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Cytologic Features of Tumor

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 November 2019) | Viewed by 43850

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Prof. Dr. José A. Jiménez Heffernan

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Department of Pathology, University Hospital La Princesa. C/ Diego de León 62, 28006 Madrid, Spain
Interests: fine-needle aspiration cytology; immunocytochemistry; cell biology; epithelial-to-mesenchymal transition; mesothelial cells; carcinoma-associated fibroblasts; thyroid cytopathology; brain tumors
Special Issues, Collections and Topics in MDPI journals

Dr. Blanca Vicandi

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Guest Editor

Department of Pathology, University Hospital La Paz. Paseo de la Castellana 261, 28046, Madrid, Spain
Interests: fine-needle aspiration cytology; cervical cytology; cervical screening; immunocytochemistry; salivary gland neoplasms; thyroid cytopathology; reactive lymphadenopathies

Prof. Dr. Pilar González-Peramato

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Guest Editor

Department of Pathology. Universidad Autónoma de Madrid. University Hospital La Paz. Paseo de la Castellana 261, 28046, Madrid, Spain Madrid, Spain
Interests: fine-needle aspiration cytology; molecular pathology; urinary cytology; renal neoplasms; testicular pathology; immunohistochemistry

Special Issue Information

Dear Colleagues,

Fine-needle aspiration cytology (FNAC) is a relatively young discipline within diagnostic pathology. It has pros and cons when compared to the gold standard pathologic diagnosis of histopathology. Its main advantage is that FNAC is a minimally invasive procedure that permits easy, safe, and rapid sampling of tumors as well as access to locations where a tissue biopsy is very difficult or impossible to perform. Its principal limitation is that sometimes the amount of material obtained is not enough for all the necessary studies. Its reduced invasiveness has permitted the appearance in the diagnostic scenario of endoscopic, ultrasound-guided FNAC of mediastinal, pancreatic, and other abdominal lesions. Furthermore, it has greatly contributed to the diagnosis and specific treatment of pulmonary and pancreatic neoplasms. Other aspects of diagnostic cytology such as effusion cytology, cervical cytology, and intraoperative cytology have also played an important role in offering a minimally invasive pathologic diagnosis.

The latest advances in molecular biology, more precisely next-generation sequencing, are certainly going to revolutionize the diagnosis of neoplasms. We all have great expectations in these methods as well as in liquid biopsy. To what extent is diagnostic pathology, as we know it today, going to be necessary? In this new diagnostic context, cytology establishes an ideal link between diagnostic morphology and molecular studies. Because of their low invasiveness, FNAC samples are ideal for obtaining material for molecular studies of solid tumors. This Special Issue will highlight recent advances in basic aspects of clinical cytopathology as well as the bridging role between diagnostic morphology and molecular studies offered by FNAC. Original research articles, short clinical series, as well as reviews on all aspects of diagnostic cytopathology are welcome.

Prof. Dr. José A. Jiménez Heffernan
Dr. Blanca Vicandi
Prof. Dr. Pilar González-Peramato
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

cytopathology
fine-needle aspiration cytology
diagnostic cytology
endoscopic ultrasound-guided FNA
intraoperative cytology
immunocytochemistry
molecular cytopathology

Published Papers (11 papers)

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Research

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9 pages, 642 KiB

Open AccessArticle

Diagnostic Agreement for High-Grade Urothelial Cell Carcinoma in Atypical Urine Cytology: A Nationwide Survey Reveals a Tendency for Overestimation in Specimens with an N/C Ratio Approaching 0.5

by Yeh-Han Wang, Jen-Fan Hang, Chien-Hui Wen, Kuan-Cho Liao, Wen-Ying Lee and Chiung-Ru Lai

Cancers 2020, 12(2), 272; https://doi.org/10.3390/cancers12020272 - 22 Jan 2020

Cited by 7 | Viewed by 4367

Abstract

In the Paris System (TPS), standardized cytomorphological criteria and diagnostic categories were proposed for reporting urine cytology. To evaluate the diagnostic agreement and interobserver concordance for assessing TPS criteria, the Taiwan Society of Clinical Cytology organized an online survey with 10 atypical urine cytology cases. A total of 137 participants completed the survey. The mean agreement of diagnosis was 51.2%, ranging from 34.3% to 83.2% for each case. For 60% (6/10) of cases, the agreement was <50%. The interobserver concordance of diagnosis and cytological criteria assessment showed poor agreement. The nuclear-to-cytoplasmic (N/C) ratio had the highest kappa value of 0.386, indicating a significantly higher interobserver concordance and reproducibility than the other three TPS criteria. The correct rate of assessing the N/C ratio increased as the N/C ratio increased (correlation coefficient: 0.891, p < 0.01). Three cases with an N/C ratio near 0.5 were overestimated. Poor interobserver concordance of diagnosis and TPS criteria was revealed. Compared with other cytological features, the N/C ratio assessment was quantitative and more reproducible, but a tendency to overestimate cells was noted when the N/C ratio was approximately 0.5. Continuing education programs should emphasize the accurate assessment of N/C ratio to improve the application of TPS. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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13 pages, 3807 KiB

Open AccessArticle

A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgkin Lymphoma in Ganp-Transgenic Mice

by Yasuhiro Sakai, Andri Rezano, Seiji Okada, Takahiro Ohtsuki, Yoshiaki Kawashima, Tetsuya Tsukamoto, Motoshi Suzuki, Michinori Kohara, Motohiro Takeya, Nobuo Sakaguchi and Kazuhiko Kuwahara

Cancers 2020, 12(1), 204; https://doi.org/10.3390/cancers12010204 - 14 Jan 2020

Cited by 6 | Viewed by 3214

Abstract

Hodgkin lymphoma (HL) is one of the most difficult neoplasms in terms of cytopathological research owing to the lack of established cytological murine models. Although HL is believed to be of lymphoid germinal center B-cell origin, HL cells exhibit unique biphenotypic characteristics of B cells and macrophages. B-cell/macrophage biphenotypic cells have also been identified in the spleen of Lyn-deficient mice. Moreover, Lyn-targeting germinal center-associated nuclear protein (GANP)-transgenic mice (Ig-ganp^Tg mice) spontaneously develop a lymphoid tumor. We aimed to investigate whether the lymphoid tumor developed in Ig-ganp^Tg mice exhibit biphenotypic characteristics of B cells/macrophages that correspond to human HL. Here, we demonstrated GANP overexpression in human HL cells and found that it may regulate transdifferentiation between B cells and macrophages. We also demonstrated that tumors were comparable with B-cell/macrophage biphenotypic Hodgkinoid lymphomas. The tumor cells expressed macrophage-related F4/80, CD68, and CD204 as well as cytoplasmic B220 and µ-/κ-chains; in addition, these cells exhibited phagocytic activity. These cells also expressed transcripts of CD30; c-fms; and the cytokines monocyte chemoattractant protein (MCP)-1, MCP-5, RANTES, tumor necrosis factor-α and thrombopoietin associated with macrophages as well as granulocyte/macrophage colony-stimulating factor, interleukin (IL)-4, IL-10, IL-12, and IL-13. Ig-ganp^Tg mice represent a novel cytological model for the study of cytopathological etiology and oncogenesis of HL. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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14 pages, 5525 KiB

Open AccessArticle

Prognostic Immune Cell Profiling of Malignant Pleural Effusion Patients by Computerized Immunohistochemical and Transcriptional Analysis

by Chengguang Wu, Fabian Mairinger, Ruben Casanova, Aashil A. Batavia, Anne-Laure Leblond and Alex Soltermann

Cancers 2019, 11(12), 1953; https://doi.org/10.3390/cancers11121953 - 05 Dec 2019

Cited by 9 | Viewed by 3649

Abstract

Malignant pleural effusion (MPE) is a severe condition of advanced tumors without effective therapy. We used digitalized immunohistochemical and transcriptional approaches to investigate the prognostic influence of immune cells and expression variance of associated immunomodulatory molecules in MPE. Cytology tissue microarrays were constructed from MPE cell blocks of 155 patients with five tumor entities. Immune cells lineage markers were quantified by computational cytopathology on immunohistochemistry. mRNA expression analysis of nine lineage markers and 17 immunomodulators was performed by NanoString. Immunohistochemically quantified high B cells to leukocytes ratio (hazard ratio (HR) = 0.70, p-value = 0.043) and low neutrophils to leukocytes ratio (HR = 1.78, p-value = 0.003) were favorable prognosticators for overall survival independent of tumor entity. Correspondingly, patients with high B cells but low neutrophils gene expression signature showed longer median overall survival of 500 days (HR = 2.29, p-value = 0.009). Regarding targetable molecule expressions, lung adenocarcinomas were characterized by high PD-L1, but mesothelioma by high LAG-3. Ovarian carcinoma was least immunogenic. Independent of tumor entity, the condition of the immune system in MPE liquids is able to provide additional prognostic cytologic information. Combined analysis of lineage specific markers and related immunomodulators may direct immune-based therapeutic decisions. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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13 pages, 3494 KiB

Open AccessArticle

A 4-Year Retrospective Analysis of Salivary Gland Cytopathology Using the Milan System for Reporting Salivary Gland Cytology and Ancillary Studies

by Charlotte Dubucs, Céline Basset, Dominique D’Aure, Monique Courtade-Saïdi and Solène M. Evrard

Cancers 2019, 11(12), 1912; https://doi.org/10.3390/cancers11121912 - 01 Dec 2019

Cited by 27 | Viewed by 4180

Abstract

The cytopathology of salivary glands presents major challenges due to the heterogeneity of benign and malignant neoplasms, which is reflected in the large range of WHO 2017 Classifications. Fine needle aspiration (FNA) of salivary gland tumours is still the favoured initial approach as it results in good sensitivity and specificity. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published in 2018 and comprises seven categories. We report results from a 4-year retrospective analysis of 328 salivary gland FNAs which were reviewed and classified according to the MSRSGC. We assess the risk of neoplasm, the risk of malignancy and the contribution of ancillary studies to the diagnosis. Benign neoplasms were the most frequent diagnosis (44.2%). Malignant and suspicious for malignancy were identified in 11.3% and 4.9% of diagnosed cases, respectively. Histopathological analysis after surgery was available for 216 (65.8%) of the cases. All malignant cases were confirmed post-surgery, and 68.8% of suspicious for malignancy were confirmed as malignant tumours. Immunocytochemistry was informative in 72.3% of cases. Immunocytochemistry and FISH provided the definitive diagnosis in 23.7% and 33% of cases, respectively. In conclusion, the MSRSGC is more effective when specific features of neoplasms can be identified. Ancillary studies help to further characterise salivary gland tumours and thereby increase the accuracy of MSRSGC. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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12 pages, 1721 KiB

Open AccessArticle

Evaluation of the Accuracy of Liquid-Based Oral Brush Cytology in Screening for Oral Squamous Cell Carcinoma

by Lena Deuerling, Kristin Gaida, Heinrich Neumann and Torsten W. Remmerbach

Cancers 2019, 11(11), 1813; https://doi.org/10.3390/cancers11111813 - 18 Nov 2019

Cited by 19 | Viewed by 5611

Abstract

This study evaluates the accuracy of the results of liquid-based oral brush cytology and compares it to the histology and/or the clinical follow-ups of the respective patients. A total of 1352 exfoliated specimens were collected with an Orcellex brush from an identical number of oral lesions, then cytological diagnoses were made using liquid-based cytology. The final diagnoses in the study were 105 histologically proven squamous cell carcinomas (SCCs), 744 potentially malignant lesions and 503 cases of traumatic, inflammatory or benign hyperplastic oral lesions. The sensitivity and specificity of the liquid-based brush biopsy were 95.6% (95% CI 94.5–96.7%) and 84.9% (95% CI 83.0–86.8%), respectively. This led to the conclusion that brush biopsy is potentially a highly sensitive and reliable method to make cytological diagnoses of oral neoplasia. The main advantage of a brush biopsy over a scalpel biopsy is that it is less invasive and is more tolerated by the patients. Therefore, more lesions can be screened and more cancers can be detected at an early stage. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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8 pages, 541 KiB

Open AccessArticle

Thyroid Bethesda Category AUS/FLUS in Our Microscopes: Three-Year-Experience and Cyto-Histological Correlation

by Roope Huhtamella and Ivana Kholová

Cancers 2019, 11(11), 1670; https://doi.org/10.3390/cancers11111670 - 28 Oct 2019

Cited by 16 | Viewed by 3645

Abstract

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) introduced a new category: Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS) comprising of heterogenous lesions with a lesser degree of atypia. Its routine use is a bit controversial. The study cohort included AUS/FLUS thyroid cytopathological diagnoses signed out at Fimlab Laboratories from the period of 1 October 2013 to 31 December 2016. We analyzed all the AUS/FLUS cases, their cytology subclassification, and their cyto-histological correlation, when available. In total, there were 331 AUS/FLUS cases from 252 patients. The mean age was 59.8 years and there were 196 females and 56 males. Repeated AUS/FLUS was diagnosed in 75 (29.8%) cases. Out of 252 patients, 118 (46.8%) were operated on. Sixty-eight were operated on after the first AUS/FLUS diagnosis, 46 after 2 AUS/FLUS diagnoses, and 4 after 3 AUS/FLUS diagnoses. In total, there were 37 (14.7%) malignancies and 40 benign tumors. The risk of malignancy for AUS/FLUS (14.7%) is in agreement with the original TBSRTC risk of malignancy. The risk of neoplasia was 30.6% in our series. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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13 pages, 2704 KiB

Open AccessArticle

Computerized Cytological Features for Papillary Thyroid Cancer Diagnosis—Preliminary Report

by Shyang-Rong Shih, I-Shiow Jan, Kuen-Yuan Chen, Wan-Yu Chuang, Chih-Yuan Wang, Yung-Lien Hsiao, Tien-Chun Chang and Argon Chen

Cancers 2019, 11(11), 1645; https://doi.org/10.3390/cancers11111645 - 25 Oct 2019

Cited by 4 | Viewed by 3704

Abstract

Fine needle aspiration cytology (FNAC) is the final diagnosis of thyroid nodules before surgery. It is important to further improve the indeterminate FNAC diagnosis results using computerized cytological features. This retrospective cross-sectional study included 240 cases, of whom 110 had histologic diagnosis of papillary thyroid cancers (PTC), 100 had nodular/adenomatous goiters/hyperplasia (benign goiters), 10 had follicular/Hurthle cell carcinomas, and 20 had follicular adenomas. Morphological and chromatic features of FNAC were quantified and analyzed. The result showed that six quantified cytological features were found significantly different between patients with a histologic diagnosis of PTC and patients with histologic diagnosis of benign goiters in multivariate analysis. These cytological features were used to estimate the malignancy risk in nodules with indeterminate FNAC results. The Area Under the Receiver Operating Characteristics (AUROC) of the diagnostic accuracy with a benign or malignant nature was 81.3% (p < 0.001), 78.7% (p = 0.014), and 56.8% (p = 0.52) for nodules with FNAC results of atypia, which is suspicious for malignancy and follicular neoplasm, respectively. In conclusion, quantification of cytological features could be used to develop a computer-aided tool for diagnosing PTC in thyroid nodules with indeterminate FNAC results. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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11 pages, 236 KiB

Open AccessArticle

Salivary Gland FNA Diagnostics in a Real-Life Setting: One-Year-Experiences of the Implementation of the Milan System in a Tertiary Care Center

by Erkka Tommola, Satu Tommola, Sinikka Porre and Ivana Kholová

Cancers 2019, 11(10), 1589; https://doi.org/10.3390/cancers11101589 - 18 Oct 2019

Cited by 23 | Viewed by 2635

Abstract

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018 following other organ specific cytopathological reporting systems and it aimed at bringing a practical, evidence-based, user-friendly classification system with characterization and management algorithms. At the Department of Pathology, Fimlab Laboratories, Tampere, Finland all salivary fine needle aspirations (FNAs) have been given cytopathological diagnoses according to the MSRSGC since January 2018. Analyses of a one-year-period (January 2018–December 2018) consisted of 183 salivary FNA samples from 138 patients with correlation to histopathology in 90 cases with surgical follow-up. The MSRSGC performance in patient based analysis was as follows: accuracy was 90.9%, sensitivity was 61.5%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 89.4%, respectively. Risks of malignancy (ROMs) in MSRSGC categories were: 0.0% (0/15) in non-diagnostic category, 100.0% (1/1) in non-neoplastic category biased by only one falsely-negative lymphoma case, 14.3% (1/7) in atypia of undetermined significance category, 0.0% (0/28) in benign neoplasm category, 27.3% (3/11) in neoplasm of uncertain malignant potential category, and 100% for both suspicious for malignancy (4/4) and malignancy (4/4) categories, respectively. The MSRSGC has been proven as a reliable classification system in salivary gland FNA routine diagnostics in a tertiary care center. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

9 pages, 914 KiB

Open AccessArticle

Safety and Usefulness of Cryobiopsy and Stamp Cytology for the Diagnosis of Peripheral Pulmonary Lesions

by Tatsuya Imabayashi, Junji Uchino, Akihiro Yoshimura, Yusuke Chihara, Nobuyo Tamiya, Yoshiko Kaneko, Tadaaki Yamada and Koichi Takayama

Cancers 2019, 11(3), 410; https://doi.org/10.3390/cancers11030410 - 22 Mar 2019

Cited by 29 | Viewed by 4006

Abstract

Reports on the use of cryobiopsy (CB) for lung cancer diagnosis are limited. The aims of the present study were to evaluate the safety and usefulness of CB using radial endobronchial ultrasonography, without a guide sheath, for the diagnosis of peripheral pulmonary lesions and determine the utility of stamp cytology, an on-site diagnostic technique for determining tumor inclusion in CB samples. We retrospectively analyzed data for 35 patients (36 lesions) with suspected peripheral lung cancer who underwent CB between August 2017 and February 2019 at our medical facility. The diagnostic yield, incidence of complications, and the utility of stamp cytology for diagnosis were investigated. The diagnostic yield of CB was 86.1% (31/36) with histological diagnosis, and 80.5% (29/36) with diagnosis using stamp cytology; the overall yield was 91.6% (33/36). Pneumothorax requiring thoracic drainage occurred in two patients, both of whom had lesions contacting the pleura. Grade 2 and grade 1 bleeding occurred in one and 25 patients, respectively. CB enables the collection of very large, nearly intact tissue samples, thus resulting in an improvement in the true diagnosis rate and facilitating the measurement of multiple biomarkers as well as rapid histological diagnosis. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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Review

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11 pages, 426 KiB

Open AccessReview

Recommendations Favoring Anal Cytology as a Method for Anal Cancer Screening: A Systematic Review

by Andreia Albuquerque, Elisabete Rios and Fernando Schmitt

Cancers 2019, 11(12), 1942; https://doi.org/10.3390/cancers11121942 - 04 Dec 2019

Cited by 36 | Viewed by 3248

Abstract

Clinicians are increasingly facing the decision of performing anal cancer screening in high-risk groups. Anal cytology is commonly the first approach. We systematically reviewed recommendations favoring anal cytology for anal cancer screening. Three databases were searched: PubMed, Scopus, and Embase, from January 2007 to 12 September 2019. The references cited by the retrieved articles and the websites of relevant organizations were also searched without language restrictions. Studies reporting guidelines from regional or national societies, institutes, or groups were included. Eight papers met the inclusion criteria and were selected, five were from the United States of America (USA) and three from Europe. There were no national recommendations published. There was one guideline specifically for solid-organ transplant recipients. The other seven targeted HIV-positive patients, with HIV-positive men who have sex with men (MSM) included as a screening group in all of these. Two recommendations favored screening in all HIV-positive patients. Five recommendations targeting HIV-positive patients made considerations about the cytology follow-up, recommending at least annual cytology in case of a normal result, and in case of squamous cytological abnormalities, a referral for anoscopy/high-resolution anoscopy. There were no recommendations for upper and lower age limits for screening. In conclusion, several societies recommend anal cancer screening using anal cytology in HIV-positive MSM patients. There is a lack of screening recommendations for other high-risk groups, with only one society recommending screening in transplant recipients. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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9 pages, 1201 KiB

Open AccessReview

Emerging Molecular Technologies in Renal Cell Carcinoma: Liquid Biopsy

by Alessia Cimadamore, Silvia Gasparrini, Francesco Massari, Matteo Santoni, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli and Rodolfo Montironi

Cancers 2019, 11(2), 196; https://doi.org/10.3390/cancers11020196 - 07 Feb 2019

Cited by 22 | Viewed by 4477

Abstract

Liquid biopsy, based on the circulating tumor cells (CTCs) and cell-free nucleic acids has potential applications at multiple points throughout the natural course of cancer, from diagnosis to follow-up. The advantages of doing ctDNA assessment vs. tissue-based genomic profile are the minimal procedural risk, the possibility to serial testing in order to monitor disease-relapse and response to therapy over time and to reduce hospitalization costs during the entire process. However, some critical issues related to ctDNA assays should be taken into consideration. The sensitivity of ctDNA assays depends on the assessment technique and genetic platforms used, on tumor-organ, stage, tumor heterogeneity, tumor clonality. The specificity is usually very high, whereas the concordance with tumor-based biopsy is generally low. In patients with renal cell carcinoma (RCC), qualitative analyses of ctDNA have been performed with interesting results regarding selective pressure from therapy, therapeutic resistance, exceptional treatment response to everolimus and mutations associated with aggressive behavior. Quantitative analyses showed variations of ccfDNA levels at different tumor stage. Compared to CTC assay, ctDNA is more stable than cells and easier to isolate. Splice variants, information at single-cell level and functional assays along with proteomics, transcriptomics and metabolomics studies can be performed only in CTCs. Full article

(This article belongs to the Special Issue Cytologic Features of Tumor)

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