Diverse glandular pathologies coexist with high-grade squamous intraepithelial lesion in cyto-histological review of atypical glandular cells on ThinPrep specimens

Objective: To identify in cytology, high‐grade squamous intraepithelial lesions with endocervical glandular extension in cases previously diagnosed as atypical glandular cells (AGC), analyse possible reasons for the diagnostic pitfall and document the frequency of glandular pathology coexisting with high‐grade cervical intraepithelial lesion in histology. Methods: Thirty‐nine ThinPrep® cervical smear (Pap) tests reported as AGC of undetermined significance and showing high‐grade lesions on histology [cervical intraepithelial neoplasia (CIN) 2 or 3, endometrial or extrauterine adenocarcinoma] were reviewed retrospectively to identify the cases of high‐grade squamous intraepithelial lesion with endocervical glandular extension, using the Bethesda 2001 system. Cyto‐histological correlation was performed. Results: A high frequency of diverse glandular pathologies coexisted with high‐grade cervical intraepithelial lesions on histology. This included endocervical glandular extension in 63%, benign glandular pathology in 33% and pre‐neoplastic or malignant glandular pathology (endocervical glandular dysplasia, adenocarcinoma in situ and metastatic breast carcinoma) in 17% cases. On cytology, the sensitivity was 40%, specificity was 80% and positive predictive value was 86% for endocervical gland extension in high‐grade squamous intraepithelial lesions. Conclusions: Special efforts to recognize endocervical glandular extension in high‐grade squamous intraepithelial lesions and glandular neoplasia coexisting with squamous intraepithelial lesions from the heterogeneous category of AGC can contribute to increasing the diagnostic accuracy. The identification of endocervical glandular extension on cervical cytology would alert the gynaecologist to perform a thorough assessment of the endocervix during colposcopy. This could also help to decide on the need to perform deeper conization rather than loop electrosurgical excision procedure to ensure negative margins when colposcopic biopsy shows CIN 2 or 3.     

Atypical glandular cells of undetermined significance on cervical smears. A study with cytohistologic correlation.

OBJECTIVE: The incidence of endocervical adenocarcinoma has increased steadily over the past two decades. Since the Bethesda System was introduced, the diagnosis of atypical glandular cells of undetermined significance (AGUS) has also risen and now accounts for 0.46-1.83% of all cervical (Pap) smears. The purpose of this study was to evaluate the significance of a diagnosis of AGUS using cytohistologic correlation. STUDY DESIGN: A retrospective review of archival material from 1993 through 1996 identified 64 patients who had smears diagnosed as AGUS and had a subsequent surgical biopsy. The smears were reviewed and cytologic features analyzed and correlated with the histologic diagnosis. RESULTS: On biopsy, 3 (5%) of the 64 cases showed endocervical adenocarcinoma in situ (AIS) (1 case with invasive adenocarcinoma also), 14 (22%) had a benign glandular lesion (endocervical polyp, tubal metaplasia, microglandular hyperplasia, reactive changes), 35 (54%) had squamous intraepithelial lesion (SIL) (15 diagnosed on the original smear), and 12 (19%) had no abnormality. Among the cytologic criteria evaluated, feathering (P = .01), palisading (P < .001) and chromatin clearing (P = .002) were shown to have a significant association with the histopathologic diagnosis of AIS/adenocarcinoma. These features were also useful in distinguishing AIS/adenocarcinoma from SIL and benign glandular changes from AIS/adenocarcinoma but not benign/reactive glandular changes from SIL. CONCLUSION: A diagnosis of AGUS correlated with a clinically significant lesion in the majority of cases. Squamous dysplasia (SIL) was the most common lesion identified. The presence of feathering, nuclear palisading and chromatin clearing increased the likelihood of a histologic diagnosis of AIS/adenocarcinoma.     

Glandular lesions of the cervix on thin-layer Pap tests. Validity of cytologic criteria used in identifying significant lesions

OBJECTIVE: To determine the cytologic features that are most helpful in characterizing significant glandular lesions of the cervix observed on the ThinPrep (TP) Pap test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) and to compare these features with those published for conventional smears. STUDY DESIGN: Thirty-nine TP preparations with cytologic evidence of glandular lesions of the cervix and histologic and/or clinical correlation were studied. These lesions included (1) 11 cases of benign/reactive conditions; (2) 10 cases of adenocarcinoma in situ (AIS), of which 1 had both AIS and carcinoma in situ; (3) 1 case of invasive adenocarcinoma; (4) 15 cases of squamous intraepithelial lesions and squamous cell carcinoma, including 4 with glandular involvement, and (5) 2 cases of adenosquamous cell carcinoma. These cases were reviewed by the first author without knowledge of the histologic diagnosis. Twenty-five previously published cytologic criteria were used to evaluate glandular cells on TP slides. Statistical analysis was performed using Fisher's exact test to determine the significance of the features studied. RESULTS: All glandular lesions had cytologic features on TP similar to those previously described on conventional smears. However, TP slides demonstrated enhanced nuclear features but less-preserved architectural patterns. Reactive lesions showed minimal overlapping without hyperchromasia or mitotic figures and with normal nuclear/cytoplasmic ratios. AIS and invasive adenocarcinoma cases had similar features. Increased cellularity and overcrowding were prominent, whereas feathering, rosettes and cell strips were present but subtle. CONCLUSION: Glandular lesions of the cervix on TP slides shared many of the characteristic features reported for conventional smears. However, nuclear details were more pronounced in TP slides, while architectural patterns, although present, were relatively subtle.     

Cervical cytology screening history of women diagnosed with adenocarcinoma in situ of the cervix: a case-control study

OBJECTIVE: To determine whether women diagnosed with adenocarcinoma in situ (AIS) of the cervix are as well screened as healthy control women. STUDY DESIGN: A case-control study was performed (307 cases, 1,228 controls) within a statewide registry. Cases consisted of women diagnosed with AIS on histology between 1995 and 2001. Screening histories were compiled from registry records. Variables of interest included number of previous negative Pap smears, time interval since last negative Pap smear, median time between previous negative Pap smears, proportion of negative Pap smears with an endocervical component and history of cervical abnormality. RESULTS: Conditional logistic regression showed that cases and controls did not differ significantly in the number of previous negative smears or in the median time between previous negative smears. Decreasing time since last negative smear was protective against AIS, with controls more likely to have had a recent negative smear. There was no difference in the proportion of previous negative smears with an endocervical component between cases and controls; however, some complex temporal relationships were observed in the regression analysis. CONCLUSION: Women who are diagnosed with AIS have a screening history similar to that of healthy, control women. The findings are consistent with the concept that AIS is predominantly a screening-detected disease.     

Utility of imprint cytology for early presumptive diagnosis in clinically suspicious cervical cancer

OBJECTIVE: To determine the utility of imprint cytology (IC) in providing an early presumptive diagnosis of clinically suspected cervical carcinoma. STUDY DESIGN: A total of 219 clinically suspicious cervical cancer cases underwent Pap test, punch biopsy and IC at the same sitting. Correlations were performed between these diagnostic modalities to determine the sensitivity and specificity of IC in diagnosis of cervical cancer. RESULTS: The overall accuracy of IC in detecting cervical cancers was 96.2%. About 78% of squamous cell carcinomas (SCC), 60% of adenocarcinomas and 100% of small cell carcinoma could be accurately typed on imprints. Twelve malignant lesions were diagnosed on IC among 26 unsatisfactory biopsies. Although there was no false positive result, 3.5% false negative diagnoses were given on IC. The sensitivity and specificity of imprint smear cytology to detect malignancy was 96.2% and 100%. Agreement between imprint cytology and Pap smear diagnosis of malignancy was 95.3%. kappa Statistics revealed excellent agreement between imprints and biopsies and between imprints and Pap smears in diagnosis of malignant lesions. CONCLUSION: IC can be used as an adjunctive technique for an early and reliable preliminary presumptive diagnosis of cancer of the uterine cervix.     

The cytologic diagnosis of adenocarcinoma in situ of the cervix uteri and related lesions. II. Microinvasive adenocarcinoma

Criteria for the cytologic diagnosis of microinvasive adenocarcinoma of the cervix have not been previously established. Such cytologic criteria were evolved through the detailed analysis of cervical smears from 40 histologically confirmed cases. The cellular features of cervical adenocarcinoma in situ (AIS) were always associated with microinvasion. Syncytia of glandular cells, small cells in very crowded sheets and papillary groupings of cells, when seen in conjunction with AIS, were suggestive of microinvasion. Dissociation of cells was common. Nuclear pleomorphism with an irregular chromatin pattern and inconspicuous-to-prominent nucleoli was frequently present. In some cases, a tumor diathesis was seen in the smear background. Using these criteria, our predictive accuracy for diagnosing microinvasive cervical adenocarcinoma is improving steadily and now approaches 50%. Ongoing investigation of these cases must include a diagnostic come biopsy to further improve the predictive accuracy for this lesion.     

Cytology suggestive of glandular neoplasia: outcomes and suggested management

Eighty-three cases having a cervical smear result showing abnormal glandular cells were identified and matched up with the diagnostic histology result. Thirty-four (41.0%) were associated with malignancy and 26 (31.3%) with a cervical intraepithelial lesion without invasion. Thirty-eight (45.8%) had conditions of the cervix as follows: 12 cases had invasive disease of the cervix; nine (10.8%) adenocarcinoma of cervix and three (3.6%) squamous carcinoma of cervix. Nineteen (22.9%) had cervical intraepithelial neoplasia (CIN/SIL) alone and seven (8.4%) had cervical glandular intraepithelial neoplasia (CGIN) +/- CIN. There were 16 (19.3%) cases with malignancies of the uterine corpus and six (7.2%) had a malignancy arising from another primary site. Twenty-three (27.7%) had no malignant or pre-malignant condition. The risk of malignancy was related to age and ranged from 18.2% in those under 35 years to 67.9% in those 55 years and over. A protocol for the management of these cases is described.     

Outcomes of pregnant patients with Pap smears classified as atypical glandular cells

J. Slama, P. Freitag, P. Dundr, J. Duskova, D. Fischerova, M. Zikan, I. Pinkavova and D. Cibula
Outcomes of pregnant patients with Pap smears classified as atypical glandular cells Objectives: The incidence of cervical cancers increases with age. Due to the trend of increasing age of first pregnancy, abnormal Pap smears including those classified as atypical glandular cells (AGC) are being found more often in early pregnancy. Once invasive cancer is excluded, conservative management of squamous intraepithelial lesions (SIL) in pregnancy is considered safe; however, optimal management of AGC is not well established. The aim of our study was to evaluate the outcome of patients with AGC diagnosed from smears during pregnancy. Methods: The study included 17 patients referred to us in early pregnancy with Pap smears reported as AGC: 11 not otherwise specified (AGC‐NOS), five favour neoplasia (AGC‐FN) and one adenocarcinoma in situ (AIS). Thirty‐one with high‐grade SIL (HSIL) Pap smears confirmed on punch biopsy in early pregnancy comprised a control group. Human papillomavirus (HPV) positivity was found in seven patients with persistent AGC‐NOS (including all four who had CIN3 postpartum). All the women were initially examined by expert colposcopy and those with AGC‐FN or AIS smears also by transrectal ultrasound to exclude invasive endocervical cancer. Follow‐up controls were carried out every 8–12 weeks and, if there were no signs of progression, revaluation was scheduled 6–8 weeks after delivery. Results: The mean age of the women was 31.4 years. Conization in one patient in the study group was performed in the 16th week of pregnancy due to colposcopic signs of microinvasive squamous cell cancer confirmed on histology. Progression to invasive cancer was not found in any of the other 16 patients in the study group or in the control group. Cervical intraepithelial neoplasia or AIS was confirmed postpartum by conization or punch biopsy in 47.1% (8/17) of patients in the study group and, in 77.4% (24/31) of patients in the control group. Conclusions: Conservative management of women with AGC in pregnancy is safe where invasive cancer is excluded. As histological verification of glandular pre‐cancerous lesions by punch biopsy is not reliable and the postpartum regression rate cannot be determined precisely, conization should be performed in all cases with AGC‐FN or AIS. Triage of persistent AGC‐NOS with HPV testing is useful in distinguishing significant underlying lesions.     

The cytologic diagnosis of adenocarcinoma in situ of the cervix uteri and related lesions. III. Pitfalls in diagnosis

Potential pitfalls in the cytologic diagnosis of adenocarcinoma in situ (AIS) of the cervix are illustrated by the presentation of three cases of benign cervical lesions initially diagnosed as AIS: cervical endometriosis, tubal metaplasia of the endocervix and changes due to a previous biopsy. The differential diagnosis of endocervical glandular abnormalities is discussed.     

Performance of cytology and colposcopy in diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-positive and HIV-negative women

As part of an extensive multi-institutional DIANAIDS-HIV-HPV-SIL project run in Italy (co-ordinated by ISS), the present study compares the performance (sensitivity, specificity, agreement) of routine cervical smear cytology with that of colposcopy in the detection of histologically-confirmed CIN lesions in 37 HIV-positive and 21 HIV-negative women, belonging to the DIANAIDS cohort of 459 women. All women were subjected to a cervical smear, colposcopy and biopsy, making possible the pairwise comparison of these techniques. In the whole series of HIV-positive and HIV-negative women, cytology had a sensitivity of 86.9% and specificity of 83.3%, the sensitivity of grade 2 abnormality on colposcopy against histology being 82.6% and specificity, 33.3%. No statistically significant difference was observed in the performance of Pap smears between the HIV-positive and HIV-negative women. The sensitivity of cytology was 89.7% vs 82.4% and the specificity, 75% vs 100%. For colposcopy, the sensitivity was 79.3% vs 88.2% and the specificity, 75% vs 50%. These data suggest that cervical Pap smear cytology is a highly sensitive and specific diagnostic tool in the clinical monitoring of lower genital tract pathology in HIV-positive women. Colposcopy, on the other hand, proved to be a somewhat less accurate diagnostic tool in these women.     

Neuroendocrine small cell carcinoma of the cervix associated with endocervical adenocarcinoma: a case report

BACKGROUND: Small-cell carcinoma (SCC) of the cervix is an uncommon member of the neuroendocrine group of cervical carcinomas that is frequently intermixed with a non-SCC component in the form of an adenocarcinoma (ADC) or squamous carcinoma. CASE: Colposcopy revealed a cervical mass in a 41-year-old woman and a Pap smear the presence of some tumor cells from SCC, which was confirmed by subsequent biopsy. The patient received 3 cycles of chemotherapy and then underwent major surgery. The cervical samples showed areas of endocervical ADC adjacent to and intermixed with the SCC. Reviewing the Pap smear, a previously missed malignancy was recognized. On subsequent molecular investigation to assess clonality by microsatellite analysis, the presence of HR-HPV DNA18 on real-time polymerase chain reaction, p16(INK4a) fluorescence in situ hybridization status and the corresponding immunohistochemical expression supported the hypothesis that the two components of the tumor shared the same cell origin. CONCLUSION: SCC of the cervix is a rare but distinct HR-HPV-18-related cervical carcinoma often intermixed with a clonally related non-small cell component consisting of an ADC or squamous carcinoma. The presence of SCC tumor cells in a cervical smear should prompt a search for malignant glandular or squamous tumor cells.     

Atypical glandular cells of undetermined significance in cervical smears after conization. Cytologic features differentiating them from adenocarcinoma in situ

OBJECTIVE: To evaluate the cytologic features of atypical glandular cells of undetermined significance (AGUS) smears following conization through a comparison with adenocarcinoma in situ (AIS) smears. STUDY DESIGN: Fifty cervical smears, diagnosed as AGUS based on groups of crowded glandular cells that raised the possibility of AIS, from 38 patients who had conization and 24 AIS smears, histologically confirmed, from 17 patients were reviewed. Subsequent follow-up biopsies or hysterectomies in 38 patients were evaluated. RESULTS: Nuclear atypia was a more reliable feature than architectural structure in differentiating postcone effect from AIS on cytology. The predominant cytologic features of the postcone smears were crowded glandular cells with a high nuclear/cytoplasmic ratio and relatively small, hyperchromatic nuclei with rather finely granular and uniformly dispersed chromatin, less distinct nuclear membranes, less frequent mitosis and presence of endometrial-type stromal cells in the background. The architecture of the crowded cells in the postcone smears was sometimes similar to that of AIS. No AIS or high grade squamous intraepithelial lesion histology was encountered in follow-up biopsies or hysterectomy specimens. CONCLUSION: The cytologic features distinguishing AGUS from AIS may be helpful in identifying the postcone effect. Since it is important to avoid miscalling the postcone effect as AIS, it is recommended that one check for a previous history of a cone biopsy.     

Cell block as an adjunct to conventional Papanicolaou smear for diagnosis of cervical cancer in resource-limited settings

OBJECTIVE: To assess the utility of indigenously prepared cell blocks (CBs) as an adjunct to a conventional smear test in providing a reliable diagnosis of clinically suspicious cervical cancer in resource-limited settings. METHODS: Eighty-six clinically suspicious cervical cancer cases underwent a conventional smear test, CB preparation from residual cellular samples and biopsies at the same sitting. Correlations were performed between these modalities in order to derive the sensitivity and specificity of the CB technique to diagnose cervical cancer. OBSERVATION & RESULTS: Out of 86 clinically suspicious cervical cancers, 72 (83.7%), 70 (81.4%) and 67 (77.9%) cases were diagnosed as malignant on tissue biopsies, CBs and smears respectively. CB-biopsy agreement in the diagnosis of malignancy was feasible in 87.5% of the cases while CB-Pap smear agreement was feasible in 92.5% of the cases. Sensitivity and specificity of CB preparation to diagnose malignancy was 92.5% and 100%, respectively, when the smear was taken as the reference test (excluding the unsatisfactory smears). When biopsy was taken as the gold standard, the sensitivity and specificity of CBs were 87.5% and 100% respectively (excluding the unsatisfactory biopsies). In 8/19 cases where the smear diagnoses were either unsatisfactory or atypical squamous cells/atypical glandular cells, CBs picked up malignant lesions. CONCLUSION: CBs prepared from the residual cellular sample of conventional cervical scrapes augment the sensitivity of the smear test. When used as an adjunct to the smear, CBs aid in providing a reliable diagnosis of cervical cancer in the majority of the clinically suspected cases and thus the biopsy load can be reduced significantly in resource-poor settings.     

Extrauterine malignancies. Role of Pap smears in diagnosis and management.

OBJECTIVE: To further elucidate the cytologic manifestations of extrauterine malignancies, to evaluate their possible distinction from primary cervical malignancies and to analyze their clinical significance and role in staging. STUDY DESIGN: Papanicolaou (Pap) smears in 33 cases with abnormal cells originating in histologically proven extrauterine carcinomas were evaluated. These cases came from the files of the Medical College of Pennsylvania and Lankenau Hospitals. RESULTS: Ovary, gastrointestinal tract and breast were the three most frequent primary sites, accounting for 28 of the 33 cases (85%). The histologic types encountered were adenocarcinoma, 29 cases (88%); mucoepidermoid carcinoma, 1 (3%); small cell carcinoma, 1 (3%); cloacogenic carcinoma and large cell lymphoma, 1 (3%). The following diagnoses were rendered at the time of initial evaluation: adenocarcinoma consistent with metastasis, 21 cases; carcinoma, primary versus metastatic, 2; adenocarcinoma, suspicious for endometrial primary, 2; suspicious for carcinoma, 1; and atypical glandular cells, 7. CONCLUSION: The yield for positive Pap smear diagnoses in extrauterine malignancies is best in patients with an established diagnosis of a primary neoplasm. The degree of tumor differentiation and extent of tumor involvement did not appear to correlate with diagnostic yield. There appeared to be no statistically significant association of tumor diathesis with primary versus metastatic carcinoma and presence or absence of documented local involvement of the endometrium, cervix or vagina. Therefore, while Pap smears can serve as a diagnostic tool in the evaluation of extrauterine malignancies, they are best utilized as an adjunct to tumor staging and patient management.     

The role of cervical cytology and colposcopy in detecting cervical glandular neoplasia

Objective:  To determine the role of cervical cytology and colposcopy in the management of endocervical neoplasia.
Setting:  Colposcopy unit and cytology laboratory in a teaching hospital.
Sample:  Group 1 included 184 smears showing endocervical glandular neoplasia from 129 patients and group 2 included 101 patients with histology showing endocervical abnormalities in a 6-year period (1993–1998). Follow-up of 6–11 years to 2004 was available.
Methods:  Group 1 were identified from the cytology computer records. Group 2 were identified from histology records on the cytology database and a record of histology cases kept for audit purposes. The clinical records were examined retrospectively.
Results:  The positive predictive value (PPV) of abnormal endocervical cells in smears was 81.1% for significant glandular/squamous [cervical glandular intraepithelial neoplasia (CGIN)/cervical intraepithelial neoplasia grade2 (CIN2 or worse)] lesions. The PPV of colposcopy was 93.5% for significant glandular/squamous lesions of the cervix. The postcolposcopy probability of a significant lesion when colposcopy was normal was 87.5%. The sensitivity of colposcopy in detecting endocervical lesions was 9.8%. The sensitivity of cervical smears in detecting a significant endocervical abnormality (CGIN or worse) was 66.3%. The false negative rate for cytology of endocervical glandular lesions was 4.0%.
Conclusions:  Endocervical glandular neoplasia detected on cytology is predictive of significant cervical pathology even when colposcopy is normal, which supports excisional biopsy in the primary assessment of these smears. The high concomitant squamous abnormality rate justifies the use of colposcopy to direct biopsies from the ectocervix. Cervical cytology is the only current screening method for cervical glandular abnormalities but sensitivity is poor.     

Interlaboratory reproducibility of atypical glandular cells of undetermined significance: a national survey

OBJECTIVE: The aim of this study was to evaluate the inter-laboratory reproducibility for atypical glandular cells (AGC) (The Bethesda System (TBS) 2001) of the laboratories involved in the screening programmes in Italy. METHODS: A set of 35 selected slides were circulated among 167 laboratories involved in local population-based cervical screening programmes. Each laboratory provided one single diagnosis per smear. The smears were read blind to the original diagnosis and to the diagnoses provided by other laboratories. A 'majority' diagnosis was defined for each case and assumed as the reference standard. The diagnosis provided from each laboratory was compared with the majority diagnosis. RESULTS: According to the majority report the 35 slides in the set were classified as negative in nine cases, AGC in eight, adenocarcinoma in eight, and squamous lesion or squamous + glandular lesion in 10. The crude agreement between all pairs of laboratories was 49.43%. K-values were 0.46, 0.21, 0.34, 0.36 and 0.32 for negative, AGC/AIS (adenocarcinoma in situ of endocervix), AdenoCa, Sq/Sq + Gl and all reporting categories respectively. Concordance according to overall K was moderate to substantial in 77% of the participating laboratories. CONCLUSIONS: The present study shows that the AGC category is not easily reproducible. The data confirmed the importance, in a screening scenario, of AGC/AIS diagnoses, but also presented difficulties in differentiating between the two diagnoses. In addition to the results obtained from the circulation of the slides, laboratories which had annually a low number of cervical smears were able to gain experience focused on particular morphological pictures.     

The Evaluation and Interpretation of Cervical Cytology: Application of the Likelihood Ratio Concept

The Papanicolaou smear (Pap test), used for the detection and prevention of neoplastic lesions of the cervix, is known to have both false negative and false positive results. Proper handling of the diagnostic uncertainty resulting from these errors demands quantification of flaws. Traditionally, sensitivity, specificity and predictive values are used for that aim. In this study another approach is advocated, namely the use of the likelihood ratio. For cervical cytology this ratio is the quotient of the probability of a Pap class within the diseased population to the probability of that same Pap class within the non-diseased group. This approach enables the characterization of each Pap class separately, and is therefore much better for clinical interpretation of the result. It is also a superior approach for quality assessment.     

Morphology of adenocarcinoma in situ and microinvasive adenocarcinoma of the uterine cervix. A cytologic and ultrastructural study

Adenocarcinoma in situ (AIS) and microinvasive adenocarcinoma of the uterine cervix and normal endocervical columnar epithelium were studied by cytology, morphometry and electron microscopy to identify differentiating features and to ascertain the cellular origin of cervical adenocarcinoma. Smears from AIS showed the characteristic cytology, consisting of glandular rosettes, palisading and crowded sheets; most nuclei had a relatively uniform oval shape. Smears from microinvasive adenocarcinoma showed more crowded sheets, with enlarged, round and irregular-shaped nuclei and prominent oval nucleoli. These nuclear features were confirmed by the morphometric results. Ultrastructurally, reserve cells in the normal tissues contained tonofibers and secretory granules and showed squamous and adenomatous features. The ultrastructural features of microinvasive adenocarcinoma were similar to those of well-differentiated invasive adenocarcinoma. The cells from both contained tonofibers and secretory granules. These findings suggested that the reserve cell is the cell of origin for cervical adenocarcinoma.     

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.     

Cervical cytology and immunohistochemical features in endometrial adenocarcinoma simulating microglandular hyperplasia. A case report

BACKGROUND: The histology of a few cases of adenocarcinoma simulating cervical microglandular hyperplasia (MGH-AdCa) has been reported. However, the cytologic features of MGH-AdCa in cervical smears and the immunohistochemical profile have not been described. CASE: A 73-year-old female presented with vaginal bleeding. The cervical Pap smear was initially interpreted by the cytotechnologist as "reactive endocervical cells" and was referred for cytopathologist review. The final interpretation was atypical glandular cells of undetermined significance (AGUS), probably neoplastic. Endometrial biopsy and total abdominal hysterectomy with bilateral salpingo-oophorectomy showed International Federation of Gynecologists and Obstetricians grade 1 endometrial carcinoma. The superficial component of the tumor resembled cervical microglandular hyperplasia (MGH); the deeper component had an endometrioid pattern. The Pap smear predominantly showed a glandular component with features of MGH. However, the presence of scattered single cells with hyperchromatic nuclei, one to three nucleoli, easily detectable mitotic figures, randomly scattered apoptotic bodies and focal, watery diathesis suggested a neoplastic process. Immunohistochemistry was studied on paraffin sections. In addition to other markers, the tumor cells were immunoreactive for carcinoembryonic antigen (CEA). CONCLUSION: Although the cervical Pap smear in this case had an MGH-like pattern, some features were atypical enough to suggest a diagnosis of AGUS, probably neoplastic. CEA immunoreactivity of MGH-AdCa could also help to differentiate it from MGH.