Determination of Autophagy in Human Cervicovaginal Smears by Cytological and Immunocytochemical Methods.

Background: Autophagy is a catabolic process whereby organelles and long-lived proteins are recycled through lysosomes to maintain cellular homeostasis. This process is being widely studied using culture techniques and animal models; however, cervicovaginal smears have not been used to detect autophagy. Aims: Our study aims to detect and evaluate autophagy in normal, malignant, infectious, and atypical cells in cervicovaginal smears by using cytological and immunocytochemical methods. Materials and Methods: Papanicolaou-stained 200 cervicovaginal smears were examined and 55 of 200 (27.5%) smears containing negative for intraepithelial lesion or malignancy (NILM) with identifiable infections and/or reactive/reparative changes (INF); briefly, NILM-INF (n = 31, 56.4%), atypical (n = 4, 7.3%), and malignant cells (n = 20, 36.3%) were evaluated as a study group. One hundred forty-five of 200 (72.5%) normal smears were accepted as the NILM without any identifiable infections (control group). The autophagy marker protein Microtubule-associated protein 1 light chain 3 A (MAP1LC3A) was used for immunocytochemical examination. Results: The staining intensity of the MAP1LC3A protein and autophagy positivity were lower in the malignant cells; however, they were higher in the NILM-INF and atypical cells. A statistically significant correlation between the malignant and normal cells was obtained for the autophagy positivity (P = 0.012). In view of the staining intensity of MAP1LC3A protein by the H-score method, a significant correlation was found between the NILM-INF and the normal cells (P = 0.015). Conclusions: Autophagy was detected in various cervicovaginal smears for the first time in this study. Our findings indicate that an autophagy process is essential in infectious cells as well as in the transformation of atypical cells into malignant cells in carcinogenesis.

The relationship between the presence of HPV infection and biofilm formation in cervicovaginal smears.

PURPOSE: To demonstrate and understand the association of HPV infection and biofilm formation. METHODS: The study consisted of cervicovaginal samples of 72 women who were evaluated at the colposcopy unit. Papanicolaou staining was used for cytological examination while "Crystal Violet Binding" assay was performed to detect biofilm formation. RESULTS: HPV-DNA was positive in 55.5% (n = 40) of the patients. The biofilm formation rate was statistically significantly higher in the HPV-positive women (45%) compared to HPV-negative women (21.9%) (P < 0.05). There was a statistically significant relationship between the presence of single HPV and "high-risk HPV" types and biofilm formation (P < 0.05). Biofilm formation was found in 80% of women with abnormal smear demonstrating atypical epithelial cells (P < 0.05). CONCLUSION: Biofilm formation is more frequent at the cervicovaginal microbiota of patients with HPV infection. This finding is especially important in cases with atypical epithelial cells at their cervicovaginal smears.

Microfilariae, a Common Parasite in an Unusual Site: A Case Report with Literature Review.

Filariasis is common in tropical countries. Wuchereria bancrofti is the most common parasite which causes lymphatic filariasis in India. This paper reports the finding of microfilariae in cervicovaginal smear of a 61-year-old post menopausal woman with a brief review of literature. There are limited numbers of reports describing the presence of microfilariae in the cervicovaginal smears and even rarely as an incidental finding. It is very important to keep in mind and screen for microfilariae in the non-endemic areas also.

Evaluation of the relationship between fungal infection, neutrophil leukocytes and macrophages in cervicovaginal smears: Light microscopic examination.

BACKGROUND: Right after opportunistic fungi become pathogenic, they face immune system cells including macrophages and neutrophil leukocytes. Although the relationship between fungi and immune cells are being widely studied by using animal models and culture techniques, cervicovaginal smears have not been used to evaluate this interaction yet. AIM: The aim of this study was to investigate the interactions between fungal infection, macrophages and neutrophil leukocytes in cervicovaginal smear. MATERIALS AND METHODS: Papanicolaou-stained cervicovaginal smears from 2307 women, aged between 18 and 73 years, were examined by light microscopy. Periodic acid-Schiff stain was also used to confirm the presence of fungal cell walls. RESULTS: Fungal infections were detected in 239 of 2307 patients (10.4%), and these cases were taken as the study group. Cases without any infectious agents (n = 1800, 78%) were considered as the control group. When the study and control groups were statistically compared in view of macrophages and neutrophil leukocytes, a significant relationship between presence of fungal infection, macrophages and neutrophil leukocytes was detected (P < 0.05). Furthermore, macrophages and neutrophil leukocytes were found to work against the fungal infection together (P < 0.05). Additionally, when the relationship between the existence of yeast or filamentous forms and these immune cells were evaluated, a significant correlation was not found (P > 0.05). CONCLUSIONS: Our findings indicate that macrophages and neutrophils may play a determining role in host defense against fungal infection together, but neither yeast nor filamentous forms affect the presence of neutrophil leukocytes and macrophages. As a result of this, both yeast and filamentous forms may have pathogenic effects.

Lymphoma of the cervix: A diagnostic pitfall on cervicovaginal smear.

Malignant lymphoma that secondarily involves the cervix is a rare condition and may be difficult to distinguish from follicular cervicitis and small cell carcinoma. Cervical lymphoma is sometimes misdiagnosed on cervicovaginal cytology due to its rarity. We report a case of a cervical lymphoma in a 65-year-old woman, which was diagnosed as a squamous cell carcinoma on cervicovaginal cytology.

Non-Hodgkin's lymphoma: A rare diagnosis on cervicovaginal cytology.

Cervicovaginal smear screening is well known to reduce morbidity and mortality rates of invasive cervical carcinoma. Herein, we report a case of 56-year-old woman whose cervicovaginal smear was found to consist of malignant cells characterized by high nuclear/cytoplasmic ratio, scant rim of cytoplasm, coarsely granular nuclear chromatin and irregular nuclear membrane that were all reminiscent of a malignant lymphoma. Histopathological examination of the hysterectomy and unilateral adnexectomy specimen confirmed the presence of a diffuse large B-cell non Hodgkin's lymphoma involving the cervix, endometrium, myometrium, serosa and the right ovary.

Eggs containing larvae of Enterobius vermicularis in vaginal smear.

Enterobius vermicularis also known commonly as pinworm is the most common intestinal parasite. It is a nematode that inhabits the human terminal ileum, colon and appendix. The fertilized female migrates to the perianal area where eggs are deposited but occasionally introduces itself into adjacent orifices, most commonly the female genitourinary tract. Thus the eggs can be seen in the vaginal smear as a result of contamination. We report a case wherein the patient presented with signs and symptoms of vulvovaginitis. In her vaginal smear there were eggs of Enterobius vermicularis which showed a coiled larva within it. In the background there were plenty of acute inflammatory cells. This patient responded favorably to antihelminthics. We report this case to highlight the morphology of the parasite and also to emphasize that such findings should not be neglected. Timely reporting and appropriate treatment of such cases will prevent further complications of this parasite including endometritis, salphingitis and peritonitis.

[Mansonelliasis identified by a cervicovaginal smear at the university hospital center of Bobo-Dioulasso (Burkina Faso)]. / Frottis cervicovaginal révélant une mansonellose au centre hospitalier universitaire de Bobo-Dioulasso, Burkina Faso

INTRODUCTION: Mansonella perstans is a genus of filaria that is often asymptomatic or responsible for unspecific symptoms. M. perstans microfilariae are uncommon on cervicovaginal smears. CASE: We report the case of a woman with pruritis and eosinophilia. Microfilariae of M. perstans were observed on both cervicovaginal and blood smears. The patient was successfully treated with a combined single dose of 400 mg of albendazole and ivermectin (150 µg/kg). CONCLUSION: We described here an atypical and rare localization of M. perstans. The routine examination of cervicovaginal smears of women admitted to Bobo-Dioulasso Hospital for screening of cervical neoplasia should allow us to determine the frequency of this parasitosis and propose appropriate treatment.

A Comparision of Surepath(TM) Liquid-Based Smear with a Conventional Smear for Cervicovaginal Cytology-with Reference to a Histological Diagnosis / 대한세포병리학회지

This study was performed to compare Surepath(TM) liquid-based smear and a conventional cervicovaginal smear with reference to a histological diagnosis. A hybrid capture test (HCII) was also performed and analyzed. We collected matched cases for cervicovaginal cytology- histology: 207 cases for conventional cytology (CC) and 199 cases for liquid-based cytology (LBC). HCII was performed in 254 patients. When a cytological diagnosis of ASCUS or above (ASCUS+) is classified as positive and a histological diagnosis of LSIL+ is classified as positive, the sensitivity and specificity for LBC was 91.7% and 75.9%, respectively and the sensitivity and specificity for CC was 62.6% and 96.1%, respectively. When a cytological and histological diagnosis of LSIL+ is classified as positive, the sensitivity and specificity for LBC was 77.5 and 96.6%, respectively and the sensitivity and specificity for CC was 49.7% and 100%, respectively. When a histological diagnosis of LSIL+ is classified as positive, the sensitivity and specificity for HCII was 78.9% and 78.1%, respectively. The concordance ratio between the cytological and histological diagnosis was 80.4% (kappa=76.0) for LBC and 56.5% (kappa=55.1) for CC. LBC is more sensitive and less specific then CC, as a cytological cutoff level of ASCUS, but more sensitive and equally specific, as a cytological cutoff level LSIL or HSIL. LBC is more reliable with a high concordance ratio between the cytological and histological diagnosis.

Immunocytochemical Staining for p16 of Atypical Squamous Cells in Cervicovaginal Smear / 대한세포병리학회지

It was reported that the main cause of intraepithelial neoplasm and squamous cell carcinoma of the uterine cervix is human papilloma virus infection, and that the expression of p16 is increased in cells infected by human papilloma virus. We performed an immunocytochemical staining for protein p16 in 17 cases of cervocovaginal smears initially diagnosed as atypical squamous cells of undetermined significance, to know whether the staining could help the differentiation of neoplastic cells from reactive atypical cells. Of 17 smears, 6 were diagnosed finally as high grade intraepithelial neoplasm or invasive squamous cell carcinoma by follow-up biopsy and smear, and 5 of the 6 were positive for p16. Three were diagnosed as koilocytosis, and one of them was weakly positive for p16. Eight were diagnosed as reactive atypical cells, and all of them were negative for p16. We thought that immunocytochemical staining of p16 in cervocovaginal smears could help the differentiation of neoplastic cells from reactive atypical cells.

Liquid-Based Cytology Using MonoPrep2(TM) System in Cervicovaginal Cytology: Comparative Study with Conventional Pap Smear and Histology / 대한세포병리학회지

We compared the diagnostic accuracy of liquid-based cervicovaginal cytology using MonoPrep2(TM) system (Monogen, Herndon, Virginia, USA), a manual system based on membrane filtration method, with conventional Pap smear. Study population included 92 patients visiting the gynecologic department under the suspicion of uterine cervical disease. In thirty of them, surgical biopsy was performed. MonoPrep2(TM) system provided well-preserved monolayer specimen with good nuclear morphology. However, about 19% of specimens were inadequate to interpret due to low cellularity. The detection rate of abnormal cells more than ASCUS (atypical squamous cells of unknown significance) was 23.9% and higher than 19.4 % of conventional Pap smear. Diagnostic concordance rate with conventional Pap smear was 81%, and severe discordance rate influencing on the management of patient was 7.6 %. Among these seven cases, MonoPrep2(TM) system was more diagnostic only in four. In comparison with histology, the sensitivity of diagnosis of MonoPrep2(TM) system was 78.9% and slightly higher than 73.5% of conventional Pap smear. However, the specificity was 81.1% and lower than 90.9% of Pap smear. In conclusion, MonoPrep2(TM) system provided diagnostic accuracies similar to the conventional Pap smear. The inexpertness of slide preparation and the low cellularity were considered to endow a limitation in more accurate evaluation.

Pregnancy-Related Cytologic Changes In Cervicovaginal Smears / 대한세포병리학회지

Due to insufficient clinical information, most cervicovaginal smears from pregnant or postpartum women have been screened without regard to pregnancy-related cytological changes. Here, we have reviewed 116 abnormal cervicovaginal smears from 103 pregnant and postpartum women. Initial cytological diagnoses revealed the following: 9 cases of high-grade squamous intraepithelial lesions (HSIL), 8 cases of low-grade squamous intraepithelial lesions (LSIL), 85 cases of atypical squamous cells of undetermined significance (ASCUS), and 14 cases involving atypical glandular cells of undetermined significance (AGUS). 31 cases, upon review, involved pregnancy-related cytological changes, comprising 25 cases of decidua cells, 4 cases of Arias-Stella reaction, and 2 cases of decidual cells coupled with Arias-Stella reaction. Interpretation errors were detected in 14 cases: 13 cases of decidual cells interpreted as either ASCUS favor reactive or ASCUS ruled out HSIL, and one case of Arias-Stella reaction was interpreted as ASCUS ruled out HSIL. Decidual cells and degenerated glandular cells with Arias-Stella reaction can result in diagnostic mistakes. In order to avoid misdiagnosis and unnecessary surgeries, both clinicians and pathologists must be aware of the pregnancy-related cytological changes. The clinician should also always inform the pathologist on the pregnancy status of the patient.

Cytologic Features of Signet Ring Cell Carcinoma of the Uterine Cervix: A Report of Two Cases / 대한세포병리학회지

Signet ring cell carcinoma is a rare type of mucinous adenocarcinoma of the uterine cervix. To the best of our knowledge, there is no report on cytologic findings of primary signet ring cell carcinoma of the uterine cervix in the literature. Recently, we experienced two cases of signet ring cell carcinoma of the uterine cervix. The finding of characteristic signet ring cells on cervicovaginal smear led to the diagnosis of signet ring cell carcinoma. However, primary signet ring cell carcinoma could not be cytologically distinguished from more common metastatic tumor. Therefore, diagnosis rests upon the recognition of signet ring cells and the absence of signet ring cell carcinoma elsewhere.

Exfoliation of Endometrial Cells on Cervicovaginal Smears / 대한세포병리학회지

The significance of endometrial cells on cervicovaginal smears is underestimated. The aim of this study is to evaluate the detection rate of endometrial cells on cervicovaginal smears. The materials consisted of two groups. Group I was 701 cervicovaginal smears from patients with no gynecological problems. Group II was 208 cervicovaginal smears from patients with abnormal uterine bleeding followed by endometrial curettage; 31 cases of endometrial adenocarcinoma(CA), 19 cases of endometrial hyperplasia(HP), 83 cases of dysfunctional uterine bleeding(DUB), and 75 cases of normal endometrium. Cervicovaginal smears were reviewed according to the criteria of The Bethesda System. Endometrial cells were identified in 15 of 701 cases(2.1%) in group I and 64 of 208 cases(30.8%) in group II. Among group II, detection rate of endometrial cells was the highest in CA (51.6%) compared to HP(26.3%), DUB(41.0%), and normal endometrium(12.0%) ( p<0.05). Cytologic atypia of endometrial cells was not found in group I, but was more frequently identified in CA(87.5%) than in HP(10.5%) or DUB(14.7%) ( p<0.05). Exfoliation of endometrial cells might be related to abnormal endometrial lesion, and reporting of endometrial cells in the cervicovaginal smear may increase a chance to detect endometrial lesions especially in patients with abnormal uterine bleeding.

A Comparision of AutoCyte PREP with Matched Conventional Smear in Cervicovaginal Cytology / 대한세포병리학회지

This study was designed to compare the performance of liquid-based preparation from the AutoCyte PREP with the conventional cervicovaginal smear in masked split-samples. In randomly selected 840 cases, the conventional smear was always prepared first, and the AutoCyte PREP used the residual cells on the collecting device. Parallel AutoCyte PREP slides and matched conventional smears were screened in a blind fashion. All abnormals and 10% random normal cases were reviewed by two pathologists in a blind fashion. The Bethesda System was used for reporting the diagnosis and specimen adequacy. The diagnoses from the two methods were agreed exactly in 767(91.3%) of 840 cases. The AutoCyte PREP demonstrated a 25% overall improvement in the detection of squamous intraepithelial lesion(SIL). The ratio of ASCUS to SIL was decreased as 0.45 compared with 1.00 of conventional smear. The AutoCyte PREP produced excellent cellular preservation and superior sensitivity for detection of atypical cells as compared to the conventional smear. It makes us to be able to subclassify ASCUS into from WNL to HSIL. We thought that the AutoCyte PREP method might contribute to increase the detection rate of abnormal cells than conventional methods.

The Cytologic Analysis of Microinvasive Squamous Cell Carcinoma of the Uterine Cervix on Cervical Smear / 대한세포병리학회지

While cytologic characteristics of squamous dysplasia, carcinoma in situ, and invasive squamous cell carcinoma of the uterine cervix are well documented, relatively few studies have dealt with the cellular features of microinvasive carcinoma. In order to describe the cellular characteristics of microinvasive squamous cell carcinoma, we retrospectively reviewed 45 cervovaginal smears(15 carcinoma in situ, 15 microinvasive cancer, 15 invasive cancer) which were confirmed by histologic examination of specimens obtained by hysterectomy at the Seoul National University Hospital during 5 years from 1995 to 1999. The cytologic features about tumor diathesis, inflammatory background, cell arrangement, anisonucleosis, nuclear membrane irregularity, nuclear chromatin pattern, and nucleoli were observed. The cytologic characteristics of microinvasive squamous cell carcinoma of the uterine cervix are syncytial pattern, mild tumor diathesis, the irregularity of nuclear membrane, irregularly distributed nuclear chromatin, and occurrence of micronucleoli. But, correlation between the depth of invasion and the cytologic feature had limited value.

Exfoliation of endometrial cells on cervicovaginal smears / 대한세포병리학회지

The significance of endometrial cells on cervicovaginal smears is underestimated. The aim of this study is to evaluate the detection rate of endometrial cells on cervicovaginal smears. The materials consisted of two groups. Group I was 701 cervicovaginal smears from patients with no gynecological problems. Group II was 208 cervicovaginal smears from patients with abnormal uterine bleeding followed by endometrial curettage; 31 cases of endometrial adenocarcinoma(CA), 19 cases of endometrial hyperplasia(HP), 83 cases of dysfunctional uterine bleeding(DUB), and 75 cases of normal endometrium. Cervicovaginal smears was reviewed according to the criteria of The Bethesda System. Endometrial cells were identified in 15 of 701 cases(2.1%) in group I and 64 of 208 cases(30.8%) in group II. Among group II, detection rate of endometrial cells was the highest in CA (51.6%) compared to HP(26.3%), DUB(41.0%), and normal endometrium(12.0%) (p<0.05). Cytologic atypia of endometrial cells was not found in group I, but was more frequently identified in CA(87.5%) than in HP(10.5%) or DUB(14.7%) (p<0.05). Exfoliation of endometrial cells might be related to abnormal endometrial lesion, and reporting of endometrial cells in the cervicovaginal smear may increase a chance to detect endometrial lesions especially in patients with abnormal uterine bleeding.

The Outcomes of 17,744 Cervicovaginal Smears in Ihha University Hospital / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to investigate the distribution of the result of 17,744 cervicovaginal smears and their pathologic results in Inha University Hospital to make a reference data. METHODS: During 28 months, May 1996 to August 1998, we performed 17,774 cervicovaginal smears and arranged them by the Bethesda system and compared them with their pathologic results. RESULTS: Among 17,744 smears, there were 93.2% of benign results, 2.9% of ASCUS, 0.9% of LSIL, 1.4% of HSIL, and 0.8% of SCC. The ASCUS/SIL ratio was 1.28. Among ASCUS, the high grade histologic outcome was composed 4.0%. Among LSIL, there were 15.7%, and HSIL 48.0%, SCC 56.1%, AGUS 9.3%, and Adenocarcinoma, the results was 69.2%. CONCLUSION: Among 17,744 smears, there were 93.2% of benign results, 2.9% of ASCUS, 0.9% of LSIL, 1.4% of HSIL, and 0.8% of SCC. The ASCUS/SIL ratio was 1.28. These results were very similar to other data and we would like to add our data to them as a reference. And the worse the smear results were, the worse the pathologic results were.

Comparison of Qualified Diagnosis of "Atypical Squamous Cells of Undetermined Significance" with Subsequent Biopsy / 대한세포병리학회지

To evaluate whether different qualifications of a cytologic diagnosis of "atypical squamous cells of undetermined significance(ASCUS)" predict a greater or lesser likelihood of tissue diagnosis of uterine cervix, we compared different cytologic qualifications of ASCUS with the tissue diagnosis. One hundred twenty-two con secutive Papanicolaou smears showing ASCUS in women who had undergone cervical biopsy within nearest 30 days were collected. The 122 smears were qualified as "favor reactive"(25%), "favor low grade squamous intraepithelial lesion (LSIL)"(24%), "favor squamous intraepithelial lesion(SIL)"(16%), "favor high grade squa mous intraepithelial lesion(HSIL)"(16%), and "not otherwise specified"(19%). Squamous intraepithelial or invasive lesion was pathologically confirmed by cervical biopsy in 13% of the "favor reactive", 27% in "favor LSIL", 70% in "favor SIL", 75% in "favor HSIL", and 35% in "not otherwise specified" smears. There were significant asso ciations between the favor reactive smear and the benign biopsy finding and between the favor SIL smear and the biopsy showing a squamous intraepithelial or more severe lesion. Nevertheless, most of favor LSIL smears exhibit reactive process in tissue biopsy. Conclusively, qualified ASCUS stratifies women into different risk groups for SIL. The cytopathologist should make the cytologic diagnosis of "ASCUS, favor LSIL" circumspectly.

Cytologic Analysis of Adenocarcinoma of the Cervicovaginal Smears / 대한세포병리학회지

We have investigated the cervicovaginal smears in order to define the cytologic features of uterine adenocarcinomas. Total 22 cases were reviewed(12 cases from the Sanggye Paik hospital, Inje university and 10 cases from the Korea Cancer Center Hospital) from January 1992 to December 1997. Five cases were endometrial adenocarcinomas and the remaining 17 cases were cervical adenocarcinomas. Se venteen cases of cervical adenocarcinomas were divided into endometrioid(6 cases), endocervical(7 cases), mixed endometrioid and endocervical(1 case), papillary (2 cases), and adenosquamous(1 case) carcinomas. The background of endocervical adenocarcinoma was hemorrhagic or inflammatory. The tumor diathesis was less prominent than that of the squamous cell carcinoma. The prominent features of the endocervical type adenocarcinomas were large and loose clusters, large intra cytoplasmic vacuoles, and prominent overlapping and peripheral palisading of nuclei. In contrast, the endometrioid adenocarcinomas showed small and compact clusters, and small intracytoplasmic vacuoles. The detection rate of endometrial adeno carcinoma was lower than that of the endocervical adenocarcinoma.