytologic features on TP similar to those previously described on conventional smears. However, TP slides demonstrated enhanced nuclear features but less-preserved architectural patterns. Reactive lesions showed minimal overlapping without hyperchromasia or mitotic figures and with normal nuclear/cytoplasmic ratios. AIS and invasive adenocarcinoma cases had similar features. Increased cellularity and overcrowding were prominent, whereas feathering, rosettes and cell strips were present but subtle. CONCLUSION: Glandular lesions of the cervix on TP slides shared many of the characteristic features reported for conventional smears. However, nuclear details were more pronounced in TP slides, while architectural patterns, although present, were relatively subtle.