• Journal of Pathology and Translational Medicine
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• v.52 no.6
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• pp.404-410
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• 2018

Background: Fine-needle aspiration cytology serves as a safe, economical tool in evaluating thyroid nodules. However, about 30% of the samples are categorized as indeterminate. Hence, many immunocytochemistry markers have been studied, but there has not been a single outstanding marker. We studied the efficacy of CD56 with human bone marrow endothelial cell marker-1 (HBME-1) in diagnosis in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III. Methods: We reviewed ThinPrep liquid-based cytology (LBC) samples with Papanicolaou stain from July 1 to December 31, 2016 (2,195 cases) and selected TBSRTC category III cases (n=363). Twenty-six cases were histologically confirmed as benign (six cases, 23%) or malignant (20 cases, 77%); we stained 26 LBC slides with HBME-1 and CD56 through the cell transfer method. For evaluation of reactivity of immunocytochemistry, we chose atypical follicular cell clusters. Results: CD56 was not reactive in 18 of 20 cases (90%) of malignant nodules and showed cytoplasmic positivity in five of six cases (83%) of benign nodules. CD56 showed high sensitivity (90.0%) and relatively low specificity (83.3%) in detecting malignancy (p=.004). HBME-1 was reactive in 17 of 20 cases (85%) of malignant nodules and was not reactive in five of six cases (83%) of benign nodules. HBME-1 showed slightly lower sensitivity (85.0%) than CD56. The specificity in detecting malignancy by HBME-1 was similar to that of CD56 (83.3%, p=.008). CD56 and HBME-1 tests combined showed lower sensitivity (75.0% vs 90%) and higher specificity (93.8% vs 83.3%) in detecting malignancy compared to using CD56 alone. Conclusions: Using CD56 alone showed relatively low specificity despite high sensitivity for detecting malignancy. Combining CD56 with HBME-1 could increase the specificity. Thus, we suggest that CD56 could be a useful preoperative marker for differential diagnosis of TBSRTC category III samples.

• The Journal of Korean Obstetrics and Gynecology
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• v.35 no.4
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• pp.174-185
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• 2022

Objectives: The purpose of this study is to report the improvement of recurrent cervical intraepithelial neoplasia (CIN) and chief complaint including dysmenorrhea, premenstrual syndrome after Korean medicine treatment. Methods: The patient who diagnosed CIN even after undergoing two times of loop electrosurgical excision procedure (LEEP) and complained dysmenorrhea with premenstrual syndrome was treated by acupuncture, moxibustion and herbal medicine as Ojeok-san-gami-bang along with mistletoe extract injection (Abnobaviscum^®). The effect of treatment was evaluated by the results of liquid based cytology and HPV genotyping. Other symptoms were evaluated according to the patient's subjective complaint. Results: Before the treatment, the result of cytology was low grade squamous intraepithelial lesion and a low-risk group for HPV was detected. At the first examination after treatment, cytology showed negative for intraepithelial lesion or malignancy and the HPV genotyping was negative. The result showed negative findings in 3 consecutive follow-up tests. In addition, the chief complaint and general conditions were improved. Conclusion: This study shows that the recurrent cervical intraepithelial neoplasia (CIN) was improved after the Korean traditional treatment and it can be effective medical alternatives or options for patients receiving mistletoe injection during follow-up.

• The Korean Journal of Cytopathology
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• v.18 no.2
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• pp.143-152
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• 2007

Sono-guided fine needle aspiration (FNA) of the thyroid is widely used, but the aspirated samples are typically not well preserved and low cellularity makes diagnosis difficult in many cases. The object of the current study is to evaluate the adequacy and diagnostic accuracy of the use of $SurePath^{TM}$ liquid-based cytology (SP-LBC) in the sonoguided fine needle aspiration of the thyroid nodule and to compare its use with that of the use of a conventional smear (CS). A total of 172 sono-guided FNAs of thyroid nodules from April to June, 2006 were prepared by the use of the split method with either SP-LBC or CS; the samples were stained with the use of hematoxylin-eosin (H&E) and Papanicolaou (Pap) stains. A cyto-histological correlation was performed in 69 (30 SP and 39 CS) cases that had been histologically confirmed. The rate of producing unsatisfactory slides by the use of the SP-LBC method (9.3%) was less than that of the use of the CS method (20.9%). The diagnostic accuracy of the SP method (93.3%) was better than that of the CS method (85.3%). The sensitivity and specificity of the SP method (94.4% and 92.3%) was better than that of the CS method (83.3% and 70%), respectively (p < 0.05). The CS of sono-guided aspirated specimens had some unavoidable limitations related to inadequate sampling such as a bloody background, low cellularity and an indication that some clinicians smeared many useless slides (averaging four to ten slides), and that most slides showed only blood that included few follicular cells. The SP method resulted in more thinly smeared slides and showed cleaner background and greater cellularity than the use of the CS method. Each follicular cell shows superior nuclear detail, and more distinct cytoplasmic features than with the use of the CS method. SP-LBC appears to be an easy, highly accurate, and reliable cytological method for employ for a diagnostic approach of thyroid disease and thyroid nodules. The SP-LBC method is a suitable alternative to the CS method to overcome diagnostic difficulties.

• Korean Journal of Clinical Laboratory Science
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• v.45 no.3
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• pp.108-113
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• 2013

The study compared the cytological features of papillary thyroid carcinoma (PTC) in liquid-based preparations (LBPs) and conventional Pap (CP) smears from fine needle aspiration (FNA), and assessed the feasibility of LBP using the Cell Scan $1500^{TM}$ processor on thyroid FNA samples. Thyroid FNA samples were obtained from 883 consecutive patients. Each sample was divided into two and used for LBPs and CP smears. All were screened independently in a double-blind manner. From the 883 cases, 95 cases were diagnosed as PTC in one or both types of preparation (10.8%). PTC was diagnosed via CP smears in 83 cases (87.4%) and via LBPs in 70 cases (73.7%). However, there were differences in categorization between the paired preparations: Twelve (12) PTCs were misinterpreted in CP smears and 25 PTCs in LBPs. There was a significant discrepancy in the rate of detection of the diagnostic features, with LBPs having a lower detection rate. One (1) case (1.2%) of CP smears and 16 cases (22.9%) of LBPs were categorized as unsatisfactory/nondiagnostic in a total of the 95 PTCs. To conclude, the detection rate of the diagnostic features of PTC is lower in Cell Scan 1500TM samples than in CP smears. However, there are some cases in which a diagnosis of PTC is made in LBPs, but not in CP smears. Therefore, definitive cancer diagnosis in thyroid FNA preparations is likely to result from agreement between direct smears and Cell Scan 1500TM preparations.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.3
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• pp.132-139
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• 2015

Recently, $p16^{INK4a}$/Ki-67 dual immunostaining has been introduced as a new biomarker protocol for early detection of uterine cervical dysplasia and cancer in liquid-based cytology (LBC). We performed the $p16^{INK4a}$/Ki-67 dual immunostaining using a CINtec$^{(R)}$ PLUS kit in a total of 109 LBC cases of cervicovaginal smear and compared its results with those from LBC, HPV hybrid capture II (HC II) test and histological diagnosis. Expression of $p16^{INK4a}$ and Ki-67 was significantly associated with cases of LSIL or higher in cytological diagnosis and cases of cervical intraepithelial neoplasia (CIN) 1 or higher in histological diagnosis (p<0.001 and p<0.001, respectively). Among forty-six cases of atypical squamous cells of undetermined significance (ASCUS) in LBC, $p16^{INK4a}$ and Ki-67 was expressed in 31 (67.4%), which were positively associated with cases of CIN I lesion or higher in histology. The sensitivity of $p16^{INK4a}$/Ki-67 dual immunostaining for finding lesions of CIN 1 or higher was 89.0%, which was higher than LBC. The specificity was 73.5%, which was higher than that of the HC II test. Based on these results, the $p16^{INK4a}$/Ki-67 dual immunostaining method can be a useful diagnostic marker for improving the sensitivity of LBC and the specificity of HC II test.

• The Korean Journal of Cytopathology
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• v.12 no.1
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• pp.1-15
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• 2001

The Bethesda System (TBS) was first developed in 1988 for the need to enhance the communication of the cytopathologic findings to the referring physician in unambiguous diagnostic terms. The terminology used in this reporting system should reflect current understanding of the pathogenesis of cervical/vaginal disease so the framework of the reporting system should be flexible enough to accommodate advances in medicine including virology, molecular biology, and pathology. Three years after the Introduction of TBS, the second Bethesda workshop was held to set or amend diagnostic criteria for each categories of TBS. TBS 1991 is now widely used. The third Bethesda workshop, The Bethesda System 2001 Workshop, was held in National Cancer institute Bethesda, Maryland from April 30 to May 2, 2001. Again, the goals of this workshop were to promote effective communication and to clarify in reporting cervical cytopathology results to clinicians and to provide with the information to make appropriate decisions about diagnosis and treatment. Nine forum groups were made and there were Web-based bulletin board discussions between October, 2000 and the first week of April, 2001. On the basis of bulletin board comments and discussions, the forum moderators recommended revised terminologies in the Workshop. Hot discussions were followed after the presentation by forum moderators during the workshop. Terminologies confusing clinicians and providing no additional informations regarding patient management were deleted in the workshop to clarify the cervicovaginal cytology results. Any informations related to the patient management were encouraged to add. So 'Satisfactory for evaluation but limited by...' of 'Specimen Adequacy' catergory was deleted. Terminology of 'Unsatisfactory' was further specified as 'Specimen rejected' and 'Specimen processed and examined, but unsatisfactory'. Terminologies of 'Benign Cellular Change' and 'Within Normal Limits' were combined and terminology was changed to 'Negative for intraepithelial lesion or malignancy'. In General categorization, category 'Other' was newly inserted and the presence of 'Endometrial cells' in women over 40 years old can be checked. Although the category 'Benign Cellular Change' was deleted, the organisms or reactive changes of this category can be listed in the descriptive diagnoses. Terminologies of ASCUS and AGUS were changed to atypical squamous cell and atypical glandular cell, respectively. Diagnostic term of 'Adenocarcinoma in situ', which is highly reproducible with reliable diagnostic criteria, was newly Inserted. The category of hormonal evaluation was deleted. Criteria for liquid-based specimen were discussed. Reporting by computer-assisted cytology was discussed and terminology for automated review was newly inserted. This is not the final edition of Bethesda 2001. The final document can be prepared before the ASCCP meeting in which Consensus Guidelines for the Management on Cytology Abnormalities and Cervical Precursors will develop in September 2001.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7971-7975
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• 2014

Background: From our previous study, we established that cyclin A1 (CCNA1) promoter methylation is strongly correlated with multistep progression of HPV-associated cervical cancer, suggesting potential use as a diagnostic maker of disease. Objectives: The purpose of the present study was to assess the prevalence of CCNA1 promoter methylation in residual cervical cells isolated from liquid-based cytology that underwent hrHPV DNA screening for cervical cancer, and then to evaluate this marker for diagnostic accuracy using parameters like sensitivity, specificity, predictive values and likelihood ratio. Methods: In this retrospective study, histopathology was used as the gold standard method with specimens separated into the following groups: negative (n=31), low-grade squamous intraepithelial lesions (LSIL, n=34) and high-grade squamous intraepithelial lesions or worse (HSIL+, n=32). The hrHPV was detected by Hybrid Capture 2 (HC2) and CCNA1 promoter methylation was examined by CCNA1 duplex methylation specific PCR. Results: The results showed the frequencies of CCNA1 promoter methylation were 0%, 5.88% and 83.33%, while the percentages of hrHPV were 66.67%, 82.35% and 100% in the negative, LSIL and HSIL+ groups, respectively. Although hrHPV infection showed high frequency in all three groups, it could not differentiate between the different groups and grades of precancerous lesions. In contrast, CCNA1 promoter methylation clearly distinguished between negative/LSIL and HSIL+, with high levels of all statistic parameters. Conclusion: CCNA1 promoter methylation is a potential marker for distinguishing between histologic negative/LSIL and HSIL+using cervical cytology samples.

• The Korean Journal of Cytopathology
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• v.19 no.2
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• pp.119-125
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• 2008

This study was performed to compare the efficacy between a DNA chip method and a Hybrid-Capture II assay (HC-II) for detecting human papillomavirus in patients with intraepithelial lesions of the uterine cervix. From May, 2005, to June, 2006, 192 patients with abnormal colposcopic findings received cervical cytology, HC-II and HPV DNA chip tests, and colposcopic biopsy or conization. We compared the results of HC-II and HPV DNA chip in conjunction with liquid based cervical cytology (LBCC) and confirmed the results of biopsy or conization. The sensitivity of the HPV DNA chip test was higher than HC-II or LBCC. The HPV DNA chip in conjunction with LBCC showed higher sensitivity than any single method and higher sensitivity than HC-II with LBCC. We confirmed that the HPV DNA chip test was more sensitive for detecting HPV in cervical lesions than HC-II, and that it would provide more useful clinical information about HPV type and its multiple infections.

• Journal of Biomedical Engineering Research
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• v.36 no.1
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• pp.1-6
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• 2015

This study aims to design a monolayer cell adsorption apparatus that would help to produce high-quality slides for Liquid-Based Cytology (LBC) of an early cancer diagnosis for human bodies. The LBC collects exfoliated cells of human bodies and spreads the cells on the slides. Through processes of dyeing and cytological examination, the LBC screens for cancers in early stage. In this study, both of a cell suction module and a cell adsorption module, which are the key elements of the monolayer cell adsorption apparatus, were developed, and using those modules, the study set, first, conditions to help both GYN and NON-GYN apply principal cells without de-endothelialization before conducting its own analysis on the utility. As a results, for GYN, apparatus was determined to be able to produce high-quality slides under the condition of 4 and for NON-GYN, the apparatus would come up with other slides of high-quality under the condition of 2. The study carried out a repetitive test on selected conditions and proved 96% of the repetitive success rate. By the results of what has been learned so far, the study presents that the apparatus has a possibility to replace device from South Korea as one of those other currently-applied systems to run the LBC and that the system will also present a new paradigm for cancer diagnosis as it makes a contribution to the improvement in the LBC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2063-2068
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• 2012

Aim: Liquid-based cytology is the most often used method for cervical cancer screening, but it is relatively insensitive and frequently gives equivocal results. Used as a complementary procedure, the high-risk human papillomavirus (HPV) DNA test is highly sensitive but not very specific. The human telomerase RNA gene (TERC) is the most often amplified oncogene that is observed in cervical precancerous lesions. We assessed genomic amplification of TERC in liquid-based cytological specimens to explore the optimal strategy of using this for cervical cancer screening. Methods: Six hundred and seventy-one residual cytological specimens were obtained from outpatients aged 25 to 64 years. The specimens were evaluated by the Digene Hybrid Capture 2 (HC2) HPV DNA test and fluorescence in situ hybridization (FISH) with a chromosome probe to TERC (3q26). Colposcopic examination and histological evaluation were performed where indicated. Results: The TERC positive rate was higher in the CIN2+ (CIN2, CIN3 and SCC) group than in the normal and CIN 1 groups (90.0% vs. 10.4%, p < 0.01). In comparison with the HC2 HPV DNA test, the TERC amplification test had lower sensitivity but higher specificity (90.0% vs. 100.0%, 89.6% vs. 44.0%, respectively). TERC amplification test used in conjunction with the HC2 HPV DNA test showed a combination of 90.0% sensitivity and 92.2% specificity. Conclusion: The TERC amplification test can be used to diagnose cervical precancerous lesions. TERC and HPV DNA co-testing shows an optimal combination of sensitivity and specificity for cervical cancer screening.