Value of histiocyte detection in Pap smears for predicting endometrial pathology. An institutional experience

OBJECTIVE: To determine the clinical implications of the finding of histiocytes in Pap smears in 1 patient population. STUDY DESIGN: The medical records and Pap smears which the presence of histiocytes was mentioned in the diagnosis between August 1996 and August 2001 were reviewed in conjunction with follow-up surgical findings. The positive predictive value (PPV) for significant endometrial pathology for the isolated finding of histiocytes on Pap smear was determined. RESULTS: Of the 238,225 women screened over a 60-month period, 325 were reported to have histiocytes in their Pap smears. Of them, 238 (73.2%) had subsequent endometrial sampling, hysterectomy or both, and follow-up Pap smears. Two hundred seven smears (87%) failed to disclose endometrial pathology. Thirty-one cases (13%) resulted in significant histopathologic findings, including 12 uterine malignancies, 8 endocervical polyps, 7 endometrial polyps, 2 submucosal leiomyomata, 1 simple hyperplasia without atypia and 1 case of tamoxifen-related changes. Upon review of the clinical records, 58% (18/31) of those patients had other significant clinical and/or cytologic findings. Five of the 18 patients (27.8%) had associated postmenopausal bleeding, 11 had additional abnormal Pap smear findings (atypical glandular cells, 6/18, or 33.3%; endometrial cells, 5/18, or 27.8%), and another 2 had both postmenopausal bleeding and atypical glandular cells (2/18, or 11.1%). The PPV for significant uterine pathology for women with the isolated finding of histiocytes on a Pap smear was 5.5% and 60% with additional clinical and/or Pap smear findings. The PPV for endometrial cancer was 1.3% in women with the isolated finding of histiocytes on a Pap smear but 20% for women with histiocytes and additional clinical/or Pap smear findings. CONCLUSION: Based on the findings of this study and recently published data, we conclude that the isolated finding of increased histiocytes in the absence of postmenopausal bleeding, endometrial cells or atypical glandular cells on a Pap smear is a poor indicator of uterine disease.     

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.     

Cytologic diagnosis of primary tubal cancer

A study was made of the 128 cases of primary tubal cancer reported to date in Japan, especially of the 61 cases with a preoperative cytologic examination, which was positive for malignancy in 28 cases (45.9%). A positive cytologic diagnosis was made on the cervicovaginal smear in 37.9% of the 58 cases so examined and on the endometrial smear in 80.0% of the 15 cases so examined. Of the 12 cases with positive endocervical smear cytologies, 11 were without endometrial invasion and 4 had no cancer cells in the cervicovaginal smear. Histologic examination of endometrial curettage specimens was positive for cancer in 8 (23.5%) of 34 cases so examined. Endometrial invasion by cancer cells was seen in 11.1% of the surgically extirpated endometrial specimens. The results of this study suggest that cytologic diagnosis is one of the most reliable methods for detecting primary tubal cancer before a surgical operation is undertaken. Its efficacy might be improved by more careful sampling and study in patients suspected of having primary tubal cancer.     

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.     

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.     

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.     

Clinical and cytologic aspects of primary fallopian tube carcinoma. A report of ten cases

The clinical and cytologic findings in ten cases of primary fallopian tube carcinoma, a very rare malignancy, are presented. All ten patients had vaginal pool (V), cervical (C), endocervical (E) and endometrial aspiration (EA) smears examined preoperatively; peritoneal smears were also prepared from cul-de-sac fluid aspirated during surgery. In the preoperative cytodiagnosis, some of V, C, E and EA smears were positive for malignant cells in six of the ten patients (60%). Examination of the EA smear was the most effective means of discovering this disease. A watery discharge was noted in two patients, both of whom were negative in the preoperative cytodiagnosis. In such patients, it is necessary to repeat the smear examinations. The cytologic appearance of this disease is contrasted to that of endometrial carcinoma.     

Vaginal intraepithelial neoplasia and the Pap smear

OBJECTIVE: To assess the sensitivity of the vaginal smear cytologic examination in detecting vaginal intraepithelial neoplasia (VAIN) and to evaluate the cytologic findings of cases of VAIN. STUDY DESIGN: Cases with a histologic diagnosis of VAIN were identified from the Barnes-Jewish Hospital South and North Campus over a period of five and nine years, respectively. Only posthysterectomy patients with a tissue biopsy diagnosis of VAIN and with a vaginal smear obtained within three months of the biopsy were included in the study. Pertinent clinical information was obtained by reviewing the medical records. Two pathologists reviewed the pathologic samples. RESULTS: Thirty-five vaginal smears from 31 posthysterectomy patients were included in the study. The mean age was 57 years (range, 29-84). The cytologic diagnoses of smears from patients with VAIN included: high grade squamous intraepithelial lesion (19 cases), low grade squamous intraepithelial lesion (10 cases), atypical squamous cells of uncertain significance (5 cases) and negative for malignancy (1 case). CONCLUSION: The sensitivity of the vaginal smear cytologic examination in detecting VAIN is 83%. Obscuring inflammation contributed to false negative diagnoses in two cases.     

Endocyte endometrial smears in the cytodiagnosis of endometrial carcinoma

The cytologic diagnosis of endometrial cancer using material obtained with the Endocyte endometrial sampler was assessed for 874 patients. The samples obtained were smeared directly on slides for fixation and staining; the smears were more difficult to assess than cervicovaginal smears, however, due to the presence of blood, the small size and density of the cells and the flattened three-dimensional architecture of the tissue fragments obtained. Only 8.2% of the samples were classified as inadequate; repeat sampling in some of those cases produced diagnostic material. All 12 cases of carcinoma (including one case in a woman less than 40 years of age) were diagnosed by cytology as malignant; however, the original cytologic sample in one of those cases was inadequate. For the diagnosis of benign versus malignant, cytology had a sensitivity of 92%, a specificity of 100% and predictive value of 100%. Cytology also diagnosed as suspicious the smears from 5 of 13 cases of endometrial hyperplasia and 2 of the 9 cases of endometrial polyps. The cytologic findings for benign and malignant samples are described and illustrated in detail. Relative to other endometrial sampling devices, the Endocyte is inexpensive and was easily used by the gynecologist and well tolerated by the patients, with no complications and minimal discomfort.     

Abrasive bronchial brushing cytology. A preliminary study of 200 specimens for the diagnosis of neoplastic and nonneoplastic bronchopulmonary lesions

Two hundred subjects with chronic respiratory symptoms with a suspicion of malignancy were selected for bronchial brushing cytology. Prior sputum examination had shown malignant squamous cells in two cases only. The cytologic appearances of the brushing smears were divided into five categories: 41 (20.5%) smears with positively malignant cells; 20 (10%) smears predominantly showing chronic inflammatory features; 31 (15.5%) smears with mainly acute inflammatory changes; 60 (30%) smears with normal cytologic features; and 48 (24%) smears unsatisfactory for cytologic interpretation. Thirteen patients with a positive cytology had a positive tissue biopsy for malignancy. Among the group with chronic inflammatory changes, acid-fast bacilli were identified in nine cases, and one smear showed frank tuberculous granuloma. In the unsatisfactory group, two cases showed malignant cells in the postbrushing sputum. There was one false-negative report for malignancy in the entire study. This study confirms the sensitivity and accuracy of bronchial brushing cytology in the diagnosis of various bronchopulmonary lesions, especially malignancy and pulmonary tuberculosis, in India.     

Cervicovaginal and endometrial cytology in ovarian cancer

The clinical significance of cytologic examination was studied in 114 patients with ovarian cancer who had received preoperative cytologic examinations. The overall positive rate of the cytologic examinations was 26.3% (30 of 114): 22 (19.3%) of the 114 cases had positive cervicovaginal smears while 13 of 31 endometrial aspiration smears (41.9%) were positive. The positive rate was not related to the volume of ascites but rather to its presence or absence. Thus, if ascites was observed, the positive rate was about 2.1 times higher than if it was absent. In two of four cases of ovarian cancer with no endometrial invasion but a positive cytologic examination of ascitic fluid, fallopian tube specimens contained cancer cells; this suggests that ovarian cancer cells may reach the cervix and/or vagina by passing through the fallopian tube, particularly if ascites is present. Since cytologic examination, especially of endometrial aspiration smears, shows a high positive rate if ovarian cancer cells are observed in the abdominal cavity, cytology should be used as an important ancillary method for the assessment of ovarian cancer.     

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.     

Diagnosing endometrial carcinoma with cervical involvement by cervical cytology

OBJECTIVE: To assess the relationship of a cervical cytologic diagnosis based on number, size and degeneration of malignant clusters and necrotic background to cervical involvement of endometrial carcinoma. STUDY DESIGN: Cervical smears of 53 women with endometrial carcinoma were evaluated for cervical involvement. The cytologic diagnosis was compared with actual involvement, and accuracy was calculated. Retrospectively, cytologic features, including number, size and degeneration of malignant clusters and necrotic background, were analyzed in involved and noninvolved cases. RESULTS: Cervical involvement was confirmed in 15 patients (28.3%). The number and size of malignant clusters in the involved cases were significantly larger than those in the noninvolved cases (P < .001 and < .01, respectively). The proportion of degenerated malignant cells and necrotic background in involved cases were significantly higher than those in noninvolved cases (P < .05). Cytologic diagnosis had a sensitivity and specificity of 62.5% and 86.8%, respectively. CONCLUSION: Cervical smears of involved cases revealed a large number and large size of malignant clusters. These findings support cytologic diagnosis based on number, size and degeneration of malignant cells and necrotic background. Cervical cytology is useful to exclude cervical involvement because of its high specificity and can help detect cervical involvement because of its moderately high sensitivity.     

Microfilariae of Wuchereria bancrofti in cytologic smears

Microfilariae of Wuchereria bancrofti were observed in cytologic material in 35 cases. The material included cervicovaginal smears (17 cases), effusions (14), urine (2), bronchial washings (1) and ovarian cyst fluid (1). The initial diagnosis was made from the cytologic smear in all cases; none had clinical filariasis. Symptomatic vaginal bleeding in 9 of the 17 cases with microfilaria-positive cervicovaginal smears was reflected in the large numbers of red blood cells found in the smear. Blood eosinophilia was present in 11 of 19 cases investigated. Eosinophils were seen in the smears in 20 cases. In the majority of the cases of effusions with microfilariae the effusions were malignant. Significant adherence of inflammatory cells and macrophages to microfilariae was present in 7 of the 35 cases. The significance of these findings is discussed.     

Analysis of cervical smears obtained within three years of the diagnosis of invasive cervical cancer

The cytologic histories of 376 women presenting with invasive carcinoma of the cervix were analyzed. In total, 202 (53.7%) of these women had had 355 smears taken during the three years preceding presentation. All 320 smears with an original cytologic diagnosis of less than cancer were reviewed. The original cytologic diagnosis was low in 95 (30.6%) of 310 adequate smears. Originally, 96 (30.9%) of the adequate smears were evaluated as negative; at review, only 55 (17.5%) of the adequate smears were evaluated as negative. Comparing the review diagnoses to the 355 total smears, the rates of negative smears were 13.5% (42 of 310) for squamous-cell carcinoma, 30.0% (12 of 40) for adenocarcinoma and 20.0% (1 of 5) for adenosquamous carcinoma (P less than .05). The cellular composition of the smear was significantly related to the cytologic detection of abnormalities: endocervical cylindrical and/or metaplastic cells were seen in only 45.5% of smears diagnosed as negative, but in 84.4% and 97.8% of smears diagnosed as atypia and cervical intraepithelial neoplasia, respectively P less than .00001). Smears without endocervical cells should be considered inadequate and should be repeated.     

Influence of the histologic and cytologic grade and the clinical and postsurgical stage on the rate of endometrial carcinoma detection by cervical cytology

The influence of postsurgical stage, histologic grade and cytologic grade of the tumor on the rate of detection of endometrial carcinoma by cervical smear was examined in a retrospective study. Cervical smears from 220 patients with endometrial carcinoma seen in the years between 1965 and 1981 were reevaluated for the presence of normal, suspicious or frankly malignant endometrial cells. The smears were positive in 33.2% of the patients, suspicious in 25.5% and negative in 40%. In three cases (1.4%), the smear was technically inadequate. Positive or suspicious smears indicated the presence of a higher grade as well as a higher stage of the lesion. In this material, the presence of normal endometrial cells as an indicator of endometrial disease, as emphasized in the literature, proved useless since normal endometrial cells without accompanying malignant cells were not seen in a single case. It appears that the reason for the lower rate of detection of low-grade endometrial carcinoma is the complete absence of any exfoliation in these lesions.     

O-9Uncommon subtypes of borderline nuclear changes: cytological features and predictive value

Introduction:  To establish the significance of cytological features which could predict clinically significant endometrial pathology, and therefore guide reporting practice in cervical samples.
Methods:  A retrospective review of SurePath liquid-based cytology (LBC) cervical samples between 2002 and 2006, obtained at screening and colposcopy. These smears contained normal endometrial cells present at inappropriate times of the menstrual cycle, endometrial cells with atypia (borderline change) and with features suspicious / diagnostic of endometrial carcinoma (glandular neoplasia). False negative and false positive cases detected on subsequent histology were also included. The control group comprised negative samples and a few abnormal smears. All smears were randomly assigned and blinded to menopausal status, age, use of oral contraceptive pill and hormone replacement therapy and presence of intrauterine device. Each smear was reviewed for 16 cytologic criteria and a cytological diagnosis was given for each.
Results:  A total of 219 smears were available for review; 137 were negative, out of which 85 contained normal endometrial cells, 41 contained endometrial cells with atypia, 10 contained endometrial cells with features suggestive of adenocarcinoma and 31 contained endometrial cells with features diagnostic of adenocarcinoma. The feature most associated with benign endometrial cells is top hat with central cell condensation. In contrast, the features associated with malignant endometrial cells are smooth nuclear membrane, pale chromatin, small nucleoli and scalloped borders.
Discussion:  The criteria identified in this study do not definitively define a neoplastic process, but appear to be helpful in individual cases. This study emphasises that endometrial changes should be always interpreted with the relevant clinical information, which would otherwise lead to overdiagnosis in premenopausal women.     

Cytology of vaginal and uterine sarcomas

OBJECTIVE: To retrospectively review, based on cytologic and histopathologic findings, the diagnoses of 13 patients with uterine sarcoma and 1 with vaginal sarcoma. STUDY DESIGN: There were 8 cases of uterine carcinosarcoma (CS), 2 of leiomyosarcoma, 2 of endometrial stromal sarcoma (ESS), 1 of endocervical stromal sarcoma (ECSS) and 1 of malignant fibrous histiocytoma (MFH) of the vagina. The presence of sarcomatous components was retrospectively investigated by microscopic observation of preoperative specimens from the endocervical canal and endometrial cells. Characteristic features of sarcomatous cells were then investigated by cytodiagnostic micrometry of malignant cells. RESULTS: Of the 14 patients, 1 with low grade ESS and 1 with homologous CS were diagnosed as negative for sarcomatous components. One case of high grade ESS had been overlooked, as were 4 cases of CS. Thus, 7 cases (50%) were diagnosed as positive for sarcomatous cells by preoperative cytologic observation. Based on these findings, 12 of the 14 cases (85.7%) were positive for sarcomatous elements on retrospective reexamination of the specimens. CONCLUSION: Careful attention should be paid to small sarcomatous cells since cases of ESS or ECSS with such cells show morphologic characteristics similar to those of stromatous cells. Furthermore, careful microscopic observation of an entire specimen is required to avoid misdiagnosis as carcinoma since it is easy to overlook sarcomatous elements in smears with carcinosarcoma if there are only a few sarcomatous cells.     

Adenoid cystic carcinoma of the uterine cervix. Cytologic features

A case of primary cervical adenoid cystic carcinoma in a 75-year-old woman is reported. Two cervical smears taken at the time of initial presentation for vaginal spotting were negative; a third smear, taken a year later prior to laparotomy, was diagnosed as positive. The cytologic findings in the positive cervical smear are described and illustrated. The differential diagnosis of the cytologic findings is discussed, and the literature on this lesion is briefly reviewed. The results in this case and others suggest that the diagnosis of cervical adenoid cystic carcinoma in an asymptomatic patient may be missed by routine smear examination.     

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.