Acta Cytologica最新文献

Introduction: Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage.

Methods: We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis.

Results: Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens.

Conclusion: Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.

Introduction: The Chernobyl nuclear accident exposed residents of contaminated territories to substantial quantities of radioiodines and was followed by an increase in thyroid cancer, primarily papillary thyroid cancer (PTC), among exposed children and adolescents. Although thyroid biopsy is an essential component of screening programs following accidental exposure to radioiodines, it is unknown whether the predictive value of biopsy is affected by different levels of environmental exposure.

Methods: A cohort of 11,732 Belarusians aged ≤18 years at the time of the Chernobyl accident with individual thyroid radiation dose estimates was screened at least once 11-22 years later. Paired cytologic conclusions and histopathologic diagnoses were possible for 258 thyroid nodules from 238 cohort members. Cytologic conclusions were divided into five reporting categories, with all follicular lesion aspirates combined into a single indeterminate category. Standard performance indicators, risk of malignancy (ROM), and odds ratios for a correct cytologic conclusion were calculated, both overall and according to quintile of thyroid radiation dose.

Results: The arithmetic mean thyroid dose estimate for the study group was 1.73 Gy (range: 0.00-23.64 Gy). The final histopathologic diagnosis was cancer for 136 of 258 biopsies (52.7%; 135 papillary and 1 follicular). The overall ROM was 96.7% for cytologies definite for PTC, 83.7% for suspicious for PTC, 33.0% for indeterminate, 8.1% for benign, and 31.0% for non-diagnostic. The ROM showed little change according to level of radiation exposure. Overall, there was no association between thyroid radiation dose and the odds ratio for a correct cytologic conclusion (p = 0.24). When analyzed according to dose quintile, the odds ratio for a correct conclusion increased two-fold at 0.10-0.29 Gy compared to a dose of 0.00-0.09 Gy and decreased at doses of 0.3-24 Gy (p value for linear trend = 0.99).

Conclusions: At radiation doses received by a cohort of young Belarusians exposed to radioiodines by the Chernobyl accident, the predictive value of thyroid biopsy for diagnosing PTC was not significantly affected by level of radiation exposure.

Introduction: The diagnostic value of rapid on-site evaluation (ROSE) in bronchoscopy for lung tumors has been widely researched. However, the diagnostic efficacy of ROSE for pulmonary tuberculosis (TB) has not been extensively assessed yet. This study aimed to examine the value of ROSE in diagnosing pulmonary TB during bronchoscopy, and the relationship between ROSE cytology patterns and acid-fast bacilli (AFB) smears and mycobacterial cultures.

Methods: A retrospective study was conducted at a single respiratory endoscopy center, including 418 patients under clinical or radiological suspicion of having pulmonary TB who underwent bronchoscopy. In addition to the use of ROSE and definitive cytology, material obtained by aspiration/lavage or brushing was sent for AFB smear and mycobacterial culture. If histopathological examination was required, endobronchial biopsy, transbronchial lung biopsy, and transbronchial needle aspiration were performed at the discretion of the clinician. A composite reference standard (CRS) was used as the diagnostic gold standard for this study. The diagnosis obtained by ROSE was compared with the final diagnosis.

Results: Of the 418 patients studied, 282 (67.5%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary TB, in 238 (84.4%); non-TB, in 44 (15.6%). In 238 pulmonary TB patients, ROSE cytology showed granulomas without necrosis were observed in 107 cases, granulomas and necrosis in 51 cases, caseous necrosis only in 25 cases, and nonspecific inflammation in 55 cases. For the diagnosis of TB according to CRS, ROSE showed the sensitivity, specificity, positive predictive value, and negative predictive value were 76.9%, 68.2%, 92.9%, and 35.3%, respectively. The positivity rate for bacterial detection through acid-fast staining and culture during bronchoscopy was 51.7%. The cytological pattern showed a higher detection rate for bacteria in cases of necrosis.

Discussion: The application of ROSE during bronchoscopy is a straightforward procedure that delivers an immediate and precise assessment regarding the adequacy of collected samples, enabling a preliminary diagnosis of pulmonary TB. ROSE has exhibited a higher sensitivity in detecting pulmonary TB compared to microbiological examinations. In addition, the cytological presentation of ROSE tends to show a higher positivity rate for microbiological testing in caseous necrosis. Therefore, samples with these characteristics should be prioritized for microbiological examination after on-site evaluation.

Introduction: Methylation assays have demonstrated potential as dependable and high-precision approaches for identifying or triaging individuals with cervical cancer (CA) or cervical intraepithelial neoplasia (CIN). Our investigation aimed to assess the efficacy of the diagnosis and triage of the PAX1/SOX1 methylation panel in detecting CIN or CA.

Methods: A total of 461 patients with abnormal high-risk human papillomavirus (hrHPV) or cytology test results were recruited for this study. Each patient underwent an assortment of assessments, comprising a cytology test, hrHPV test, colposcopy examination, and PAX1 and SOX1 methylation tests.

Results: The extent of methylation of both genes demonstrates a positive correlation with the severity of CIN lesions and CA. To determine the correlation for patients with CIN2 or worse (CIN2+), the area under curve was 0.821 (95% CI: 0.782-0.853) for PAX1 and 0.800 (95% CI: 0.766-0.838) for SOX1, while for CIN3 or worse (CIN3+), 0.881 (95% CI: 0.839-0.908) for PAX1 and 0.867 (95% CI: 0.830-0.901) for SOX1. The PAX1/SOX1 methylation marker panel performed sensitivity and specificity of 77.16% and 91.67% for CIN2+, 84.76% and 90.50% for CIN3+, respectively. Regarding triaging hrHPV+ patients, the PAX1/SOX1 methylation test only referred 11.83% of the patients who are unnecessary for colonoscopy examination, which is comparatively lower than cytology, thereby signifying a promising triage strategy for hrHPV-positive women. Furthermore, we observed that the positive PAX1/SOX1 methylation test result for untreated CIN1 or fewer patients would result in a higher likelihood of progression upon a 24-month follow-up visit.

Conclusion: The present investigation demonstrates that the PAX1/SOX1 methylation marker panel exhibits favorable diagnostic performance in CIN detection and holds the potential to be employed for individual CIN tests or hrHPV-positive triage.

Introduction: The aim of this study was to evaluate fine-needle aspiration biopsy (FNAB) as a diagnostic tool for lymphoproliferative orbital lesions in light of recent improvements in cytomorphological and immunologic analyses.

Method: Retrospective case series including all orbital FNABs with a lymphoproliferative outcome at Karolinska University Hospital, Stockholm, Sweden during the period 2005-2015.

Results: Of the 38 patients included, 31 (82%) were conclusively diagnosed as having lymphoma according to the first FNAB. Disease in 20 patients (65%) could be subclassified. The diagnosis in 7 patients (18%) was either inconclusive, suggestive of lymphoma, or reactive lymphatic infiltrate. These 7 patients were re-investigated, and the initial suspected diagnosis of malignant lymphoma was confirmed in four. Two of the remaining 3 patients were initially diagnosed as having non-lymphoproliferative disease; however, this was later changed to a lymphoproliferative diagnosis following reinvestigation, while the results of both reFNAB and incisional biopsy were inconclusive in the third.

Conclusion: In the majority of the 38 patients, a definitive diagnosis of lymphoma could be made based on FNAB alone, using cytomorphological and immunological workup, and subclassification was possible in 20 patients (65%). Primary low-grade malignant orbital lymphomas are traditionally treated with low-dose radiotherapy regardless of subtype, and incisional biopsy was not needed to initiate treatment. Our findings suggest that FNAB is a valid first option for the diagnosis of suspected orbital lymphomas due to the minimal risk of complications compared to incisional biopsy, and the fact that it can be performed as an outpatient procedure with no anesthesia.

Introduction: Liquid-based cytology (LBC) has replaced conventional smear (CS) in the world. In this study, through a series with a large number of cases, we aimed to make a comparison and general evaluation in all groups, primarily epithelial abnormalities, according to LBC and CS methods. This study was carried out in a private pathology laboratory located in a metropolitan city, where cytological materials sent from many clinics were examined.

Material and methods: There were 165,915 cases whose smears were examined between 2012 and 2020, most of them conventional (131,224 CS, 34,691 LBC). Cases were evaluated on the basis of the Bethesda 2014 classification and divided into sub-diagnostic categories after they were divided into two main groups as "with epithelial abnormalities" and "without." χ2 and Fischer's precision statistical tests were conducted using SPSS 23.0 package. In the CS process, cervical samples were obtained using an endocervical brush and a spatula. Cells were directly spread onto the slides and promptly fixed in 95% ethanol, followed by staining with the standard Papanicolaou stain. For LBC ThinPrep, cervical specimens were gathered using a cervix brush. The brush was washed in a vial and discarded. Finally, cells were isolated through vacuum filtration and transferred to the slide using air pressure.

Results: Squamous cell abnormalities (atypical squamous cells of undetermined significance [ASC-US], atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion [ASC-H], low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL], squamous cell carcinoma, atypical glandular cells of undetermined significance) were reported in 5,696 (3.43%) cases. ASC (ASC-US + ASC-H)/SIL ratio (1.36/2.04) was found to be 0.67 (recommended Bethesda ratio is <3). ASC-US (p < 0.001), ASC-H (p < 0.001), and HSIL(p < 0.001) detection rate of LBC was found to be significantly higher than CS. ASC-US (1.8/1.2), ASC-H (0.08/0.008), and HSIL (0.6/0.3) case ratios of LBC/CS were found to be significantly higher in LBC. LSIL (1.72/1.66) rate was similar.

Conclusion: LBC is superior to CS in detecting epithelial lesions. In addition to being used as a screening method, it is clear that it makes a great contribution to reducing cervical carcinomas due to HPV typing. Definitive comments regarding comparison of methods on reactive changes and microorganism detection are challenging. Preanalytical factors might account for these situations.

Background: Fine-needle aspiration cytology (FNAC) is a cornerstone technique for the initial assessment of breast lesions, offering a rapid and minimally invasive option for cytological evaluation. While FNACs can forego the need for core needle biopsies (CNBs), variations in technique, subjective interpretation, and intrinsic limitations present diagnostic challenges. The International Academy of Cytology (IAC) established the Yokohama system and is developing the WHO Reporting System for Breast Cytopathology jointly with IARC, to standardize diagnostic criteria, aiming to enhance diagnostic precision and consistency. Due to the preference for CNBs, expertise in breast FNAC is low in the developed world.

Summary: This review assesses common pitfalls in breast cytopathology. These common and uncommon entities may easily lead to false-negative or false-positive diagnoses, due to morphological overlap or misleading clinical and radiological contexts. For instance, pauci-cellular lesions, such as lobular carcinomas, often lead to false-negative diagnoses, whereas complex sclerosing lesions, fibroadenomas, and papillary lesions may show concerning features, resulting in a false positive. The same is true for some benign inflammatory pathologies, such as steatonecrosis, and uncommon lesions, such as collagenous spherulosis. Ductal carcinoma in situ can lead to both false-negative and false-positive diagnoses, and high-grade lesions are impossible to tell apart from invasive carcinomas. These are discussed in detail. Procedural and preanalytical conditions, and the role of ancillary testing, are also briefly addressed.

Key messages: Breast FNAB is a powerful diagnostic technique, fast and minimally invasive. Even in contexts which lack expertise, this technique can be successfully adopted with a cautious approach and as long as pitfalls are kept in mind, benefiting patients and healthcare systems.

Introduction: The diagnosis of salivary gland secretory carcinoma (SC) in fine-needle aspiration specimens is challenging because its low-grade nature makes it difficult to differentiate it from various benign or malignant salivary gland neoplasms. Currently, the gold standard is demonstration of ETV6-NTRK3 fusion gene. However, the decision for ordering this costly molecular testing can be facilitated by the correct recognition of its cytomorphological features. The aim of the review was to determine the accuracy of fine-needle aspiration cytology (FNAC) in diagnosis of salivary gland SC. The secondary objective was to recognize varied cytomorphological patterns, characteristic features of SC and differentiate it from other neoplasms.

Methods: PubMed/MEDLINE, Science Direct, Embase, Cochrane review, and PROSPERO databases were searched for studies having the following key search terms: ("secretory carcinoma of salivary gland" OR "mammary analogue secretory carcinoma of salivary gland") AND ("Cytology" OR "Cytological features" OR "aspirate" OR "cytodiagnosis") published in the time frame of 2010 to June 2023. Studies reporting cytological features of the salivary gland tumors which were confirmed/diagnosed as SC on molecular investigation, were included in the systematic review. Finally, seventeen studies reporting a total of 45 cases were included in the metanalysis.

Results: The sensitivity of the FNAC in diagnosing SC in salivary gland is 27.7% (95% CI: 16.6-42.5%). The LR+ (positive likelihood ratio) was 0.654 (0.344-1.245), LR- (negative likelihood ratio) was 1.023 (0.538-1.946), and diagnostic odds ratio was 0.421 (0.129-1.374). The molecular testing and/or immunohistochemistry performed on cell block increased the diagnostic accuracy.

Conclusion: Recognition of subtle cytomorphological patterns, i.e., papillary formation, clusters, and singly dispersed cells along with presence of fine intracytoplasmic vacuolations were the characteristic findings in majority of cases, confirmed with diagnostic molecular profiling. This may be helpful in identification of this rare entity with limited published literature and help in increasing diagnostic accuracy.

Background: Thyroid nodules are prevalent among the general population, thus imposing substantial demands upon healthcare providers to establish effective management paradigms when investigating these lesions. A pivotal component in the diagnostic process involves the cytomorphological evaluation of fine-needle aspiration (FNA) specimens extracted from the nodule under scrutiny. This examination serves the critical purpose of enabling a comprehensive assessment for the risk of either a neoplasm or malignancy, thereby providing the clinical team with the requisite information to render decisions regarding potential surgical intervention and/or a structured clinical follow-up. A subset of FNA specimens obtained from the thyroid gland present a vexing challenge for interpretation and cannot be classified based on cytomorphology as either benign or malignant and are classified as "indeterminate" for neoplasm or malignancy. The indeterminate thyroid FNA diagnosis in the third iteration of the Bethesda classification is termed as "atypia of undetermined significance" (AUS).

Summary: The thyroid FNA specimens classified as "atypical" constitute a perplexing category, necessitating considerations such as repeated cytological evaluations, supplementary molecular analyses, diagnostic lobectomy, or vigilant surveillance. This review article draws upon the most recent Bethesda classification guidelines and delineates various potential pitfalls encountered during the interpretation of atypia observed in thyroid fine-needle aspiration and histopathologic counterparts. Additionally, it proffers strategic algorithms devised to effectively navigate these diagnostic challenges.

Key messages: It is important to recognize the value of an integrated approach when triaging AUS lesions, considering various clinical, morphological, and sometimes also immunocytochemical or molecular features.

Background: Salivary gland lesions possess diagnostic challenges on fine-needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of cytomorphology. Herein, we review common salivary gland neoplasms, their cytomorphologic features, their diagnostic pitfalls, and ancillary studies helpful in achieving an accurate diagnosis.

Summary: There are many cytomorphologic overlaps between benign and malignant salivary gland entities. Moreover, metaplasia, cystic changes, and degenerative changes are common findings adding to diagnostic dilemmas. These complicating factors contribute to a minute risk of malignancy in salivary gland lesions that are interpreted as benign on FNA. In rare cases, even malignant salivary gland neoplasms are misinterpreted as benign on aspirated material due to the many cytomorphologic overlaps. For example, benign and malignant neoplasms containing stroma such as myoepithelioma and adenoid cystic carcinoma may be misinterpreted as pleomorphic adenoma. Moreover, diagnosis of salivary gland neoplasms with basal cell features can be confusing on FNA materials; for example, basal cell adenoma can be misinterpreted as adenoid cystic carcinoma. Mucoepidermoid carcinomas have many different appearances on aspirated material due to variable amounts of mucin, degree of nuclear atypia, cellular content, and squamous metaplasia. Acinic cell carcinoma exhibits large cells with abundant cytoplasm on FNA, which can be mistaken for oncocytic cells in oncocytoma or Warthin tumor. Salivary duct carcinoma shows distinct features of malignancy and thus can be mistaken for secondary tumors involving the salivary glands or other malignant salivary gland tumors. The presence of tumor-associated lymphocytes is another underlying cause of misdiagnosis, especially when considering the differential diagnosis of an intraparotid lymph node. Ancillary studies such as immunohistochemistry and molecular studies are gaining more attention to be utilized on FNA cases. PLAG1 immunostaining, CD117, DOG1, mammaglobin, and androgen receptor (AR) are examples of commonly used immunostains in diagnosis of salivary gland lesions. MYB gene fusion, rearrangements of the MAML2 gene, and ERBB2/HER2 are examples of molecular alterations useful in diagnosis of salivary gland neoplasms. In conclusion, the aim of salivary gland cytology is to differentiate benign entities from the malignant ones and to prevent unnecessary aggressive treatments.

Key messages: The diagnostic pitfalls are enormous in salivary gland cytology. Familiarity with cytomorphology of different entities and their cytomorphologic overlaps, and application of ancillary studies improves the diagnostic yield, patient management and prevents unnecessary aggressive procedures.