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Cyto-Histological Correlations in Pathology Diagnosis

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 14934

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Dr. Ivana Kholová

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1. Head of Cytopathology, Fimlab Laboratories, 33100 Tampere, Finland
2. Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland
Interests: cytology; FNA; HPV primary screening; cardiovascular pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

After a successful first edition of the Special Issue “Cyto-Histological Correlations in Pathology Diagnostics” (https://www.mdpi.com/journal/diagnostics/special_issues/Cyto-Histopathogical) with a total of 13 papers—including 10 original research papers—dealing with various aspects of cyto-histological correlation and its role in cytological diagnosis, from gynecytology through effusions to fine-needle aspirations, we are pleased to announce a second edition.

Cyto-histological correlation is a comparison of cytological and histological diagnoses from the same lesion. It is a part of laboratory routine diagnostics at the case level and a quality assurance parameter if series-based. It mirrors our everyday routine diagnostics.

Series covering both gynecological and non-gynecological cytology, including fine needle aspirations, effusions, and brushing, are welcomed. Diagnostic issues and possible pitfalls should be discussed. Aspects of lesions imaging, sampling, processing, and staining can be highlighted in the cyto-histological correlation. Last but not least, as in the first edition, new and old cytology terminology series are encouraged as submissions.

You may choose our Joint Special Issue in Reports.

Dr. Ivana Kholová
Guest Editor

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. Diagnostics 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 2600 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.

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Published Papers (9 papers)

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14 pages, 1303 KiB

Open AccessArticle

Assessment of Ki-67 Proliferative Index in Cytological Samples of Nodal B-Cell Lymphomas

by Mojca Založnik, Simona Miceska, Simon Buček, Nataša Nolde, Mojca Gjidera, Ulrika Klopčič, Zorica Čekić, Živa Pohar Marinšek, Gorana Gašljević and Veronika Kloboves Prevodnik

Diagnostics 2024, 14(15), 1584; https://doi.org/10.3390/diagnostics14151584 - 23 Jul 2024

Viewed by 563

Abstract

Background: The Ki-67 proliferative index (PI) is part of the diagnosis of nodal B-cell lymphoma (nBCL), but its determination in cytological samples is not standardized. We aimed to establish an approach for the accurate determination of the Ki-67 PI in cytological slides to differentiate between indolent and aggressive nBCLs. Methods: Patients diagnosed with nBCL by fine-needle aspiration biopsy and subsequent excision biopsy were included. Cell suspensions were prepared from biopsy samples for CD3/Ki-67 double immunocytochemical staining and flow-cytometric verification of lymphoma B-cell counts. The Ki-67 PI was assessed by manual counting and eyeballing in cytology and eyeballing in histology. The cut-off values for the differentiation between aggressive and indolent lymphomas were determined for each method. Results: A strong correlation between manual and flow-cytometric counting of lymphoma B cells was confirmed (interclass correlation coefficient (IC coef.) = 0.78). The correlation of the Ki-67 PI determined in cytological and histological slides was also strong (IC coef. > 0.80). Histologically, 55 cases were classified as indolent and 31 as aggressive nBCLs. KI-67 PI cut-off values of 28.5%, 27.5%, and 35.5% were established for manual counting and eyeballing in cytology and eyeballing in histology, respectively, with high sensitivity and specificity. Conclusions: The Ki-67 PI, assessed by manual counting and eyeballing in cytological samples, accurately differentiates between indolent and aggressive nBCLs. Full article

(This article belongs to the Special Issue Cyto-Histological Correlations in Pathology Diagnosis)

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11 pages, 1005 KiB

Open AccessArticle

The Incidence of Thyroid Cancer in Bethesda III Thyroid Nodules: A Retrospective Analysis at a Single Endocrine Surgery Center

by Iyad Hassan, Lina Hassan, Nahed Balalaa, Mohamad Askar, Hussa Alshehhi and Mohamad Almarzooqi

Diagnostics 2024, 14(10), 1026; https://doi.org/10.3390/diagnostics14101026 - 16 May 2024

Viewed by 1300

Abstract

Background: Fine-needle aspiration cytology (FNAC) is widely used to diagnose and monitor thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the standard for interpreting FNAC specimens. The risk of malignancy in Bethesda III nodules, also known as Atypia of Undetermined Significance (AUS), varies significantly throughout several studies published worldwide. This retrospective study examines the risk of cancer in thyroid FNAC categorized as Bethesda III as identified in the final histopathology of thyroidectomy specimens at a single endocrine surgery center. Methods: This retrospective cohort analysis included 1038 consecutive patients who underwent elective thyroid surgery with complete follow-up data between January 2020 and March 2024. Preoperative data on clinical and pathological characteristics have been collected. The final histopathology report from the thyroidectomy specimen was compared to the results of the preoperative FNAC on nodules that were judged to be Bethesda category III. Statistical methods were performed using SPSS version 29. Results: A total of 670 ultrasound-guided FNACs (64.5%) performed during the study period were included in the final analysis. The study population was predominantly female, represented by 79.6% of patients with a mean age of 42.5 (SD 12.1), while 20.4% were male and significantly older with mean age of 45.13 years (p = 0.02). The FNAC inadequacy rate was 5.1%, which was associated with a high risk of malignancy (6 out of 34; 17.6%). Out of the total sample size of 170 patients classified as group III, 57 were found to have malignancies in final surgical histopathology, representing 33.5% of the cases within this category. The secondary gender-related outcome analysis showed that female patients classified under the Bethesda II category had a significantly higher risk of malignancy, with a rate of 21.2%, compared to males who had a malignancy rate of 3.4% in the same Bethesda category (p = 0.001, chi-square test). However, the female patients exhibited prognostically superior non-invasive tumors compared to male individuals (p = 0.02, chi-square test). Conclusion: This study’s results indicate that Bethesda categories II and III are associated with a higher risk of malignancy in comparison to the reports of the first and third editions of the TBSRTC, particularly for female patients classified under category II. Full article

(This article belongs to the Special Issue Cyto-Histological Correlations in Pathology Diagnosis)

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12 pages, 1155 KiB

Open AccessArticle

Comprehensive Genomic Studies on the Cell Blocks of Pancreatic Cancer

by Ricella Souza da Silva, Maria João Pina, Luís Cirnes, Luís Gouveia, André Albergaria and Fernando Schmitt

Diagnostics 2024, 14(9), 906; https://doi.org/10.3390/diagnostics14090906 - 26 Apr 2024

Viewed by 1186

Abstract

Pancreatic cancer is one of the deadliest malignancies, characterized by late-stage diagnosis and limited treatment options. Comprehensive genomic profiling plays an important role in understanding the molecular mechanisms underlying the disease and identifying potential therapeutic targets. Cell blocks (CBs), derived from EUS-FNA, have become valuable resources for diagnosis and genomic analysis. We examine the molecular profile of pancreatic ductal adenocarcinoma (PDAC) using specimens obtained from CB EUS-FNA, across a large gene panel, within the framework of next-generation sequencing (NGS). Our findings revealed that over half (55%) of PDAC CB cases provided adequate nucleic acid for next-generation sequencing, with tumor cell percentages averaging above 30%. Despite challenges such as low DNA quantification and degraded DNA, sequencing reads showed satisfactory quality control statistics, demonstrating the detection of genomic alterations. Most cases (84.6%) harbored at least one gene variant, including clinically significant gene mutation variants such as KRAS, TP53, and CDKN2A. Even at minimal concentrations, as long as the extracted DNA is of high quality, performing comprehensive molecular profiling on PDAC samples from cell blocks has remained feasible. This strategy has yielded valuable information about the diagnosis, genetic landscape, and potential therapeutic targets, aligning closely with a precision cytopathology approach. Full article

(This article belongs to the Special Issue Cyto-Histological Correlations in Pathology Diagnosis)

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13 pages, 1946 KiB

Open AccessArticle

Rapid Remote Online Evaluation in Endoscopic Diagnostics: An Analysis of Biopsy-Proven Respiratory Cytopathology

by Hatice Elmas, Binnur Önal, Stefan Steurer, Birgit Hantzsch-Kuhn, Martin Claussen, Elnur Mehdi, Ümit Ince, Klaus F. Rabe, Guido Sauter and Lutz Welker

Diagnostics 2023, 13(21), 3329; https://doi.org/10.3390/diagnostics13213329 - 28 Oct 2023

Cited by 2 | Viewed by 1274

Abstract

Background: This prospective study assesses the use of rapid remote online cytological evaluation for diagnosing endoscopical achieved biopsies. It focuses on its effectiveness in identifying benign and malignant conditions using digital image processing. Methods: The study was conducted between April 2021 and September 2022 and involved analyses of 314 Rapid Remote Online Cytological Evaluations in total (154 imprint cytologies, 143 fine needle aspirations and 17 brush cytologies) performed on 239 patients at the LungenClinic Grosshansdorf. During on-site evaluation via telecytology, the time requirement was recorded and the findings were compared with the cyto-/histological and final diagnoses. Results: By means of rapid remote online evaluation, findings of 86 cytological benign, 190 malignant and 38 unclear diagnoses were recorded (Ø assessment time, 100 s; range, 11–370 s). In 27 of the 37 specimens with unclear diagnoses, the final findings were malignant tumours and only 6 were benign changes. The diagnosis of another 4 of these 37 findings remained unclear. Excluding these 37 specimens, rapid remote online evaluation achieved a sensitivity of 90.5% with a specificity of 98.5% and a correct classification rate of 92.4% with regard to the final diagnosis of all cases. As expected, an increase in the sensitivity rate for the cytological detection of malignant tumours (76.1% vs. 92.5%) was found especially in fine-needle aspirations. Conclusions: Rapid remote online analysis allows the fast quantitative and qualitative evaluation of clinically obtained cytological specimens. With a correct classification rate of more than 93%, sampling deficiencies can be corrected promptly and diagnostic and therapeutic approaches can be derived. Full article

(This article belongs to the Special Issue Cyto-Histological Correlations in Pathology Diagnosis)

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21 pages, 2071 KiB

Open AccessArticle

Diagnostic Value of Labial Minor Salivary Gland Biopsy: Histological Findings of a Large Sicca Cohort and Clinical Associations

by Konstantinos Triantafyllias, Mirjam Bach, Mike Otto and Andreas Schwarting

Diagnostics 2023, 13(19), 3117; https://doi.org/10.3390/diagnostics13193117 - 3 Oct 2023

Cited by 1 | Viewed by 1345

Abstract

(1) Background: The aim of this study was to analyze labial minor salivary gland biopsy (MSGB) findings of a large sicca cohort and to examine their associations with Sjogren’s syndrome (SS)-associated laboratory markers, phenotypic characteristics and systemic manifestations. Moreover, we sought to explore the ability of MSGB to identify SS patients among subjects with pre-diagnosed fibromyalgia (FM). (2) Methods: Included were all patients of three rheumatology departments having undergone a diagnostic MSGB within 9 years. Next to the examination of histological and immunohistochemical findings, we focused on activity and chronicity parameters of the underlying disease, autoantibodies, presence of systemic and hematologic involvement, as well as chronic pain and SS comorbidities. (3) Results: Among the 678 included patients, 306 (45.1%) had a positive focus score (FS). The remaining patients (n = 372) served as control subjects. There were significant correlations between FS and hypergammaglobulinemia (p < 0.001), ANA and rheumatoid factor positivity (both; p < 0.001), a weak significant correlation with erythrocyte sedimentation rate (rho = 0.235; p < 0.001) and a negative correlation with nicotine use (p = 0.002). Within the primary SS subgroup, FS was associated significantly with glandular enlargement (p = 0.007) and systemic hematologic manifestations (p = 0.002). Next to FS, CD20 cell staining showed an excellent diagnostic performance in the diagnosis of SS by an area under the curve of 0.822 (95%CI 0.780–0.864; p < 0.001). Interestingly, 42.1% of all patients with fibromyalgia (FM) having received an MSGB could be diagnosed with SS. (4) Conclusion: By examining one of the largest cohorts in the literature, we could show that MSGB histological and immunohistochemical findings not only play a key role in the classification and diagnosis of SS but could also provide important information regarding SS phenotype and systemic manifestations. Furthermore, MSGB may help differentiate patients with FM from patients with subclinical SS who suffer primarily from chronic pain. Full article

(This article belongs to the Special Issue Cyto-Histological Correlations in Pathology Diagnosis)

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11 pages, 7168 KiB

Open AccessArticle

Diagnosis of Low-Grade Urothelial Neoplasm in the Era of the Second Edition of the Paris System for Reporting Urinary Cytology

by Konstantinos Christofidis, Napoleon Moulavasilis, Evangelos Fragkiadis, Dimitrios Goutas, Andreas C. Lazaris, Dionisios Mitropoulos and Panagiota Mikou

Diagnostics 2023, 13(16), 2625; https://doi.org/10.3390/diagnostics13162625 - 8 Aug 2023

Cited by 3 | Viewed by 1738

Abstract

Background: The Paris System for Reporting Urinary Cytology (TPS) is considered the gold standard when it comes to diagnostic classifications of urine specimens. Its second edition brought some important changes, including the abolition of the diagnostic category of “low-grade urothelial neoplasm (LGUN)”, acknowledging the inability of cytology to reliably discern low-grade urothelial lesions. Methods: In this retrospective study, we assessed the validity of this change, studying the cytological diagnoses of histologically diagnosed low-grade urothelial carcinomas during a three-year period. Moreover, we correlated the sum of the urinary cytology diagnoses of this period with the histological diagnoses, whenever available. Results: Although all the cytological diagnoses of LGUN were concordant with the histological diagnoses, most low-grade urothelial carcinomas were misdiagnosed cytologically. Subsequently, the positive predictive value (PPV) of urinary cytology for the diagnosis of LGUN was 100%, while the sensitivity was only 21.7%. Following the cyto-histopathological correlation of the sum of the urinary cytology cases, the sensitivity of urinary cytology for the diagnosis of high-grade urothelial carcinoma (HGUC) was demonstrated to be 90.1%, the specificity 70.8%, the positive predictive value (PPV) 60.3%, the negative predictive value (NPV) 93.6% and the overall accuracy 77.2%, while for LGUN, the values were 21.7%, 97.2%, 87.5%, 58.6% and 61.9%, respectively. Risk of high-grade malignancy was 0% for the non-diagnostic (ND), 4.8% for the non-high-grade urothelial carcinoma (NHGUC), 33.3% for the atypical urothelial cells (AUCs), 65% for the suspicious for high-grade urothelial carcinoma (SHGUC), 100% for the HGUC and 12.5% for the LGUN diagnostic categories. Conclusions: This study validates the incorporation of the LGUN in the NHGUC diagnostic category in the second edition of TPS. Moreover, it proves the ability of urinary cytology to safely diagnose HGUC and stresses the pivotal role of its diagnosis. Full article

(This article belongs to the Special Issue Cyto-Histological Correlations in Pathology Diagnosis)

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12 pages, 968 KiB

Open AccessArticle

Updates from Our Institutional Experience with Thyroid Nodules Diagnosed as Metastases

by Esther Diana Rossi, Carmine Bruno, Pietro Tralongo, Federica Policardo, Federica Vegni, Angela Feraco, Qianqian Zhang, Alfredo Pontecorvi, Guido Fadda, Celestino Pio Lombardi, Marco Raffaelli, Antonino Mulè and Luigi Maria Larocca

Diagnostics 2023, 13(14), 2388; https://doi.org/10.3390/diagnostics13142388 - 17 Jul 2023

Viewed by 1319

Abstract

Background: Thyroid metastases (TMs) are a rare entity, ranging between 0 and 24% in the autopsy series. In the assessment of the best management, the discrimination between a primary and a metastatic thyroid lesion is crucial. In this regard, fine needle aspiration cytology (FNAC) is likely to play a crucial role especially when ancillary techniques (i.e., immunocytochemistry (ICC) and molecular testing) are carried out. Methods: We searched for all the TMs diagnosed using FNAC and analyzed between 2014 and 2023. The cases were processed with liquid-based (LBC) and ICC and molecular testing performed on LBC-stored material. Results: We reported 2.2% (19 cases) of TMs out of 1022 malignancies. TMs included: 1 larynx carcinoma (LX-Ca), 1 melanoma, 2 breast carcinomas (B-Ca), 3 lung carcinomas (LG-Ca), 4 gastro-intestinal carcinomas (GI-Ca), and 8 clear cell renal carcinomas (CCRC). All patients had a previous cancer history, between 300 and 2 months from the primary cancers. The morphological features were supported by ICC, which were contributive in 100% of cases. All TMs cases were characterized by multiple thyroid nodules except the melanoma case. Four cases underwent total thyroidectomy (1 B, 1 LX, 1 melanoma, and 1 CCRC) whilst 15 TMs were treated with radio-chemotherapy. Conclusions: FNAC empowered the diagnostic workup of patients with TMs avoiding useless surgery. The low sensitivity of cytology might be reinforced by the application of ancillary techniques. We found a predominant rate of kidney metastatic carcinomas, followed by lung and breast. TMs are frequently multifocal and in a context of a systemic disease so a tailored therapy seems to be the best treatment. Full article

(This article belongs to the Special Issue Cyto-Histological Correlations in Pathology Diagnosis)

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15 pages, 3708 KiB

Open AccessArticle

Utility and Limitations of Fine-Needle Aspiration Cytology in the Diagnosis of Lymphadenopathy

by Hwa Jeong Ha, Jeeyong Lee, Da Yeon Kim, Jung-Soon Kim, Myung-Soon Shin, Insup Noh, Jae Soo Koh, Eun Ju Kim and Seung-Sook Lee

Diagnostics 2023, 13(4), 728; https://doi.org/10.3390/diagnostics13040728 - 14 Feb 2023

Cited by 9 | Viewed by 3731

Abstract

Background: Fine needle aspiration cytology (FNAC) is a valuable tool for evaluating lymphadenopathy. The purpose of this study was to assess the reliability and effectiveness of FNAC in the diagnosis of lymphadenopathy. Methods: Cytological characteristics were evaluated in 432 patients who underwent lymph node FNAC and follow-up biopsy at the Korea Cancer Center Hospital from January 2015 to December 2019. Results: Fifteen (3.5%) of the four hundred and thirty-two patients were diagnosed as inadequate by FNAC, with five (33.3%) of these diagnosed as metastatic carcinoma on histological examination. Of the 432 patients, 155 (35.9%) were diagnosed as benign by FNAC, with seven (4.5%) of these diagnosed histologically as metastatic carcinoma. A review of the FNAC slides, however, showed no evidence of cancer cells, suggesting that the negative results may have been due to FNAC sampling errors. An additional five samples regarded as benign on FNAC were diagnosed as non-Hodgkin lymphoma (NHL) by histological examination. Of the 432 patients, 223 (51.6%) were cytologically diagnosed as malignant, with 20 (9.0%) of these diagnosed as tissue insufficient for diagnosis (TIFD) or benign on histological examination. A review of the FNAC slides of these 20 patients, however, showed that 17 (85.0%) were positive for malignant cells. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV), and accuracy of FNAC were 97.8%, 97.5%, 98.7%, 96.0%, and 97.7%, respectively. Conclusions: Preoperative FNAC was safe, practical, and effective in the early diagnosis of lymphadenopathy. This method, however, had limitations in some diagnoses, suggesting that additional attempts may be required according to the clinical situation. Full article

(This article belongs to the Special Issue Cyto-Histological Correlations in Pathology Diagnosis)

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Review

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17 pages, 680 KiB

Open AccessReview

The Role of Checkpoint Inhibitor Expression Directly on Exfoliated Cells from Bladder Cancer: A Narrative Review

by Luca Di Gianfrancesco, Alessandro Crestani, Antonio Amodeo, Paolo Corsi, Davide De Marchi, Eugenio Miglioranza, Giuliana Lista, Francesca Simonetti, Gian Maria Busetto, Martina Maggi, Francesco Pierconti, Maurizio Martini, Isabella Monia Montagner, Debora Tormen, Antonio Scapinello, Filippo Marino and Angelo Porreca

Diagnostics 2023, 13(19), 3119; https://doi.org/10.3390/diagnostics13193119 - 3 Oct 2023

Cited by 1 | Viewed by 1167

Abstract

Bladder cancer (BCa) is a common type of cancer that affects the urinary bladder. The early detection and management of BCa is critical for successful treatment and patient outcomes. In recent years, researchers have been exploring the use of biomarkers as a non-invasive and effective tool for the detection and monitoring of BCa. One such biomarker is programmed death-ligand 1 (PD-L1), which is expressed on the surface of cancer cells and plays a crucial role in the evasion of the immune system. Studies have shown that the PD-L1 expression is higher in BCa tumors than in healthy bladder tissue. Additionally, PD-L1 expression might even be detected in urine samples in BCa patients, in addition to the examination of a histological sample. The technique is being standardized and optimized. We reported how BCa patients had higher urinary PD-L1 levels than controls by considering BCa tumors expressing PD-L1 in the tissue specimen. The expression of PD-L1 in urinary BCa cells might represent both a diagnostic and a prognostic tool, with the perspective that the PD-L1 expression of exfoliate urinary cells might reveal and anticipate eventual BCa recurrence or progression. Further prospective and longitudinal studies are needed to assess the expression of PD-L1 as a biomarker for the monitoring of BCa patients. The use of PD-L1 as a biomarker for the detection and monitoring of BCa has the potential to significantly improve patient outcomes by allowing for earlier detection and more effective management of the disease. Full article

(This article belongs to the Special Issue Cyto-Histological Correlations in Pathology Diagnosis)

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