{"title":"\"Immunocytochemistry in Cytology: Myth or Reality\": Unraveling the Myth - Immunocytochemistry Applications in Thyroid Lesions.","authors":"Mitsuyoshi Hirokawa, Ayana Suzuki","doi":"10.1159/000540366","DOIUrl":"10.1159/000540366","url":null,"abstract":"<p><strong>Background: </strong>Fine-needle aspiration cytology serves as an important preoperative diagnostic tool for thyroid nodules. Despite its excellent diagnostic accuracy, diagnoses based solely on morphological observation can be challenging. Therefore, various ancillary diagnostic techniques have been applied, including immunocytochemistry (ICC). This review discusses the application and evaluation of ICC in thyroid fine needle aspiration.</p><p><strong>Summary: </strong>Currently, three immunostaining preparation methods are available for cytological materials: liquid-based cytology, cell block, and cell transfer. ICC proves valuable in scenarios such as tumour diagnosis, assessment of differentiation and grading of carcinomas, estimation of primary organs in metastatic carcinomas, and detection of gene abnormalities. However, ICC, while useful, is not as accurate as immunohistochemistry and is more difficult to evaluate.</p><p><strong>Key messages: </strong>If the pitfalls and limitations are understood and effectively navigated, ICC could play a significant role in decreasing the non-diagnostic rate, thus leading to more accurate and valuable diagnoses and reductions in the re-aspiration rate.</p>","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"1-9"},"PeriodicalIF":1.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irena Srebotnik Kirbiš, Ruben Rodrigues Roque, Margareta Strojan Fležar
{"title":"Integrated On-Slide Positive Controls for Immunocytochemistry on Cytology Slides.","authors":"Irena Srebotnik Kirbiš, Ruben Rodrigues Roque, Margareta Strojan Fležar","doi":"10.1159/000540413","DOIUrl":"10.1159/000540413","url":null,"abstract":"<p><strong>Introduction: </strong>Integrated on-slide positive controls are a standard quality assurance and quality control measure for immunohistochemistry on formalin-fixed paraffin-embedded tissue sections. They ensure identical analytical conditions for the control and patient samples. Our aim was to develop a procedure for preparing integrated on-slide positive controls for immunocytochemistry (ICC) on methanol-fixed cytospins.</p><p><strong>Methods: </strong>Leftover diagnostic cytology samples with sufficient cells and confirmed expression of Calretinin, MOC31, TTF1, and hormone receptors were used as control samples. Cells from the control samples were deposited on the peripheral part of objective slides using standard cytocentrifuge equipment. Cytospins were immediately fixed in methanol for at least 30 min and then covered with polyethylene glycol (PEG). Completely dry and solid PEG was removed from the central part of the objective slides and stored at room temperature. Patient samples were subsequently added to the central part of a PEG-protected slide, with an appropriate positive control placed on the peripheral part, and then fixed in methanol. ICC was performed on the Ventana/Roche automated platform ULTRA, using optimized and validated protocols for TTF1, hormone receptors, and double immunostaining for Calretinin/MOC31. The quality of ICC reactions for both deposits on the same slide and potential cell carryover was evaluated retrospectively.</p><p><strong>Results: </strong>In the period from October 2021 to December 2023, the majority of integrated positive controls (364/368, 99%) consistently exhibited unequivocally positive reactions for TTF-1 (n = 93), hormone receptors (n = 84), and double staining for Calretinin/MOC31 (n = 191), with easily interpretable ICC reactions on corresponding patient samples. No obvious carryover of cells from the control sample to the patient sample was observed during this period.</p><p><strong>Conclusion: </strong>A novel approach developed for preparing integrated on-slide positive controls for ICC on methanol-fixed cytospins using standard cytocentrifugation is low-cost and can be widely applied in diagnostic cytology laboratories. Simultaneous ICC procedures for the control and patient samples on the same slide ensure identical analytical conditions for both samples, providing the highest level of quality control while reducing costs. Interpreting both ICC reactions on the same slide is time-efficient and convenient.</p>","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"1-7"},"PeriodicalIF":1.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"State of the Art and Science of Immunocytochemistry.","authors":"Irena Srebotnik Kirbis","doi":"10.1159/000539634","DOIUrl":"10.1159/000539634","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p><p><strong>Key messages: </strong>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.</p>","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"1-9"},"PeriodicalIF":1.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta CytologicaPub Date : 2024-01-01Epub Date: 2024-01-19DOI: 10.1159/000536387
Robert J McConnell, Olga Kamysh, Patrick L O'Kane, Ellen Greenebaum, Alexander V Rozhko, Vasilina V Yauseyenka, Victor F Minenko, Vladimir Drozdovitch, Yuliya Yarets, Tatiana Kukhta, Kiyohiko Mabuchi, Mark P Little, Elizabeth K Cahoon, Lydia B Zablotska
{"title":"Radiation Dose Does Not Affect the Predictive Value of Thyroid Biopsy for Diagnosing Papillary Thyroid Cancer in a Belarusian Cohort Exposed to Chernobyl Fallout.","authors":"Robert J McConnell, Olga Kamysh, Patrick L O'Kane, Ellen Greenebaum, Alexander V Rozhko, Vasilina V Yauseyenka, Victor F Minenko, Vladimir Drozdovitch, Yuliya Yarets, Tatiana Kukhta, Kiyohiko Mabuchi, Mark P Little, Elizabeth K Cahoon, Lydia B Zablotska","doi":"10.1159/000536387","DOIUrl":"10.1159/000536387","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"34-44"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Using the DNA Integrity Number to Analyze DNA Quality in Specimens Collected from Liquid-Based Cytology after Fine-Needle Aspiration of Breast Tumors and Lesions.","authors":"Akiyoshi Hoshino, Yoshiyasu Oana, Yasuyo Ohi, Yukari Maeda, Masako Omori, Yuki Takada, Tadashi Ikeda, Keiichi Sotome, Hinako Maeda, Takako Yanagisawa, Osamu Takeuchi, Satoshi Kuronuma, Takafumi Sangai, Yukiko Shibahara, Yoshiki Murakumo, Makoto Saegusa, Naoki Kanomata, Satoi Nagasawa, Rin Yamaguchi, Masayuki Yoshida, Yuji Kozuka, Hiroshi Matsumoto, Koichiro Tsugawa, Ichiro Maeda","doi":"10.1159/000538071","DOIUrl":"10.1159/000538071","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"145-152"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta CytologicaPub Date : 2024-01-01Epub Date: 2024-07-18DOI: 10.1159/000540011
Anjali Gupta, Parikshaa Gupta, Nalini Gupta, Sahajal Dhooria, Pankaj C Vaidya, Nidhi Prabhakar, Amanjit Bal, Joseph L Mathew
{"title":"Pulmonary Langerhans Cell Histiocytosis: Diagnosis in Bronchoalveolar Lavage Liquid-Based Cytology Samples.","authors":"Anjali Gupta, Parikshaa Gupta, Nalini Gupta, Sahajal Dhooria, Pankaj C Vaidya, Nidhi Prabhakar, Amanjit Bal, Joseph L Mathew","doi":"10.1159/000540011","DOIUrl":"10.1159/000540011","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by the accumulation of Langerhans cells within the lung tissue. The diagnosis of PLCH traditionally involves clinical, radiological, and lung biopsy histopathological evaluations.</p><p><strong>Case presentation: </strong>We present 2 cases where the diagnosis of PLCH was confirmed through the analysis of bronchoalveolar lavage (BAL) fluid cytology using immunoperoxidase technique, highlighting the significance of this minimally invasive technique in the diagnostic process. Clinical and radiological examination suggested advanced interstitial lung disease characterized by a fibrocystic pattern in both cases. The cytologic analysis of the BAL fluid revealed typical histiocytes with longitudinal grooves and eosinophils, which was better seen on liquid-based cytology (LBC) smears. ICC with CD1a, Langerin, and S-100 confirmed the diagnosis of PLCH.</p><p><strong>Conclusion: </strong>Detecting PLCH through the examination of BAL cytology poses challenges, yet it is achievable, particularly with the assistance of LBC and ICC.</p>","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"379-383"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141722747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta CytologicaPub Date : 2024-01-01Epub Date: 2024-05-24DOI: 10.1159/000539418
Helen J Trihia, Philippe Vielh
{"title":"Pitfalls in Cytopathology.","authors":"Helen J Trihia, Philippe Vielh","doi":"10.1159/000539418","DOIUrl":"10.1159/000539418","url":null,"abstract":"","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"177-178"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Utility of Pipet Curet Cytology and Biopsy as a Diagnostic Method for Endometrial Endometrioid Carcinoma.","authors":"Makiko Kurata, Takuma Tajiri, Masataka Ueda, Chie Inomoto, Tomoko Sugiyama, Hirotaka Fujita, Nozomi Nomura, Tomohisa Machida, Tetsuji Iida, Ippei Ooiwa, Yoshihiro Nishijima, Hiroshi Kajiwara, Toshinari Muramatsu, Naoya Nakamura","doi":"10.1159/000541279","DOIUrl":"10.1159/000541279","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to determine the utility of Pipet Curet cytology (PCC) and Pipet Curet biopsy (PCB) for diagnosing uterine endometrial endometrioid carcinoma (EEC).</p><p><strong>Methods: </strong>We divided 77 patients with EEC into two groups per Federation of Gynecology and Obstetrics (FIGO) grades: G1 (n = 44) and G2/3 (n = 33) and compared the diagnostic sensitivity of PCC, PCB, and PCC and PCB combined, retrospectively. Next, we investigated any diagnostic discordance between PCC-based and PCB-based diagnoses per FIGO grade group.</p><p><strong>Results: </strong>The diagnostic sensitivity of PCC, PCB, and the two modalities combined was significantly higher for G2/3 EECs than for G1 EECs (72.7% vs. 45.5%, p = 0.0209; 84.8% vs. 63.6%, p = 0.0434; and 93.9% vs. 65.9%, p = 0.0046, respectively), likely due to more friable cancer cells in higher grade EEC cases. Among our 77 EEC patients, there were 4 patients (5.19%) with PCC-based concordant but PCB-based discordant results against EEC, in the G2/3 group predominantly. Diagnostic sensitivity of all cases increased from 72.7% (56/77) by PCB alone to 77.9% (60/77) by use of both modalities combined.</p><p><strong>Conclusion: </strong>Cytologic evaluation can reduce the number of false-negative histologic diagnoses. By providing complementary information, the two modalities combined from the Pipet Curet procedure would be valuable as a diagnostic method for EEC.</p>","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"413-422"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta CytologicaPub Date : 2024-01-01Epub Date: 2024-10-14DOI: 10.1159/000541997
Rubina Razack, Justin A Bishop, Julandi Alwan, Liezel Coetzee, Daniel Rudolph De Wet, Wasim Mahomed, Marc Merven, Pawel Tomasz Schubert, Amir Afrogheh
{"title":"Cytopathology of a Newly Described Salivary Gland Neoplasm: A Case Report of Microsecretory Adenocarcinoma Presenting in the Parotid Gland.","authors":"Rubina Razack, Justin A Bishop, Julandi Alwan, Liezel Coetzee, Daniel Rudolph De Wet, Wasim Mahomed, Marc Merven, Pawel Tomasz Schubert, Amir Afrogheh","doi":"10.1159/000541997","DOIUrl":"10.1159/000541997","url":null,"abstract":"<p><strong>Introduction: </strong>Microsecretory adenocarcinoma (MSA) is a novel entity defined by distinctive histology, a specific immunophenotype, and unique molecular fusion MEF2C::SS18. It occurs mainly in intra-oral minor salivary glands and the skin, with only one reported case affecting the parotid gland. To the best of our knowledge, no cytomorphological features of MSA have been published to date. We report the first case of fine-needle aspiration biopsy (FNAB) cytology of MSA diagnosed in the parotid gland.</p><p><strong>Case presentation: </strong>A 48-year-old man presented with a 3.5 × 2.5-cm parotid mass. FNAB of the tumour revealed a cellular smear comprising a predominantly epithelial cell population showing luminal differentiation with secretory features and a distinctive background matrix with both myxoid and mucinous qualities. Scattered, but conspicuous multinucleated giant cells were present, a feature not commonly observed in salivary gland aspirates. Histology of the excised tumour revealed classic features of MSA with supportive immunohistochemistry and SS18 break apart fusion detected by fluorescence in situ hybridisation (FISH). Next-generation sequencing confirmed a MEF2C::SS18 gene fusion.</p><p><strong>Conclusion: </strong>MSA is a rare neoplasm and should be considered in the cytological differential diagnosis of low-grade salivary gland neoplasms. Its unique cytomorphological features should raise the possibility of MSA in salivary gland FNABs. The diagnosis can be established on cellular cell block preparations using immunohistochemistry and FISH or PCR.</p>","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"516-524"},"PeriodicalIF":1.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}