The Bethesda System Research Articles

Follicular neoplasms with nuclear atypia versus other types of atypia: Should follicular neoplasms be stratified according to the presence of nuclear atypia?

The third edition of The Bethesda System (TBS) subclassifies the atypia of undetermined significance (AUS) category on the basis of the presence of nuclear atypia (AUS-Nuclear). This approach is supported by studies showing significant differences in the risk of malignancy (ROM) between AUS-Nuclear and those without (AUS-Other). Although aspirates of follicular neoplasms (FNs) are characterized by marked architectural atypia, TBS recognizes the infrequent occurrence of FNs with mild nuclear atypia (FN-Nuclear). Furthermore, limited studies have shown significant differences in ROM between FN-Nuclear and those without (FN-Other). This study explored potential differences in ROM, molecular-derived risk of malignancy (MDROM), and molecular alterations between FN-Nuclear and FN-Other. A retrospective database search identified 93 FN aspirates. Cytology slides, molecular reports, and histologic follow-ups were reviewed. Both groups' benign call rate (BCR), positive call rate (PCR), MDROM, and ROM were computed and compared. Eighty-six percent of aspirates (80 of 93) comprised FN-Other, whereas 14% (13 of 93) were FN-Nuclear. The BCR and PCR for FN-Other were 51% and 49%, respectively. In contrast, they were 23% and 77% for FN-Nuclear, respectively. The MDROM significantly differed between FN-Other (30%) and FN-Nuclear (56%) (p<.05). HRAS mutation was the most common molecular alteration in FN-Nuclear, whereas mutations in NRAS/KRAS and copy number alterations were more common in FN-Other. The ROM1/ROM2 in FN-Other and FN-Nuclear were 16%/31% and 54%/88%, respectively. These results reveal that FN-Nuclear exhibits significantly higher MDROM and ROM than FN-Other, which provides support for a subclassification scheme for FNs based on the presence of nuclear atypia.

Clinicopathologic Features and Cytologic Correlation of ALK-Rearranged Papillary Thyroid Carcinoma: A Series of Eight Cases

Anaplastic lymphoma kinase (ALK) gene fusions are rare in papillary thyroid carcinoma (PTC) but may serve as a therapeutic target. This study aims to evaluate the preoperative cytologic findings and clinicopathologic features of a series of eight ALK-rearranged PTCs from our pathology archives and consultations. All cases were confirmed by ALK D5F3 immunohistochemistry and six with additional targeted RNA-based next-generation sequencing (NGS). The original fine-needle aspiration (FNA) cytology diagnosis included the Bethesda System (TBS) category II in three (37.5%), TBS III in two (25%), TBS V in two (25%), and TBS VI in one (12.5%). Six cases had available FNA cytology and were reviewed. The cytologic features showed microfollicular architecture as well as limited or reduced nuclear elongation and chromatin alterations in all six. Nuclear grooves and pseudoinclusions were absent in two cases, rarely or focally noted in three, and frequently found in one. Two cases initially diagnosed as TBS II, showing microfollicular architecture without well-developed nuclear features, were revised to TBS III (with architectural atypia only). For histologic correlations, four were infiltrative follicular variant PTCs, three as classic subtype PTC with predominant follicular growth, and one as solid/trabecular subtype PTC. All eight cases demonstrated reduced PTC nuclear features with respect to nuclear elongation and chromatin alterations compared to those typically identified in “BRAF-like” PTCs. The NGS testing revealed EML4::ALK fusion in three, STRN::ALK fusion in two, and ITSN2::ALK fusion in one. In conclusion, although ALK-rearranged PTCs have been associated with neutral gene expression profile from a BRAF-RAS scoring perspective, the “RAS-like” nuclear features were more commonly identified in this series, resulting in frequent indeterminate diagnosis of preoperative FNA.

Prevalence of High-Risk Human Papillomavirus Infection, Associated Risk Factors, and Relationship With Cervical Precancerous Lesions in Perimenopausal and Older Women in an Area With High Cervical Cancer Incidence in China.

Purpose This study delves into the epidemiology of high-risk human papillomavirus (HR-HPV) infection and its link to precancerous lesions among perimenopausal (40-59 years) and elderly (60-65 years) women in a Chinese county with a notably high incidence of cervical cancer. By uniquely focusing on these age groups in underdeveloped regions, the research aims to offer novel strategies for the management and prevention of cervical cancer. It seeks to inform targeted interventions and public health policies that could significantly benefit women at heightened risk for HPV, addressing a critical gap in current prevention efforts in economically disadvantaged communities. Methods This observational study was conducted at the Maternal and Child Health and Family Planning Service Centre in Lueyang County, from September 2021 to January 2022. It assessed 2008 women aged 40-65 for HPV screening, with 342 undergoing further cytological examination. The study evaluated the prevalence of HPV infection across different age groups and risk categories. It utilized a questionnaire to collect participants' basic information, health behaviors, and other relevant data to analyze factors influencing HR-HPV infection. Statistical analyses comprised chi-square tests, trend analysis, logistic regression, and multiple imputation techniques to address missing data. Results The prevalence of HR-HPV infection among women aged 40-65 years in Lueyang County was 18.43%. Older women exhibited a higher incidence of HPV infection, abnormal ThinPrep Cytology Test (TCT) results (Shaanxi Fu'an Biotechnology Co.Ltd., Baoji City, China), and low/high-grade squamous intraepithelial lesions (LSIL/HSIL) (P<0.05). The most prevalent HR-HPV genotypes in the overall, perimenopausal, and elderly groups were HPV-52, -53, and -58; HPV-52, -53, and -16; and HPV-58, -52, and -53, respectively. The prevalent HR-HPV genotypes in the abnormal The Bethesda System (TBS) results were HPV-16, -52, -33, -58; -16, -52, -58; and-16, -33, and -52. HPV-16, -18, -33 prevalence increased with increasing lesion severity (P<0.05). In this study, factors affecting HR-HPV in the three age groups were found to be mainly related to sexual behavior and education level, including history of lower genital tract diseases, multiple pregnancies, contraceptive methods without tubal ligation, age at first marriage greater than 18 years, never washing the vulva after sex, abstinence from sex, education level of junior high school or above, and spouse's education level of high school or above. Conclusions These findings suggest that the elevated rate of abnormal TBS in the older age group may be attributed to the higher prevalence of persistent infection-prone HR-HPV genotypes (HPV-58, -52, and-53), multiple infections, and potent oncogenic HR-HPV genotypes (HPV-16 and -33). Additionally, the higher HR-HPV prevalence in older patients may be related to lower education attainment, reduced screening rate, and limited condom usage. Therefore, strategies targeting perimenopausal and older women should prioritize enhancing health awareness, increasing screening rates, and encouraging condom utilization.

Interpace, Affirma, and Thyroseq Performance Characteristics in 341 Bethesda Category III/IV Thyroid Nodules

Abstract Introduction/Objective Multiple FDA-approved molecular testing platforms are used by our institution for evaluating genomic characteristics of thyroid nodules. We aim to correlate molecular results and final histopathology (HPE) of thyroid nodules with cytologic diagnosis of The Bethesda System (TBS) Category III or IV. Methods/Case Report We included 341 cases of thyroid nodules diagnosed as TBS-III or TBS-IV with subsequent molecular analysis performed on 1 of 5 platforms (Interpace ThyraMIR Thyroid miRNA Classifier, Afirma Genomic Sequencing Classifier, Thyroseq Genomic Classifier, Next-Generation Sequencing (NGS) Fusion Panel, or RosettaGX Reveal Thyroid miRNA Classifier). All findings reported on molecular analysis and all benign or malignant neoplasms diagnosed on final HPE were considered “significant findings.” Performance characteristics of all 5 molecular platforms were analyzed. Results (if a Case Study enter NA) Of 341 cases, 80.1% (n=273) were classified as TBS-III and 19.9% (n=68) were classified as TBS-IV. The overall concordance of molecular and final HPE when available was 60.9% (n=28). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) are respectively 75.0%, 60.0%, 75.0%, and 60.0% for Interpace; 65.0%, 60.0%, 85.0%, and 33.0% for Afirma; and 75.0%, 50.0%, 75.0%, and 50.0% for Thyroseq platforms. Of TBS-III cases, 66.3% (n=181), 25.6% (n=70), 4.8% (n=13), 1.5% (n=4), and 1.8% (n=5) underwent molecular testing via Interpace, Afirma, Thyroseq, NGS, and Rosetta platforms, respectively. Only 9.2% (n=25) of TBS-III cases had subsequent HPE. Concordance of molecular and final HPE for TBS-III cases was 52.0% (n=13) with a PPV of 75.0% and NPV of 40.0%. Concordances of molecular and final HPE according to molecular platform are: 57.1% (n=4) on Interpace, 53.3% (n=8) on Afirma, and 50.0% (n=1) on Thyroseq. Of TBS-IV cases, 52.9% (n=36), 36.8% (n=25), 5.9% (n=4), 2.9% (n=2), and 1.5% (n=1) underwent molecular testing via Interpace, Afirma, Thyroseq, NGS, and Rosetta platforms, respectively. Only 30.9% (n=21) of TBS-IV cases had subsequent HPE. Concordance of molecular and final HPE for TBS-IV cases was 71.4% (n=15) with a PPV of 86.0% and NPV of 43.0% Concordances of molecular and final HPE according to molecular platform are: 71.4% (n=5), 66.7% (n=6), and 75.0% (n=3) on Interpace, Afirma, and Thyroseq respectively. Conclusion Our study reports similar performance characteristics of 3 commonly used molecular platforms (Interpace, Afirma, and Thyroseq) for genomic evaluation of thyroid nodules.

AUTOMATED COUNTING OF SQUAMOUS EPITHELIAL CELLS IN LIQUID-BASED CYTOLOGY SAMPLES

Cytologic screening is only effective with adequate material. The Bethesda System (TBS), an international system for standardizing the results of cervical cytology, establishes criteria for adequacy. According to the TBS, a sample prepared by liquid-based cytology (LBC) can be classified as adequate if it contains not less than 5,000 squamous epithelial cells. There are methods of manual assessment of the cellularity of cytological samples. However, the uniformity of cellular material distribution of LBC samples makes possible the application of automatic tools for assessing the adequacy of the material based on the cellularity criterion. This paper compares the results of digital LBC samples adequacy assessment using the automated artificial neural network method Vision Cyto Pap and the manual assessment method. Analysis of the results of counting squamous epithelial cells in 506 LBC samples showed a significant correlation (r = 0.93) between the automated and manual method. The high diagnostic parameters (sensitivity = 93.8 % and specificity = 99.2 %) of the automated Vision Cyto Pap method allow to conclude that the algorithms of such a tool can be used to determine the adequacy of the cytological material by the number of squamous epithelium cells with sufficient reliability.

Cytomorphological study of cervical Pap smear based on the Bethesda system 2014

: The Papanicolaou (Pap) smear used worldwide for cervical screening was developed by Dr George Papanicolaou in 1940s. The Pap smear is a simple, safe and effective test to detect cervical cancer at an early stage.: To study the spectrum of lesions in cervical Pap smear based on The Bethesda System(TBS) 2014 and to determine frequency of premalignant and malignant lesions.: The present prospective study included 200 cases above 20 years of age. The cytological interpretation of smears were made according to TBS 2014. When there was difficulty in differentiating HSIL from other lesions p16 immunostaining was done and evaluated according to the criteria proposed by Wentzensen et al. : Chi – square test was used to see the association between different attributes. Statistical analysis was performed using SPSS version 22. P value &amp;#60;0.05 was considered significant.: The most common lesion was NILM with 175 cases (87.5%) followed by 7(3.5%) SCC, 4(2%) HSIL, 2(1%) cases each of ASCUS, AGC-NOS, LSIL and 1(0.5%) case of ASC-H. Among 200, 7(3.5%) cases were unsatisfactory for evaluation. The subjects were not uniformly distributed (P &amp;#60;0.001). The p16 marker was used in 6(3%) doubtful cases of HSIL among which 2(33.33%) cases were positive. Cervical Pap smear is a useful technique to detect the inflammatory, premalignant and malignant lesions of cervix which helps the clinician to plan further management.

The Bethesda System for reporting cervical cytology.

The seminal observations of Dr. George Papanicolaou have grown, through the untiring efforts of many authors, into a universally accepted format of cytology reporting. This has helped immensely to improve the understanding of pathogenesis of cervical cancer. The insights into the complexity of interaction of the etiological and the host factors have further helped in reframing of the reporting system. The Bethesda System (TBS) stands out as a model of standardized reporting in cervicovaginal cytology. Apart from its reproducibility, it reflects the most current understanding of cervical cancer. The most important feature is its clinical relevance. Each category of this classification has clear clinical implications, which are based on solid evidence and worldwide consensus. Moreover, the authors have tried to keep it updated through continuous revisions, incorporating the technological and scientific advances. The component of specimen adequacy reflects the importance it has given to the quality assurance of the laboratory preparation. The minimization of categories, simple terminology, and the supporting image atlas – both in the print form and the web-based form, have made TBS an exemplary teaching-learning resource. The wide accessibility of TBS has been the most important factor in being adopted by a majority of pathology community all over the world.

USG guided FNAC of thyroid improving diagnostic accuracy

Introduction: USG guided FNAC of thyroid particularly facilitates accurate FNAC of non-palpable small lesions. It has the major advantage of real time monitoring which help in accurate localisation of needle tip during aspiration. It is very useful in the non diagnostic or unsatisfactory cases (according to Bethesda System Bethesda category I). It has been suggested to reduce the rate of non-diagnostic material and subsequently reduce the false-negative interpretation. Aims: 1) To evaluate the Diagnostic accuracy of USG-guided FNAC of Thyroid. 2) To evaluate cellular yield of aspirated material in USG-guided FNAC. Materials and Methods: The present study included 100 patients with thyroid swelling undergoing USG guided FNAC who previously were diagnosed by FNAC as Non diagnostic or Unsatisfactory (According to Bethesda System Bethesda category I). USG guided FNAC was done & Smears were made. Then microscopy was done following the Bethesda system (TBS). Result: Total 100 patients with thyroid swelling undergoing USG guided FNAC who previously were diagnosed by FNAC as Bethesda category I. In present study, Out of 100 patients, maximum no. of patients were in 41 to 50 years age groups (54 cases) and majority were Female (84 Cases). The revised diagnosis in these cases according to TBS were as follow, Nodular goiter (29%), Colloid goiter (26%), lymphocytic thyroiditis (14%), Hashimoto thyroiditis (9%), Graves’ disease (2%) & granulomatous thyroiditis (1%). Suspicious for malignancy (4%) and papillary carcinoma (4%) and Follicular neoplasm (3%). There was increased cellular yield of aspirated material in 92% of cases with USG guidance. In present study false negative & True Positive rates were–92% & 8% for Conventional FNAC technique, as concluded after repeat FNAC under USG guidance.

Usefulness of Five-Parameter System Reconfirmed for Cytopathology of Oral Squamous Cell Carcinoma regardless of Differentiation Degree

Background: We previously introduced the Five-Parameter System (FPS), which exclusively evaluates keratinized cellular findings, for use in cytology examinations of oral well-differentiated squamous cell carcinoma (SCC) and carcinoma in situ (CIS) specimens, as they occasionally lack nuclear atypia and can be challenging for categorization by The Bethesda System (TBS). This study was conducted to determine whether FPS parameters are detectable even in oral SCC/CIS specimens with apparent nuclear atypia. Summary: Oral cytology specimens were obtained together with biopsy tissue samples. They were obtained from 59 malignant (HSIL and SCC) and 29 not-definitely malignant (NILM to ASC-H) specimens diagnosed using TBS. Following re-confirmation of the original TBS categorization, the specimens were re-evaluated using FPS. One or more of the FPS parameters were noted in 69 of 70 malignant specimens examined, of which 11 had been diagnosed by TBS as not-definitely malignant. The remaining one malignant specimen was diagnosed as SCC with only TBS. FPS parameters #1 (concentric arrangement), #2 (large cell number), #3 (bizarre-shaped cells), #4 (keratoglobules), and #5 (uneven filamentous cytoplasm) were observed only in malignant cases, while none were revealed in not-definitely malignant specimens. Finally, TBS supplemented with FPS achieved sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 100%. Key Messages: FPS parameters are included in most examinations of oral cytology specimens. Thus, FPS is highly recommended for use in cytology examinations of oral SCC regardless of differentiation degree to confirm judgment based on TBS, a mandatory standard, as well as to cover its limitation of mainly evaluating nuclear atypia. FPS is considered to be an important diagnostic tool for oral cytology, especially in triage cases, which are challenging for TBS. Cytopathology should not be limited to only nuclear findings but be based on whole-cell morphology.

Assessment of cytological features of glandular lesions of the cervix on conventional smear preparations-a comprehensive study from a tertiary care hospital.

Atypical glandular cells (AGC) as a diagnostic category in cervicovaginal cytology remains as a challenge to cytopathologists. The aim of the present study is to identify the cytological features helpful in categorizing AGC as reactive or neoplastic upon correlation with histology. The study was a retrospective review of cervical smears, with histopathological follow up, reported as glandular lesions for a period of 9 years. The architectural and nuclear features studied were adapted from The Bethesda System (TBS) to stratify the lesions as AGC, AGC-FN (atypical glandular cells favour neoplasia) and adenocarcinoma. The cytological categories were correlated with histology. A total of 89 cases of which 67 (AGC NOS = 34, AGC FN = 19, adenocarcinoma = 14) with histology were reviewed. Neoplastic lesions were encountered in 14 cases (34.6%). Of the cases diagnosed as AGC-NOS, AGC-FN and adenocarcinoma, 26.5%, 68.4% and 100% respectively were neoplastic on histopathology. Squamous lesions accounted for 14.9% of all the glandular lesions. Rosette or acinar formation and loss of polarity frequently observed in neoplastic lesions as compared to reactive changes (p = 0.0004, p = 0.001). Of the nuclear features, nuclear hyperchromasia or coarse clumping of chromatin along with nuclear membrane irregularity and nuclear pleomorphism was frequently associated with neoplastic lesions as compared to reactive conditions (p = 0.007, p = 0.001, p = 0.0002). A diagnosis of AGC at cytology harbors significant number of malignant lesions when confirmed on biopsy. Architectural features complemented with nuclear characteristics helps in differentiating between reactive and neoplastic conditions. Hence stratifying glandular lesions at cytology according to TBS helps in the management.

Differential outcomes of patients with thyroid FNA diagnoses of AUS/FLUS with and without nuclear atypia: The potential need for separation in the Bethesda System.

In the current version of The Bethesda System (TBS) for thyroid cytopathology, the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category has an estimated risk of malignancy of 10% to 30%. Diagnostic criteria include presence of nuclear atypia, suggestive of papillary thyroid carcinoma (PTC), as well as other types of atypia, which can be seen with non-malignant entities. Aim of this study was to investigate differential outcomes of AUS/FLUS, based on specific morphologic criteria, and assess their respective malignancy risks. From a total of 1233 patients undergoing thyroid FNAs between 2010 and 2014 at the University of Washington, 119 had AUS/FLUS without nuclear atypia, and 64 with nuclear atypia. Outcomes for patients with and without nuclear atypia (with the exception of 24 patients lost to follow-up) were evaluated and results were compared. 16/57 (28.1%) patients with AUS/FLUS and nuclear atypia subsequently had carcinomas on thyroidectomy, statistically higher than the 8/102 patients (7.8%, P = .001) without nuclear atypia. When comparing only patients who underwent surgery (n = 63), again those with AUS/FLUS and nuclear atypia had statistically higher rates of carcinoma (16/31, 51.6%), compared to those without (8/32, 25%; P = .0394). Overall, 24/159 (15.1%) of patients with AUS/FLUS had carcinoma on subsequent histology. Malignancy rates for AUS/FLUS were in line with TBS estimated risks. However, our data demonstrate that the presence or absence of nuclear atypia is associated with different malignancy rates, suggesting the possibility that the AUS/FLUS category may best be split into two subcategories with different implied risks of malignancy.

Frequency of unsatisfactory cervical cytology smears in cancer screening of Japanese women: A systematic review and meta-analysis.

The Bethesda system (TBS) has been used for cervical cytological diagnosis in Japan since 2008. Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS. A systematic review and meta‐analysis were carried out to assess the unsatisfactory specimen rate in the primary cervical cancer screening setting in Japan. Ovid Medline and Ichushi‐Web databases were searched from inception through to May 2017. Prospective and retrospective studies that reported the proportion of unsatisfactory specimens in healthy asymptomatic Japanese women in a cervical cancer screening program were eligible for inclusion; 17 studies were included in the meta‐analysis. The random‐effects model meta‐analysis calculated summary estimates of the unsatisfactory rate of 0.60% (95% confidence interval [CI], 0.18‐1.96%; I 2 = 99%) for conventional cytology and 0.04% (95% CI, 0.00‐0.35%; I 2 = 99%) for liquid‐based cytology (LBC). However, comparative results between conventional and liquid‐based cytology, based on four direct and nine comparative studies, showed no significant difference (summary odds ratio = 3.5 × 10−2 favoring LBC [95% CI, 6.9 × 10−4‐1.7]; I 2 = 98%). In the subgroup analyses and meta‐regressions, use of non‐cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates. Meta‐regression also suggested chronological improvement in unsatisfactory rates for both tests. In Japanese cervical cancer screening programs, conventional cytology remains prevalent. Future research needs to focus on evaluating the impact of screening programs using LBC by comparing the accuracy, performance, and cost‐effectiveness with conventional cytology in the Japanese population.

The effects of the Bethesda System 2014 on endometrial cell reporting and follow-up endometrial biopsies in women 45 years of age and over

The Bethesda System (TBS) guidelines for reporting the presence of endometrial cells on Papanicolaou tests increased the reporting age from 40 (TBS 2001) to 45 (TBS 2014) years. Exfoliated endometrial cells (EMC) are usually a normal finding. Nevertheless, benign-appearing EMC occasionally correspond to endometrial hyperplasia or malignancy, especially in older, postmenopausal women. This study assesses the impact of this age cutoff change. This retrospective review compares endometrial biopsies following TBS 2001 and TBS 2014. Papanicolaou tests with EMC reported in women older than age 40 or 45 years were correlated with follow-up endometrial biopsies performed between May 25, 2014, to May 26, 2015, and May 27, 2015, to May 26, 2016, respectively. The number of reported EMC declined from 770 to 492 (a 36.1% decrease). The follow-up endometrial biopsy rate for Papanicolaou tests reporting EMC using TBS 2001 was 13.6% (105 of 770) versus TBS 2014 at 13.8% (68 of 492; P = 0.92). For TBS 2001, 15% of women aged 45 and older had follow-up biopsies (65 of 434; P = 0.62). Most follow-up biopsies showed benign endometrium. In the TBS 2001 group, 1 biopsy showed malignancy and another showed complex hyperplasia with atypia. Both patients were older than 45 years. The TBS 2014 group contained 1 biopsy of malignancy and 1 with simple hyperplasia with focal atypia. The implementation of TBS 2014 reduced the frequency of reporting benign-appearing endometrial cells. The follow-up biopsy rate has remained essentially the same, but the total number of biopsies performed decreased, with a similar low yield of significant abnormalities.

The 2014 Bethesda System and Pap-Smear

Dear Editor, Bethesda style reporting system, such as the system used in the cervix, is employed to report thyroid cytopathology and pancreaticobiliary tract cytology and urine cytology. Therefore, it is beneficial for gynecologists, endocrinologists, thyroid surgeons, gastroenterologists, general surgeons, and urologists (1). The Bethesda system (TBS) was modified in 2014, which altered compared to the 2001 version. According to the new evidence in 2014, the TBS is enhanced. The evidence includes an additional understanding of human papilloma virus (HPV) biology, HPV vaccination in at least hundred countries, and the high utilization of liquid base cytology in decades. It is also noteworthy that additional screening options such as Pap test with high-risk HPV (i e, cotesting) and primary high-risk HPV test are also considered (2). The following explanations can reveal the reason to modify TBS. 1. If the number of squamous cells is less than 5000 in the liquid base cytology, it is inadequate and HPV DNA test cannot be precisely analyzed (3). 2. The general categorization section declares that the reporting system of the endometrial cell for females is altered through 40 45 years old. Since the normal endometrial cell can exfoliate, detected in Pap smear, the reporting age altered. It leads to increase of the predictive value. It is noteworthy that the working group suggested that endometrial evaluation should be done only in postmenopausal situations and stated in the educational note. 3. The interpretation (result) section, non-neoplastic finding subsection and the following items are added which are optional to report. a. Keratotic changes: Keratin formation is not a normal process in a squamous cell of cervix and vagina. HPV, trauma and pessary are the main reasons of keratotic changes. It should be considered that cervical cancer are ruled out when the keratotic changes reported (4). b. Tubal metaplasia: While metaplasia is a benign process, an excess estrogen happens and turns it as a pathologic process. c. Pregnancy-associated changes: True stromal decidual nature of the cells in pregnancy, such as smudgy chromatin with nucleolus, can be mistaken with a high-grade squamous intraepithelial lesion. Therefore, changes associated with pregnancy should be reported as a normal process (5). 4. In the inflammation section, the lymphocytic (follicular) cervicitis was added. Due to the high-prevalence of sexually transmitted diseases, cellular changes consistent with herpes simplex and cytomegalovirus were added in the organism section. 5. In squamous epithelial abnormality section, the two-tiered classification system for low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) were approved again. On the other hand, squamous abnormality as LSIL and a few cells suggestive of concurrent HSIL were not added to the report. In glandular cell abnormality section, there is difference with the last Bethesda system. 6. The following notes were added after the other malignant neoplasm section: a. In adjunctive testing, provide a brief description of the test method(s); b. And report the result to be easily understood by the clinician.

An Audit on Adequacy of Pap Smears

Conventional Pap smear is a commonly done screening test for cervical cancer. Accurate interpretation depends upon the specimen adequacy which is considered to be the single most important quality indicator of “The Bethesda System (TBS)”. To audit specimen adequacy and compare results based on 2014 TBS. Retrospective audit from 1 April to 31 December 2015. Data was collected from case notes and Pap smear reports. A total of 146 Pap smears were done during the study period. Majority of the women (34 %) were between 41 and 50 years. Fifty-five per cent had a small family size of two children. Seventy-six per cent were premenopausal while 34 % were post-menopausal. Transformation zone/endocervical component (TZ/EC) was seen in 87 % of smears. Blood was seen in 2.7 % and inflammatory cells in 59.6 % of smears. All smears were satisfactory for interpretation by the cytologist. In the final interpretation, atrophic smears were seen in 2/146 (1.4 %), low-grade epithelial abnormality and high-grade abnormality were seen in one smear each (0.7 %). Colposcopy and directed biopsy were normal in both. A total of 43.8 % were normal. A total of 53.4 % were inflammatory. In this audit, 100 % smears were satisfactory for interpretation and above the literature standard of 99.5 %.

Validation of the Modification of the Prolonged Papanicolaou Stain for the Diagnosis of Cervical Cancer

Objectives: To validate the modification of the prolonged Papanicolaou stain based on the quality control of time, units and staining stages (micro- and macroscopic), and on the stain reactivation based on the control. Study Design: A prospective study was performed on 125,358 cervical smears in Lima (Peru). The microscopic quality control included evaluating the cytological characteristics through the staining quality index (SQI) and the quality criteria for samples described by the Bethesda System (TBS). The macroscopic quality control is based on the interslide staining as a set corresponding to a poststaining vertical angle. The stains were reactivated with the addition of 0.15 and 2 g of phosphotungstic acid for Orange G and EA-50, respectively. Results: Both the nonneoplastic and the neoplastic findings comply with the quality criteria of the TBS (SQI value = 0.94). The yield per battery of staining fluctuated between 5,616 and 17,954 Pap smears, and the reactivation of stains produced a stain yield of up to four times the initial amount of the smears, saving USD 5,598.88 from 2013 to 2014. Conclusion: The modification of prolonged Papanicolaou staining is an excellent alternative, with a cost-benefit ratio that generates savings and a higher yield per battery of staining.

Cytomorphology of vaginal pap smears-A spectrum of lesions in a tertiary hospital

Background: Pap test is an important and easy diagnostic tool to detect any abnormalities on vaginal cytology. It is routinely done in women of reproductive age group. In addition to detecting cellular and epithelial abnormalities; certain infections, rare entities including neoplastic and non-neoplastic conditions can also be identified. Aims and Objectives: 1. To study the spectrum of abnormalities on vaginal pap cytology as per The Bethesda System (TBS) 2001.2. To study the utility of pap smears in early diagnosis of premalignant lesions. Materials and Methods: This prospective study was conducted in Dr. B.R. Ambedkar Medical College, Bangalore where routine pap smears referred from the Obstetrics and Gynaecology Department were studied. Important clinical data like vaginal discharge, inter menstrual bleed, post–coital bleed and lower pain abdomen were collected. Pap smears were analysed, interpreted and categorised based on TBS2001. Importance of detecting premalignant lesions were highlighted in our study. Results: 525 pap smears were interpreted in a 2 year prospective study out of which 400 cases were analysed after excluding 125 unsatisfactory case. The age range was 18-78 yrs (mean age of 48 yrs). 120 (30%) cases of nonspecific inflammation were identified. Specific infectious etiologies included 186 (46.5%) cases range including most common candida and Bacterial vaginosis to 2 rare infections, one case each of filariasis and granulomatous cervicitis. Significant number(82 cases) of premalignant conditions were diagnosed. 12 malignancies-10 SCC and 2Adenocarcinomas were reported. Conclusions: Certain rare infectious entities were detected in our study which pose challenge due to infrequent occurance in our daily practice. Close follow- up and histological examination are necessary in premaligant lesions to avoid spread and untimely death of the patient. Thus emphasising effective utility of this simple and cost-effective tool. Keywords: Vaginal p

Young investigator challenge: Atypia of undetermined significance in thyroid FNA: Standardized terminology without standardized management--a closer look at repeat FNA and quality measures.

The Bethesda system (TBS) for the reporting of thyroid cytopathology established the category of atypia of undetermined significance (AUS) with a 7% target rate and a 5% to 15% implied malignancy risk. Recent literature has reported a broad range of AUS rates, subsequent malignancy rates, and discrepant results from repeat fine-needle aspiration (FNA) versus surgical follow-up. Therefore, this study examined AUS data from the Hofstra North Shore-LIJ School of Medicine to determine the best clinical follow-up. Thyroid aspirates interpreted as AUS in 2012-2014 at the Hofstra North Shore-LIJ School of Medicine were collected. Repeat FNA and surgical follow-up data were tabulated to establish AUS, secondary AUS (diagnosed upon repeat FNA follow-up of a primary FNA AUS diagnosis), atypia of undetermined significance/malignancy (AUS:M) ratios (according to the TBS categories), and malignancy rates for AUS. The AUS rate was 8.5% (976/11,481), and there was follow-up data for 545 cases. The AUS:M ratio was 2.0. Repeat FNA was performed for 281 cases; 57 proceeded to surgical intervention. Repeat FNA reclassified 71.17% of the cases. The malignancy rates for AUS cases proceeding directly to surgery and for those receiving a surgical intervention after a repeat AUS diagnosis were 33.33% and 43.75%, respectively. Repeat FNA resulted in definitive diagnostic reclassification for 67.61% of primary AUS cases and reduced the number of patients triaged to surgery, with 56.58% of the cases recategorized as benign. Cases undergoing surgery after repeat AUS had a higher malignancy rate than those going straight to surgery, and this emphasizes the value of repeat FNA in selecting surgical candidates. In addition, this study highlights the utility of AUS rate monitoring as a quality measure that has contributed to the ability of the Hofstra North Shore-LIJ School of Medicine to adhere closely to TBS recommendations.

Pap Test Reporting Rates for Conventional Smear and Liquid-Based Cervical Cytology from the Largest Academic Women's Hospital in China: Analysis of 1,248,785 Pap Test Reports

Objective: The Obstetrics and Gynecology Hospital of Fudan University (OGHFU) in Shanghai is the largest academic women's hospital in China. Between 2009 and 2014, the use of liquid-based cytology (LBC) significantly increased while gradually adopting the Bethesda System (TBS), and in 2012 local regulations mandated that pathologists replace technicians to sign out Pap tests. Design: A retrospective OGHFU database search documented all Pap test reports between 2009 and 2014 by specimen type, either LBC or conventional Pap smears (CPS), and final reporting category. A total of 1,224,785 Pap reports were analyzed to document variations in Pap test reporting during a period of major change in cervical screening in China. Results: LBC gradually replaced CPS, which declined from over 65% of Pap tests in 2010 to 6.4% in 2014. Of 514,811 Pap reports using the traditional class system, class I (negative) reports accounted for 98.3% of results. With the introduction of TBS reporting, pathologist reviews and substantial replacement of CPS by LBC, the laboratory abnormal Pap test rate increased significantly to almost 5%. Conclusions: Changes in cervical cytology reporting between 2009 and 2014 in China's largest academic women's hospital reflected both increased use of LBC and the introduction of pathologist TBS reporting. Abnormality rates increased significantly and fell within CAP benchmark ranges.

Application analysis of the cervical cell pathology liquid production technology in cervical intraepithelial neoplasia screening

Objective To study the application value of the cervical cell pathology liquid production technology in cervical intraepithelial neoplasia(CIN)screening. Methods 4 212 patients were chosen and detected by TCT and the pap staining,TBS(the Bethesda system)to finish thin layer liquid based cytology grading diagnosis,including 558 patients with cervical biopsy,the pathological results were analyzed. Results for histopathological examination results of CIN1,CIN2,CIN3 and cervical cancer cases,a thin layer of liquid based cytology detection rate was 76.00%(57/75),78.21%(61/78),95.76%(113/118),100.00%(7/7),the comparison between the CIN3 CIN2 group,a thin layer of liquid based cytology detection rate had differences in significant statistical significance(χ2=14.53,P<0.01),with the histopathological detection of cervical lesions,thin layer of liquid based cytology detection rate was obviously rising trend.Cervical liquid based cytology screening cervical lesion(CIN and above),the sensitivity was 85.61%(238/278),83.73%(206/246),positive predictive value 76.28%(238/312),negative predictive value 72.79%(206/283). Conclusion The positive results and histopathological results coincidence rate of using thinprep cytologic test to screening for cervical intraepithelial neoplasia(CIN)is high,the precancerous lesions in screening and prevention has important significance,which is worth clinical promotion. Key words: Thinprep cytologic test; The pap staining; Cervical intraepithelial neoplasia(CIN)