Atypical glandular cells of undetermined significance. Histologic findings and proposed management

OBJECTIVE: To increase understanding of the clinical significance of atypical glandular cells of undetermined significance (AGUS) on cervical cytology and to suggest a management plan. STUDY DESIGN: All Pap smears classified as AGUS over a period of five years at the University of Michigan Medical Center were reviewed and the diagnosis confirmed. The charts of these patients were reviewed for demographics, significant previous medical history, symptoms, diagnostic studies performed and final histologic diagnoses. RESULTS: In 1993-1998, a total of 208,041 Pap smears were read. Two hundred seven smears from 189 patients were classified as AGUS, for an incidence of 0.1%. There were 136 patients with follow-up information and 114 patients with histologic diagnoses. In 55 of the 114 patients (48%), significant histologic abnormalities were observed, including 11 endometrial cancers, 1 invasive adenocarcinoma of the cervix, 3 adenocarcinomas in situ of the cervix, 18 CIN 3 lesions and 5 CIN 2 lesions. Among 20 patients with Pap smears subclassified as "atypical glandular cells of undetermined significance, favor benign process," there were two CIN 2, five CIN 3 and one adenocarcinoma in situ of the cervix. CONCLUSION: A diagnosis of AGUS requires an aggressive workup because of the high rate of cancer and precancerous lesions. The evaluation, at the very least, should include colposcopy with directed biopsies and endocervical curettage. Postmenopausal patients, those with irregular bleeding and those with high risk characteristics should also undergo endometrial biopsy.     

Clinical and histological significance of atypical glandular cell on Pap smear

BACKGROUND: Atypical glandular cell (AGC) on Pap smear is uncommon but may represent a variety of benign and malignant lesions. AIM: The aim of this study was to evaluate the association between AGC on Pap smear and significant pathological finding to tailor management protocols. METHODS: Between 2002 and 2005, 60 women with AGC on Pap smears were referred to our colposcopy clinic. Forty-one women underwent colposcopy-directed biopsy, endocervical curettage, endometrial sampling and cervical conisation to determine the cytological and histological correlations of AGC on Pap smears. RESULTS: The mean age of the patients was 46.9 +/- 11.5 years (range, 23-80 years). Of these patients 13 patients (31.7%) were postmenopause and 28 patients (68.2%) were in reproductive age. We found eight (19.5%) significant pathological findings including four (9.7%) high-grade squamous intraepithelial lesion, one (2.4%) adenocarcinoma of uterus, one (2.4%) adenocarcinoma of cervix, one (2.4%) squamous cell carcinoma of cervix and one (2.4%) papillary serous tumour of ovary. CONCLUSION: AGC on Pap smear was associated with a clinically significant diagnosis in approximately 20% of our cases. The women with a diagnosis of AGC on cervicovaginal smear are needed to be evaluated at least with colposcopy, endocervical and endometrial curettage. Clinicians should be careful about the significance of AGC on Pap smears.     

Clinical significance of atypical glandular cells on cervical cytology

OBJECTIVE: To evaluate the prevalence and histologic outcomes of patients with atypical glandular cells of undetermined significance (AGUS), diagnosed by Pap test, and concurrent risk factors. DATA SOURCES: A PubMed/MEDLINE/Ovid HealthStar search of the English literature was conducted from January 1988 through March 2004. METHODS OF STUDY SELECTION: The search criteria included the terms "atypical glandular cells of undetermined significance," "AGUS," or "AGC." All studies investigating the clinical significance of patients with an AGUS Pap test were included, except for those where consecutive Pap tests were not studied. Diagnostic outcomes were then determined. TABULATION, INTEGRATION, AND RESULTS: Of the 916 studies identified, 24 met our inclusion criteria. Of the 2,389,206 Pap tests included in these studies, 6,829 (0.29%) had AGUS. Follow-up was available for 3,890 tests. These data showed the following rates of pathology: 8.5% low-grade squamous intraepithelial lesions (LSIL), 11.1% high-grade squamous intraepithelial lesions (HSIL), 2.9% adenocarcinoma in situ, 1.4% endometrial hyperplasia, and 5.2% malignancy. The most common malignancies were endometrial adenocarcinoma (57.6%), cervical adenocarcinoma (23.6%), ovarian and fallopian tube carcinoma (6.4%), squamous cell carcinoma of the cervix (5.4%), and other (6.9%). Of the AGUS Pap tests, the remaining 71.0% corresponded to benign findings, including reactive changes, polyps, and normal histology. Patients with AGUS, which favors a neoplastic process, or with a concurrent ASCUS have a greater likelihood of disease. CONCLUSION: Histologic diagnosis showed that 29.0% of these Pap tests had findings requiring follow-up or therapeutic intervention, including a 5.2% rate of malignancy. Based on these findings, 99.6% of the diagnoses are within the region of surveillance when AGUS Pap tests are evaluated with colposcopy and directed biopsy, endocervical curettage, an endometrial biopsy in patients with risk factors for endometrial cancer, and pelvic examination.     

Cytologic and biopsy findings leading to conization in adenocarcinoma in situ of the cervix

OBJECTIVE: To investigate the utility of currently available screening tests in preoperatively detecting adenocarcinoma in situ of the cervix. METHODS: Patients with a cone biopsy diagnosis of adenocarcinoma in situ from 1987 to 2000 at our institution were identified. Results from Papanicolaou smears, cervical biopsies, and endocervical curettages preceding the diagnostic cone biopsy were collected from medical records and referring providers. Fisher exact test (two-tail) was used for statistical analysis. RESULTS: The preoperative screening results preceding a cone biopsy containing adenocarcinoma in situ were available in 118 patients. Among 94 Papanicolaou smears, 65 (69%) glandular lesions and 29 (31%) squamous or unspecified lesions were reported. Biopsy and/or endocervical curettage after the 29 squamous or unspecified lesions on Papanicolaou smear detected 15 additional glandular lesions, totaling 80 (85%) of 94 cases of glandular disease detected before conization. Among all 118 cases with some form of preoperative data available, glandular disease was predicted in 100 cases (85%). In cases of suspected glandular disease, 86% were treated with cold knife cone compared with 22% in cases of suspected squamous abnormalities (P <.001). CONCLUSION: The sensitivity of detecting a glandular abnormality before a cone biopsy containing adenocarcinoma in situ is 69% with the Papanicolaou smear and 85% with the addition of biopsy and endocervical curettage. This underscores the importance of using preoperative assessment to appropriately plan treatment for a suspected glandular lesion.     

A cytohistologic study of atypical glandular cells detected in cervical smears during cervical screening tests in Iran

Atypical glandular cells (AGC) often cause diagnostic uncertainty in cervicovaginal smears. To determine the incidence of significant pathologies associated with AGC on Papanicolaou test, AGC smears were correlated with subsequent biopsy diagnoses. A retrospective review of archives of our cytology files for cervicovaginal smears diagnosed as AGC from April 1998 to March 2001 was performed. In 9390 cervicovaginal smears, AGC were reported in 76 (0.81%) cases, with histologic follow-up in 42 patients (55.3%). Twenty-two patients (52.4%) had preneoplastic or neoplastic, squamous, or glandular lesions on histologic examination. Among them were cervical intraepithelial neoplasia, basal cell abnormality of undetermined significance, cervical adenocarcinoma, endometrial hyperplasia or adenocarcinoma, vaginal adenocarcinoma, endocervical glandular dysplasia, metastatic breast carcinoma, and simple nonvillous trophoblastic tissue. Therefore, presence of AGC in cervical smears may exhibit a spectrum of findings, ranging from benign/reactive changes to squamous or glandular premalignancy or malignancy. A majority of these lesions are squamous dysplasia, and a significant number of patients had glandular malignancy. The results of the current study underline the importance of follow-up for patients with the diagnosis of AGC. To our knowledge, this is the first report in Iran showing the significance of AGC diagnosis.     

Atypical glandular cells of undetermined significance. Subtyping as a predictor of outcome

OBJECTIVE: To determine whether subtyping of atypical glandular cells of undetermined significance (AGUS) cervical smears into reactive process favored (AGUS-RPF) and not otherwise specified (AGUS-NOS) correlates with rates of underlying pathology. STUDY DESIGN: We performed a retrospective chart review of 129,676 routine Pap smears at Kaiser Permanente, San Diego, from June 1998 to November 1999. One hundred fifty of the 129,676 were evaluated as AGUS (0.12%). Subjects with concomitant AGUS/SIL Pap smears, a prior history surgery for dysplasia, prior AGUS, a history of cancer or prior hysterectomy were excluded from the study. The remaining AGUS smears were then subtyped into AGUS-NOS and AGUS-RPF based on the criteria of the 2nd Workshop of the Bethesda System. Sixty-eight subjects with an initial AGUS smear underwent evaluation with colposcopy, endocervical curettage, endometrial biopsy and directed cervical biopsies. Significant pathology was determined to be any tissue diagnosis that required further treatment more than a follow-up Pap smear. AGUS subclassifications and underlying pathology were then compared using the chi 2 test with Fisher's Exact Test. RESULTS: Twenty-seven patients (40%) had AGUS-NOS, and 41 (60%) had AGUS-RPF. There were no significant differences between the groups in regard to age, race, parity, menopause status, HRT use or tobacco use. CONCLUSION: Subtyping AGUS cervical smears correlates with underlying rates of pathology. However, AGUS-RPF smears were still associated with an approximately 10% incidence of significant underlying pathology. Patients with AGUS on cervical smears need thorough evaluation, regardless of subtyping.     

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.     

Controversial categories in cytopathology of the uterine cervix. II. AGUS: atypical glandular cells of undetermined significance

AGUS (Atypical Glandular Cells of Undetermined Significance), or AGCUS, is a category for reporting doubtful or suspicious glandular changes of the uterine cervix. Glandular lesions are not well known by the cytopathologist and their cytologic criteria are not completely reproducible. Only with the introduction of The Bethesda System (TBS) in 1988, the presence of endocervical cells is considered essential to correctly evaluate a cervical specimen. The origin of atypical glandular cells, endometrial or endocervical, should be distinguished. Moreover, endocervical AGUS should be further qualified as favor reactive or favor neoplastic or Adeno-carcinoma in situ (AIS) . Recently, it has been proposed to classify endocervical AGUS in a) AIS; and b) AGUS that cannot rule out AIS when incomplete criteria of AIS are present. Moreover, the origin of AGUS is sometimes impossible to know. In these cases, the diagnosis is AGUS not otherwise specified (NOS). The clinical management of AGUS presents different options depending on its origin or its further qualification: cytologic follow-up, colposcopy and eventual biopsy, endocervical or endometrial curettage, hysteroscopy, human papillomavirus typing, etc. including conization and hysterectomy. In conclusion, an appropriate clinical management is needed to detect glandular or squamous lesions that can be frequently identified in the AGUS follow-up.     

Dysplasia associated with atypical glandular cells on cervical cytology

OBJECTIVES: To estimate the rates of and identify risk factors for disease in women with atypical glandular cells of undetermined significance (AGUS). METHODS: From 1998-2001, 477 Pap tests at Hartford Hospital were classified as AGUS and met the inclusion criteria of this study. Findings were evaluated for 2 years from the initial test. Disease was defined as histology results with a finding of high-grade squamous intraepithelial lesion or greater. RESULTS: Disease was diagnosed in 9% of the women, including malignancy in 3%. Women with malignant-appearing AGUS Pap tests had a higher rate of disease (29%) than women with benign-appearing (5%, P < .01) and unspecified AGUS Pap tests (13%, P < .03). Malignancies were associated with all subclassifications of AGUS Pap tests. Women aged less than 35 years were more likely to have disease than women aged 35 years or older (P < .02). Most women aged younger than 35 years had a squamous abnormality, whereas women aged 35 years or older had a greater diversity of squamous and glandular lesions and accounted for all cases of endometrial cancer, adenocarcinoma in situ, and cervical adenocarcinoma. Women with persistent AGUS Pap tests had a 31% rate of disease. The rate of disease among women with AGUS Pap tests collected by liquid-based cytology was 11%, compared with 6% among samples collected by the conventional method. CONCLUSION: These data suggest that women with atypical glandular cells are at substantial risk for dysplasia and malignancy. The rate of disease varies with the method of Pap test collection, age, presence of persistent AGUS Pap tests, and AGUS subclassification.     

Recurrent invasive adenocarcinoma after hysterectomy for cervical adenocarcinoma in situ

BACKGROUND: Unlike its squamous counterpart, therapy for cervical adenocarcinoma in situ with positive endocervical cone margin remains controversial. CASE: A 52-year-old gravida 2, para 1,0,1,1, presented with vaginal bleeding. Gynecologic history was significant for cervical cold knife conization with a positive endocervical margin and endocervical curettage with atypical endocervical cells. Repeat cone biopsy was considered unsafe given the large initial cone specimen. An extrafascial hysterectomy was performed 5 weeks later and pathology confirmed a disease-free cervix. Pap smear performed 1 year later was interpreted as recurrent adenocarcinoma but later downgraded to inflammation. Inspection and random biopsies of the vaginal cuff revealed only inflammation. Two subsequent Pap smears also returned inflammation. Seventeen months after the hysterectomy physical examination revealed a 2 x 3-cm smooth mass at the vaginal cuff. Biopsy revealed invasive adenocarcinoma. The patient underwent an upper vaginectomy followed by postoperative pelvic radiation. CONCLUSION: This case suggests that despite extrafascial hysterectomy for presumed adenocarcinoma in situ of the cervix, a residual focus could remain and present later as invasive adenocarcinoma.     

Clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance

OBJECTIVE: To assess the clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance (AGUS) and determine the most appropriate evaluation of these patients. STUDY DESIGN: Between 1993 and 1995, 44,217 Papanicolaou smears were evaluated at Allegheny University Hospitals, Medical College of Pennsylvania Campus. There were 108 (0.24%) cases of AGUS smears during that time. No clinical information was available for 14 patients, and 19 were lost to follow-up. The charts of the remaining 75 cases were retrospectively reviewed. RESULTS: Tissue specimens were available for 62 of the 75 patients. There were 26 (42%) with no significant histopathologic findings, 13 (21%) with polyps, 5 (8%) cases of endometrial hyperplasia, 2 (3%) with endometrial adenocarcinoma, 12 (19%) with cervical intraepithelial neoplasia (CIN), 1 (2%) with adenosquamous carcinoma of the cervix, 2 (3%) with cervical adenocarcinoma in situ and 1 (2%) case of metastatic breast cancer. The total number of patients with significant histopathology other than polyps was 23 (37%). The median age of the patients was 49 years. There were more cases of endometrial hyperplasia and endometrial cancer (19%) in women 49 years or older than in younger women; only one (3%) case of endometrial hyperplasia was detected in the younger age group (P = .057). Patients who underwent more-aggressive evaluation (colposcopy and biopsies plus endometrial sampling, cone biopsy or hysterectomy) had greater numbers of abnormal histopathologic findings (55%) than patients who underwent endometrial sampling only (21%) or those who underwent colposcopy and biopsy only (33%). This difference approaches statistical significance (P = .057). A significant proportion of patients with a history of CIN and a cytologic diagnosis of AGUS were found to have CIN (47%), while 8% of those with no history of CIN were found to have CIN (P = .002). Fifty percent of patients with a history of cancer (all had breast cancer) and AGUS had abnormal histopathology. Patients with a subclassification of AGUS "favor neoplasia" had a greater proportion of significant histopathology (72%) as compared to AGUS "unspecified" (26%) and AGUS "favor reactive" (20%) (P = .003). CONCLUSION: A significant proportion of women with a cytologic diagnosis of AGUS have abnormal histopathology. Heightened awareness should be raised in patients with AGUS and a history of CIN or cancer and in those with the AGUS subclassification "favor neoplasia."     

Is colposcopy always necessary with atypical glandular cells of undetermined significance on Papanicolaou smears?

The objective of this study was to review a 5-year experience with atypical glandular cells of undetermined significance (AGUS) on Papanicolaou smear and to use the information to devise a triage method for patients presenting with this abnormality. Our Papanicolaou smear database was used to identify patients who were found to have AGUS results between January 1, 1994 and December 31, 1998. The medical records of these patients were reviewed for the results of follow-up studies, including repeat Papanicolaou smear, endocervical curettage, colposcopic directed biopsies, and endometrial biopsy. During the study period, 27,859 Papanicolaou smears were performed, with 306 (1.1%) being reported as AGUS; 18 patients had two AGUS smears. An additional 24 patients did not meet study criteria. The study group then consisted of 264 patients, of whom 244 (92.4%) reported for follow-up. There were 167 (63.3%) with atypical endocervical cells of undetermined significance (AECUS), 14 (5.3%) with atypical endometrial cells of undetermined significance, and 83 (31.4%) with AECUS plus a squamous cell abnormality. The overall prevalence of a high-grade squamous intraepithelial lesion (HSIL) was 11.8%. The prevalence of HSIL in the AECUS plus squamous cell abnormality group was 25.4%. None of the atypical endometrial cell group had HSIL. In the AECUS, favor dysplasia category, 29.4% had HSIL, whereas in the AECUS, favor reactive process or in unqualified, 2.3% had HSIL. Eighty-one patients underwent endometrial biopsy: three (3.7%) were found to have endometrial adenocarcinoma, and two (2.5%) had complex atypical endometrial hyperplasia. The prevalence of HSIL in patients with AECUS, favor reactive process or AECUS, unqualified Papanicolaou smears is low. Colposcopy is not necessary as an initial triage process for this category of patients. A significant percentage of patients with AECUS, favor dysplasia or AECUS with a squamous epithelial abnormality Papanicolaou smears have HSIL; this subset of patients should be investigated with colposcopy.     

An Approach to Atypical Glandular Cells on Pap. Smears

There is no doubt that we are seeing more cases of both in situ and invasive adenocarcinoma of the cervix. Unlike intra-epithelial squamous lesions of the cervix, in situ glandular lesions of the cervix cannot be detected colposcopically. Cytology, therefore, becomes the mainstay for the initial diagnosis of glandular lesions. Unfortunately, the terminology of glandular lesions of the cervix used in cytology can be confusing. This review discusses the various diagnostic categories for classifying atypical glandular cells found on a Papanicolaou (Pap.) smear and management guidelines as approaches to handling atypical glandular cells diagnosed on Pap. smears.     

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.     

False-negative Pap smear in uterine malignancy

For the period 1964 to 1976, Papanicolaou smears of 384 patients with uterine malignancies admitted to Cook County Hospital were studied. There were 36 negative Pap smears in a group of 307 patients with invasive cervical carcinoma (11.7% false-negative rate), and three negative Pap smears in a group of 45 patients with in situ squamous cell carcinoma of the cervix (6.6% false-negative rate). Forty-seven of 77 patients with endometrial carcinoma had negative cytologic examinations (51.9% false-negative rate). Because routine cervicovaginal cytology is not as satisfactory for the detection of endometrial carcinoma as it is for squamous cell carcinoma of the cervix, the importance of other screening techniques for endometrial carcinoma is discussed.     

Clinical evaluation of atypical glandular cells of undetermined significance

OBJECTIVE: This study was undertaken to determine the clinical implications of the finding of atypical glandular cells of undetermined significance in cervical cytologic specimens in our patient population. STUDY DESIGN: A retrospective study was performed. All cervical cytologic examinations with the diagnosis of atypical cells of undetermined significance between January 1992 and June 1997 were identified by means of a computerized database. Medical records were reviewed to identify patient demographic characteristics and to determine the presence or absence of associated pathologic conditions of the cervix and endometrium. The chi2 test and analysis of variance were applied to dichotomous and continuous variables, respectively, to determine the implications of a cytologic evaluation of atypical glandular cells of undetermined significance. RESULTS: Cytologic results reported as atypical glandular cells of undetermined significance were obtained in a patient cohort of 492. Atypical glandular cells of undetermined significance was the only cytologic diagnosis in 224 patients; 268 patients had both atypical glandular cells of undetermined significance and an additional squamous abnormality, including atypical squamous cells of undetermined significance and cervical intraepithelial neoplasia I, II, or III. Two patients were excluded because of a history of endometrial cancer. A histologic evaluation was obtained within 1 year in 353 cases. Among the 353 patients who had a histologic evaluation performed, 227 (64%) had benign cervical and endometrial findings. There were 18 glandular lesions (5%), including complex hyperplasia with atypia, adenocarcinoma in situ of the cervix, adenocarcinoma of the cervix, and adenocarcinoma of the endometrium. A squamous lesion was present in 108 patients (31%). Most squamous lesions (81%) were found in patients with atypical glandular cells of undetermined significance associated with a squamous abnormality, whereas only 19% were found in patients with atypical glandular cells of undetermined significance as the only diagnosis. Women <35 years old had a much higher frequency of histologic abnormalities than did women >50 years old (P <.0001), with most of these lesions being squamous. Women >50 years old had a much higher frequency of glandular histologic abnormalities (P <.001). CONCLUSION: More than a third of women with Papanicolaou smears reported as showing atypical glandular cells of undetermined significance will be found to have a histologic abnormality. Women <35 years old with a cytologic evaluation of atypical glandular cells of undetermined significance have a higher frequency of histopathologic findings, with most being squamous lesions. Women with a cytologic evaluation of atypical glandular cells of undetermined significance who are >50 years old have more glandular lesions than do younger women. The term atypical glandular cells of undetermined significance is a misnomer. The significance of this cytologic finding has been defined and represents a marker for serious pathologic processes.     

Prediction of high-grade cervical disease with human papillomavirus detection in women with glandular and squamous cytologic abnormalities

The objective of this study was to assess whether human papillomavirus (HPV) detection with hybrid capture II (HC II) can help predict the presence and the nature, glandular or squamous, of histologic cervical lesions in women referred due to atypical glandular cells (AGC) or high-grade squamous intraepithelial lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a histologic assessment of their cervix. Histologic analysis showed 38 women with (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%) glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost 70% of AGC-HPV-negative patients did not have a pathologically proven cervical neoplasia, whereas 76% of women with AGC-HPV-positive result were diagnosed with a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV detection did not contribute to their differentiation from glandular lesions. We conclude that in women with AGC, HPV positivity strongly correlated with the presence of glandular or squamous cervical lesion but did not help distinguishing women with squamous from those with glandular neoplasia.     

Invasive adenocarcinoma of mixed endocervical and clear cell type, associated with invasive squamous cell carcinoma of the cervix uteri. A case report

A case of invasive adenocarcinoma (predominantly of endocervical type but also with clear cell elements blended in part of the growth) associated with squamous cell carcinoma of the uterine cervix is reported in a young woman aged 18 years. Malignant squamous and atypical glandular cells were detected in Papanicolaou (Pap) smears, which raised the question of a mixed tumor. A diagnosis of cervical cancer was justified by means of a punch biopsy and the patient was treated by modified radical hysterectomy. Histologic and immunohistochemical examination of the hysterectomy specimen revealed two distinct types of an invasive malignant tumor, i.e., of glandular and squamous cell origin, closely related but not integrated. Interestingly, the glandular component comprised both endocervical and clear cell elements. Careful consideration of squamous or glandular atypia in cytological smears may lead to a more precise diagnosis, especially in young women.     

Evaluation of cytologic screening results of the cervix

The aim of this study was to evaluate retrospectively cytologic screening for cancers and precancerous lesions of the cervix and to research whether biopsy is overused among women with a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS). We examined 28 469 smears obtained over 5 years. The patients were referred when the result of the smear was abnormal for a colposcopic biopsy, endocervical curettage, or a repeat Papanicolaou smear. The results of the screening of 28 469 smears are as follows: 699 (2.45%) ASCUS, 67 (0.23%) low-grade squamous intraepithelial lesions (LGSIL), 43 (0.15%) high-grade squamous intraepithelial lesions (HGSIL), 1 epidermoid carcinoma, 31 (0.10%) atypical glandular cells, and 1 adenocarcinoma. Histologic examination of the cervix was done in 119 patients (17.0%) of ASCUS, 13 patients (10.9%) of LGSIL, and 15 patients (12.6%) of HGSIL and cervical carcinoma. In the 119 women with histological examination, histologic examination was generally performed in patients with ASCUS neoplastic Papanicolaou smear, and histologic diagnosis of low-grade, high-grade, or invasive lesion of the cervix was made in 23.5% of women with ASCUS; in these patients, 46.4% were cytologic LGSIL and 53.5 % were cytologic HGSIL and cervical carcinoma. In the aspect of these findings, we concluded that for patients with a cytologic diagnosis of ASCUS, more aggressive interventions should be performed.     

Loss to follow-up of cervical smears without endocervical columnar cells is not disturbing

OBJECTIVE: To investigate the six-month recommended follow-up after mass screening of Pap smears because of the absence of endocervical columnar cells (ECC-) or ECC+ smears with atypical squamous or glandular cells of undetermined origin (ASCUS/AGUS) or low-grade squamous or glandular intraepithelial lesions (LSIL/LGIL) in a Dutch mass screening cervical cancer programme. METHODS: Data were extracted from computerised medical records of national representative Dutch general practices. We have studied the attendance at and the outcome of the subsequent Pap smears after a 6-month recommendation. RESULTS: The six-month follow-up was linked to 8.7% of the Pap smears (n = 1,002); 77.6% were without endocervical columnar cells (ECC-). Clear differences were found between the follow-up of ECC+ and ECC- smears; after 36 weeks of follow-up of 43.5% the women had an ECC- smear and 66.9% had other conditions. For initial ECC- Pap smears, 84.1% had no abnormalities in the subsequent Pap smear; for initial ECC+ Pap smears, in about 64% of the cases no abnormalities were found (p < 0.0001). CONCLUSIONS: Repeating ECC- smears has a low follow-up rate but also lacks evidence-based necessity. However, for the other 6-month recommended Pap smears, one in five women had still not responded within one year, so improvement is necessary.