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  1. Article: Cyto-Histopathological Correlations in Pathology Diagnostics.

    Kholová, Ivana

    Diagnostics (Basel, Switzerland)

    2022  Volume 12, Issue 7

    Abstract: Cyto-histopathological correlation is a key player in measuring quality in a quality programme [ ... ]. ...

    Abstract Cyto-histopathological correlation is a key player in measuring quality in a quality programme [...].
    Language English
    Publishing date 2022-07-13
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics12071703
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Comments to: Nationwide differences in cytology fixation and processing methods and their impact on interlaboratory variation in PD-L1 positivity.

    Kirbis, Irena Srebotnik / Kholová, Ivana

    Virchows Archiv : an international journal of pathology

    2023  Volume 482, Issue 4, Page(s) 797–798

    MeSH term(s) Humans ; B7-H1 Antigen ; Cytodiagnosis ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/pathology
    Chemical Substances B7-H1 Antigen
    Language English
    Publishing date 2023-02-02
    Publishing country Germany
    Document type Letter ; Comment
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-023-03503-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Insufficient endobronchial ultrasound-guided transbronchial needle aspiration specimens. When and why? The analysis of criteria and reasons behind the insufficient specimens.

    Vuorisalo, Antti / Huhtala, Heini / Paavonen, Timo / Kholová, Ivana

    Diagnostic cytopathology

    2024  Volume 52, Issue 5, Page(s) 271–287

    Abstract: Background: The classification terminology systems for pulmonary cytology specimens have recently emerged. Inadequate samples, classified as "nondiagnostic," raise challenges in determining the threshold of cell numbers and the risk of malignancy (ROM).! ...

    Abstract Background: The classification terminology systems for pulmonary cytology specimens have recently emerged. Inadequate samples, classified as "nondiagnostic," raise challenges in determining the threshold of cell numbers and the risk of malignancy (ROM).
    Methods: The study retrospectively reviewed 248 endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples: 46 insufficient samples, 60 low cellularity samples, and 142 adequate samples. Characteristics as cellularity, number of benign and malignant cells, and background features were assessed. Receiver operating characteristic curve analysis was performed to establish cell sufficiency thresholds for the diagnosis.
    Results: Out of the 248 samples analyzed, 108 were classified as benign, 94 as malignant, and 46 as insufficient. The study found that the cellularity thresholds for diagnosis in cell blocks and cytological samples were ≥50 cells and ≥100 cells, respectively. The thresholds for tumor cell counts were ≥1 - 10 cells for both types of cells, respectively. Considerably, some low cellularity samples were initially classified as insufficient despite meeting the diagnostic thresholds upon revision. The ROM varied across sample categories, with insufficient samples having a ROM of 10.9%, benign samples 15.7%, suspicious samples 92.0%, and malignant samples 100%.
    Conclusion: Insufficient EBUS-TBNA samples raise challenges in diagnosis and management. This study identified the root cause of insufficient samples, including factors related to humans, diagnostic methods, sampling, and laboratory processing. By understanding the root causes, diagnostic recommendations can be developed to improve the diagnostic process. The findings emphasize the importance of standardized classification and terminology systems for clear communication among healthcare professionals and institutions, ultimately improving patient care and enabling quality assurance measures.
    MeSH term(s) Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/pathology ; Retrospective Studies ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung/pathology ; Bronchoscopy/methods ; Lymph Nodes/pathology
    Language English
    Publishing date 2024-02-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632710-2
    ISSN 1097-0339 ; 8755-1039
    ISSN (online) 1097-0339
    ISSN 8755-1039
    DOI 10.1002/dc.25284
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: How the Milan System for Reporting Salivary Gland Cytopathology works in cytopathology practice: Meta-analysis of prospective studies and comparison with retrospective studies.

    Lagerstam, Henri / Kalfert, David / Maleki, Zahra / Kholová, Ivana

    Cancer cytopathology

    2024  

    Abstract: Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is widely accepted and endorsed by professional societies. Although several studies focusing on the MSRSGC have been published, few have been prospective studies. The ... ...

    Abstract Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is widely accepted and endorsed by professional societies. Although several studies focusing on the MSRSGC have been published, few have been prospective studies. The objective of this study was to evaluate the effectiveness of the MSRSGC in cytopathology practice.
    Methods: A comprehensive literature search was conducted to identify all prospective studies on the MSRSGC. The risk of malignancy (ROM), risk of neoplasm, and diagnostic accuracy for each diagnostic category were calculated. Data were tabulated in Microsoft Excel, and analyses were performed with the Open Meta-Analyst program.
    Results: Seven prospective and seven retrospective studies were identified. The total number of fine-needle aspirations (FNAs) was 1587 in the prospective studies and 1764 in the retrospective studies. The ROM values for the nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories in prospective versus retrospective studies were 21.0% versus 26.6%, 9.4% versus 8.1%, 34.9% versus 39.6%, 2.4% versus 2.1%, 36.6% versus 31.2%, 86.0% versus 66.0%, and 97.0% versus 96.7%, respectively. Sensitivities, specificities, and diagnostic odds ratios were 83.1% (95% confidence interval [CI], 71.1%-90.8%) versus 89.1% (95% CI, 83.6%-92.9%), 98.4% (95% CI, 96.6%-99.3%) versus 94.9% (95% CI, 91.9%-96.9%), and 310.7 (95% CI, 121.2-796.6) versus 218.8 (95% CI, 107.3-438.1).
    Conclusions: This meta-analysis indicated that the MSRSGC works well in FNA cytopathology practice and improves diagnostic accuracy in all diagnostic categories. The ROMs of prospective studies were in concordance with the MSRSGC reference values.
    Language English
    Publishing date 2024-04-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2594979-2
    ISSN 1934-6638 ; 1934-662X
    ISSN (online) 1934-6638
    ISSN 1934-662X
    DOI 10.1002/cncy.22815
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: False-Positive Atypical Endocervical Cells in Conventional Pap Smears: Cyto-Histological Correlation and Analysis.

    Pulkkinen, Johanna / Huhtala, Heini / Kholová, Ivana

    Acta cytologica

    2023  Volume 67, Issue 6, Page(s) 604–617

    Abstract: Introduction: Endocervical glandular atypia is relatively rarely diagnosed by Pap smears. A significant proportion of follow-up histological samples show no premalignant or malignant lesions. The observed cytomorphological findings in premalignant ... ...

    Abstract Introduction: Endocervical glandular atypia is relatively rarely diagnosed by Pap smears. A significant proportion of follow-up histological samples show no premalignant or malignant lesions. The observed cytomorphological findings in premalignant glandular lesions overlap with histologically proven reactive lesions.
    Methods: A total of 45 conventional Pap smears diagnosed as atypical endocervical cells, not otherwise specified (AEC, NOS) with human papillomavirus (HPV) status available were blindly evaluated in a search for 38 cytomorphological features representing background, architectural, cellular, and nuclear features. Of the cases, 30 represented histologically proven benign changes, and 15 represented histologically proven adenocarcinoma in situ (AIS) or endocervical adenocarcinoma (EAC) cases. The benign biopsies were re-evaluated, and the associations of the cytomorphological features or combinations of them with specific histological features and entities were statistically examined.
    Results: The most frequent histological findings in the benign group were squamous metaplasia, inflammation, tubal metaplasia, and microglandular hyperplasia. The statistical analysis revealed cytological features associated with squamous metaplastic changes, inflammation, and microglandular hyperplasia. Unfortunately, no cytomorphological feature was sufficiently specific to confidently leave the lesion without follow-up and histological correlation. Degeneration and nuclear crowding were the most salient features that distinguished the instances of glandular atypia with benign follow-up histology from those with histologically proven AIS or EAC (26.7 vs. 60.0%, p = 0.030, and 50.0 vs. 86.7%, p = 0.017).
    Conclusion: Additional methods besides cytomorphology are required to reliably distinguish smears with AEC, NOS harbouring only benign histological changes from those exhibiting endocervical glandular malignancy.
    MeSH term(s) Female ; Humans ; Papanicolaou Test ; Vaginal Smears ; Hyperplasia/pathology ; Cervix Uteri/pathology ; Uterine Cervical Neoplasms/diagnosis ; Uterine Cervical Neoplasms/pathology ; Adenocarcinoma in Situ/pathology ; Carcinoma, Squamous Cell/pathology ; Metaplasia/pathology ; Inflammation/pathology
    Language English
    Publishing date 2023-08-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 80003-x
    ISSN 1938-2650 ; 0001-5547
    ISSN (online) 1938-2650
    ISSN 0001-5547
    DOI 10.1159/000533256
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The diagnostic accuracy of pleomorphic adenoma in fine needle aspiration: Features leading to false positive and false negative diagnoses and the utility of cell blocks.

    Tommola, Erkka / Tommola, Satu / Kholová, Ivana

    Diagnostic cytopathology

    2023  Volume 51, Issue 5, Page(s) 283–293

    Abstract: Objective: Fine needle aspiration (FNA) is a well-established tool in preoperative diagnosis of salivary gland lesions with diagnostic accuracy of 90%. Pleomorphic adenoma (PA) is the most common salivary gland tumor comprising 45%-74% of all salivary ... ...

    Abstract Objective: Fine needle aspiration (FNA) is a well-established tool in preoperative diagnosis of salivary gland lesions with diagnostic accuracy of 90%. Pleomorphic adenoma (PA) is the most common salivary gland tumor comprising 45%-74% of all salivary gland tumors with FNA diagnostic accuracy of 89.5%-96.2%. The aim of the present study was to determine and analyze potential cytomorphological pitfalls and evaluate the diagnostic accuracy in FNA diagnosis of PA.
    Methods: Salivary gland specimens with both cytological and histological diagnoses were searched over a 10-year-period (2009-2018) from a laboratory information system of Pathology Department, Fimlab Laboratories, Tampere and matched to determine concordant and discordant PA cases. Sufficient material in histological and cytological sample was found in 401 cases. In 218 cases (54.4%) diagnosis was true-negative PA, in 169 cases (42.1%) diagnosis was true-positive PA and there were 14 discordant cases: 4 false-positive cases and 10 false-negative cases. False-negative cases were reclassified and subgrouped according to The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC).
    Results: Cytomorphologically, cell type predominance was more often myoepithelial in true-positive cases (65%) and epithelial both in false-negative (70%, p = .007) and false-positive cases (75%, p = .027). Well-formed ducts were present in cytology in all true-positive cases (p < .001). Only 10% of true-positive cases did not show any matrix in cytology (p < .001). Nuclear changes were common in false-negative cases (80%, p = .002) and false-positive cases (75%, p = .003). Beneficial cell block (CB) was more common in true-positive cases (85%) than in false-negative cases (50%, p = .041) or in false-positive cases (50%, p = .116) and a lack of beneficial CB led more often to a false diagnosis (70% false diagnosis without beneficial CB versus 29% false diagnosis with beneficial CB).
    Conclusion: The present study showed diagnostic accuracy of 96.5% for FNA in PA diagnosis. Sensitivity, specificity, positive predictive value and negative predictive value were 94.4%, 98.2%, 97.7%, and 95.6%, respectively. The benefit of CBs was more evident in true-positive cases (85%).
    MeSH term(s) Humans ; Adenoma, Pleomorphic/diagnosis ; Adenoma, Pleomorphic/pathology ; Biopsy, Fine-Needle ; Salivary Glands/pathology ; Salivary Gland Neoplasms/diagnosis ; Salivary Gland Neoplasms/pathology ; Predictive Value of Tests ; Retrospective Studies
    Language English
    Publishing date 2023-02-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632710-2
    ISSN 1097-0339 ; 8755-1039
    ISSN (online) 1097-0339
    ISSN 8755-1039
    DOI 10.1002/dc.25109
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  7. Article ; Online: Vanishing thyroid gland tumors: Infarction as consequence of FNA?

    Kholová, Ivana

    Diagnostic cytopathology

    2016  Volume 44, Issue 7, Page(s) 568–573

    Abstract: Background: Fine-needle aspiration (FNA)-induced secondary changes were described in various organs. Complete replacement of tumor by necrosis causes diagnostic and management problems.: Methods: Seven cases of totally or partially vanished thyroid ... ...

    Abstract Background: Fine-needle aspiration (FNA)-induced secondary changes were described in various organs. Complete replacement of tumor by necrosis causes diagnostic and management problems.
    Methods: Seven cases of totally or partially vanished thyroid lesions were identified from the archive of Department of Pathology, Fimlab Laboratories within 5 year period. Histopathological slides were revised in all cases.
    Results: Total thyroidectomy or lobectomy samples were from 4 females and 3 males patients aged 37-83 years (mean 67.1 years). Imaging data were available in 6 cases. Cytology slides and data were available only in 3 cases: two revealed follicular neoplasm and one was insufficient according to Bethesda system. In 5 cases, final histopathology revealed total necrosis of the lesion with only one case with available cytological diagnosis of oncocytic follicular neoplasm. In remaining 2 cases, replacement by necrosis was partial. Of note, in three cases, oncocytic metaplasia was present.
    Conclusions: Total histopathological blocking with thorough check of capsular areas is recommended in necrotic tumors. Vanishing thyroid lesion phenomenon is rare, but in cases of disappearance of tumor, preoperative cytology diagnosis is the only clue for the patient management. Diagn. Cytopathol. 2016;44:568-573. © 2016 Wiley Periodicals, Inc.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/adverse effects ; Diagnostic Errors ; Female ; Humans ; Infarction/etiology ; Male ; Middle Aged ; Necrosis/etiology ; Thyroid Gland/blood supply ; Thyroid Gland/pathology ; Thyroid Neoplasms/pathology
    Language English
    Publishing date 2016-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632710-2
    ISSN 1097-0339 ; 8755-1039
    ISSN (online) 1097-0339
    ISSN 8755-1039
    DOI 10.1002/dc.23479
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  8. Article ; Online: Myth-busting the zone of injury concept: a prospective study on the vascular response to high-energy lower extremity trauma.

    Cepas, Adas / Kiiski, Juha / Majava, Marja / Kholová, Ivana / Kaartinen, Ilkka

    Plastic and reconstructive surgery

    2023  

    Abstract: Background: Although the zone of injury concept is widely accepted, no histologic studies of vessel wall changes causing the phenomena are reported. This prospective study investigated the vascular response to high-energy lower extremity trauma to ... ...

    Abstract Background: Although the zone of injury concept is widely accepted, no histologic studies of vessel wall changes causing the phenomena are reported. This prospective study investigated the vascular response to high-energy lower extremity trauma to evaluate the validity of the zone of injury concept.
    Methods: The histologic appearance of arterial and venous walls in the zone of injury was studied in 19 patients (median age 46 [interquartile range 29.5-62.5] years) who underwent osteosynthesis and free-flap reconstruction due to high-energy lower extremity open fracture. Vascular samples were harvested from the injured extremity and control samples were harvested from the free-flap donor site. Histologic and morphometric characteristics of the vessels were analyzed microscopically and using digital pathology QuPath software.
    Results: Vascular samples were harvested on post-injury days 1-11. Intimal thickness was >3 times greater in arteries harvested from the zone of injury than in control samples (P<0.01) and the intima/media ratio was 2-fold that in control samples (P=0.01). Arterial intimal fibrosis was more evident in vessels harvested from the zone of injury (P<0.01), but medial fibrosis and medial thickness did not differ significantly between groups. Venous intimal thickening (P<0.01) and the intima/media ratio (P=0.02) were superior in samples from the zone of injury. Fibrosis-related changes did not differ between groups (P=0.45).
    Conclusions: These findings support the validity of the zone of injury concept by providing a novel histologic basis for this phenomenon. Intimal thickening and arterial intimal fibrosis are prominent histologic features of vessels affected by major lower extremity trauma.
    Language English
    Publishing date 2023-08-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208012-6
    ISSN 1529-4242 ; 0032-1052 ; 0096-8501
    ISSN (online) 1529-4242
    ISSN 0032-1052 ; 0096-8501
    DOI 10.1097/PRS.0000000000010980
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The autonomic nerves around the vein of Marshall: a postmortem study with clinical implications.

    Depes, Denis / Mennander, Ari / Immonen, Paavo / Mäkinen, Artturi / Huhtala, Heini / Paavonen, Timo / Kholová, Ivana

    APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

    2024  

    Abstract: This study aims to analyze the vein of Marshall (VOM) in human autopsy hearts and its correlation with clinical data to elucidate the morphological substrates of atrial fibrillation (AF) and other cardiac diseases. Twenty-three adult autopsy hearts were ... ...

    Abstract This study aims to analyze the vein of Marshall (VOM) in human autopsy hearts and its correlation with clinical data to elucidate the morphological substrates of atrial fibrillation (AF) and other cardiac diseases. Twenty-three adult autopsy hearts were studied, assessing autonomic nerves by immunohistochemistry with tyrosine hydroxylase (sympathetic nerves), choline acetyltransferase (parasympathetic nerves), growth-associated protein 43 (neural growth), and S100 (general neural marker) antibodies. Interstitial fibrosis was assessed by Masson trichrome staining. Measurements were conducted via morphometric software. The results were correlated with clinical data. Sympathetic innervation was abundant in all VOM-adjacent regions. Subjects with a history of AF, cardiovascular cause of death, and histologically verified myocardial infarction had increased sympathetic innervation and neural growth around the VOM at the mitral isthmus. Interstitial fibrosis increased with age and heart weight was associated with AF and cardiovascular cause of death. This study increases our understanding of the cardiac autonomic innervation in the VOM area in various diseases, offering implications for the development of new therapeutic approaches targeting the autonomic nervous system.
    Language English
    Publishing date 2024-03-12
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 93340-5
    ISSN 1600-0463 ; 0903-4641
    ISSN (online) 1600-0463
    ISSN 0903-4641
    DOI 10.1111/apm.13400
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  10. Article ; Online: Updates in head and neck cytopathology: Insights from European Congress of Pathology Short Course.

    Kholová, Ivana / Chandra, Ashish / Faquin, William C / Rupp, Niels J / Touska, Philip / O'Regan, Esther

    Cytopathology : official journal of the British Society for Clinical Cytology

    2024  Volume 35, Issue 3, Page(s) 344–349

    Abstract: Cytological specimens play a pivotal role in head and neck nodule/mass work up and diagnoses. The specimens´ importance has grown with the onset of personalized medicine and the routine use of molecular markers in the diagnostic work up. The Updates in ... ...

    Abstract Cytological specimens play a pivotal role in head and neck nodule/mass work up and diagnoses. The specimens´ importance has grown with the onset of personalized medicine and the routine use of molecular markers in the diagnostic work up. The Updates in Head and Neck Cytopathology Short Course ran during the 35th European Congress of Pathology held in Dublin, Ireland, in 2023 and brought together experts in cytopathology, pathology, and related fields to share their expertise and experience in the field of head and neck cytopathology and its future directions. Topics such as a one-stop clinic, the Milan System for Reporting Salivary Gland Cytopathology, next generation sequencing, and human papilloma virus detection in the head and neck area were covered during the short course. These topics are briefly summarized in the present review.
    MeSH term(s) Humans ; Biopsy, Fine-Needle ; Salivary Glands/pathology ; Head/pathology ; Neck/pathology ; Ireland ; Salivary Gland Neoplasms/pathology ; Retrospective Studies
    Language English
    Publishing date 2024-02-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1034190-0
    ISSN 1365-2303 ; 0956-5507 ; 1350-4037
    ISSN (online) 1365-2303
    ISSN 0956-5507 ; 1350-4037
    DOI 10.1111/cyt.13368
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