Clinical evaluation of atypical glandular cells of undetermined significance upon cervical cytologic examination in Israeli Jewish women

There were 45 patients (mean age 41.3 years) in the study cohort. The smears of 14 of them (31%) were reported as due to AGUS alone and 31 (69%) smears had coexistent squamous pathology. Seven (16%) patients had a recent history of abnormal vaginal or postcoital bleeding. Four patients had a history of nongynecologic cancer: three had breast cancer and one had carcinoma of the rectum. One of the patients was pregnant at the time of her AGUS cytology finding. All 45 patients were colposcoped and biopsied shortly after AGUS was confirmed: 16 women (36%) underwent colposcopy with cervical biopsies, 29 (64%) underwent colposcopy with cervical biopsies and endocervical curettage, and 25 (55%) of the women who underwent cervical biopsies required diagnostic conisation during their workup. Since our protocol dictates that women with AGUS and without clear external lesions undergo endocervical curettage, the 16 women who had clear external lesions did not undergo this procedure. Table 1 Table 1 Histopathology in the study women with AGUS smears ( n =45) Diagnosis n (%) Normal 10 (22) Cervicitis 4 (9) CIN I 7 (15) CIN II–III 21 (47) Carcinoma 3 (7) CIN=cervical intraepithelial neoplasia; AGUS=atypical glandular cells of uncertain significance. shows the pathology identified in the smears of the study group. Table 2 Table 2 Histopathology in women with AGUS smears with and without coexistent squamous abnormalities Diagnosis AGUS alone ( n =14) AGUS+ASCUS ( n =31) Normal 4 6 Cervicitis 2 2 CIN I 3 4 CIN II–III 4 17 Carcinoma 1 2 a P =NS between the two groups. ASCUS=atypical squamous cell of undetermined significance; CIN=cervical intraepithelial neoplasia; AGUS=atypical glandular cells of uncertain significance. compares the pathology found in women with AGUS with and without concomitant squamous abnormalities. A patient diagnosed with coexistent ASCUS carried a risk factor of 61.3% for the existence of a clinically significant lesion, compared with a risk of 35.7% for AGUS alone. When Fischer's exact test was used to compare these groups, however, the women with coexistent squamous abnormalities detected by a Pap smear were not found to have significantly more cervical lesions than women with AGUS alone ( P >0.05). Only one of the 45 patients with AGUS was found to have adenocarcinoma of the cervix. CIN=cervical intraepithelial neoplasia; AGUS=atypical glandular cells of uncertain significance. P =NS between the two groups. ASCUS=atypical squamous cell of undetermined significance; CIN=cervical intraepithelial neoplasia; AGUS=atypical glandular cells of uncertain significance. In total, 14 (31%) of the study patients were postmenopausal, and our results indicated that both premenopausal and postmenopausal patients were at risk for clinically significant lesions. Moreover, there was no difference between pre- and postmenopausal women in terms of pathology. Even so, endometrial biopsy is recommended in postmenopausal women with Pap-diagnosed AGUS who do not have an external lesion on cervical or endocervical biopsy. All of our postmenopausal study women had significant cervical lesions and did not require endometrial biopsy.

This study was conducted over a period of 2 years and 6 months (from January 2001 to June 2003). During this period, 11 800 patients were examined by the Colposcopic Unit of the Balfour-Maccabi Women's Healthcare Center (Tel-Aviv, Israel). This unit is a public facility and is subsidised by the national governmental health insurance scheme. Two senior gynecologists who are specialists in cervical medicine performed the colposcopies (RB and ES). Of these 11 800 samples, 45 (0.38%) Pap smears showed AGUS and comprised our study data. These 45 women were examined by colposcopic examination, colposcopic-directed biopsy, cone biopsy, and/or endocervical curettage. The medical records of all AGUS patients were reviewed and the retrieved data consisted of the woman's age, gravidity, parity, menopausal status, as well as any history of abnormal bleeding, smoking, use of oral contraceptives, intrauterine devices, replacement of hormones, prior abnormal Pap smear, or previous cancer. In addition, the results of the clinical evaluation of their AGUS smear were collected, including the findings of the physical examination, colposcopy, cytology, and biopsy results. Cervical biopsies were classified according to the modified Richart classification system for cervical intraepithelial neoplasia (CIN), where lesions consistent with flat condyloma and CIN I are referred to as ‘low-grade CIN’ and lesions consistent with CIN II or CIN III are grouped together as ‘high-grade CIN’ ( Richart, 1990 ). The AGUS pap smears in this study were reviewed by a single cytopathologist. For the purposes of this study, a ‘clinically significant lesion’ was defined as CIN II, CIN III, or carcinoma. CIN I was not considered a clinically significant lesion and was therefore classified as benign.

Glezerman et al (1989) noted a remarkable, although not statistically significant, increase in the number of Israeli Jewish women patients with cervical cancer. Sadan et al (2003) retrospectively analysed the results of 297 849 Pap smears during 9 years (1991–1999), and their data indicated similar incidence rates for premalignant lesions in Jewish Israeli women as observed in Western countries. Bar-Am et al (1995) found that the prevalence of abnormal cytology among the Israeli women was almost the same as that of a non-Jewish group (24 out of 1000 and 26 out of 1000, respectively), and that the distribution of the known risk factors among the study group (number of sexual partners, age at first intercourse, and age at first pregnancy) was practically the same as those in the non-Jewish population. The authors documented an increase of 29.2% (from 17 out of 1000 to 24 out of 1000) in the prevalence of cervical premalignant lesions among the Israeli women in their study group and noted that they were younger when they became sexually active, had a larger number of sexual partners, and fewer of them were married. In addition, fewer of them were observant of Jewish ritual practices, one of which is abstinence from intercourse during menstruation and for 1 week afterwards. We designed the current study to document whether this growing similarity between Jewish Israeli and other groups of women was also reflected by the pattern of AGUS in their Pap smears and our findings showed that here, too, this population no longer enjoys a comparatively lower risk. The optimal clinical evaluation of the diagnosis of AGUS by the Pap test has yet to be determined. Therefore, the clinician is faced with uncertainty as to the aggressiveness of the abnormal cells and the proper sequence of clinical evaluation. Some physicians choose a conservative approach to AGUS and treat it much like ASCUS, with repeated cytologic examination alone, whereas others take a more comprehensive approach, performing colposcopy and biopsy of the endocervix. The diagnosis of AGUS is made in routine clinical practice in 0.13–2.5% of the smears; most rates quoted in the literature are less than 1% ( Goff et al , 1992 ; Nasu et al , 1993 ; Lee et al , 1995 ; Ferris et al , 1996 ; Kennedy et al , 1996 ; Raab et al , 1997 ; Zweizig et al , 1997 ). Thus, our diagnostic rate of 0.38% in this study is in agreement with the current literature. The present study reviewed a series of 45 patients with AGUS as diagnosed by a cytologic screening exam. In previous studies, as well as this one, AGUS has been associated with significant histologic abnormalities in 53.3% of all cases, including cancer in 6.7% ( Richart, 1990 ; Goff et al , 1992 ; Eddy et al , 1997 ; Zweizig et al , 1997 ; Veljovich et al , 1998 ). With one exception, all of these abnormalities were confirmed by cytologic evaluation as being due to AGUS and squamous in nature. In our study, the prevalence of significant cervical disease was equally distributed between premenopausal and postmenopausal cases. The number of clinically significant lesions in the group we studied is sufficiently high to suggest that a complete evaluation (colposcopy with cervical biopsies, endocervical curettage, and diagnostic conisation when needed) of all women with an AGUS smear is warranted. An endometrial biopsy is warranted in the absence of persistent AGUS in the cervical findings from the biopsy ( Zweizig et al , 1997 ). We found significant squamous lesions in 51% of the AGUS smears and only 2.2% glandular lesions. The possible explanation for the relative absence of glandular pathology is the fact that the cells were so badly deformed that they appeared to be glandular to the cytopathologist but were actually squamous in origin. Finally, the results of this study strongly support that the presence of AGUS cells upon a routine cytologic specimen examination indicates the existence of a pathologic condition that mandates appropriate management.