Acta Cytologica最新文献

Introduction: Around 85% of non-small cell lung cancers (NSCLCs) are diagnosed at an advanced stage (IIIB to IV), where therapeutic options depend on molecular analysis. However, diagnostic material for molecular testing is often represented by cytological samples which are generally scarce and span a wide range of preparation types. Thus, the primary objective is to efficiently manage materials for molecular profiling. This study aims to evaluate the suitability of different cytological samples to assess morphological and molecular characteristics of advanced NSCLC.

Methods: Sixty-seven cytological samples obtained from patients with advanced NSCLC were utilized. The series encompassed different procedure types (fine-needle aspiration cytology, transbronchial needle aspiration, effusions) processed by cell blocks in 54% (n = 36), direct smears in 33% (n = 22), and liquid-based cytology (LBC) in 13% (n = 9). Cytological diagnoses were routinely performed, and molecular analysis was conducted using next-generation sequencing (NGS) and real-time polymerase chain reaction (RT-PCR) methods.

Results: Adequate quantity and quality of nucleic acids were obtained from all the samples, allowing molecular profiling. Combined NGS and RT-PCR analysis showed wild-type profiles in 62.7% (n = 42) and mutated profiles in 37.3% (n = 25) of the samples. Kirsten Rat Sarcoma Virus (KRAS) mutations were identified in 19.5% (n = 13) of samples, EGFR mutations in 10.4% (n = 7) and v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations in 2.9% (n = 2). Identified chromosomal alterations were v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) duplication in 2.9% (n = 2).

Conclusions: The cytological sample types examined in this study proved to be suitable for molecular testing, in addition to conventional morphologic diagnosis, showing versatility and adaptability to different clinical contexts. Molecular testing on cytological samples is accurate and fast, representing a valid tool for molecular profiling of advanced NSCLC.

Background: The thyroid gland is a treasure trove of pathology ranging from the benign to the overtly malignant. Both neoplastic and nonneoplastic thyroid lesions can exhibit oncocytic change. Here we present an overview of cytologic and histopathologic findings encountered in these oncocytic neoplasms with a focus on the molecular aspects that drive their tumorigenesis.

Summary: Oncocytic change is unique to a subset of thyroid lesions ranging from nonneoplastic nodular hyperplasia to high-grade malignancy. It can also be encountered in non-follicular-derived neoplasms as well as in the adjacent parathyroid glands. At the genetic level, these lesions demonstrate a different genetic signature from classic follicular-derived lesions, often involving alterations of mitochondrial genes.

Key messages: Oncocytic change can be seen in nonneoplastic and neoplastic thyroid pathology. Rarely, oncocytic change can be seen in medullary thyroid carcinoma and certain subtypes of papillary thyroid carcinoma as well as the parathyroid gland. Oncocytic neoplasms of the thyroid harbor molecular alterations often involving mitochondrial genes, which is distinct from other thyroid neoplasia.

Background: We review the pathological, cytopathological, and molecular features centered on renal oncocytoma and its differential diagnosis. The recent expansion of entities under the category of renal tumors with oncocytic or eosinophilic cytoplasm has important implications on how cytologic diagnosis is clinically considered.

Summary: In this first of two parts, we discussed the pathological spectrum of oncocytic or eosinophilic tumors of the kidney that includes oncocytoma; chromophobe renal cell carcinoma (ChRCC) - including its eosinophilic variant (eosinophilic ChRCC); hybrid oncocytic/chromophobe tumors, either sporadic or syndromic; oncocytic papillary RCC, acquired cystic disease-associated RCC; succinate dehydrogenase (SDH)-deficient RCC; and eosinophilic solid and cystic (ESC) RCC. We describe the histomorphological and immunohistochemical features of these tumors, including the newly accepted entities, and focus on the molecular alterations reported. A practical approach for differential diagnosis and broader correlation to available cytologic findings are provided, with more in-depth cytologic descriptions for oncocytoma and eosinophilic ChRCC included in part 2 of this review. Most of the oncocytic tumors have an indolent behavior, although few aggressive cases have been reported in patients with ESC RCC, eosinophilic vacuolated tumor, and SDH-deficient RCC.

Key messages: In this era where surveillance management for low-grade oncocytic renal tumors is considered, precise diagnosis is important as it will have an impact on their subsequent management. Further, accurate diagnosis is important especially in renal tumors associated with hereditary neoplasms for monitoring and genetic counseling for their family members.

Introduction: Fallopian tube (FT) cytology is an evolving and as yet not well-established field. Through this study, we aimed to establish the utility of FT brush cytology by stratification into cytological diagnostic categories.

Methods: Cytological specimens were collected using an endobrush from the fimbrial end of the tubes at the time of gynaecological surgeries, and LBC preparation (liquid-based cytology slides prepared by SurePath technique) and cell blocks were prepared. Smears were stratified into unsatisfactory/non-diagnostic (ND), benign, atypical, suspicious of malignancy (SOM), and malignant. Correlation with histopathology was done, and the risk of malignancy (ROM) was calculated for each category. Negative predictive value (NPV) and positive predictive value (PPV) were calculated. Diagnostic accuracy was calculated.

Results: A total of 392 tubal cytology specimens of 225 patients were collected. 8.2% (n = 32) of the specimens were unsatisfactory/ND, 87% (n = 343) were benign, 2.6% (n = 10) were atypical, 0.8% (n = 3) were SOM, and 1% (n = 4) were malignant. All the cases in the SOM and malignant categories were serous carcinomas on histopathology. Of the ten atypical cases, all were non-malignant on histopathology: two were serous tubal intraepithelial lesions and negative for serous tubal intraepithelial carcinoma (STIC), four showed salpingitis, and four showed normal histology. ROM for ND, benign, and atypical categories was 0%. ROM for the malignant category, as well as the SOM category, was 100%. NPV for the benign category, as well as the benign and atypical categories, was 100%. PPV for the malignant category, as well as the malignant and SOM categories, was 100%. Cell blocks were prepared for all cases, and the grey zone categories of atypical and SOM were reduced from 13 to 8. The diagnostic accuracy was 91.3% without and 99.4% with consideration of the ND category.

Conclusion: FT brush cytology shows excellent concordance with the follow-up histopathology in all categories, barring the ND category. Excellent concordance with histopathology was seen in cases of the benign category, which comprised the majority of the samples (87.5%). Although excellent concordance was also seen in the other categories with the final histopathology, the number of samples in these categories was less for a definite conclusion. Cell block preparation, though useful, especially in the grey zone categories, did not offer statistically significant results. Another important finding was that not even a single case of incidental STIC was found. This finding raises questions on the accepted current routine practice of preventive salpingectomy for all in the correct setting.

Introduction: Thyroid cytopathology, particularly in cases of atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS), suffers from suboptimal sensitivity and specificity challenges. Recent advancements in digital pathology and artificial intelligence (AI) hold promise for enhancing diagnostic accuracy. This systematic review included studies that focused on diagnostic accuracy in AUS/FLUS cases using AI, whole slide imaging (WSI), or both.

Methods: Of the 176 studies from 2000 to 2023, 13 met the inclusion criteria. The datasets range from 145 to 964 WSIs, with an overall number of 494 AUS cases ranging from eight to 254. Five studies used convolutional neural networks (CNNs), and two used artificial neural networks (ANNs). The preparation methods included Romanowsky-stained smears either alone or combined with Papanicolaou-stained or H&E and liquid-based cytology (ThinPrep). The scanner models that were used for scanning the slides varied, including Leica/Aperio, Alyuda Neurointelligence Cupertino, and PANNORAMIC™ Desk Scanner. Classifiers used include Feedforward Neural Networks (FFNNs), Two-Layer Feedforward Neural Networks (2L-FFNNs), Classifier Machine Learning Algorithm (MLA), Visual Geometry Group 11 (VGG11), Gradient Boosting Trees (GBT), Extra Trees Classifier (ETC), YOLOv4, EfficientNetV2-L, Back-Propagation Multi-Layer Perceptron (BP MLP), and MobileNetV2.

Results: The available studies have shown promising results in differentiating between thyroid lesions, including AUS/FLUS. AI can be especially effective in removing sources of errors such as subjective assessment, variation in staining, and algorithms. CNN has been successful in processing WSI data and identifying diagnostic features with minimal human supervision. ANNs excelled in integrating structured clinical data with image-derived features, particularly when paired with WSI, enhancing diagnostic accuracy for indeterminate thyroid lesions.

Conclusion: A combined approach using both CNN and ANN can take advantage of their strengths. While AI and WSI integration shows promise in improving diagnostic accuracy and reducing uncertainty in indeterminate thyroid cytology, challenges such as the lack of standardization need to be addressed.

Background: Immunocytochemistry (ICC) is a widely available and extensively used ancillary method in diagnostic cytopathology with great variability in all test phases and a low level of adequate quality management. The non-standardized ICC landscape is now challenged with the introduction of the new European (EU) In Vitro Diagnostic Medical Devices Regulation (IVDR). According to this regulation, ICC on cytological slides falls under the category of Laboratory-Developed Tests (LDT), which requires rigorous standardization, validation, and thorough quality management.

Summary: Complete standardization of pre-analytical and analytical steps in ICC is impossible due to the complexity of the method and the constantly evolving antibodies, detection systems, and platforms. However, similar to the approach in immunohistochemistry, improving and standardizing "best practices" in quality management will result in high-quality, correct, accurate, and reliable ICC results. In this review, the current challenges of ICC in diagnostic cytopathology will be discussed, along with practical insights into ICC standardization and validation.

Key messages: Control slides prepared in the same manner as the patient samples, optimized ICC protocols, and participation in external quality control for ICC are the pillars of good quality management and essential to ensure safe and reliable patient diagnostics.

Introduction: Fine-needle aspiration (FNA) is a valuable diagnostic tool for evaluating breast lesions, yet its use is less frequent compared to core needle biopsies in high-resource settings. This study aimed to assess the diagnostic performance and clinical utility of FNA in correlation with surgical pathology outcomes.

Methods: We performed a 3-year retrospective search (2021-2023) using our institutional database to identify cases of breast mass FNAs performed by interventional radiologists under ultrasound guidance. We retrieved and re-evaluated all glass slides from the archive. Additionally, we reviewed the cytopathology reports and correlated the cytologic diagnoses with concurrent or subsequent surgical pathology results.

Results: A total of 65 breast FNA cases from patients were reviewed. The diagnostic outcomes were 55% negative for malignancy, 23% insufficient for diagnosis, 11% atypical, 8% suspicious for malignancy, and 3% positive for malignancy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of FNA for detecting malignancy were 76%, 96%, 93%, and 85%, respectively. One false positive case, categorized as atypical due to degenerative changes, was later confirmed as benign apocrine metaplasia. Three false-negative cases, initially categorized as non-diagnostic, were later diagnosed as invasive ductal carcinoma, Hodgkin lymphoma, and papillary carcinoma. An additional false-negative case, categorized under negative for malignancy, was later diagnosed as invasive ductal carcinoma.

Conclusion: Breast FNAs, while less frequently performed than core needle biopsies, provide significant diagnostic insights, particularly for cystic lesions. The study demonstrates high specificity and PPV for FNA in detecting malignancy, underscoring its value as a diagnostic tool when integrated with imaging and clinical assessment. These findings support the continued use of FNA in the diagnostic evaluation of breast lesions.

Introduction: The International Academy of Cytology and the American Society of Cytopathology developed the International System of Serous Fluid Cytopathology (TIS) to standardize cytological reports. Effusions in pleural, peritoneal, and pericardial cavities are valuable sources of information for medical diagnosis, especially in oncological scenarios. The TIS classification is divided into five categories: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspected malignancy (SFM), and malignant (MAL). It facilitates global communication between specialists, aiming for future clinical management guidelines based on malignancy risk assessment.

Methods: This quantitative analytical and retrospective study evaluated serous fluids (pleural, pericardial, and peritoneal) sent to the Instituto de Patologia de Araçatuba (IPAT), São Paulo, Brazil, from public and private hospitals between January 2017 and December 2022. Epidemiological and clinical data were collected from institutional files, including biopsies and immunohistochemical results.

Results: The study included 719 patients with 763 serous fluid samples (pericardial, pleural, and peritoneal) analyzed over 6 years. The majority of samples were from pleural effusions (n = 438; 57.4%), followed by peritoneal (n = 293; 38.4%) and pericardial effusions (n = 32; 4.2%). Samples were classified using the International Serous Fluid Cytopathology System (TIS), revealing the following distribution: ND (0.41%), NFM (70.30%), AUS (0.95%), SFM (11.90%), and MAL (16.44%). The risk of malignancy calculated for each category was ND 66.67%, NFM 23.39%, AUS 28.57%, SFM 48.28%, and MAL 84.17%.

Conclusion: The ROM was out of the interval proposed by the TIS in all categories. These findings suggest the applicability of TIS even outside of the cancer center environment, although the presented ROM frequencies were out of the recommended range.