Cytology of cervical intraepithelial glandular lesions.

Cytological criteria for the identification of glandular intraepithelial lesions (GIL) have not yet been fully described, especially for the precursors of adenocarcinoma in situ (AIS), thus these lesions may frequently remain unrecognized. As most patients diagnosed with AIS or mild to moderate GIL (grades I, II) are free from clinical symptoms, cytology has a very responsible role in the detection of these lesions. The aim of the study was to achieve the most appropriate cytologic diagnosis of intraepithelial lesions of endocervical columnar epithelium, analyzing the cytology findings in patients with histologically verified AIS and GIL (I, II). The value of cytology in the detection and differential diagnosis was assessed in 123 patients with definitive histologic diagnosis of glandular lesions (AIS, n = 13; GIL I, n = 11; and GIL II, n = 7), and glandular lesions associated with squamous component (AIS associated with cervical intraepithelial neoplasia (CIN) or invasive squamous cell carcinoma (SCC), n = 58; GIL I or GIL II associated with CIN, n = 28; and GIL associated with microinvasive squamous carcinoma (MIC), n = 6). In 95.1% of patients, lesions were detected by cytologic analysis that indicated additional diagnostic procedure. In terms of differential diagnosis, cytology showed higher accuracy in predicting lesion severity vs. type of epithelial alteration (75.6% vs. 55.3%) and abnormalities of columnar epithelium (95.7%; vs. 74.2%). The accuracy of cytology was higher in pure (AIS, 61.5% and GIL I, II, 22.2%) than in mixed lesions (25.9% and 20.6%). Continuous improvement in cervical specimens and cytodiagnostic skills, better understanding of intraepithelial adenocarcinoma and precursors, and their inclusion in the classification of cytologic and histologic findings are expected to upgrade the detection of these lesions, and to reduce the invasive cervical adenocarcinoma morbidity and mortality.

Cervix cancer screening in Croatia within the European Cervical Cancer Prevention Week.

Croatia still has opportunistic screening and the organized national screening has been planned. The European Cervical Cancer Prevention Week was held twice in Croatia, in January 2008 and 2009. Within the first one in 2008, information campaign "For All Women" via mass media was held, and women were invited to the organized free gynecological examination and Papanicolaou test (Pap test) in the University Department of Gynecology and Obstetrics, Zagreb University Hospital Center. Following invitation 481 women attended the testing; the median age was 55 years. There were more women aged > or = 50 (n = 353), with the highest participation in the age group 55-59 years (n = 94). Some women came because of subjective symptoms (n = 10), but the majority of them came only for testing (n = 471). According to history of previous cytological testing, 400 women have had > or = 1 negative findings, 71 women have had > or = 1 positive findings, 9 women attended Pap test for the first time, and 1 woman does not know about previous testing. Cervical cytology was abnormal in 35 women (7.28%), the median age was 42 years with the highest proportion in the age group 30-34 years (n = 7); among all of them 21 women (60%) had no abnormal Pap test previously. The findings were: Atypical squamous cells of undetermined significance--ASC-US (n = 9), ASC cannot exclude high-grade squamous intraepithelial lesion--ASC-H (n = 1), cervical intraepithelial neoplasia--CIN 1 (n = 13), CIN 2 (n = 1), CIN 3 (n = 6), carcinoma planocellulare (n = 2), atypical glandular cells--AGC-favor reactive endocervical cells (n = 3). Among women aged < or = 49 there were 20.47% abnormal findings and among those aged > or = 50, 2.55%. According to 21 positive Pap tests previously, among women aged < or = 49 there were 30.71% while among those aged > or = 50 there were 9.07%. Within the European Cervical Cancer Prevention Week in 2009, employed women from one national company were invited by internal information to the same procedure. A smaller group of younger asymptomatic women came for testing (n = 53), median age 39 years. According to history of previous cytological testing, 50 women have had > or = 1 negative findings, 3 women have had > or = 1 positive findings. In this study, Pap test was positive in 3.77% (n = 2). National screening programme should be focused on the participation of all personally invited women, especially younger age groups and under-screened women. Well designed information campaign should be implemented in national screening programme.

Digital morphometry of cytologic aspirate endometrial samples.

Unlike cervical cytology, morphological cytology criteria in the differential diagnosis of endometrium have not yet been clearly defined, and methods to allow for more precise evaluation of endometrium status have been searched for. The aim of the present study was to assess the value of morphometric nucleus analysis of cytologic aspirate endometrial samples in proliferative, hyperplastic and malignant endometrium by use of digital image analysis. Morphometric analysis was performed on archival cytologic aspirate endometrial samples (at least 10 per group) stained according to Papanicolaou (n = 77) and May-Grünwald-Giemsa (MGG; n = 80) with the following histopathologic diagnoses: proliferative endometrium, hyperplasia simplex, hyperplasia complex, hyperplasia complex atypica, and adenocarcinoma endometriodes endometrii (grade I, II and III). Interactive image analysis (nuclear area, convex area, perimeter, maximum and minimum radius, length and breadth, as well as nucleus form factor and elongation factor) was performed by use of the SFORM software (VAMSTEC, Zagreb) on at least 50 (Papanicolaou stain) and 100 (MGG stain) well preserved endometrial epithelial cell nuclei without overlapping, at magnification of x1000. Statistical data analysis was done by use of the Statistica Ver. 6 statistical package. Multivariate analysis (ANOVA) distinguished malignant, hyperplastic and proliferative endometrium according to all morphometric variables with both staining methods (p < 0.05). However, on interactive testing of the groups (Kruskal-Wallis test), hyperplasias without atypia yielded no significant differences (p > 0.05) from atypical hyperplasia, adenocarcinoma and proliferative endometrium only according to the nucleus form factor and elongation factor (Papanicolaou stain), whereas malignant and atypical hyperplastic endometrium (MGG stain) differed statistically significantly (p < 0.05) from proliferative and hyperplastic endometrium without atypia according to all study parameters except for the nucleus form factor (p > 0.05). According to the cytologic staining method, morphometric parameters were considerably higher in MGG stained endometrial samples, reaching the level of statistical significance (p < 0.05) except for the nucleus form factor and elongation factor (p > 0.05) in the groups of hyperplasia simplex and complex, well differentiated adenocarcinoma (form factor) and atypical hyperplasia (elongation factor). A combination of cytomorphology and the morphometric variables assessed in this study can yield useful information on the cytologic state of endometrium, with special reference to the possible differentiation of the group of hyperplasia without atypia from the group of adenocarcinoma and atypical hyperplasia.

Liquid-based cytology--new possibilities in the diagnosis of cervical lesions.

Liquid-based cytology (LBC) enables the use of supplementary methods in the diagnosis and prognosis of cervical lesions. The aim of this study was to analyze the correlation between p16-INK4a immunoexpression in ThinPrep cervical cytologic samples and human papillomavirus (HPV) detection by polymerase chain reaction (PCR) from the same sample. LBC-ThinPrep (Cytyc, USA) cervical cytology samples, prepared and stained by Papanicolaou method, were analyzed using modified Bethesda cytologic classification named "Zagreb 2002". A second ThinPrep slide, prepared from the same sample, was immunostained for p16INK4a using CINtec p16INK4a Cytology Kit (DakoCytomation, Denmark). Increased expression of the high-risk (HR) HPV E6 and E7 oncogenes results in a highly specific increase in p16 protein expression and overexpression of p16INK4a acts as a potential biomarker for cervical cancer progression from premalignant lesions. Brown nuclear and/or cytoplasmic staining of abnormal cells was considered a positive result. Residual material was used for 13 HR HPV-DNA detection by the PCR based AMPLICOR HPV test (Roche Molecular Systems). A total of 120 ThinPrep Pap tests with the following cytologic diagnoses: 17 within normal limits, 17 atypical squamous cell (ASC) (7 ASC of undetermined significance /ASCUS/ and 10 ASC of high-grade squamous intraepithelial lesions cannot be excluded /ASC-H/), 26 low-grade squamous intraepithelial lesions (LSIL) corresponding cervical intraepithelial neoplasia (CIN) 1, 57 high-grade SIL (HSIL) i.e. 24 CIN II and 33 CIN III and 3 squamous cell carcinoma (SCC) were included in the study. All CIN III (n = 33) and SCC (n = 3) specimens expressed p16INK4a immunoreactivity, whereas the HR HPV test was positive in 97% (32/33) of CIN III and 100% (3/3) of SCC specimens. The p16INK4a biomarker was positive in 87.5% (21/24) of CIN II and 69% (18/26) of CIN I, while the HR HPV was positive in 75% (18/24) of CIN II and 50% (13/26) of CIN I. In ASCUS cytology, p16INK4a and HR HPV showed the same rate of positivity (28.5%; 2/7). Expression of p16INK4a was detected in all cytologic (10/10) ASC-H lesions, in contrast to HR HPV detected in only 20% (2/10) of ASC-H cases. These data suggest the p16INK4a evaluation in ThinPrep cervical samples to be significantly associated with HR HPV testing by PCR in the same sample for the diagnosis of HSIL lesions and cervical carcinomas. A prospective study with longer follow up may clarify the predictive values in the management of LSIL and ASC diagnosis.

Cytologic characteristics of adenoid cystic carcinoma of the cervix uteri--case report.

Adenoid cystic carcinoma is a rare malignancy, usually found in the salivary glands, although this unusual tumor can be found at other sites of the body. In particular, regarding adenoid cystic carcinoma of the cervix (ACCC) most frequently reports are given for postmenopausal women. In this respect, our work is one among very few in the literature that considers a cytologic picture of this uncommon cervix carcinoma. The case of 74 year old patient with postmenopausal bleeding is described. Both Pap smear and air dried smear of the uterine cervix were analyzed. The cytologic findings revealed very few small clusters of abnormal glandular cells, as well as some amorphous eosinophilic globule-like material, with granulomatous and necrotic background. The latter includes a lot of histiocytes, multinucleated giant cells, large aggregates of epitheloid cells and lymphocytes. Histology revealed the diagnosis of ACCC. We emphasize the importance of careful screening of Pap smear that might be crucial in the case of suspicious clinical findings in postmenopausal women, when the possibility of ACCC has to be considered.