Critical Appraisal of the 2017 Bethesda System for Reporting Thyroid Cytopathology with Cytohistological Concordance and Estimation of Risk of Malignancy - An Institutional Study.

Aim: Bethesda System for reporting thyroid cytopathology established in 2009 was updated for the first time in 2017. Since its introduction very few studies have been done on the utility of recently introduced "The 2017 Bethesda System for Reporting Thyroid Cytopathology" (TBSRTC II) and estimation of risk of malignancy in various categories. Material and methods: This was a prospective study done on thyroid lesions in which lesions were evaluated cytologically and classified according to TBSRTC II. Histopathological correlation was done, wherever possible. ROM was calculated for each Bethesda category in both ways as per TBSRTC II i.e. with NIFTP and excluding NIFTP from the malignant category. Results: Using 2017 TBSRTC, 190 cases of thyroid FNACs were classified into 6 diagnostic categories. Cytohistological correlation was available in 60 cases. ROM was calculated which changed only in category III and V as only these two categories showed one case each of NIFTP. However there was an overestimation of ROM in category II and III as there are selection biases and not all thyroid nodules underwent surgical resections. Conclusion: To conclude, the risk of malignancy calculated in two ways in the recent 2017 Bethesda system may have higher clinical relevance as those lesions with high ROM are defined for surgical excision. Thus we recommend that "The 2017 Bethesda system for Reporting Thyroid Cytopathology" should be implemented uniformly in our country as it provides a homogenous and standardised terminology resulting in better management of patients with thyroid nodular disease.

Comparison of risk of malignancy and predictive value of diagnostic categories defined by Papanicolaou Society of Cytopathology system and WHO reporting system for pancreaticobiliary cytopathology in solid pancreatic lesions.

Background: The standardized diagnostic categories defined by the World Health Organization (WHO) reporting system support the interdisciplinary interpretation of cytological findings in the management of pancreatic cancer. Objective: To compare this classification to the Papanicolaou Society of Cytopathology (PSC) system in terms of predictive value and risk of malignancy (ROM) in solid pancreatic lesions. Design: Retrospective cohort study. Methods: All consecutive patients with solid pancreatic lesions who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) sampling at the University of Szeged from 2014 to 2021 were retrospectively enrolled. The predictive value and ROM of cytological findings were determined with comparison to histologic outcome and/or clinical follow-up. Results: A total of 521 EUS-FNAs were performed with a malignancy rate of 81.76%. In both classification systems, the absolute ROM of "non-diagnostic," "negative for malignancy," "atypical," "suspicious for malignancy," and "malignant" categories were 48.2%, 2.3%, 78.1%, 100.0%, and 99.4%, respectively. Despite the heterogeneous nature of the "neoplastic: other" category of the PSC system, the absolute ROM for solid lesions was 100%. Pancreatic neoplasm: high-risk/grade category including only two endosonographically solid cases of high-grade intraductal papillary mucinous neoplasms showed 100% ROM. There were no differences between PSC and WHO systems in sensitivity, specificity, and negative and positive predictive values: excluding the "atypical" category, these were 99.7%, 95.6%, 97.7%, and 99.5%, respectively. The "atypical" category considered benign resulted in a higher decrease in validity and negative predictive value, compared to "atypical" considered true malignant (93.6% vs 97.7% and 65.8% vs 97.7%). Conclusion: For solid pancreatic lesions, the WHO system was identical to the PSC system in terms of ROM and predictive values.

EIF1AX mutation in thyroid nodules: a histopathologic analysis of 56 cases in the context of institutional practices.

EIF1AX mutation has been identified as a driver mutation for papillary thyroid carcinoma (PTC) by The Cancer Genome Atlas (TCGA) study. Subsequent studies confirmed this mutation in PTC and Anaplastic Thyroid Carcinoma (ATC) but also reported EIF1AX mutation in Follicular nodular disease (FND) and benign thyroid nodules. In this study, we review thyroid nodules with EIF1AX mutation from two institutions: a tertiary care hospital (YNHH, n = 22) and a major cancer referral center (MSKCC, n = 34) and report the varying histomorphology in the context of additional genetic abnormalities and institutional practices. Pathology diagnoses were reviewed according to the WHO 5th edition and correlated with the type of EIF1AX mutation and additional concurrent molecular alterations, if any. Most cases were splice site type mutations. Cases consisted of 9 FND, 7 follicular (FA) or oncocytic adenomas (OA), 2 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and 38 follicular-cell derived thyroid carcinomas. Of 8 cases with isolated EIF1AX mutation, 7 were FND, FA or OA (88%) and one was an oncocytic carcinoma (12%). Of 12 cases with EIF1AX and one additional molecular alteration, 9 (75%) were FND, FA or OA, 2 (17%) were NIFTPs and one (8%) was a poorly differentiated thyroid carcinoma. All 36 cases with EIF1AX mutation and ≥ 2 molecular alterations were malignant (100%) and included TP53 and TERT promoter mutations associated with ATC (n = 8) and high-grade follicular cell-derived non-anaplastic carcinoma (HGC, n = 2). Isolated EIF1AX mutation was noted only in thyroid nodules seen at YNHH and were predominantly encountered in benign thyroid nodules including FND. Accumulation of additional genetic abnormalities appears to be progressively associated with malignant tumors.

Parsing the thyroid cytopathology suspicious for malignancy diagnosis through molecular-derived risk of malignancy and other related parameters: Insights into nodule characteristics and practice patterns.

INTRODUCTION: Thyroid cytopathology cases with suspicious for malignancy (SFM) diagnosis often result in resection. However, molecular testing offers details that may provide additional insights. In this study, the molecular profiles of SFM cases from two institutions that routinely used ThyroSeq v3 (TSV3) were examined. MATERIALS AND METHODS: Following institutional review board approval, SFM thyroid cytopathology cases with TSV3 results were retrieved from the databases of two institutions. Molecular information including molecular-derived risk of malignancy (MDROM), cytologic-histologic correlation data, and other related parameters were calculated. Statistical comparisons were made with a p <.05 considered significant. RESULTS: The core data set comprised 114 SFM cases that passed TSV3 quality assurance. All TSV3 results were reported as positive or negative for genomic alterations and all except five cases provided a probability of malignancy estimate. The overall combined baseline MDROM of 75.7% (95% CI, 70.0-81.4) was comparable to the risk of malignancy (74%) published in the Bethesda System. There was a statistically significant difference between the combined MDROMs of resected and unresected cohorts (79.0% vs 58.6%; p = .0153). Interestingly, the MDROMs of the resected cohorts from the two institutions were statistically different (75.0% vs 85.3%; p = .020). Cytologic-histologic correlation revealed malignant outcome in 88.5% of resected cases. CONCLUSIONS: Molecular analyses of SFM cases demonstrated higher risk genomic alterations that were associated with histologically overt neoplasms, resulting in increased malignancy outcome compared to baseline. MDROM analysis revealed differences in the cytopathologic practice patterns regarding follicular-patterned neoplasms at the two institutions.

Utility of Image Morphometry in the Atypical Urothelial Cells and High-Grade Urothelial Carcinoma Categories of the Paris System for Reporting Urinary Cytology.

Introduction: Urinary cytology (UrCy) is highly sensitive to diagnosing high-grade urothelial carcinoma (HGUC) but cannot predict muscularis propria invasion. Further, the atypical urothelial cell category (AUC) may have variable outcomes. Image morphometry (IM) may be a valuable adjunct technique in this setting. Hence, we evaluated IM in the AUC and HGUC categories to improve the diagnostic performance. Materials and Methods: The following six nuclear parameters were evaluated by IM on 3150 cells: nucleo-cytoplasmic (N:C) ratio, nuclear area, diameter, perimeter, standard deviation of the nuclear area (SDNA; pleomorphism) and integrated density (ID; nuclear chromasia), using the ImageJ software, in three cohorts based on the histopathology outcome: 20 cases of AUC - benign non-neoplastic outcome (AUC-B); 22 cases of HGUC Muscle invasive (HGUC-MI) and 21 cases of HGUC non-muscle invasive (HGUC-MF). Results: A retrospective analysis of urine cytology. The patient's ages ranged from 36 to 85 years, with a mean age of 60.6. The male-to-female ratio was 5.4:1. A total of 20 cases of AUC-B and 43 cases of HGUC were selected for IM analysis. HGUC cases had higher nuclear parameters than AUC-B, and HGUC-MI had higher SDNA, ID, diameter, and area than HGUC-MF. SDNA and ID predict muscularis propria invasion in HGUC. Conclusions: Image morphometry successfully differentiates HGUC cases from benign non-neoplastic ones and might help to identify muscularis propria invasion in HGUC using a combination of nuclear parameters.

Application of the international system for reporting serous fluid cytopathology on pleural effusion cytology with paired pleural biopsy: A new insight and novel approach on risk of malignancy.

INTRODUCTION: The risk of malignancy (ROM) remains an area of interest for further evaluation in reporting systems including in International System for reporting serous fluid cytopathology (TIS), which is a standardized system for reporting effusion cytology. Herein, we report our findings in further investigation of ROM in TIS by studying on paired pleural effusion specimens and corresponding pleural biopsies with emphasis on negative for malignancy, and atypia of undetermined significance categories. MATERIALS AND METHODS: The  Johns Hopkins Hospital pathology database was retrospectively searched for patients with a pleural biopsy (PBX) and a paired pleural effusion (PF) cytology specimens over a 4-year period. We employed the TIS categories. The following statistical parameters were evaluated: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ROM. RESULTS: A total of 223 patient cases were included. Effusions TIS reclassification and ROM were as follows: 1.8% non-diagnostic (ROM 75%), 75.8% negative for malignancy (ROM 23%), 4.9% atypical cells of undetermined significance (ROM 45%), 2.2% suspicious for malignancy (ROM 80%), and 15.2% malignant (ROM 100%). Overall accuracy, sensitivity, specificity, PPV and NPV were calculated and were 79.4%, 45%, 97.7%, 91.2% and 77%, respectively. Among, discordant cases diagnosed negative for malignancy on PF and positive for malignancy on PBX, there were significant number of lymphomas, mesotheliomas, and sarcomas. Lung cancer was the most common carcinoma; however, rare types of carcinomas were noted. Cells blocks and immunohistochemistry (IHC) studies were utilized to confirm either malignant conditions or rule out malignancy in both cell blocks and histology biopsies. CONCLUSION: This study demonstrates the high specificity and ROM for 'malignant' and 'suspicious for malignancy' categories in the TIS reporting system and highlights the modest negative predictive value for the 'negative for malignancy' category. Although Tissue biopsies are usually considered as 'gold standard', any definitive diagnosis of malignancy of body fluid should be considered positive for malignancy in further clinical decision-making.

Diagnostic Accuracy of Papanicolaou Society of Cytopathology System for Reporting Respiratory Cytology: A Systematic Review and Meta-Analysis.

INTRODUCTION: This study conducts the first meta-analysis to evaluate the diagnostic accuracy and the aggregated risk of malignancy associated with each category of the Papanicolaou Society of Cytopathology (PSC) system for reporting respiratory cytology. METHODS: A systematic search was conducted in PubMed, Scopus, and Web of Science using the keywords "(Lung, Respiratory specimens) AND (Papanicolaou Society of Cytopathology System)." Articles were assessed for risk of bias using the QUADAS-2 tool. After excluding inadequate samples, sensitivity and specificity for various cut-off points. Summary receiver operating characteristic curves and diagnostic odds ratios were pooled to assess diagnostic accuracy. RESULTS: Five studies, totaling 3,489 cases, were included. Sensitivity and specificity for the "Atypical and higher risk categories" considered positive were 60% (95% CI, 51-68%) and 87% (95% CI, 81-92%), respectively. For the "Suspicious for malignancy and higher risk categories" considered positive, sensitivity and specificity were 49% (95% CI, 40-58%) and 95% (95% CI, 92-97%), respectively. Sensitivity and specificity for the "Malignant" category considered positive for malignancy were 42% (95% CI, 33-52%) and 97% (95% CI, 92-99%), respectively. The pooled area under the curve ranged from 68 to 75% for each cut-off. CONCLUSION: This meta-analysis underscores the PSC system's accuracy in reporting respiratory cytology. It highlights the diagnostic importance of the "Suspicious" and "Malignant" categories in identifying malignancy, and the utility of the "Atypical" category for initial screening. These findings support the PSC system's role in enhancing diagnostic accuracy and clinical decision-making in respiratory cytology.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Sydney system for lymph node FNA biopsy cytopathology: A detailed analysis of recent publications and meta-analysis and a proposal for the components of an ideal prospective study of a cytopathology reporting system.

BACKGROUND: The Sydney system for fine-needle aspiration biopsy of lymph nodes has five categories, stressing the role of correlation of cytopathology with clinical, ultrasound, and ancillary findings to achieve diagnosis. The five categories constitute a hierarchical system with increasing risk of malignancy from benign to atypical, suspicious, and malignant categories, which informs recommendations for further workup to achieve a final diagnosis as possible. This article analyzes 10 publications using the Sydney system and a meta-analysis of nine of these studies. The primary goal of the analysis is to ascertain the causes of the large ranges in risk of malignancy for the "atypical" and "inadequate" compared to "benign," "suspicious," and "malignant" categories, which were comparable to well-established reporting systems. Research protocols are proposed to improve future studies. METHODS: PubMed literature search from January 2021 to December 2023 identified studies evaluating performance of the Sydney system. RESULTS: Ten studies showed heterogeneity with clinical setting, study design, ultrasound use and rapid on-site evaluation, operator, cutoff points for "positive" cases, with inherent partial verification biases, resulting in a wide range of risk of malignancy, specificity, and sensitivity values. CONCLUSION: Analysis shows the large range is due to heterogeneity of the studies, which suffer from biases and variable statistical analysis that are ultimately included in any meta-analysis, detracting from the usefulness of the risk of malignancy derived by the meta-analysis. Components for ideal analyses of reporting systems are presented.

Comparing Four Different Risk Malignancy Indices in Differentiating Benign and Malignant Ovarian Masses.

Background: Accurate prediction of ovarian masses preoperatively is crucial for optimal management of ovarian cancers. Objective: The objective of this study was to identify the risk of malignancy index (RMI) incorporating menopausal status, serum carbohydrate antigen 125 levels, and imaging findings for presurgical differentiation of benign from malignant ovarian masses and to evaluate the diagnostic ability of four different RMIs. Materials and Methods: Women presenting with ovarian masses from August 2018 to January 2020 were evaluated preoperatively with detailed history, examination, imaging, and tumor markers. RMI 1-4 was calculated for all patients. Evaluation of the diagnostic utility of four different RMIs for preoperative identification of malignancy was based on the increment of the area under the receiver operating characteristic curve. Histopathological diagnosis was used as the gold standard test. Results: One hundred and twenty-one patients fulfilling the eligibility criteria were enrolled in this study. Benign tumors constituted 61 (50.4%) out of 121 cases, followed by malignant tumors and borderline tumors constituting 49 (40.49%) cases and 11 (9.09%) cases, respectively. The sensitivity of RMIs 1, 2, 3, and 4 was 77.0%, 63%, 77.0%, and 77.0%, respectively, and the specificity was 84%, 86%, 77%, and 71%, respectively. The RMI 2 had higher specificity at predicting malignancy than other RMIs while diagnostic accuracy was highest in RMI 1. Conclusion: The RMI method is a simple and cost-effective technique in preoperative differentiation of ovarian masses.

Sydney Reporting System for Lymph Node Fine-Needle Aspiration and Malignancy Risk Stratification: Is It of Clinical Value?

Lymphadenopathy is a common presentation of both reactive and malignant diseases, and lymph node fine-needle aspiration cytology (LN-FNAC) is an effective and inexpensive screening method. It can prevent unnecessary invasive surgery and excisional biopsy, especially in benign cases. Unfortunately, the lack of universally accepted terminology for reporting results has hindered its widespread support. The Sydney system proposal for lymph node cytopathology categorization and reporting introduced five diagnostic categories to address the lack of universally accepted terminology for reporting results in lymphadenopathy. Our study analyzed 188 lymph node fine-needle cytology (FNC) samples from King Abdulaziz University Hospital, Saudi Arabia, examining clinical follow-up data, pathology records, patient information, and final diagnosis from January 2019 to December 2022. Most specimens were from axillary lymph nodes, with 99.5% tissue correlation. The Sydney system category classification identified 56.9% of cases as malignant, while 26.1% were benign. The final surgical specimen diagnosis revealed a higher percentage of malignant diagnoses, with the highest risk of malignancy (ROM) in malignant/category V. In conclusion, our study demonstrates that LN-FNAC offers high diagnostic accuracy for lymph node (LN) aspirates, with the Sydney approach potentially aiding risk stratification and achieving consistency in cytologic diagnosis, but further multi-centric research is needed.

Diagnostic performance of fine-needle aspiration in soft tissue tumors: Application of the World Health Organization System for Reporting Soft Tissue Cytopathology and risk of malignancy assessment.

BACKGROUND: Recently, a new World Health Organization Reporting System for Soft Tissue Cytopathology (WHO System) was introduced. To analyze the value of this system, routine fine-needle aspiration soft tissue tumor (STT) cases were reviewed. METHODS: Cytology samples of STTs collected between 1954 and 2022 at the Institut Curie were used (2214 cases, including 1376 primary tumors). All specimens were classified according to the predominant cytomorphological pattern and the WHO System. The diagnostic accuracy and risk of malignancy (ROM) in each category were calculated. RESULTS: Final diagnoses revealed 1236 malignancies and 978 benign or low-risk tumors. The original cytological evaluation led to 21 false-negative results (0.85%) and 29 false-positive results (1.17%). Sensitivity, specificity, positive predictive value, and negative predictive value were 98.3%, 92.1%, 97.5%, and 94.2%, respectively. Overall diagnostic accuracy was 94.2%. The ROM calculated according to the WHO System was 29.87%, 2.49%, 39.62%, 51.43%, 68.42%, and 97.69% in the nondiagnostic, benign, atypical, soft tissue neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories, respectively; however, it varied broadly depending on the morphological pattern (62.78% in spindle cell tumors, 84.58% in myxoid tumors, 3.00% in lipomatous tumors, 78.15% in epithelioid tumors, 94.26% in pleomorphic tumors, and 100% in round cell tumors). CONCLUSIONS: Cytology of STTs is a powerful diagnostic method. Some cytological patterns overlap in different morphological groups, and the possibility of false-negative and false-positive diagnoses may persist. This analysis evidenced utility of the WHO System, especially when combined with morphological pattern assessment. Subclassification in particular diagnostic categories allowed for calculation of the ROM, which is crucial for optimal patient management.

The Bethesda System for Reporting Thyroid Cytopathology in the African American population: A tertiary centre experience.

BACKGROUND: The reported risk of malignancies (ROM) remains controversial for fine needle aspiration (FNA) of thyroid nodules in the African American (AA) population. Herein, the ROM along with frequency was assessed for each of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnostic categories. MATERIALS AND METHODS: The electronic pathology archive of a large academic hospital was retrospectively searched for cytopathology reports of thyroid nodules in AA patients (2010-2019) and Non-African American (NAA) control cases. The patients' demographic, thyroid nodule characteristics, FNA results using TBSRTC and surgical diagnoses were recorded, whenever available. RESULTS: Three hundred ninety-one cases were identified, 317 females (81.1%) and 74 males (18.9%) with median age 50.0 (SD = 14.4). The mean size of the nodules was 2.1 cm (SD = 1.4). The Bethesda categories were: 5.4% (I), 35.0% (II), 35.3% (III), 7.7% (IV), 3.3% (V) and 13.3% (VI). The overall ROM of thyroid nodules was 43.8% (89/203) on surgical follow-up (203/391). The ROM in each Bethesda categories were: 33.3% (I), 11.6% (II), 35.2% (III), 15.8% (IV), 83.3% (V) and 100% (VI) on surgical follow-up. The frequency of thyroid nodules was higher in AA females; however, the ROM was higher in AA males (48.3%) compared with AA females (41.2%). CONCLUSION: The ROM in Categories I, II and III was higher than those reported in the TBSRTC while being similar in Categories IV, V and VI. The overall risk of thyroid malignancy in our AA patient population was higher than those in the literature. The overall ROM of thyroid nodules in AA males was higher than of AA females.

Oncocytic/Hürthle cell lesions have the same implied risk of neoplasm/malignancy as their follicular counterparts.

INTRODUCTION: There are conflicting results on whether the presence of oncocytes modifies the risk of neoplasm (RON) or malignancy (ROM) for thyroid fine-needle aspirates (FNAs): Atypia of undetermined significance AUS and Follicular Neoplasm, FN, or Oncocytic Neoplasm, ON. To our knowledge, the effect of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has not yet been studied. We compared RON and ROM between follicular type AUS (AUS-FT) and oncocytic type AUS (AUS-OT) and between FN and ON. MATERIALS AND METHODS: We retrospectively analysed all thyroid FNAs with the diagnostic category of AUS-other or Neoplasm (2005-2015). AUS-FT had predominance of microfollicles and AUS-OT had predominance of oncocytes. Histology follow-up was then reviewed and RON, ROM was then calculated and compared (significant at p < 0.05). We repeated the search for 2018 to evaluate for NIFTP effect. RESULTS: Pre-NIFTP, 859/5063 cases (17%) were AUS-FT, AUS-OT, FN, and ON. Histology follow-up was available for 297 cases (35%). RON was 83/183 (45%) for AUS-FT, 35/76 (46%) for AUS-OT, 15/25 (60%) for FN and 11/13 (85%) for ON. Post-NIFTP, RON was 11/31 (35%) for AUS-FT, 5/8 (63%) for AUS-OT, 1/2 (50%) for FN and 4/5 (80%) for ON. For both periods, RON, ROM of AUS-FT was not significantly different than AUS-OT, and no significant differences were observed comparing FN and ON. CONCLUSION: The predominance of oncocytes does not modify the implied RON, ROM for categories of AUS or FN\ON, even after the adoption of NIFTP.

How important are the cytomorphologic subtypes of the salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan system for reporting salivary gland cytology? An institutional experience 2018-2024.

INTRODUCTION: Salivary gland neoplasm of uncertain malignant potential (SUMP) is an important diagnostic category of the Milan System for reporting salivary gland cytology (MSRSGC). Further subcategorization by cytomorphologic subtypes has been recommended to risk-stratify cases. In this study, our institutional experience with the risk of neoplasm (RON) and risk of malignancy (ROM) based on cytomorphologic subcategorization of SUMP is reported. We also report the prevalence of malignancy (POM) at our institution. METHODS: The pathology database was queried for cases of fine-needle aspiration (FNA) diagnosed as SUMP along with follow-up at our institution from 2018-February 2024. This study was approved by an institutional review board. RESULTS: Of 1159 cases of salivary gland FNA specimens reported as per MSRSGC at our institution, 14.8% (171/1159 cases) were diagnosed as SUMP, with these reports verified by at least 16 cytopathologists. Surgical follow-up was available for 139/171 (81.3%) of these cases, for which the original cytomorphologic subgroups were as follows: 65 (46.8%) basaloid, 48 (34.5%) oncocytic/oncocytoid, 14 (10.1%) myoepithelial, 9 (6.5%) other, 2 (1.4%) clear cell, and 1 (0.7%) mucinous. The POM within SUMP at our institution is within a range of 29.8%-36.7%. When considering all cases, our institutional RON for SUMP was 97.8% (136/139), and the ROM was 36.7% (51/139). Notably, a significant portion of cases (36%, 50/139) underwent review at a daily intradepartmental consensus conference. Analysis revealed that SUMP cases that underwent consensus review had a ROM of 46% (23/50), versus 31.5% (28/89) in independently verified cases (p = .13). Of the cytomorphologic subgroups, basaloid SUMP in particular was more likely to be benign on resection when the case had been independently verified than after consensus review (p = .0082). When considering only the independently verified cases, the ROM for each subgroup was as follows: 38.7% (12/31) in oncocytic/oncocytoid, 20% (9/45) in basaloid, 33.3% (2/6) in myoepithelial, 60% (3/5) in "other", and 100% (1/1) in both mucinous and clear cell (p = .0407). CONCLUSION: While the RON is high across all cytomorphologic subgroups of SUMP, the ROM does vary across the groups, with basaloid cytomorphology having the lowest ROM. This effect is seen in independently verified cases but not in cases having undergone consensus review.

Diagnostic significance of clay-like materials aspirated from thyroid nodules.

Objective: The simplest way to determine the adequacy of aspirated materials is the on-site gross visual assessment of aspirated materials. However, few studies have examined the gross findings of thyroid aspirates. This study aimed to clarify the diagnostic significance of clay-like material aspirated from thyroid nodules. Material and Methods: We reviewed 69,848 thyroid nodules that underwent aspiration cytology at Kuma Hospital between January 2007 and August 2021. Among them, 355 (0.5%) nodules with aspirated materials described as clay-like materials were retrospectively examined. Results: Among 355 nodules, 322 (90.7%) were categorized as cystic fluid or benign. The aspirated materials were mainly composed of non-epithelial components, including colloid or proteinaceous materials, foamy histiocytes, and degenerative red blood cells. In original ultrasound reports, the incidence of intermediate and high suspicion was 11.0%. Malignant cells were observed in 21 nodules (5.9%), one-third of which were papillary thyroid carcinomas. The materials aspirated from papillary and follicular thyroid carcinomas exhibited necrotic carcinoma cells derived from infarcted areas. The overall risk of malignancy was 3.9%. The risk of malignancy in nodules interpreted as highly suspicious on ultrasound examination was 37.5%. Conclusion: As clay-like materials aspirated from thyroid nodules were considered sufficient specimens, the recognition contributes to avoiding unnecessary second punctures. The presence of clay-like materials was indicative of the colloid and/or blood components of benign cystic lesions, or, more rarely, of infarcted carcinoma. The ultrasound examination results tended to overestimate nodules. We should reaffirm that on-site gross visual assessment of aspirated materials is a fast and reasonably accurate predictor of the on-site adequacy of the samples.

Atypical Endometriosis: A Comprehensive Systematic Review of Pathological Patterns and Diagnostic Challenges.

Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as a potential precursor to endometriosis-associated ovarian cancers (EAOC), particularly endometrioid and clear cell subtypes. AE presents challenges in diagnosis due to its diverse clinical and pathological features, often requiring careful histological evaluation for accurate identification. Architectural AE, defined by localized proliferation of crowded glands with atypical epithelium resembling endometrial neoplasia, and cytologic AE, characterized by nuclear atypia within the epithelial lining of endometriotic cysts, are key subtypes. Immunohistochemical and molecular studies have revealed aberrant expression of markers such as Ki67, COX-2, BAF250a, p53, estrogen receptor, progesterone receptor, and IMP-3. Long-term follow-up studies suggest relatively low recurrence and malignant transformation rates among patients with AE, but uncertainties persist regarding its exact malignancy potential and optimal management strategies. Integration of artificial intelligence and shared molecular aberrations between AE and EAOC may enhance diagnostic accuracy. Continuous interdisciplinary collaboration and ongoing research efforts are crucial for a deeper understanding of the relationship between endometriosis and carcinogenesis, ultimately improving patient care and surveillance.

Risk of malignancy and overall survival associated with the diagnostic categories in the World Health Organization Reporting System for Pancreaticobiliary Cytopathology.

BACKGROUND: The World Health Organization (WHO) classification system revised the Papanicolaou Society of Cytopathology (PSC) system for reporting pancreaticobiliary cytopathology. To better stratify intraductal and/or cystic neoplasms by cytologic grade, the neoplastic, other category was replaced by two new categories: pancreaticobiliary neoplasm, low-risk/grade (PaN-Low) and pancreaticobiliary neoplasm, high-risk/grade (PaN-High). Low-grade malignancies were placed in the malignant category, and benign neoplasms were placed in the benign/negative for malignancy category. METHODS: An institutional pathology database search identified patients who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic lesions from January 2015 to April 2022. The absolute risk of malignancy (ROM) was determined by histologic and/or clinical follow-up of at least 6 months, and overall survival rates were calculated across diagnostic categories, comparing the WHO and PSC systems. RESULTS: In total, 1012 cases were reviewed and recategorized. The ROM for the WHO system was 8.3% for insufficient/inadequate/nondiagnostic, 3.2% for benign/negative for malignancy, 24.6% for atypical, 9.1% for PaN-Low, 46.7% for PaN-High, 75% for suspicious for malignancy, and 100% for malignant. Comparatively, the ROM for the PSC system was 7.4% for nondiagnostic, 3.0% for negative for malignancy, 23.1% for atypical, 0% for neoplastic, benign, 7.3% for neoplastic, other, 75% for suspicious for malignancy, and 100% for malignant. The WHO system demonstrated superior stratification for overall survival. CONCLUSIONS: The WHO system significantly improves the stratification of ROM and overall survival across diagnostic categories by introducing the PaN-Low and PaN-High categories and reassigning low-grade malignancies to the malignant category. Analyzing EUS-FNA samples with the WHO system provides critical insights for guiding clinical management.

Deciphering Serous Effusions Using the New International System for Reporting Serous Fluid Cytopathology.

Introduction Serous effusion cytopathology is a minimally invasive, cost-effective procedure and plays a crucial role in diagnosing a spectrum of pathological conditions, ranging from benign to malignant. The International System for Reporting Serous Fluid Cytopathology (ISRSFC) offers a standardized framework for reporting serous effusions, aiding in better communication and clinical decision-making. Aims and objectives This study aimed to categorize effusions using the ISRSFC reporting system. In addition, we sought to estimate the risk of malignancy (ROM) for each diagnostic category and evaluate the diagnostic performance of conventional smear versus cell block techniques. Materials and methods This cross-sectional study was conducted in the Department of Pathology over one year. We applied the ISRSFC criteria to serous effusions and categorized them accordingly. The ROM for each category was assessed with histopathology serving as the gold standard. Then, the diagnostic performance including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy was evaluated using conventional smear and cell block techniques. Results The study included 185 serous effusion cases, with ages ranging from two months to 85 years. The male-to-female ratio was 1.1:1. Most effusions were pleural fluids constituting about 133 cases (71.9%), followed by peritoneal fluids (47 cases, 25.4%) and pericardial fluids (five cases, 2.7%). Among the fluids, four (2.2%) were diagnosed as non-diagnostic (ND), 152 (82.2%) as negative for malignancy (NFM), four (2.2%) as atypia of undetermined significance (AUS), nine (4.8%) as suspicious for malignancy (SFM), and 16 (8.6%) as malignant (MAL). The overall ROM was 25% for ND, 8.5% for NFM, 50% for AUS, 77% for SFM, and 100% for MAL. The sensitivity, negative predictive value (NPV), and diagnostic accuracy were superior when combining conventional smear with the cell block technique. Conclusions Our findings underscore the use of ISRSFC in categorizing effusion samples, assessing the ROM, and guiding clinical management. Moreover, our study highlights the benefits of employing a combined approach using conventional smears and cell blocks for enhanced diagnostic accuracy in serous effusions.

The World Health Organization Reporting System for Lung Cytopathology-A Review of the First Edition.

The World Health Organization Reporting System for Lung Cytopathology is the first international system that was developed to standardize the reporting of lung cytopathology specimens across all settings of cytopathology practice. The system is composed of five diagnostic categories, which apply to all lung cytopathology specimen types. Each category contains cytomorphologic criteria, an estimated risk of malignancy, and clinical management recommendations. International uniformity in the reporting of lung cytopathology will refine the communication between cytopathologists and clinicians and ultimately improve patient care. Furthermore, standardizing the cytomorphologic criteria for each lesion will improve reproducibility among cytopathologists and highlight areas in lung cytopathology that require further research. The system also provides best practice recommendations for the selection of ancillary tests to aid in the diagnosis of each lesion, or group of lesions, keeping in mind that resources will vary across different practice settings. The goal of this review is to summarize the cytomorphologic criteria, potential diagnostic pitfalls, ancillary testing, estimated risk of malignancy, and clinical management recommendations for each diagnostic category.