Khorsandi N, Vohra P, Samghabadi P
… +4 more, De La Sancha Verduzco C, Lung D, Chou F, Long SR
Cancer Cytopathol
· 2025 May · PMID 40326922
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INTRODUCTION: Racial differences have been identified in the distribution of cervical high-risk human papillomavirus (hrHPV) subtypes; however, there is limited understanding of hrHPV subtypes in anal specimens based on...INTRODUCTION: Racial differences have been identified in the distribution of cervical high-risk human papillomavirus (hrHPV) subtypes; however, there is limited understanding of hrHPV subtypes in anal specimens based on patient race/ethnicity. This knowledge gap limits possible vaccination and/or treatment efforts and may not provide optimal coverage in diverse populations. MATERIALS AND METHODS: This preliminary study evaluates anal hrHPV subtype distribution and cytological outcomes in a diverse population accessing care at a large, urban, publicly funded hospital over a 2-year period. The primary objectives were to analyze anal hrHPV subtypes and associated cytologic diagnoses, focusing on disparities among demographic groups, including racial and ethnic diversity, and among individuals living with human immunodeficiency virus (HIV). RESULTS: Ninety-two patients were identified with a predominance of male (87%) and gay-identifying (50%) individuals and a significant representation from Hispanic/Latinx (36%) and White (36%) backgrounds. A majority (88%) were living with HIV, and only a small fraction (7%) had received HPV vaccination. The most common hrHPV subtypes identified were non-16 and 18 hrHPV subtypes (46%). No significant differences were identified in distribution of HPV subtypes among different races/ethnicities or between sexual and gender minorities and heterosexual, cisgender-identifying individuals. However, individuals with HIV were more likely to have atypical cytologic diagnoses and non-16/18 HPV subtypes. CONCLUSIONS: The findings underscore the prevalence of non-16/18 hrHPV subtypes in a racially and ethnically diverse urban population, particularly among individuals living with HIV. The study highlights the need for expanded HPV subtype surveillance and vaccine development to ensure equitable prevention strategies across diverse populations.
Yang WL, Crothers BA, Liu TJ
… +9 more, Hsu SW, Yeh CH, Liu YS, Shao G, Lin MY, Tsao TY, Tung MC, Chu PY, Hang JF
Cancer Cytopathol
· 2025 May · PMID 40317981
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BACKGROUND: The Paris System (TPS) introduced standardized nuclear-to-cytoplasmic (N/C) ratio thresholds for urine cytology to improve high-grade urothelial carcinoma (HGUC) detection, but these criteria remain subjectiv...BACKGROUND: The Paris System (TPS) introduced standardized nuclear-to-cytoplasmic (N/C) ratio thresholds for urine cytology to improve high-grade urothelial carcinoma (HGUC) detection, but these criteria remain subjective. This study used AIxURO, an artificial intelligence-based model, to measure N/C ratio and nuclear area to identify abnormal cells in whole slide images (WSIs). METHODS: A total of 106 urine cytology slides from 46 lower urinary tract (LUT) and 60 upper urinary tract (UUT) cancer cases, diagnosed as atypical urothelial cell (15.1%), suspicious for high-grade urothelial carcinoma (SHGUC) (23.6%), and HGUC (61.3%), with biopsy-confirmed HGUC or carcinoma in situ (CIS), were digitized and analyzed by AIxURO. The model quantified suspicious and atypical cells, N/C ratios, and nuclear areas, with statistical differences assessed using Kruskal-Wallis tests. RESULTS: AIxURO identified fewer suspicious cells than atypical cells (20.5 vs. 242.0, p < .001). Suspicious cells had higher N/C ratios (0.66 vs. 0.58, p < .001) and larger nuclear areas (102.3 vs. 85.7 µm, p < .001). Although N/C ratios did not differ significantly between UUT and LUT cases, nuclear areas varied among abnormal cells (CIS: 101.5 µm; HGUC: 83.5 µm). In HGUC cytology cases, the CIS category had larger nuclear areas than HGUC for both suspicious (116.3 vs. 100.4 µm) and atypical cells (101.5 vs. 82.2 µm). CONCLUSIONS: AIxURO provides objective quantification of N/C ratios and nuclear areas, refining TPS criteria for distinguishing suspicious from atypical cells. A lower N/C ratio cutoff (0.66) for SHGUC/HGUC may be more appropriate than the TPS threshold (>0.7). Findings support using consistent N/C ratio criteria across UUT and LUT cases.
Tang H, Xia H, Sun N
… +4 more, Hernandez PV, Wang M, Adeniran AJ, Cai G
Cancer Cytopathol
· 2025 May · PMID 40289395
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BACKGROUND: Accurate diagnosis of neuroendocrine neoplasms (NENs) is challenging, especially in poorly differentiated neuroendocrine carcinomas (NECs). This study was aimed to search the best or best combination of neuro...BACKGROUND: Accurate diagnosis of neuroendocrine neoplasms (NENs) is challenging, especially in poorly differentiated neuroendocrine carcinomas (NECs). This study was aimed to search the best or best combination of neuroendocrine markers in the diagnostic workup of NENs via analysis of the real-world data and machine learning algorithms. METHODS: Cytology cases with a workup of four neuroendocrine markers (chromogranin, synaptophysin, CD56, and INSM1) were retrieved. Sensitivity, specificity, and area under the curve of receiver operating characteristic curve (AUC-ROC) were calculated for each marker alone or in combination. Two machine learning algorithms, neural network and random forests, were also tested. RESULTS: The study cohort included 106 NENs (64 NECs and 42 well-differentiated neuroendocrine tumors [NETs]) and 36 non-NEN cases. The combination of synaptophysin and INSM1 had sensitivity of 0.95, specificity of 0.92, and AUC-ROC of 0.93. Addition of CD56 to the combination further increased the sensitivity and AUC-ROC to 1 and 0.96, respectively, in all NENs as well as NEC cases. In addition, the combination of chromogranin, synaptophysin and INSM1 had sensitivity of 1, specificity of 0.92, and AUC-ROC of 0.96 in NETs. Machine learning models, specifically random forests and neural network, confirmed the efficacy of combining synaptophysin, INSM1, and CD56. CONCLUSIONS: The combination of synaptophysin, INSM1, and CD56 has the best performance in diagnostic workup of all NENs, although chromogranin may be selected for NETS. The random forests and neural network models support the common practice rule of requiring at least two out of three markers to be positive for optimal marker utilization.
Lametti A, Brimo F, Kanber Y
… +2 more, Caglar D, Auger M
Cancer Cytopathol
· 2025 May · PMID 40272265
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The third edition of The Bethesda System for Reporting Thyroid Cytopathology includes category IV, follicular neoplasm (FN), which is used to classify fine-needle aspirates of thyroid nodules that may correspond to invas...The third edition of The Bethesda System for Reporting Thyroid Cytopathology includes category IV, follicular neoplasm (FN), which is used to classify fine-needle aspirates of thyroid nodules that may correspond to invasive follicular-derived neoplasia other than papillary thyroid carcinoma. This diagnosis is infrequently rendered, and may represent a challenge for pathologists. This review presents a practical approach to FN and its subtype oncocytic follicular neoplasm (OFN). First, minimal criteria for the diagnosis must be achieved, namely sufficient cellularity, architectural features consistent with neoplasia, and follicular cell or oncocytic cytomorphology. Second, select diagnoses that are common or important differential diagnoses for FN or OFN must be ruled out, via a combination of morphological findings and limited ancillary tests, when available. These include follicular nodular disease, parathyroid sampling, metastatic carcinoma, noninvasive follicular thyroid neoplasm with papillary-like nuclear features, medullary thyroid carcinoma, certain subtypes of papillary thyroid carcinoma, and lymphocytic thyroiditis. This approach should allow for a careful selection of cases where diagnostic thyroid lobectomy is an appropriate therapeutic modality.
Cancer Cytopathol
· 2025 May · PMID 40249200
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Pancreatic cyst fluid (PCF) specimens present significant interpretive challenges. Accurate preoperative diagnosis is essential for guiding patient management, as pancreatic cysts vary from benign to pre-malignant and ma...Pancreatic cyst fluid (PCF) specimens present significant interpretive challenges. Accurate preoperative diagnosis is essential for guiding patient management, as pancreatic cysts vary from benign to pre-malignant and malignant. Appropriate triage differentiates low-risk cysts requiring surveillance from high-risk cysts necessitating surgical resection, the latter of which have increased likelihood of progressing to or harboring invasive carcinoma. Optimal PCF assessment integrates radiological, cytological, biochemical, and molecular findings if available. Key biochemical markers such as carcinoembryonic antigen and glucose can improve the detection of neoplastic mucinous cysts. However, cytology remains the most specific modality for identifying high-risk cysts. Cytomorphologic interpretation is particularly challenging due to the scant cellularity and degenerative changes often present in these specimens. This review provides practical insights to improve the evaluation of pancreatic cysts, emphasizing the importance of a multidisciplinary approach and highlighting diagnostic pearls and common pitfalls to aid in accurate interpretation and optimal patient care.
Trieu J, Gilman A, Konstantinoff K
… +2 more, Lozano MD, Saieg M
Cancer Cytopathol
· 2025 May · PMID 40232932
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The prevalence of pancreatic lesions has increased over the years because of an increase in accessibility to and the quality of cross-sectional imaging. This commentary describes the common non-neoplastic and neoplastic...The prevalence of pancreatic lesions has increased over the years because of an increase in accessibility to and the quality of cross-sectional imaging. This commentary describes the common non-neoplastic and neoplastic pancreatic lesions. The images in this commentary depict classic cross-sectional images, sonographic findings, and the cytopathologic diagnosis of each lesion. Most common non-neoplastic lesions include pseudocysts, autoimmune pancreatitis, and chronic pancreatitis. Most common neoplastic lesions include serous cystadenomas, intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, solid pseudopapillary neoplasms, neuroendocrine tumors, pancreatic ductal adenocarcinoma, acinar cell carcinoma, and metastases to the pancreas. The aim of this Cytoimaging Correlation Series is to demonstrate the multidisciplinary involvement in the diagnosis of pancreatic pathology and to highlight main findings in the most common entities found in everyday practice.
Ma W, Rodrigues Simoes NJ, Seery PP
… +4 more, Li T, Tafe LJ, Kerr DA, Liu X
Cancer Cytopathol
· 2025 May · PMID 40227522
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BACKGROUND: Cytological evaluation is essential for assessing pericardial effusions (PEs) in non-small cell lung cancer (NSCLC). This study retrospectively examined the clinicopathological, molecular, and prognostic char...BACKGROUND: Cytological evaluation is essential for assessing pericardial effusions (PEs) in non-small cell lung cancer (NSCLC). This study retrospectively examined the clinicopathological, molecular, and prognostic characteristics of patients with NSCLC with PE. METHODS: Clinical data from 80 patients with NSCLC with PE treated at an academic center over the course of 15 years were reviewed. PE specimens were categorized according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC). The analysis included patient demographics, molecular alterations, cytopathology, histology, and survival outcomes. RESULTS: Of the 80 patients, 36 (45%) were female and 90% had stage IV disease. A smoking history was noted in 58 patients (72.5%), and 22 patients (27.5%) presented with tamponade. Lung adenocarcinoma predominated (87.5%). The ISRSFC categorized 25% of the specimens as negative for malignancy (NFM), 7.5% as atypia of undetermined significance (AUS), 3.75% as suspicious for malignancy (SFM), and 63.75% as malignant (MAL). Immunohistochemistry in 57 specimens identified thyroid transcription factor 1 (65%) as the most frequently positive marker. Molecular analysis revealed p53 mutations (59.1%) as the most prevalent, followed by KRAS (34.1%) and EGFR (15.9%). Kaplan-Meier analysis showed significantly better survival for NFM patients than non-NFM patients (MAL, SFM, and AUS; p = .0036). Bloody PEs and tamponade were associated with worse outcomes. The immunotherapy group achieved the most prolonged survival among stage IV patients (9.07 months; p = .017). Cox regression confirmed cytology-negative status as an independent prognostic factor. CONCLUSIONS: Cytological evaluation and ISRSFC classification are crucial for NSCLC-associated PEs. A multidisciplinary approach integrating cytology, immunohistochemistry, and molecular profiling is essential for optimal management and prognosis.
Swid MA, Shen AE, Young AJ
… +2 more, Rahman T, Monaco SE
Cancer Cytopathol
· 2025 May · PMID 40202788
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BACKGROUND: There is increasing interest in designing new fine-needle aspiration (FNA) needles to maximize tissue acquisition. This study compares cytological preparations from a new rotating FNA needle (CytoCore) with c...BACKGROUND: There is increasing interest in designing new fine-needle aspiration (FNA) needles to maximize tissue acquisition. This study compares cytological preparations from a new rotating FNA needle (CytoCore) with conventional FNA (ConvFNA) using semiquantitative evaluation and quantitative image analysis (IA). METHODS: FNA were performed on ex vivo tissue in quadruplicate for each needle type (ConvFNA and CytoCore), including different sizes (22 G and 25 G) and variable procedure time (5 and 20 s). The Nikon Elements (v5.41.02) was used to quantify the cellularity and size of the largest tissue fragment on cell blocks. RESULTS: A total of 96 cytology specimens were evaluated were evaluated from benign and malignant specimens. For both ConvFNA and CytoCore, a longer procedure time (20 s) tended to produce greater cellularity and larger tissue fragments in the cell block specimens for both needles when analyzed with image analysis and was statistically significant for the CytoCore needle (p < .01). The ConvFNA tended to perform better with short procedure time. There was no statistically significant difference using different needle gauges. CONCLUSION: This study shows that IA can help to quantitatively evaluate sample cellularity in the cell blocks from specimens acquired with different needles. A longer procedure time tended to produce more cellular samples and larger tissue fragments in the cell block for both ConvFNA and CytoCore needles and was statistically significant for CytoCore. Additional larger studies, including those with true clinical cases, should be considered to evaluate the different needle types further.
Maher MH, Treekitkarnmongkol W, Ghatak S
… +13 more, Dai J, Liu S, Nguyen T, Duose DY, Kim MP, Hu TY, Hurd MW, Paris PL, Kirkwood KS, Maitra A, Luthra R, Sen S, Roy-Chowdhuri S
BACKGROUND: Classification and risk stratification of pancreatic cysts are challenging because of limited radiographic and cytomorphologic features. Although molecular profiling has emerged as an ancillary test for pancr...BACKGROUND: Classification and risk stratification of pancreatic cysts are challenging because of limited radiographic and cytomorphologic features. Although molecular profiling has emerged as an ancillary test for pancreatic cyst fluid (PCF), additional high-sensitivity and -specificity biomarkers are still needed for improved classification. METHODS: In this study, PCF from 93 patients, including intraductal papillary mucinous neoplasms (n = 65), mucinous cystic neoplasms (n = 9), serous cystadenomas (n = 9), pancreatic cyst not otherwise specified (n = 8), and pseudocysts (n = 2), were evaluated for biomarkers. Molecular profiling by next-generation sequencing was performed, and a subset of the cases (n = 32) were interrogated with 2083 microRNAs (miRNAs) to evaluate their use for pancreatic cyst risk stratification. RESULTS: As independent PCF biomarkers in 32 cases with histologic diagnoses, three miRNAs performed significantly better than mutant KRAS, mutant GNAS, carcinoembryonic antigen (CEA), and serum carbohydrate antigen 19-9 (CA19-9) in discriminating high-risk from low-risk cysts. The three elevated miRNAs in combination with mutant KRAS, mutant GNAS, and serum CA19-9 displayed similar diagnostic performance (miR-4461: area under the curve [AUC], 0.950; 95% confidence interval [CI], 0.800-1; miR-6723-5p: AUC, 0.958; 95% CI, 0.850-1; miR-6755-3p: AUC, 0.942; 95% CI, 0.816-1) in discriminating high-risk from low-risk cysts, when compared to mutant KRAS, mutant GNAS, CEA, and serum CA19-9 (AUC, 0.950; 95% CI, 0.825-1). In the absence of CA19-9, the three-marker panel of KRAS, GNAS, and miRNAs showed marginally improved performance compared with KRAS, GNAS, and CEA, which highlights the potential utility of miRNAs as biomarkers in PCF analysis. CONCLUSIONS: These findings demonstrate that a multiomics biomarker approach with elevated PCF miRNAs with mutant KRAS, mutant GNAS, and serum CA19-9 may help in better detecting high-risk cysts for early clinical intervention.
Because of many factors, the landscape of cervical cancer prevention is again at a pivot point within the United States. Primary human papillomavirus (HPV) screening has been recommended as the preferred testing method b...Because of many factors, the landscape of cervical cancer prevention is again at a pivot point within the United States. Primary human papillomavirus (HPV) screening has been recommended as the preferred testing method by the American Cancer Society since 2020. Although primary HPV testing provides high negative predictive value in screening, women who screen positive for HPV need triage using methods that have an optimal balance between sensitivity for precancer and the number of colposcopies required for detection. The triage test ideally should maximize specificity while also reassuring patients who test negative, although it should be acknowledged that no screening or triage test can entirely exclude disease in a screen-positive patient. While cervical cytology (the Papanicolaou test) triage of primary HPV screen-positive patients is currently recommended by most screening strategies, additional triage tests, specifically extended HPV genotyping and combined p16/Ki-67 dual-stain immunocytochemistry, are now approved by the US Food and Drug Administration and incorporated into cervical cancer screening and management guidelines. Incorporating these triage methods into practice should be achieved by using appropriate validation/verification and implementation steps and, in the case of dual-stain immunocytochemistry, appropriate cytologist/cytopathologist training. The US Food and Drug Administration approval of vaginal self-collection in May 2024 is another significant advance for increasing access to screening. These samples can only be tested using primary HPV screening platforms, and guidance for management has been endorsed by the ASCCP's enduring guidelines process. This review discusses issues that warrant consideration before implementation and provides practical guidance for the incorporation of self-collected specimens and extended genotyping/dual-stain tests into the workflow of the cytopathology laboratory.
BACKGROUND: Hepatocellular carcinoma (HCC) may be diagnosed and further subclassified in surgical specimen as per the recent World Health Organization (WHO) classification into several distinct subtypes with prognostic i...BACKGROUND: Hepatocellular carcinoma (HCC) may be diagnosed and further subclassified in surgical specimen as per the recent World Health Organization (WHO) classification into several distinct subtypes with prognostic implications. The aim of this study was to apply this WHO classification on fine-needle aspiration biopsy (FNAB) samples of HCC and describe their features. METHODS: This was a retrospective analysis of all ultrasound-guided FNAB of liver mass lesions in patients with suspected HCC (n = 164) over a 7-year period. Detailed morphological assessment of cytopathological features and grading was done and correlated with each other. HCC was subtyped further in cases with available cell blocks (n = 126). RESULTS: A total of 164 cases of HCC were evaluated on FNAB with age range of 18-88 years (mean, 60 years), and with 140 (85.4%) male and 24 (14.6%) female patients. Grading performed on 160 cases of HCC (after excluding fibrolamellar HCC) revealed 23 well differentiated, 127 moderately differentiated, and 10 poorly differentiated HCCs. Subtyping was feasible in 126 cases, of which 26 cases (20.6%) showed specific subtypes that were steatohepatitic (8), lymphocyte-rich (8), fibrolamellar (4), neutrophil-rich (3), macrotrabecular massive (2), and clear cell HCC (1) with remaining cases (100) being conventional HCC, no special type. CONCLUSION: The study demonstrates the feasibility of subtyping HCC (as per the current WHO classification) for the first time on FNAB with cell blocks that carries implication for prognostication and emphasizes the importance of obtaining tissue diagnosis by FNAB with cell blocks.
Thomas K, Trinh H, Fei A
… +3 more, Khazai L, Sun H, Gan QJ
Cancer Cytopathol
· 2025 Mar · PMID 39992713
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BACKGROUND: Although histologic and fine-needle aspiration cytologic features of angiosarcoma are well established, little is known about its cytologic features in fluids. This study presents the cytomorphologic features...BACKGROUND: Although histologic and fine-needle aspiration cytologic features of angiosarcoma are well established, little is known about its cytologic features in fluids. This study presents the cytomorphologic features of 22 patients who had angiosarcoma involving pleural, pericardial, ascites, and liver cyst fluids. METHODS: Patient data, including clinical histories, radiology, pathology, treatments, and follow-up, were collected. RESULTS: Twenty-two angiosarcoma fluid specimens (pleura, n = 17; pericardium, n = 2; ascites, n = 2; and liver cyst, n = 1) were identified. All patients had prior angiosarcoma diagnoses, and 10 (45%) had prior radiation exposure. Cellularity varied, with low cellularity predominant (73%). Cytologic architecture typically consisted of clusters of epithelioid cells (91%), single epithelioid cells (55%), and spindled cells (36%). Malignant nuclear characteristics, such as irregular nuclear membranes, chromatin clumping, and prominent nucleoli, were consistent (100%). Vasoformative features included endothelial wrapping (73%), intracytoplasmic lumina (18%), hemophagocytosis (9%), and intracytoplasmic lumina with cells (5%). Low cellularity samples usually lacked vasoformative features (27%). Prominent nucleoli, often with multiple or club-shaped forms, appeared in all cases (100%). Atypical mitotic figures (45%), associated fibromyxoid material (14%), and possible necrosis (5%) were also observed. The interval between cavity fluid involvement and primary diagnosis averaged 616 days (range, 14-2778 days). The mean time from the first positive fluid to death was 141 days (range, 3-568 days). CONCLUSIONS: Angiosarcoma in fluids is rare. Cytomorphologic features, although nonspecific, include malignant nuclear features, prominent nucleoli, atypical mitoses, and occasional vasoformative features. Accurate diagnosis necessitates a careful review of the patient's history and judicious use of immunohistochemical staining.
Acanfora G, Iaccarino A, Cerbelli B
… +45 more, Di Cristofano C, Bellevicine C, Barberis M, Bonoldi E, Bubendorf L, Calaminus A, Campione S, Canberk S, Cavazza A, Cazzaniga G, Chijioke O, Clery E, Eccher A, Engels M, Fiorentino V, Graziano P, Kern I, Kholova I, Laatta J, Labiano T, Leopizzi M, Lozano MD, Luis R, Maffei E, Marando A, Martini M, Merenda E, Montella M, Morales AA, Nishino M, Pagni F, Hofman P, Pernazza A, Roy-Chowdhuri S, Saieg M, Savic Prince S, Siddiqui MT, Stoos-Veic T, Strojan Fležar M, Sundov D, VanderLaan P, Vrdoljak-Mozetič D, Zeppa P, Troncone G, Vigliar E
Cancer Cytopathol
· 2025 Mar · PMID 39992702
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INTRODUCTION: The aim of this project is to assess interobserver agreement for programmed death-ligand 1 (PD-L1) scoring on of non-small cell lung cancer (NSCLC) on cytological specimens in a large-scale multicenter stud...INTRODUCTION: The aim of this project is to assess interobserver agreement for programmed death-ligand 1 (PD-L1) scoring on of non-small cell lung cancer (NSCLC) on cytological specimens in a large-scale multicenter study, by exploiting the cell block-derived tissue microarray (cbTMA) approach. METHODS: A total of 65 cell blocks (CB) diagnosed as NSCLC were retrospectively collected and selected for TMA preparation. Hematoxylin-eosin and PD-L1 stained slides were digitized and uploaded on a free web sharing platform. Participants were asked to provide PD-L1 assessment by using the clinically relevant cutoff of tumor proportion score (TPS) (<1%; 1%-49%; >50%). Interobserver agreement was calculated using Fleiss's κ. RESULTS: Of 65 CBs, 11 were deemed not suitable; therefore, an overall number of 54 cores were used for the preparation of four TMAs. A total of 1674 evaluations were provided by 31 cytopathologists from 21 different institutions in nine countries. The statistical analysis showed a moderate overall agreement (κ = 0.49). The highest agreement was achieved in the TPS >50% category (κ = 0.57); moderate agreement was observed in TPS <1% category (κ = 0.51) and the lowest κ value was obtained for TPS 1%-49% category (k = 0.32). CONCLUSIONS: The overall moderate agreement observed showed that there is still room for improvement in inter-pathologist agreement for PD-L1 evaluation on cytological samples, highlighting the need for standardization in sample preparation, focused training in PD-L1 evaluation on cytological material, and the integration of machine learning tools to improve interobserver consistency.
Cancer Cytopathol
· 2025 Feb · PMID 39912378
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BACKGROUND: Pericardial effusion can be due to any etiology but may cause significant morbidity and mortality; however, malignant effusions are rare, and accurate and timely diagnosis is essential for appropriate further...BACKGROUND: Pericardial effusion can be due to any etiology but may cause significant morbidity and mortality; however, malignant effusions are rare, and accurate and timely diagnosis is essential for appropriate further management. Data on the actual comparison of pericardial cytology and surgical specimens are limited, and this study was conducted to evaluate an institutional cohort and compare these two samples. METHODS: The institutional electronic database system was retrospectively searched between January 2019 and December 2023 for pericardial biopsies/surgical specimens (PSSs) and cytology. RESULTS: A total of 202 surgical specimens of the pericardium were identified from patients with a median age of 67 years and a range of 18-97 years. Of these 202 cases, 190 specimens also underwent cytological evaluation, which included 153 cases that were negative for malignancy, nine cases that were indeterminate/atypical, and 28 cases that were positive for malignancy. Agreement between cytology and PSSs was reached in 172 cases, with 153 being benign and 19 being malignant. However, a cytology-histology discrepancy was found in 18 cases. Of these 18 cases, nine showed positive cytology but all had negative concurrent PSSs except for one with focal atypia, and the remaining nine were indeterminate/atypical on cytology. Eight of these nine indeterminate cases were negative on the PSS, whereas one atypical cytology case with low cellularity showed a positive PSS. CONCLUSIONS: If atypical cases are excluded, cytology demonstrates a better diagnostic yield for detecting malignancy compared to surgical specimens (n = 28 cases vs. n = 20 cases, respectively).
Cancer Cytopathol
· 2025 Feb · PMID 39912368
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BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) harbors gene fusions involving TFE3 with one of many different partner genes. Because of their diverse morphologies, the differential diagnosis is broad and ch...BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) harbors gene fusions involving TFE3 with one of many different partner genes. Because of their diverse morphologies, the differential diagnosis is broad and challenging. Publications focusing on the cytomorphology of TFE3-rRCC are sparse. METHODS: Fifteen cytology cases of TFE3-rRCC from 12 patients were retrieved, comprising seven primary kidney cases and eight metastatic cases. RESULTS: Cytology smears showed tumor cells with moderate granular or vacuolated cytoplasm, arranged in diverse patterns, such as three-dimensional clusters, nested/sheeted formations, isolated cells, papillary, and tubular/acinar structures. The tumor cells exhibited enlarged eccentric, round or oval nuclei, possibly situated peripherally, with small to prominent nucleoli and irregular nuclear membranes. Macrophages, hyalinized globules, or necrosis were occasionally seen. Core and cell block histology often showed papillae with surface-oriented nuclei. Tumor cells were also arranged in nested, sheeted, and tubular patterns. Tumor cells were immunoreactive to TFE3 (100%), AMACR (100%), PAX8 (88%), and CD10 (83%) and showed focal staining for CA9 (64%), CK7 (20%), and CD117 (25%). TFE3 rearrangement was confirmed in 13 of 15 cases through fluorescence in situ hybridization or RNA fusion next-generation sequencing testing. Metastasis was observed in nine of 12 patients (80%), with retroperitoneal lymph nodes being the most common site, followed by distant lymph nodes, lung, brain, adrenal gland, and bone. Six patients (50%) underwent nephrectomy alone, two patients (17%) received chemotherapy alone, and four patients (33%) received combined nephrectomy and chemotherapy. CONCLUSIONS: Timely recognition of TFE3-rRCC's distinct cytomorphologic and histomorphologic features is essential for accurate diagnosis and effective treatment.