Acta Cytologica最新文献

Introduction: Fine-needle aspiration cytology (FNAC) reporting systems for adrenal gland cytology lack global uniformity. Implementing a standardized global reporting system would improve diagnostic accuracy, risk assessment, clinical communication, and uniformity in adrenal gland cytology practices worldwide. The current systematic review and meta-analysis aimed to assess the proposed WHO-standardized reporting categories for adrenal gland cytology and evaluate the role of FNAC in adrenal lesion diagnosis.

Material and methods: A comprehensive search was conducted in PubMed, Scopus, and Embase databases up to June 2024. Studies with more than 15 patients were included. The QUADAS-2 tool was employed for quality assessment of the selected studies. Heterogeneity and publication bias among the studies were also evaluated. Cytological categories were recategorized according to the proposed WHO reporting system. Pooled sensitivity, specificity, and risk of malignancy (ROM) ranges for each cytological category were calculated.

Results: Fifteen studies met the inclusion criteria. Pooled diagnostic performance across studies showed high sensitivity (92.2%) and high specificity (99.5%). Heterogeneity and publication bias were low. Range and pooled ROM across cytology categories were as follows: inadequate/nondiagnostic/unsatisfactory - 0% to 100% (18%), benign - 0% to 14.7% (3.7%), atypical category - 0% to 50% (46.2%), "suspicious for malignancy" - 0% to 100% (76.5%), and malignant category - 94.4% to 100% (99.6%).

Conclusion: High sensitivity and specificity, as well as ROM values across categories, demonstrate that the proposed WHO cytological categories offer reliable risk stratification for adrenal lesions, supporting accurate diagnosis and treatment decisions. The low heterogeneity and minimal publication bias ensure that the findings are applicable across various clinical settings and patient populations.

Introduction: Birefringence analysis is an essential tool in both histological and cytological diagnostics, particularly with stains such as picrosirius red for collagen and Congo red for amyloid. However, polarized light microscopy remains limited in many laboratories due to cost and accessibility barriers. We describe a low-cost "do-it-yourself" (DIY) approach using commercial polarizing films to adapt a standard brightfield microscope for birefringence visualization.

Methods: Thirty gastrocnemius muscle sections stained with picrosirius red were analyzed using both a commercial polarized light system and the DIY setup. Quantitative image analysis was performed with ImageJ, and agreement between methods was assessed with ROC curve analysis.

Results: The DIY method achieved an AUC of 0.6252 (p = 0.0309) and 99% inter-observer concordance, demonstrating fair agreement with the commercial system.

Conclusion: This simple, validated method expands access to birefringence-based diagnostics and has potential applications in cytological contexts, such as amyloid detection in fine-needle aspirates and collagen assessment in cytospin preparations.

Introduction: Bronchoalveolar lavage (BAL) brings an important contribution in diagnosing pulmonary diseases. The analysis of standard cell distribution and the assessment of iron-laden macrophages (the Golde score) are integral to standard medical reports. However, the traditional cytological method of manual cell counting is subject to interobserver variability and staining quality issues.

Methods: To address these issues, we trained AI-based algorithms to enhance the accuracy of differentiated cell counts of macrophages, lymphocytes, neutrophils, eosinophils, ciliated cells, and squamous cells as well as the Golde score, which assesses the hemosiderin content in macrophages. For this purpose, we assembled an internal sample cohort with 16 Hemacolor, 16 Papanicolaou, and 5 iron-stained smears. For validation, we used 10 slides each of Papanicolaou and Hemacolor staining and 5 with iron staining.

Results: The algorithm achieved fair to excellent correlation compared to two cytologists: For Papanicolaou staining, the correlations were macrophages 0.96, lymphocytes 0.98, neutrophil granulocytes 0.99, eosinophils 0.58, ciliated cells 0.61, squamous cells 0.31. In Hemacolor staining the correlations were macrophages 0.97, lymphocytes 0.92, neutrophils 0.99, eosinophils 0.99, ciliated cells 0.58, squamous cells -0.145. The automated Golde score calculation deviated on average by 19 points from the manual evaluation.

Conclusion: The study demonstrates the potential of AI-supported methods for BAL analysis in diagnostic cytology. The high accuracy in recognizing cell types and calculating the Golde score underlines the benefits of expanding the training data for broader clinical applications. Further research is encouraged to support the use of digital cytology on conventional smears in clinical practice.

Cornflake artifacts that appear in cervical cytology are formed by a poorly dehydrated series of Papanicolaou (Pap) stains and dried before mounting. This study focused on the humidity conditions during Pap staining to investigate the cause of the appearance of cornflake artifacts in Pap smears. One SurePath™ liquid-based cytology cell specimen, diagnosed as negative for intraepithelial lesions or malignancy and human papillomavirus using the uniplex E6/E7 PCR method, was used. The draft humidity was adjusted to 30%, 50%, 70%, and 80%. Subsequently, poorly dehydrated series of Pap staining according to the method was performed. After the last xylene immersion, smears that were not dried and dried after 1, 3, and 5 min were mounted. Cornflake artifacts were not observed in smears that had not been dried and dried for 1 min under any humidity condition. In the smear dried for 3 min before mounting, cornflake artifacts were observed at only 80% humidity, and the ratio of cornflake artifacts to normal squamous cells was 0.04 corn/nsc. The ratios when smears were dried for 5 min before mounting at 30%, 50%, 70%, and 80% humidity were 6.44, 6.80, 6.53, and 1.46 corn/nsc, respectively. This study revealed that the appearance of cornflake artifacts in Pap stains under poor dehydration conditions is related to high humidity.

Introduction: Nasopharyngeal carcinoma (NPC) represents a significant burden in Asia, especially in Southern China, with cervical lymph nodes being one of the most common sites of metastasis. At times, peripheral lymphadenopathy may be the only manifestation of an occult primary tumor.

Case presentation: We report three cases: the first with classical cervical lymphadenopathy, while two with rare unusual presentations - right preauricular and right periorbital lesions. The cytological evaluation in all revealed metastatic undifferentiated NPC, which led to the identification of an occult nasopharyngeal primary.

Conclusion: This series highlights the indispensable role of FNAC with a dual-stain approach and intricate diagnostic challenges in deciphering occult undifferentiated NPC. To the best of our knowledge, this is the first series to formally document a significant observation - stain-dependent cytologic shift in undifferentiated NPC: tumor cells appeared as dispersed with hyperchromatic homogeneously dark-stained naked nuclei mimicking lymphoma on May-Grünwald-Giemsa (MGG), but as loosely cohesive clusters or syncytial sheets with vesicular nuclei on Papanicolaou. MGG alone risks mimicking lymphoma, and Papanicolaou alone risks mimicking metastatic carcinoma. Such perplexing cytomorphological variations with two stains risk erroneous diagnoses, yet offer a unique clue to undifferentiated NPC. Thus, extensive cytologic sampling with dual-stain strategy enables early recognition of an aggressive, elusive, and often misdiagnosed malignancy, significantly improving survival in cases that would otherwise be fatal.

Background: The International Academy of Cytology in collaboration with the International Agency for Research on Cancer has developed a standardized World Health Organization Reporting System (WHO System) for the cytopathology of the lymph nodes, spleen, and thymus. Fine-needle aspiration biopsy (FNAB) of the spleen and thymus, performed under ultrasound or computed tomography guidance, constitutes a minimally invasive, well-tolerated, and cost-effective diagnostic technique. Despite a limited number of published studies on the diagnostic accuracy of FNAB in these organs, it remains a valuable tool particularly when combined with rapid on-site evaluation and ancillary techniques, such as immunophenotypic analysis by flow cytometry or immunocytochemistry and molecular testing.

Summary: The WHO System categorizes thymic and splenic cytopathology into five diagnostic categories: "Inadequate/Insufficient/Nondiagnostic," "Benign," "Atypical," "Suspicious for malignancy," and "Malignant." This standardized approach aims to enhance diagnostic accuracy, provide risk assessment, and facilitate clinical decision-making. However, applicability of FNAB in the thymus and spleen is still debated, particularly concerning sample adequacy, diagnostic accuracy, and potential complications such as hemorrhage, especially for splenic FNAB. Thymic FNAB is primarily used for diagnosing thymic hyperplasia, thymoma, thymic carcinomas, and lymphomas. However, distinguishing these entities and their subtypes is challenging. Splenic FNAB is valuable in evaluating splenomegaly, infections, lymphomas, and other neoplasms, particularly in staging and monitoring disease progression. While using FNAB to evaluate these organs is not yet a widely adopted standard practice, its role in minimizing unnecessary surgical interventions and guiding therapeutic strategies is being increasingly recognized.

Key messages: The WHO System for the thymus and spleen seeks to establish a harmonized, evidence-based framework for cytopathological diagnosis, incorporating key diagnostic criteria, malignancy risk assessment, and standardized reporting protocols. Future research is needed to refine and develop diagnostic role of FNAB, enhance its integration with advanced molecular techniques, and optimize its use in personalized medicine.

Introduction: Hyperthyroidism-related epithelial hyperplasia is seldomly listed as a pitfall in thyroid cytology. Therefore, we focused on the cytomorphological characteristics of epithelial hyperplasia and compared these features with papillary thyroid carcinoma (PTC).

Methods: Study group consisted of 76 patients (133 FNA specimens) histologically diagnosed with hyperthyroidism-related epithelial hyperplasia without a concomitant malignancy. The control group contained 21 histologically verified FNAs of PTCs. A total of 48 cytomorphological features were quantitatively evaluated.

Results: Statistically significant differences between the study groups were discovered on the architectural, cellular, and nuclear levels. Nuclear features varied most: nuclear elongation, grooves, irregular nuclear membrane, pseudoinclusions, the presence of nucleoli or small eccentric nucleoli were clearly more common in PTC group.

Conclusion: Fine-needle aspiration referrals with clinical data and thyroid function test results can facilitate the interpretation of cytomorphological features and reduce the use of undetermined categories in cases of hyperthyroidism-related epithelial hyperplasia.

Introduction: Distinguishing between nondiagnostic (ND) and benign (B) categories in lung cytopathology remains clinically challenging, especially given the significant overlap and the high risk of malignancy (ROM) often reported for ND cases. The 2022 WHO Reporting System for Lung Cytopathology addresses these issues but acknowledges that ND may carry up to a 60% ROM. We conducted a large, multicenter study to clarify the ND-B boundary and evaluate how radiologic findings influence ROM.

Methods: From 12 institutions, 363 consecutive lung cytopathology cases categorized as insufficient/inadequate/ND (I/I/ND) or B with histopathological follow-up were analysed. The locally categorized cytopathological cases were subclassified centrally into: ND with insufficient cellularity (IS-C), artefactual/sample preparation error (IS-P), non-representative (NR1: no suspicious lesion; NR2: suspicious lesion); and B (B1: benign cells, no suspicious lesion; B2: benign cells, suspicious lesion). ROM was defined as the percentage of histologically confirmed malignancies in each group.

Results: Overall, 60.6% (220/363) of cases were confirmed as malignant on histopathological evaluation. Within the ND category (n = 149), 70.5% (105/149) were malignant, exceeding the malignancy risk range estimated by the WHO system (40-60%). In comparison, the ROM for cases classified as B (n = 214) was 53.7% (115/214), which is consistent with the WHO system reference range. Notably, when ND or B cytopathology coincided with suspicious imaging findings (NR2 [n = 57] or B2 [n = 124]), the ROM exceeded 75% (134/181). These results indicate that subclassification based on imaging findings provides a more refined estimation of malignancy risk. Cases with B cytopathology may still carry a high likelihood of malignancy when imaging features are suspicious, reinforcing the importance of integrated diagnostic evaluation.

Conclusions: These findings demonstrate that imaging correlation is critical for accurate risk assessment in the overlap between the ND and B cytopathology categories. Subclassification of ND and B cases based on imaging features and consistent reporting of ROM can help identify patients who may benefit from repeat sampling or further diagnostic evaluation. This approach has the potential to enhance diagnostic accuracy and improve clinical decision-making.

Introduction: This study aimed to elucidate the spectrum of clinical manifestations, cytomorphology, immunophenotype, and the molecular genetic features of lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) in the context of serous effusions (SE).

Methods: A retrospective analysis evaluated the cytomorphological features, immunophenotype, and the cyto-histological correlations of twenty-one LBL/ALL associated with SE. Concurrently, bone marrow (BM) aspiration samples were analyzed using an integrated approach, including flow cytometry, reverse transcription PCR (RT-PCR), next-generation sequencing (NGS), or whole transcriptome sequencing (WTS).

Results: Of the 21 cases of SE LBL/ALL, 16 cases were T-LBL/ALL and 5 cases were B-LBL/ALL. The cases included 17 pleural, 2 peritoneal, and 2 pericardial fluid samples. Both T-LBL/ALL and B-LBL/ALL in SE exhibit a blast-like morphology, characterized by small to medium size, irregular nuclear membranes, and inconspicuous nucleoli, alongside frequent nuclear fragmentation and apoptotic bodies. LBL/ALL express immaturity markers such as terminal deoxynucleotidyl transferase (7/17, 41.2%), CD10 (6/12, 50%), CD43 (8/8, 100%), and CD99 (6/6, 100%). T-LBL/ALL and B-LBL/ALL specifically express T-cell markers (CD2 [3/6, 50%], CD3 [10/12, 83.3%], CD5 [2/11, 18.2%], CD7 [10/10, 100%]) or B-cell markers (CD20 [3/5, 60%], CD79a [4/4, 100%], PAX5 [5/5, 100%]), respectively. A high proportion of primitive and immature lymphocytes exceeding 25% in BM was observed in T-LBL/ALL (5/7) and in one case of B-LBL/ALL. No BCR/ABL gene rearrangements were detected in any cases. Furthermore, fusion gene MLL::ENL and PLCALM::MLLT10, as well as mutations in genes including WT1, NOTCH1, PAX5, IKZF, ARID1A, BCOR, SETD2, ARID2, TET2, JAK3, NF1, and CEBPA, were identified in LBL/ALL through RT-PCR, NGS, or WTS analyses.

Conclusion: The integration of clinical manifestations, cytological evaluation, and gene expression profiles is instrumental in achieving accurate diagnosis, subclassification, and prognosis of LBL/ALL within the context of SE.