Atypical glandular cells: improvement in cytohistologic correlation by the 2001 Bethesda system

The objective of this article was to evaluate clinical significance of glandular atypia on Papanicolaou smear, to compare the Bethesda system (TBS) 2001 with the 1991 revision, and to determine whether there is any improvement in the cytohistologic correlation by the new system. Cytology files of 18,955 patients were reviewed for diagnosis of atypical glandular cells of undetermined significance (AGUS), and histopathology files were searched. Cervical smears of these patients were reclassified according to TBS 2001. Of the 18,955 specimens, 89 (0.46%) were diagnosed as AGUS. Of these 89 women, 76 (85.3%) accepted the follow-up protocol of our hospital. In reevaluation according to TBS 2001, 31 specimens were reevaluated as atypical glandular cells (AGC) and 3 were reevaluated as adenocarcinoma in situ, 8 as AGC with concomitant squamous cell abnormalities, 1 as atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesions, and 33 as negative. Thirty-one (93.9%) of these 33 negative cases were in the AGUS-reactive category in the initial examination. The difference between the rates of the malignant pathologies in the AGUS (25%, 19/76) and in the AGC (42.8%, 18/42) categories was significant (chi(2)= 4.0, P= 0.04). The new terminology of AGC is more likely to suggest a clinically significant lesion than TBS 1991. Repeated cytologic testing during follow-up seems to be unacceptable.     

Atypical glandular cells on cervical smears.

OBJECTIVES: A standardized propaedeutic research to determine the clinical significance of cervical smears with atypical glandular cells. METHODS: Of the 8,807 women seen at the Division of Lower Genital Tract Pathology and Colposcopy, S?o Paulo, Brazil, during a 5-year study, 57 (0.65%) had atypical glandular cells. Forty-two of them underwent colposcopy and hysteroscopy with 12-month follow-up. Conization and/or hysterectomy were performed if both exams were negative. The chi-square test and Fisher's exact test were used for statistical analysis. RESULTS: A clinically significant lesion of the cervix and endometrium was diagnosed in 59.5% of the cases. The lesion was restricted to the cervix in women younger than 40 years, but could also be located in the body of the uterus in women older than 40 years. CONCLUSIONS: Colposcopic evaluation in all women and study of the uterine cavity in women aged 40 years or older is necessary in the presence of this cytologic finding.     

Radiation-induced benign glandular cells in posthysterectomy smears: a cytomorphologic and clinical analysis

In this retrospective study, we aimed to investigate the frequency and cytomorphologic characteristics of benign glandular cells (BGCs) in hysterectomized individuals. We also discussed the possible effect of radiation therapy on these cells. We reviewed our cytopathology archive material through a 5.5-year period and found 1460 posthysterectomy vaginal smears. Of these, 508 smears were from patients who had undergone hysterectomy for a gynecological malignancy. Review of this vaginal cytology material revealed 17 posthysterectomy patients whose smears contained BGCs. We obtained detailed clinical information in 16 of these. In addition to routine Papanicolaou staining, mucicarmine stain was also used to demonstrate cytoplasmic mucin in some cases. All the patients had a history of gynecological malignancy and had radiation therapy. Glandular cells appeared singly or in rows and honeycomb groups and did not show cytologic atypia. We concluded that radiation might give rise to a metaplastic process in which basal cells of squamous epithelium of the vagina transform into glandular cells. Most probably this process is independent of radiation dosage and period and is irreversible. We also propose that the possibility of encountering glandular cells in posthysterectomy smears is higher than expected, if the mucin stains have been used for the microscopic examination.     

Histologic and clinical significance of atypical glandular cells on pap smears.

OBJECTIVE: To determine the association between atypical glandular cells (AGC) on Pap smear and clinically significant histology, in a large health region. METHODS: A cytologic database of over one million Pap smears was reviewed for a result of AGUS/AGC. Cytologic and histologic follow up was obtained to establish the presence of significant histology. RESULTS: 456 patients available for follow up had AGUS/AGC cytology results (0.043% of all Pap smear results). 197(45.2%) patients had a clinically significant diagnosis including 40 with adenocarcinoma in situ (AIS) of the cervix and 48 with endometrial cancer. CONCLUSION: AGC on a Pap smear is frequently associated with a clinically significant diagnosis.     

Fluctuations in quantitative features of intermediate cells in normal cervical smears during the menstrual cycle of ovulating women and contraceptive users

In this study we report on the variation in nuclear and cytoplasmic size of intermediate cells in normal cervical smears, in relationship to the week of the menstrual cycle and in relationship to the mode of contraception. A total of 18000 cells from 360 different women was studied. A significant difference in nuclear size of intermediate cells in smears from ovulating women not using contraception was found in comparison with intermediate cells in smears from women using contraceptive pills (ANOVA: F(1.312) = 4.98, p less than 0.02). Also a significant difference in the nuclear size of intermediate cells in smears from women using norgestrel- (or levonorgestrel)-containing formulas compared with lynestrenol-containing formulas was found (ANOVA: F(1.232) = 5.82, p less than 0.01). The influence of exogenous and endogenous hormones on cell populations in cervical smears is discussed. It is concluded that in studies on intermediate cells in cervical smears the contraceptive status of the women has to be taken into account.     

Situation analysis of atypical squamous cells of undetermined significance smears in Songklanagarind Hospital

OBJECTIVE: To review the incidence, management, follow-up rate and colposcopic diagnosis of atypical squamous cells of undetermined significance (ASCUS) detected on cervical smears in Songklanagarind Hospital, Thailand. METHODS: A retrospective study of ASCUS smears taken during January 2000 to March 2001 at Songklanagarind Hospital was performed. The type of management was classified and the follow-up rate was detected. Cases with colposcopy, tissue biopsy, endocervical curettage, conization and hysterectomy specimen were reviewed. In the cases without tissue biopsy, the final diagnoses were based on the colposcopic examination. RESULTS: Among the 25068 Pap smears examined, the incidence of ASCUS was 0.62%. Of these, only 56.13% received the further evaluation. The non-compliance rate was 18.71%. The incidences of cervical intraepithelial neoplasia (CIN) and invasive cancer among the cases who received colposcopy were 15.96% and 2.13%, respectively. The incidence of CIN or invasive cancer in ASCUS favor reactive and ASCUS favor neoplasia were not different statistically significant. CONCLUSIONS: Management of ASCUS smears by follow-up may be inappropriate. A practice guideline which consists of active management, intensive follow-up system and well-organized data management should be used to improve the situation.     

Risk factors of having high-grade cervical intraepithelial neoplasia/invasive carcinoma in women with atypical glandular cells of undetermined significance smears

The objective of this study was to find the risk factors of having high-grade cervical intraepithelial neoplasia/invasive carcinoma in women with atypical glandular cells of undetermined significance (AGUS) smears. A retrospective study of the women with AGUS smears during the 3-year period was performed to determine the correlation between the suspected variables and the histopathologic diagnoses. Among 44,071 smears performed, 119 (0.27%) smears were reported as AGUS. Colposcopies were performed in 102 (88.7%) cases, and high-grade cervical intraepithelial neoplasia/invasive carcinoma was found in 18 (17.6%) cases. Among the following variables, which included age, menopausal status, hormonal contraception, history of previous Pap smears, medical diseases, clinical symptoms, and subclassification of AGUS, both hormonal contraception and AGUS favor neoplasia were risk factors with an odds ratio of 5.4 and 5.0, respectively. Although clinical symptoms seemed to be a significant variable in univariate analysis, it appeared as a confounding factor in multivariate analysis.     

宫颈管不典型腺体细胞临床意义探讨

目的 探讨宫颈管中不典型腺体细胞(AGCUS)的临床意义。方法 1998年3月至2001年8月对门诊1664例患者采用瑞典欧立宫毛刷法施行宫颈管细胞学筛查，117例宫颈管细胞中出现不典型腺体细胞(占7．0％)。为明确此种细胞的性质及来源，对AGCUS患者进行子宫分段诊刮及组织病理学检查。结果 病理学检查为正常子宫内膜组织6l例(占52．1％)，子宫内膜良性病变35例(占29．9％)，子宫内膜不典增生14例(占ll、9％)，子宫内膜腺癌7例(占5.9％)。14例子宫内膜不典型增生中，3例行手术治疗，术后有l例诊断为子宫内膜腺癌。结论 不典型腺体细胞在宫颈管细胞学中出现率较低，但常是子宫严重疾病的标志，对这类患者应作进一步的检查和跟踪随访。     

The significance of atypical glandular cells on routine cervical cytologic testing in a community-based population

OBJECTIVES: We sought to determine the follow-up rate of women with glandular atypia on routine Papanicolaou smears in a community-based population and to describe the associated pathologic findings. STUDY DESIGN: Over a 12-month period, all patients with Papanicolaou smears with atypical glandular cells of undetermined significance were reviewed for demographic and clinical characteristics and followed up for a period of 12 to 24 months. RESULTS: Of the 48,890 Papanicolaou smears examined, 141 (0.29%) were diagnosed with atypical glandular cells of undetermined significance. Of these, 22 (17.6%) had no record of any subsequent investigation, and only 64 (51.2%) were monitored with both colposcopy and biopsy. Of the 64 biopsy specimens, 39 (60.9%) were positive for disease. Twenty-six (66.7%) were of squamous origin, with the most advanced lesion being cervical intraepithelial neoplasia 3. An additional patient had a combined cervical intraepithelial neoplasia and adenocarcinoma in situ lesion. Four (10.3%) additional patients had glandular cervical lesions, 2 benign polyps and 2 adenocarcinoma in situ lesions. Seven (17.9%) patients had endometrial lesions (benign polyps, 2 patients; complex atypical endometrial hyperplasia, 1 patient; and endometrial carcinoma, 4 patients). One patient had ovarian cystadenocarcinoma. Postmenopausal women were 5 times more likely to have a glandular lesion. Women with abnormal vaginal bleeding were also more likely to have a glandular lesion. These same patient groups were also more likely to have endometrial disease. CONCLUSION: The incidence of atypical glandular cells of undetermined significance on Papanicolaou smears in this community-based population was 0.29%, which is consistent with estimates from institution-based populations. Nearly 50% of women studied were not followed up with tissue biopsy. Of those with a tissue biopsy, 61% had positive findings, including 5 with cancer. Although postmenopausal status and abnormal vaginal bleeding were associated with endometrial or glandular disease, studies of larger patient populations should be conducted to examine potential risk factors for these conditions.     

Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears

OBJECTIVE: To evaluate the association between high-risk human papillomavirus (HPV) DNA detection and histological diagnosis in women referred for atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA using Hybrid Capture II (HC II). All women underwent colposcopic examination, and cervical biopsy was performed for 95 patients. Fifty-one women referred due to AGC with normal colposcopy and normal second Pap smear were scheduled for control visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of women with AIS Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five percent of women with invasive cervical carcinoma (squamous or adenocarcinoma) tested positive for HPV DNA. HPV DNA detection was significantly associated with histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI 14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in their Pap smear. These data implicate the use of HPV testing in triage of women with AGC Pap smears.     

A retrospective study into the occurrence of cervical glandular atypia in cone biopsy specimens from 1977–1978 with clinical follow-up

Cervical glandular atypia (CGA) is now increasingly recognized in cone biopsy specimens removed for suspected cervical intra-epithelial neoplasia, although little is known of its natural history or pre-malignant potential. One hundred and eighty-three cone biopsy specimens received in our department during 1977 and 1978 from the City and Women's hospitals, Nottingham were reviewed and assessed for the presence of squamous CIN and CGA. One hundred and sixty-seven cone biopsies contained CIN and 28 of these also contained CGA. Ten cone biopsies contained high-grade CGA, the remaining 17 containing low-grade CGA. One cone biopsy contained high-grade CGA only. Twenty-one of the 28 cases of CGA had been followed up by annual pelvic examination and cervical cytology. None of these cases have developed abnormal cervical cytology or invasive cervical carcinoma after 13 years follow-up, even though 13 cone biopsies contained CGA which appeared to be incompletely excised. We concluded that if CGA is pre-malignant, the latent period for its progression to invasive carcinoma is in excess of 13 years. CGA of either grade is not, in itself, an indication for hysterectomy, allowing a conservative approach to management in the first instance.     

Effect of Cervical Disease History on Outcomes of Women Who Have a Pap Diagnosis of Atypical Glandular Cells of Undetermined Significance

OBJECTIVE: To determine the relationship between history of cervical dysplasia or carcinoma and the development of cervical dysplasia or adenocarcinoma in women who have a diagnosis of atypical glandular cells of undetermined significance (AGUS), favor endocervical origin, or AGUS, not otherwise specified. METHODS: A 6-year retrospective review of the pathology files was performed for 93 women who were diagnosed in 1992 with AGUS, favor endocervical origin, or AGUS, not otherwise specified. Data collected included previous history of cervical disease, follow-up diagnoses, time interval between follow-ups, and procedures performed. RESULTS: Of women with follow-up who had or did not have a previous history of cervical dysplasia, 32.0 and 12.0%, respectively, developed a squamous dysplasia or adenocarcinoma in situ. This difference was statistically significant (P<0.05). Of the women who had or did not have a previous history of cervical dysplasia and had Pap smear follow-up, only 4.2 and 4.3%, respectively, had a false-negative diagnosis on the most immediate subsequent smear. CONCLUSIONS: Women who have AGUS, favor endocervical origin, or AGUS, not otherwise specified, and no history of cervical dysplasia have a significantly lower risk of developing or having cervical dysplasia than women who have the same diagnosis and a history of cervical dysplasia. This may warrant different treatment protocols for these two groups. For the women with AGUS and no previous history of cervical dysplasia, a repeat Pap smear, rather than colposcopy with curettage, may be warranted.     

National audit of women with abnormal cervical smears in New Zealand

OBJECTIVE: To evaluate the follow-up of women with abnormal cervical smears identified by the National Cervical Screening Programme (NCSP) in New Zealand. DESIGN: Survey and clinical audit. SETTING: The study took place in New Zealand. POPULATION: The population included women aged 20-69 years enrolled on the NCSP with first abnormal smear recorded in 1999. METHODS: Participants were interviewed, and clinical data collected from the NCSP-register, and from clinicians. MAIN OUTCOME MEASURES AND RESULTS: The overall response rate was 57%. The proportions of women whose initial assessment, treatment or follow-up fell outside recommended times were between 17 and 35%. Of women with high-grade smears, 72% underwent a treatment procedure. Of these, 91% were excision biopsies, 6% hysterectomies and 4% ablation procedures. Approximately 10% of women had persistent or recurrent abnormalities at 6 and 12 months after treatment. CONCLUSIONS: Overall, results were largely reassuring, but limited by the low response rate. Most women were managed within current clinical guidelines. Areas requiring improvement were identified, in particular in relation to longer than recommended waiting times for assessment and treatment.     

Underlying pathology of women with "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" smears, in a region with a high incidence of cervical cancer

AIM: To evaluate the histopathology of women who had "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions" (ASC-H) on cervical cytology in a region with high incidence of cervical cancer. METHODS: This study was conducted at Chiang Mai University Hospital, Chiang Mai, Thailand. All women with ASC-H, who had undergone colposcopic and histolopathologic evaluation between October 2004 and January 2007, were recruited. Similar cohorts with other squamous cell abnormalities on a Pap-smear, who had undergone colposcopy during the same period, were included as comparative groups. RESULTS: During the study period, 85 women who had ASC-H smears underwent colposcopic and histopathologic evaluation. The mean age was 45.3 years (range, 20-64 years). The histopathologic results of these 85 women were as follows: cervical intraepithelial neoplasia (CIN) II-III, 52 (61.2%); invasive cancer, 7 (8.2%); CIN I, 6 (7.1%); and no lesions, 20 (23.5%). The incidence of underlying CIN II or higher in an ASC-H smear (69.4%) was intermediate between atypical squamous cell of undetermined significance (22.7%), low-grade squamous intraepithelial lesion (44.7%) and high-grade squamous intraepithelial lesion (90.5%) smears. There was no statistically significant difference in the incidence of CIN II or higher between women who were 40 years old or more and those who were younger (68.7% and 71.4%, respectively, P=0.81), or between pre-menopausal and post-menopausal women (71.4% and 63.6%, respectively, P=0.49). CONCLUSION: Reporting ASC-H cytology in our population is strongly associated with significant cervical pathology, particularly invasive cancer that is possibly at a rate higher than previously reported. Women who have ASC-H smears should therefore be referred for immediate colposcopy regardless of age and menopausal status.     

2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests

A group of 146 experts representing 29 organizations and professional societies met September 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. Recommendations for managing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion (LSIL) are essentially unchanged. Changes were made for managing these conditions in adolescents for whom cytological follow-up for 2 years was approved. Recommendations for managing high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) also underwent only minor modifications. More emphasis is placed on immediate screen-and-treat approaches for HSIL. Human papillomavirus (HPV) testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for HPV testing as an adjunct to cervical cytology for screening in women 30 years of age and older was formally adopted with only very minor modifications.     

Coexisting cancers with atypical glandular abnormalities by liquid-based cytology: A retrospective study in tertiary hospital in a high cervical cancer incident country

ObjectiveTo determine the incidence of coexisting cancers in women with glandular cell abnormalities detected from liquid-based cytology and to compare the detection rate of premalignant and malignant lesions among various subtypes of glandular cell abnormalities.Materials and methodsFrom January 2014 to December 2016, liquid-based cytology was performed in 85,517 women. Using the Bethesda system 2001 criteria, abnormal cervical cytology was diagnosed in 3650 women (4.3%). Glandular cell abnormalities were diagnosed in 110 women (0.13%). Ten women with pre-existing genital tract cancers and 13 women who lost to follow up were excluded. Clinical characteristic, colposcopic finding, and histopathological data were reviewed in 87 women.ResultsHigh-grade premalignant and malignant lesions were diagnosed in 34 patients (39.1%). Co-existing cancer was diagnosed in 31 patients (35.6%); 15 cervical cancers (17.2%) and 16 endometrial cancers (18.4%). The detection rate of significant lesions (CIN2+ or malignant lesions) in patients with AGC-NOS was 14.9%, AGC-FN was 38.9% and AIS/adenocarcinoma was 90.9% (p < 0.001).ConclusionGlandular cell abnormalities associated with high incidence of coexisting endometrial and cervical cancers. Comprehensive genital tract screening to evaluate gynecologic malignancy is strongly recommended in all women with glandular cell abnormalities.     

Analysis of transforming gene regions of human papillomavirus type 16 in normal cervical smears

Summary Exfoliated cells from the uterine cervix of 102 Hungarian women with no cytological abnormality were screened using the polymerase chain reaction (PCR) for human papillomavirus (HPV) type 16 infection. Twenty-nine patients with histologically confirmed cervical intraepithelial neoplasia (CIN) served as reference cases. PCR was performed with 2 different HPV 16 specific oligonucleotide primer pairs flanking a 300 and a 200 base-pair fragment from the early 6 (E6) and early 7 (E7) genes, position 215–514 and 605–805. The specimens exhibited the same proportions of type 16 sequences specific for the tested regions. 8.8% (9/102) of normal samples showed amplification for HPV type 16 E6 and E7 regions, while 48.3% (14/29) of CIN biopsies were positive for the same gene sequences.