Histiocytes and the detection of endometrial adenocarcinoma

Histiocytes have long been recognized as part of the milieu of endometrial carcinoma in gynecologic smears. In an effort to determine whether a quantitative assessment of histiocytes, especially in the absence of endometrial cells, could increase the effectiveness of the cervicovaginal smear for diagnosis of endometrial carcinoma, smears obtained prior to a tissue diagnosis of endometrial adenocarcinoma were evaluated from 44 postmenopausal women. Smears from 97 age-matched patients in the same clinic were also evaluated and used as a control group for the endometrial carcinoma patients. All smears were evaluated for the presence of histiocytes and for the presence of benign or malignant endometrial cells, with the histiocytes quantitated as minimal (less than 5 per high-power field [HPF]), moderate (5 to 10/HPF) or heavy (greater than 10/HPF). Sensitivity and specificity were calculated to assess the role of histiocytes in the presence and in the absence of endometrial cells using cytologic findings. Our data indicate that the presence of moderate or heavy numbers of histiocytes on cervicovaginal smears of postmenopausal women increased the cytologic sensitivity from 61% to 82% when considered a marker of disease along with endometrial cells. These results suggest that attention to the presence of histiocytes on cervicovaginal smears may increase the utility of cytology for the diagnosis of endometrial lesions and may be a useful guideline for the cancer-related gynecologic examination.     

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.     

A retrospective clinical audit of cervical smears reported as 'glandular neoplasia'.

The aims of this study were to review the diagnostic pathway of women with smears reported as 'glandular neoplasia' and to outline the management, colposcopy findings, treatment and final histological diagnosis in these women. The design was a retrospective review. A total of 114 women were identified over a 5-year period from the cytology database at the Royal Liverpool University Hospital Cytology Department, whose hospital case notes were available for review. Methods included a review of the case notes for the demographic details, indication for smear, colposcopic findings, investigation and/or treatment procedures, histology, final diagnosis and current disease status. Of 114 smears reported as 'glandular neoplasia', 67 were reported as consistent with cervical glandular intra-epithelial neoplasia (CGIN), six with endocervical adenocarcinoma, 36 with endometrial adenocarcinoma and five with other glandular neoplastic abnormalities. The average age was 46.5 years. 79 (69.3%) smears were routine call/recall and 36 (30.7%) women were symptomatic. The positive predictive value (PPV) for a significant histological abnormality in the CGIN smear group was 80.6% (23.9% invasive carcinomas, 43.3% CGIN and 13.4% CIN) and the PPV of an 'endometrial adenocarcinoma' smear was 86.1%. Smears indicating glandular neoplasia are associated with a high probability of clinically significant lesions, the PPV of a CGIN smear being over 80%. Immediate referral for colposcopy and assessment by an experienced colposcopist is recommended.     

Atypical glandular cells of undetermined significance favor endometrial origin. Criteria for separating low grade endometrial adenocarcinoma from benign endometrial lesions

OBJECTIVE: To evaluate cytologic criteria for separating atypical glandular cells of undetermined significance favor endometrial origin (AGUS-EM), on Papanicolaou-stained (Pap) smears into favor benign and favor malignant categories. STUDY DESIGN: All patients who had a Pap smear diagnosis of AGUS-EM, not further qualified, followed by tissue follow-up were identified from the surgical pathology and cytopathology files from January 1992 through December 1996. The Pap smears were scored blindly for the presence or absence of 40 cytologic criteria, and univariate analysis was performed to determine which criteria were most indicative of malignancy by tissue follow-up. RESULTS: The presence of an atrophic smear, nuclear size greater than twice that of an intermediate cell nucleus and absence of clusters with irregular borders were highly indicative of adenocarcinoma, although other criteria were also helpful in identifying malignancy. CONCLUSION: There are no combinations of cytologic criteria that definitely separate AGUS-EM cases into those with benign or malignant findings on follow-up. However, some isolated criteria were useful in the differential diagnosis in a [table: see text] significant number of cases.     

Diagnostic accuracy of liquid‐based endometrial cytology in the evaluation of endometrial pathology in postmenopausal women

C. Remondi, F. Sesti, E. Bonanno, A. Pietropolli and E. Piccione
Diagnostic accuracy of liquid‐based endometrial cytology cytology in the evaluation of endometrial pathology in postmenopausal women Objective: The aim of this study was to compare liquid‐based endometrial cytology with hysteroscopy and endometrial biopsy regarding its diagnostic accuracy in a series of postmenopausal women with abnormal uterine bleeding (AUB) or asymptomatic women with thickened endometrium assessed by transvaginal ultrasound as a screening procedure. Methods: Inclusion criteria were: menopausal status; the presence of AUB and/or thickened endometrium assessed by ultrasound (cut‐off 4 mm); a normal Papanicolaou (Pap) smear; and no adnexal pathology at ultrasound. Exclusion criteria were: previous endometrial pathology; and previous operative hysteroscopy. Of 768 postmenopausal women referred to our general gynaecology clinics, 121 fulfilled the inclusion criteria and were recruited to the trial. Twenty‐one refused to participate. Cytological sampling was carried out by brushing the uterine cavity using the Endoflower device with no cervical dilation and the vial was processed using a ThinPrep® 2000 automated slide processor. The slides were stained using a Pap method. Results: In 98 cases with histological biopsies, endometrial cytology detected five cases of endometrial carcinoma, 10 of atypical hyperplasia and 47 of non‐atypical hyperplasia; 36 cases were negative. In two cases cytology was inadequate because of uterine cervical stenosis. Taking atypical hyperplasia or worse as a positive test and outcome, the diagnostic accuracy of the endometrial cytology was 93.5%, with a sensitivity of 92% and specificity of 95%, a positive predictive value of 73% and a negative predictive value of 99%. All the carcinomas were detected by cytology. Only 42% of women with a positive diagnosis were symptomatic. The cytological sampling was well tolerated by all patients. No complication was registered. Conclusions: Liquid‐based endometrial cytology can be considered an useful diagnostic method in the detection of endometrial pathology as a first‐line approach, particularly if associated with transvaginal ultrasound.     

Significance of histiocytes on otherwise-normal cervical smears from postmenopausal women. A retrospective study of 108 cases

OBJECTIVE: To evaluate the significance of histiocytes on normal cervical smears from postmenopausal women and correlate them with endometrial pathology. STUDY DESIGN: Histiocytes were classified into three types. The clinical history was obtained from cytologic and surgical reports. RESULTS: Among 108 cervical smears, 13 had large, foamy histiocytes (type A), 88 had histiocytes resembling superficial endometrial stromal cells (type B), and 7 had variably sized histiocytes alone or in association with inflammatory or multinucleated cells (type C). Endometrial pathology was identified in 13 patients (12.0%): 4/13 with type A histiocytes (2 endometrial adenocarcinomas, 2 endometrial polyps), 8/88 with type B histiocytes (8 endometrial polyps) and 1/7 with type C histiocytes (endometrial polyp). Among 70 patients with no clinical indications for endometrial sampling except for the presence of histiocytes, 4 demonstrated endometrial pathology (all endometrial polyps). In contrast, endometrial pathology was identified in 9/38 with clinical indications for endometrial sampling. Among the 13 patients with endometrial pathology, 9 had a significant clinical history (sensitivity of 69.2%), and 4 had histiocytes as the only indication for endometrial biopsy (sensitivity of 30.8%). CONCLUSION: A significant clinical history is more predictive of endometrial pathology and outweighs the significance of histiocytes as an indication for endometrial biopsy.     

Atypical glandular cells: criteria to discriminate benign from neoplastic lesions and squamous from glandular neoplasia

OBJECTIVE: To evaluate the presence of some criteria in cervical smears with atypical glandular cells and their correlation with histological patterns to identify pre-neoplastic and neoplastic lesions. METHODS: Seventy-three women referred with an atypical glandular cell smear, who had undergone conization or hysterectomy, were included in this study. Referral Pap smears were reviewed using the set of 27 cyto-morphological criteria that was correlated with the histological diagnosis. RESULTS: Histological results showed intraepithelial or invasive neoplasia in 35 (48%) cases and benign lesions in 38 (52%) cases. After logistic regression and decision tree analysis an increased nuclear/cytoplasmic ratio and the presence of dyskeratotic cells were strongly associated with intraepithelial or invasive neoplasia and the differential cyto-morphological criteria for glandular lesions were decreased cytoplasm, irregular nuclear membranes and the presence of nucleoli. CONCLUSION: The analysis of individual cyto-morphological criteria can better predict intraepithelial or invasive neoplasia and differentiate glandular from squamous lesions.     

Significance of cytologically normal endometrial cells in cervical smears from postmenopausal women

OBJECTIVE: To determine the significance of cytologically normal endometrial cells in cervicovaginal (CV) smears from postmenopausal women over age 55 years. STUDY DESIGN: From January 1995 to January 1998, 220 women had CV smears demonstrating cytologically normal endometrial cells. The menopausal status, hormone replacement therapy (HRT) and information related to subsequent CV smears and endometrial sampling within 12 months of the initial diagnosis was recorded. RESULTS: Eighty-one of the 220 cases (36.8%) had histologic sampling of the endometrium. Thirty-four of 81 (42%) showed no endometrial pathology. Endometrial pathology was identified in 28 of 81 (34%), of which 19 were endometrial polyps (23.4%), 4 were endometrial hyperplasia (4.9%), 4 were endometrial carcinoma (4.9%) and 1 was a leiomyoma (1.2%). Nineteen (23.4%) were insufficient for diagnosis. Ninety-one of 220 women were on HRT, and 129 were not. In the group without HRT, endometrial disease was identified in 22/51 (43%) cases as compared to 6/30 (20%) in the group with HRT (P < .001). Endometrial carcinoma was identified in three (5.8%) cases and one (3.3%) case without and with HRT, respectively. CONCLUSION: Although the finding of normal endometrial cells in Pap smears from postmenopausal women was without any clinical significance in the majority of women in this study, in a small number it was associated with endometrial hyperplasia and carcinoma. Women who were not on HRT had a higher incidence of endometrial pathology.     

Significance of AGUS Pap smears in pregnant and postpartum women

OBJECTIVE: To study the clinical significance of atypical glandular cells of undertermined significance (AGUS) in pregnant and postpartum women. STUDY DESIGN: We evaluated 35 women who were pregnant (30) or within three months postpartum (5) and had a cytologic diagnosis of AGUS. Twenty-seven (77%) patients had follow-up: 17 (63%) patients underwent colposcopic examination and biopsy, and 10 (37%) had repeat Pap smears. Eight patients were lost to follow-up. RESULTS: Five (29.4%) patients had a squamous intraepithelial lesion (SIL), including three high grade and two low grade, on subsequent biopsy. The remaining (70.6%) patients had benign pathology, which included 5 chronic cervicitis, 4 endocervical and/or endometrial polyps, 2 Arias-Stella reaction and 1 microglandular hyperplasia. Among the patients with repeat Pap smears, two had persistent AGUS/atypical squamous cells of undetermined significance, the remaining cases were within normal limits. CONCLUSION: Pregnancy-related changes may present with glandular atypia. In addition, about one-third of pregnant and postpartum women with a diagnosis of AGUS had SIL on subsequent biopsy; that rate is similar to that in nonpregnant women. Therefore, pregnant women with a cytologic diagnosis of AGUS should be followed closely.     

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.     

Pap smears in women with endometrial carcinoma

OBJECTIVE: To correlate Pap smear findings with the histology of endometrial carcinoma and stage of the disease. STUDY DESIGN: Between 1995 and 1998, 76 women with endometrial carcinoma, having had Pap smears done within two to three months of hysterectomy at Memorial Sloan-Kettering Cancer Center, formed the basis for this study. All Pap smears and histologic sections were reviewed. RESULTS: Thirty-four patients had normal Pap smears (45%), and 42 had abnormal ones (55%). The mean age of the two groups was 65.1 and 65.2 years, respectively. Histologic subtypes included 44 International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrioid adenocarcinoma (low grade) and 32 high grade carcinomas, including 19 FIGO grade 2 or 3 endometrioid adenocarcinomas, 5 papillary serous carcinomas (PSC), 2 clear cell carcinomas (CC), 1 adenosquamous carcinoma, 3 endometrioid adenocarcinomas mixed with PSC and 2 endometrioid adenocarcinomas mixed with CC. The proportions of patients with low and high grade tumors with abnormal Pap smears were 43% (19/44) and 72% (23/32), respectively (P=.01). The proportions of patients with abnormal Pap smears and no myometrial invasion, invasion of <50% and >50% myometrial thickness were 40% (8/20), 62% (26/42) and 57% (8/14), respectively (P =.27). Vascular invasion was identified in 56% (9/16) of patients with abnormal Pap smears and in 55% (33/60) of patients with normal ones (P = .93). The proportions of patients having abnormal Pap smears with stage I and stages II, III or IV disease were 48% (30/62) and 86% (12/14), respectively (P =.01). CONCLUSION: Although the Pap smear is not a sensitive screening test for endometrial cancer and a negative Pap smear does not rule it out, this study revealed that abnormal Pap smears are significantly associated with high grade of tumor and stage II-IV endometrial carcinoma. However, they are not associated with patient age, depth of myometrial invasion or vascular invasion.     

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.     

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.     

Endometrial hyperplasia with berrylike squamous metaplasia and pilomatrixomalike shadow cells. Report of an intriguing cytohistologic case

BACKGROUND: The usefulness of endometrial cytology as a diagnostic method in asymptomatic women, especially in postmenopause, in the interpretation of composite pictures characterized by borderline features between atypical hyperplasia and well-differentiated adenocarcinoma, especially if associated metaplastic features are present, is somewhat controversial. CASE: An asymptomatic, 50-year-old, postmenopausal woman underwent a Pap smear and endometrial cytology for routine screening, disclosing three-dimensional, sometimes pseudopapillary groupings of hyperplastic endometrial glandular cells with focal atypia in direct continuity with large, squamoid cells of the keratinizing type and shadow cells. Histologic examination of endometrial tissue was advised, and two subsequent endometrial biopsies and hysteroscopic ablation were performed. The borderline character of the lesion (complex atypical hyperplasia vs. well-differentiated adenocarcinoma) with concomitant squamous metaplasia and pilomatrixomalike shadow cells prevented diagnostic agreement between several pathologists. CONCLUSION: Diagnostic cytology with direct endometrial sampling represents a valuable diagnostic screening tool for the differential diagnosis between normal and pathologic endometrium, a mucosal picture that deserves a subsequent (histologic) diagnostic procedure. In a few cases, as in the one presented above, even histologic examination, especially of so-called borderline lesions, reveals squamous or other types of metaplasia that can lead to interobserver discrepancies.     

Cytohistologic correlation between AGUS and biopsy-detected lesions in postmenopausal women

OBJECTIVE: To evaluate histologic findings in patients aged 50 and older whose cervical smears revealed atypical glandular cells of undetermined significance (AGUS). STUDY DESIGN: Computerized records spanning a four-year period were retrospectively analyzed. Thirty patients over age 50 had cervical smears interpreted as AGUS and had follow-up biopsies within 12 months following the abnormal smear. The most important histologic diagnosis from the biopsy specimens was correlated with the subcategory of the cervical smear. RESULTS: Five smears interpreted as AGUS, favor reactive, revealed abnormal histology in four cases: three endometrial polyps and one squamous carcinoma. Two smears interpreted as AGUS, favor dysplasia, revealed squamous intraepithelial lesions on biopsy in both cases. Seventeen smears interpreted as AGUS, favor endometrial cells, revealed abnormal histology in 13 cases: 1 endocervical polyp, 6 endometrial polyps, 3 endometrial hyperplasias and 3 adenomyosis. Six patients with smears interpreted as AGUS, unclassifiable, revealed abnormal histology in five cases: two endocervical polyps, one endometrial polyp, one endometrial carcinoma and one ovarian carcinoma. CONCLUSION: The presence of AGUS in cervical smears from women over 50 was highly predictive of abnormal lesions detected by histologic examination. Although three cancers were detected on histologic follow-up, the most common lesions detected were endometrial polyps.     

The "suspicious" gynecologic smear

"Suspicious" gynecologic smears from 842 patients over a seven-year period were analyzed for their causes and outcomes. The frequency of the cytologic diagnosis of "suspicious" ranged between 0.5% in 1979 and 1.44% in 1975 of all smears examined. Review of the smears showed that this classification was used to report a variety of conditions, including equivocal possible precancerous changes as well as the presence of severe inflammation, degenerative or atrophic changes, abnormal glandular cells and metaplasia. The cytologic follow-up, following anti-inflammatory or hormonal therapy, showed a conversion to negative findings in 65.1% of all cases, usually within 12 months. In 294 cases, histologic analysis became necessary, revealing precancerous changes or cancer in 147 patients (17.5% of the study group). Smears of postmenopausal women with suspicious glandular or endometrial cells received special analysis. Significant numbers of such cases had histologic findings positive for malignancy (20% of smears with glandular cells and 21.3% with endometrial cells), as did also smears showing post-irradiative changes (34.6%) or atrophic and degenerative changes (17.1%). Therefore, "suspicious" smears in these groups were considered to indicate an increased risk of malignancy. A regimen for the proper management of cases with "suspicious" smears has been established.     

CIN 2/3 and cervical cancer after an ASCUS pap smear. A 7-year, prospective study of the Norwegian population-based, coordinated screening program

OBJECTIVE: To estimate the risk of being diagnosed with cervical intraepithelial neoplasia (CIN) 2/3 or invasive cervical cancer (ICC) based on diagnostic and screening procedures performed after a diagnosis of atypical squamous cells of undetermined significance (ASCUS) and to compare this risk to that in women with a normal Pap smears. STUDY DESIGN: A 7-year, prospective, cohort study was performed in the Norwegian population-based, coordinated screening program. After excluding women in the midst of follow-up of an abnormal Pap smear or with a history of CIN 2/3 or ICC, the study population consisted of women 25-69 years of age with a normal (n = 526,661) or ASCUS Pap smear (n = 10,037) in 1995-1996. Risk estimates were calculated by logistic and parametric survival regression. RESULTS: Within 7 years of an ASCUS smear, 1,017 women (10.1%) were diagnosed with CIN 2/3 and 62 (0.62%) with ICC. Women with an ASCUS index Pap smear had a relative risk of 15-30 of being diagnosed with histologically verified CIN 2/3 or ICC within the first 2 years of follow-up as compared to women with a normal index smear. In long-term follow-up, women with an ASCUS index smear followed by a normal smear, which cancelled further clinical follow-up, were at > 3.5 times higher risk of both CIN 2/3 and invasive cancer as compared to women with a normal index smear. CONCLUSION: Pap smear follow-up of women with an ASCUS smear does not identify all women at higher risk of CIN 2/3 and ICC. Other diagnostic procedures should be implemented to improve the screening program.     

Split-sample analysis of discarded cells from liquid-based Pap smear sampling devices

OBJECTIVE: To examine cells that were retained on sampling devices used to collect ThinPrep (Cytyc Corp., Boxborough, Massachusetts, U.S.A) Pap smears in order to evaluate both the number and significance of cells that are routinely discarded with these devices after liquid-based specimens are collected. STUDY DESIGN: One hundred Pap smears from 100 women were prospectively procured after gynecologic Pap smears were collected for the ThinPrep Pap test. The sampling end of the collection devices was cut off and placed in a vial that contained SUREPATH preservative fluid (TriPath Imaging, Inc., Burlington, North Carolina, U.S.A). The residual cell samples were processed using the SurePath PREPSTAIN slide processor (TriPath). A single liquid-based slide was prepared from the sampling devices from each of the 100 specimens collected. The slides produced from the discarded devices were reviewed for the following: squamous cells, endocervical component, epithelial cell abnormalities and miscellaneous findings. The slides prepared from the "throw-away" (TA) material were subsequently compared with the primary ThinPrep Pap smear slide. RESULTS: Twenty-five percent of the TA samples had an equal or greater number of squamous cells per high-power microscopic field when compared to the primary ThinPrep slide, with 8% of the TA slides demonstrating greater overall cellularity. An endocervical component was present on 27 of 66 cervical samples (40.9%). Three of five cases (60%) interpreted as atypical squamous cells of undetermined significance had similar cells on the TA slides. Two cases of atypical glandular cells of undetermined significance had no abnormal cells on the TA slides. Twelve of 14 cases (85.71%) of low grade squamous intraepithelial lesion contained similar cells on the TA slides. Two of four cases (50%) of high grade squamous intraepithelial lesion also had similar abnormal cells on the TA slides. Miscellaneous findings included 1 case of benign endometrial cells and 4 Candida infections present on both preparations, along with 1 case of Trichomonas vaginalis organisms present on the ThinPrep slide only. In 1 specimen, several multinucleated histiocytic giant cells were present only on the TA slide. CONCLUSIONS: Specimens prepared from TA collecting devices used for the ThinPrep Pap test are less sensitive than the primary specimen for the detection of cervical lesions. This is in contrast to split-sample studies involving ThinPrep and conventional smears. Our study documented the presence of normal and abnormal cells discarded from ThinPrep sampling devices in a high percentage of cases. Discarded abnormal cells on the TA slides were, however, few when compared to the primary specimen, with only 1 exception involving a high grade lesion.     

Müllerian adenosarcoma of the uterus: report of a case with imprint cytology

BACKGROUND: Müllerian adenosarcoma is a rare morphologic variant of uterine sarcoma that, although well described histologically, is scarcely mentioned in the cytologic literature. CASE: A 75-year-old female was suspected of having atypical endometrial hyperplasia on an endometrial smear. However, subsequent imaging techniques revealed the presence of a bulky, polypoid mass filling the uterine cavity. On pathologic examination of the hysterectomy specimen, the polypoid tumor was diagnosed as mullerian adenosarcoma, homologous, with sarcomatous overgrowth, in which the sarcomatous component was compatible with high grade endometrial stromal sarcoma. Imprint smears of the tumor consisted of two morphologic patterns, sarcomatous and glandular. The sarcomatous tumor cells, with coarse chromatin and relatively scant cytoplasm, formed small aggregates or appeared alone. These cells were semiround or oval and had conspicuous nucleoli. In addition to these observations, small and large clusters of glandular cells with mild atypism were interspersed with the sarcomatous cells. CONCLUSION: Cytologic examination of müllerian adenosarcoma well reflects its pathologic features.     

Sensitivity and specificity of the Pap smear for glandular lesions of the cervix and endometrium

OBJECTIVE: To investigate the sensitivity and specificity of the Pap smear for detection of adenocarcinoma in situ of the cervix (AIS), endocervical adenocarcinoma (ECAC) and endometrial adenocarcinoma (EAC) as well as the overall specificity of the smear for detection of glandular lesions in general. STUDY DESIGN: Computer records of the laboratory of the QE II Health Sciences Center, Halifax, were searched for patients who had AIS, ECAC or EAC diagnosed on histology between June 1, 1999, and May 31, 2001 and who had had a Pap smear within the preceding year. Computer records were also searched for patients who had a Pap smear result consisting of suspicious or positive for AIS or adenocarcinoma (AC) with subsequent tissue diagnosis during the same time. The histologic and cytologic findings were correlated. RESULTS: One hundred percent of patients with AIS, 80% with ECAC and 22% with EAC on histology had positive findings on a Pap smear performed within a year of the histologic diagnosis. One hundred percent of patients with a Pap smear result consisting of suspicious or positive for AIS or AC and follow-up histology had a lesion on histology: 13% AIS, 13% ECAC, 37% EAC, 23% other AC, 10% high grade squamous lesion and 0.3% low grade squamous lesion. CONCLUSION: This study confirmed the good overall specificity of the Pap smear for glandular lesions in general. It also confirmed the good sensitivity for glandular lesions of the cervix and the poor sensitivity for glandular lesions of the endometrium. It thus confirmed that the Pap smear is not an effective screening tool for endometrial AC, and that the quest for alternative screening methods should continue.