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Acta Cytologica Jun 2024Pitfalls in Pap test could be defined as false positive, false negative or underdiagnosed results which can lead to unnecessary diagnostic procedures or delayed and... (Review)
Review
BACKGROUND
Pitfalls in Pap test could be defined as false positive, false negative or underdiagnosed results which can lead to unnecessary diagnostic procedures or delayed and inadequate treatment. It can be a consequence of misinterpretation of certain morphological entities which are described in this paper.
SUMMARY
the paper presents the overview of the morphological features and look-alikes of the common sources of pitfalls such as atrophy, repair, IUD change, tubal metaplasia, hyperchromatic crowded groups, and radiation changes. Rare causes of pitfalls such as Arias-Stella changes, pemphigus, tumor diathesis per se, rare types of cervical cancer, including verrucous and papillary squamous cell cancer, gastric type and endometrioid adenocarcinoma are also described.
KEY MESSAGES
The awareness of pitfalls in cervical cytology is important for cytopathologists and clinicians to avoid future errors. Review of Pap tests with erroneous diagnosis is important for quality control in cytology laboratory, and it must be considered as educational and experience building procedure. Cytopathologist should not pull back in significant diagnoses, especially in HPV negative cases.
PubMed: 38834045
DOI: 10.1159/000539637 -
Ultrastructural Pathology Jul 2024Thyroid carcinoma ranks as the 9th most prevalent global cancer, accounting for 586,202 cases and 43,636 deaths in 2020. Computerized image analysis, utilizing...
Can the analysis of chromatin texture and nuclear fractal dimensions serve as effective means to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features from other malignancies with follicular pattern in the thyroid?: a study.
OBJECTIVE
Thyroid carcinoma ranks as the 9th most prevalent global cancer, accounting for 586,202 cases and 43,636 deaths in 2020. Computerized image analysis, utilizing artificial intelligence algorithms, emerges as a potential tool for tumor evaluation.
AIM
This study aims to assess and compare chromatin textural characteristics and nuclear dimensions in follicular neoplasms through gray-level co-occurrence matrix (GLCM), fractal, and morphometric analysis.
METHOD
A retrospective cross-sectional study involving 115 thyroid malignancies, specifically 49 papillary thyroid carcinomas with follicular morphology, was conducted from July 2021 to July 2023. Ethical approval was obtained, and histopathological examination, along with image analysis, was performed using ImageJ software.
RESULTS
A statistically significant difference was observed in contrast (2.426 (1.774-3.412) vs 2.664 (1.963-3.610), = .002), correlation (1.202 (1.071-1.298) vs 0.892 (0.833-0.946), = .01), and ASM (0.071 (0.090-0.131) vs 0.044 (0.019-0.102), = .036) between NIFTP and IFVPTC. However, morphometric parameters did not yield statistically significant differences among histological variants.
CONCLUSION
Computerized image analysis, though promising in subtype discrimination, requires further refinement and integration with traditional diagnostic parameters. The study suggests potential applications in scenarios where conventional histopathological assessment faces limitations due to limited tissue availability. Despite limitations such as a small sample size and a retrospective design, the findings contribute to understanding thyroid carcinoma characteristics and underscore the need for comprehensive evaluations integrating various diagnostic modalities.
Topics: Humans; Thyroid Neoplasms; Retrospective Studies; Cross-Sectional Studies; Fractals; Adenocarcinoma, Follicular; Chromatin; Thyroid Cancer, Papillary; Diagnosis, Differential; Cell Nucleus; Female
PubMed: 38828684
DOI: 10.1080/01913123.2024.2362758 -
Histopathology Jun 2024Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and...
Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage.
AIMS
Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential.
METHODS AND RESULTS
Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology.
CONCLUSIONS
Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.
PubMed: 38828674
DOI: 10.1111/his.15231 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jun 2024To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. There were 4 995...
To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes. There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages (<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all <0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics (>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA (<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups (<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types (<0.05). Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients' age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.
Topics: Humans; Lung Neoplasms; Male; Adenocarcinoma of Lung; Female; Retrospective Studies; Anaplastic Lymphoma Kinase; Mutation; ErbB Receptors; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Receptor, ErbB-2; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-ret; Adenocarcinoma; Proto-Oncogene Proteins; Adenocarcinoma, Mucinous; Middle Aged
PubMed: 38825903
DOI: 10.3760/cma.j.cn112151-20231019-00277 -
Digestive and Liver Disease : Official... Jun 2024Factors associated with the risk of pancreatic adenocarcinoma (PDAC) may play a role in the development and progression of Intraductal Papillary Mucinous Neoplasms...
BACKGROUND
Factors associated with the risk of pancreatic adenocarcinoma (PDAC) may play a role in the development and progression of Intraductal Papillary Mucinous Neoplasms (IPMNs). However, data are limited.
AIM
To compare exposome factors in three groups of patients with "high or low-risk" IPMNs, as assessed at diagnosis and during a 24-months follow-up, and with PDAC.
METHODS
Patients were matched (same sex, age ±5) 1:1. Exposure variables were compared across groups using Kruskal-Wallis, ANOVA, or Chi-square tests with Bonferroni correction.
RESULTS
A total of 151 patients were enrolled in each of the three groups (453 overall). The proportion of current smokers was progressively higher in "low-risk", "high-risk" IPMNs and PDAC patients (8.1 %, 11.2 %, 23.3 %; p = 0.0002). The three groups did not differ in terms of ever or heavy smoking, BMI, history of diabetes, cancer, cholecystectomy or chronic pancreatitis, use of statins or aspirin, and family history of cancer. A history of peptic ulcer was more common in PDAC (7.2 %) than in either "low-risk" (2.0 %) or "high-risk" (2.6%) IPMNs (p = 0.02, not significant after Bonferroni correction).
CONCLUSION
Active smoking seems associated with the progression of IPMNs to malignancy, and cessation of active smoking might be advised in patients with IPMN.
PubMed: 38825412
DOI: 10.1016/j.dld.2024.05.017 -
Archives of Pathology & Laboratory... May 2024Intraoperative (frozen section) analysis of lung lesions (nodules, masses, ground-glass opacities) can occasionally be diagnostically challenging.
CONTEXT.—
Intraoperative (frozen section) analysis of lung lesions (nodules, masses, ground-glass opacities) can occasionally be diagnostically challenging.
OBJECTIVE.—
To describe selected pitfalls in thoracic frozen sections with a focus on the differential diagnosis between adenocarcinoma and its mimics, and to provide tips to prevent misinterpretation.
DATA SOURCES.—
Peer-reviewed literature and the author's experience.
CONCLUSIONS.—
A common challenge in thoracic frozen sections is the differential diagnosis between lung adenocarcinoma and its mimics. Diagnostic difficulties arise because mimics of adenocarcinoma often entrap reactive lung epithelium that can appear atypical on frozen section slides. Entities that can be misinterpreted as adenocarcinoma include ciliated muconodular papillary tumor/bronchiolar adenoma, hamartoma, inflammatory myofibroblastic tumor, and pulmonary Langerhans cell histiocytosis. Knowledge of the key clinical, radiologic, and histologic features of these entities can help prevent overdiagnosis of adenocarcinoma. Pathologic findings that facilitate the distinction between adenocarcinoma and its mimics at frozen section include the appearance and contour of the lesion at low magnification, growth patterns, cilia, stromal features, shape of the epithelial cells (cuboidal versus columnar), nuclear features of malignancy (crowding, hyperchromasia, irregular contours), and abruptness of the junction between the lesion and adjacent uninvolved lung. Knowledge of the clinical context, imaging findings, and the surgical consequence of the intraoperative diagnosis can also prevent diagnostic errors. Finally, since adenocarcinomas of the lung are often relatively bland and lack the stromal desmoplasia seen in adenocarcinomas of other organs, familiarity with the morphologic spectrum of lung adenocarcinomas at frozen section analysis is important.
PubMed: 38818706
DOI: 10.5858/arpa.2024-0023-RA -
Frontiers in Endocrinology 2024This study aimed to analyze the effect of preoperative fine needle aspiration cytology (FNAC) combined with BRAF mutation detection as compared to that of fine needle...
BACKGROUND
This study aimed to analyze the effect of preoperative fine needle aspiration cytology (FNAC) combined with BRAF mutation detection as compared to that of fine needle aspiration cytology alone on the diagnostic performance of papillary thyroid carcinoma (PTC) combined with Hashimoto's thyroiditis (HT).
METHOD
Patients with thyroid nodules in Hashimoto's thyroiditis, who underwent fine-needle aspiration cytology examination and BRAF mutation detection in the puncture eluate at the outpatient clinic, were selected. Finally, 122 patients received surgical treatment and were included in the study. We used postoperative pathological results as the gold standard. Accordingly, we compared the sensitivity, specificity and accuracy of preoperative FNAC alone and FNAC combined with BRAF mutation detection in for the diagnosis of PTC combined with HT.
RESULTS
For PTC patients with HT, the sensitivity of FNAC diagnosis was 93.69%, the specificity was 90.90% and the accuracy was 93.44%. However, the sensitivity, specificity and accuracy of FNAC combined with BRAF mutation detection were 97.30%, 90.90% and 96.72%, respectively. Therefore, combined detection can improve the sensitivity and accuracy of diagnosis (p<0.05).
CONCLUSION
FNAC combined with eluent BRAF mutation detection can improve the sensitivity and accuracy of diagnosis of PTC in the background of HT.
Topics: Humans; Hashimoto Disease; Proto-Oncogene Proteins B-raf; Biopsy, Fine-Needle; Female; Male; Thyroid Cancer, Papillary; Middle Aged; Adult; Mutation; Thyroid Neoplasms; Sensitivity and Specificity; Aged; DNA Mutational Analysis
PubMed: 38818506
DOI: 10.3389/fendo.2024.1366724 -
Journal For Immunotherapy of Cancer May 2024The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been...
BACKGROUND
The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets.
METHODS
This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples.
RESULTS
A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3 DCs promote CD8 T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3 DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion.
CONCLUSION
Our findings expound valuable insights into the role of the interaction between LAMP3 DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.
Topics: Humans; Dendritic Cells; Thyroid Cancer, Papillary; Lysosomal-Associated Membrane Protein 3; Thyroid Neoplasms; Male; Female; Tumor Microenvironment; Middle Aged; Tumor Escape; T-Lymphocyte Subsets; Neoplasm Proteins
PubMed: 38816233
DOI: 10.1136/jitc-2024-008983 -
Lung Cancer (Amsterdam, Netherlands) Jun 2024We aimed to reveal the clinicopathological differences between epidermal growth factor receptor (EGFR)-mutated and wild-type (WT) lung adenocarcinoma (LUAD) focusing on...
OBJECTIVES
We aimed to reveal the clinicopathological differences between epidermal growth factor receptor (EGFR)-mutated and wild-type (WT) lung adenocarcinoma (LUAD) focusing on the predominant subtype.
METHODS
This study included 352 with EGFR mutation and 370 with WT patients in consecutive stage I LUAD classified by the predominant subtype, and their clinicopathological characteristics and prognosis were analyzed. Using the Cancer Genome Atlas Program (TCGA) cohort, we analyzed differences in gene expression between EGFR mutation and WT groups. Furthermore, we performed immunohistochemical evaluations for 46 with EGFR mutation and 47 with WT patients in consecutive stage I papillary predominant adenocarcinoma (PPA).
RESULTS
Compared to the PPA with WT [n = 115], those with EGFR mutation [n = 99] exhibited smaller invasive size (p = 0.03) and less frequent vessel invasion (p < 0.01). However, PPA with EGFR mutation showed significantly worse 5-ys recurrence-free survival (RFS) rates compared to those with WT (70.6 % versus 83.3 %, p = 0.03). Contrarily, no significant differences were observed in other predominant subtypes. In the TCGA cohort, PPA with EGFR mutation tended to show higher expression of galectin-3, which is associated with tumor metastasis and resistance to anoikis, compared to those with WT (p = 0.06). Immunohistochemical evaluation revealed that galectin-3 expression was significantly higher in PPA with EGFR mutation than in those with WT (p < 0.01).
CONCLUSIONS
The prognosis of PPA with EGFR mutation proved to be less favorable compared to that with WT, and galectin-3 is highly expressed in EGFR-mutated PPA.
Topics: Humans; ErbB Receptors; Male; Female; Mutation; Lung Neoplasms; Adenocarcinoma of Lung; Aged; Middle Aged; Prognosis; Neoplasm Staging; Biomarkers, Tumor; Galectin 3; Aged, 80 and over; Adult; Adenocarcinoma, Papillary
PubMed: 38805901
DOI: 10.1016/j.lungcan.2024.107830 -
International Journal of Nanomedicine 2024The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in... (Observational Study)
Observational Study Clinical Trial
BACKGROUND
The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in patients with thyroid cancer to determine if levels can predict the risk of recurrence.
METHODS
Patients >20 years old as newly diagnosed with papillary thyroid cancer who had received a thyroidectomy were recruited. Urine samples were collected at 12 months after enrollment to the study, and 1 year later. Urine exosomes containing different peptides were identified and compared.
RESULTS
A total of 70 patients were enrolled in the study, and were classified by the interval between surgery and enrollment: 42 patients with < 5 years between surgery and enrollment, 14 patients between 5-10 years, and 14 patients longer than 10 years. No recurrence was observed in any patient during the 2 years after enrollment. No significant differences were found in the levels of serum proteins or urine exosomal peptides between groups, or between intervals. Known risk factors for high-risk thyroid cancer had only a mild correlation with serum protein levels and urine exosomal peptides.
CONCLUSION
Our study revealed the long-term basal fluctuation ranges of serum proteins and urine exosomal peptides in patients with thyroid cancer who underwent thyroidectomy. For high-risk patients after thyroidectomy, concentrations of serum proteins or urine exosomal peptides within the ranges may indicate there is a lower risk of thyroid cancer recurrence during long-term follow-up.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT03488134.
Topics: Humans; Thyroidectomy; Exosomes; Male; Thyroid Neoplasms; Female; Middle Aged; Prospective Studies; Adult; Neoplasm Recurrence, Local; Peptides; Thyroid Cancer, Papillary; Aged; Biomarkers, Tumor
PubMed: 38803995
DOI: 10.2147/IJN.S458931