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Article ; Online: Thymic epithelial tumours: histopathological classification and differential diagnosis.

von der Thüsen, Jan

2023 Volume 84, Issue 1, Page(s) 196–215

Abstract: The epithelial and lymphoid compartments of the thymus can give rise to a wide variety of tumours, including thymomas, thymic carcinomas, lymphoreticular proliferations, germ cell tumours, and sarcomas. While some of these have close similarity to their ... ...

Abstract	The epithelial and lymphoid compartments of the thymus can give rise to a wide variety of tumours, including thymomas, thymic carcinomas, lymphoreticular proliferations, germ cell tumours, and sarcomas. While some of these have close similarity to their counterparts in other organs, both in terms of histology and immunohistochemistry, as well as molecular features, others are unique to the thymus. The epithelial tumours, which can develop in the thymus, will be discussed in this review, with a particular emphasis on resolving differential diagnosis by means of morphology, immunohistochemical profiles, and molecular diagnostics.
MeSH term(s)	Humans ; Diagnosis, Differential ; Thymus Neoplasms/diagnosis ; Thymus Neoplasms/pathology ; Thymoma/diagnosis ; Thymoma/pathology ; Neoplasms, Glandular and Epithelial/diagnosis
Language	English
Publishing date	2023-11-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.15097
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Article ; Online: Thoracic tumour pathology.

Mino-Kenudson, Mari / von der Thüsen, Jan

Histopathology

2023 Volume 84, Issue 1, Page(s) 3–5

MeSH term(s)	Humans ; Thoracic Neoplasms ; Pathology
Language	English
Publishing date	2023-12-12
Publishing country	England
Document type	Editorial
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.15103
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Article ; Online: COVID-19 in the Netherlands: lessons from a nationwide query of dutch autopsy, histology, and cytology pathological reports.

Lopuhaä, Boaz / Voorham, Q J M / van Kemenade, Folkert J / von der Thüsen, Jan H

Virchows Archiv : an international journal of pathology

2024 Volume 484, Issue 3, Page(s) 429–439

Abstract: Since the onset of the COVID-19 pandemic, autopsies have played a valuable role in understanding the pathophysiology of COVID-19. In this study, we have analyzed COVID-19-related pathology reports from autopsies, histology, and cytology on a nationwide ... ...

Abstract	Since the onset of the COVID-19 pandemic, autopsies have played a valuable role in understanding the pathophysiology of COVID-19. In this study, we have analyzed COVID-19-related pathology reports from autopsies, histology, and cytology on a nationwide level. Pathology reports from all 43 pathology laboratories in the Netherlands stating "COVID," "Corona," and/or "SARS" were queried from the Dutch Nationwide Pathology Database (Palga). Consecutive reports of the included patients were also retrieved. Out of 5065 entries, a total of 1833 eligible COVID-19-related pathology reports between January 2020 and June 2021 were included in this collection of reports. Lung histopathology reports reflected differences in the severity of abnormalities (acute diffuse alveolar damage, alveolar histiocytes, and thrombi during the first three pandemic waves (Wuhan variant) versus the fourth wave (alpha variant)). Autopsy reports from 2020 state significantly shorter disease duration and younger age of death compared to autopsy reports from 2021. All reports together reflected a more granular pathology with comorbidities such as chronic histiocytic intervillositis, perniosis, and thrombi found in a variety of organs (lungs, kidneys, and small and large intestines). This nationwide overview of pathology reports provides data related to deaths as well as comorbidities in a clinical setting of COVID-19. Certain findings reported in SARS-CoV-infected lungs and placentas were also reported in post-COVID-19 tissue of the same kind. Consecutive reports after the earliest reports with COVID-19 allowed for follow-up reports. These follow-up reports can help with post-viral studies regarding long-term effects of COVID-19 as well as identifying the effects of different SARS-CoV-2 variants.
MeSH term(s)	Female ; Humans ; Pregnancy ; Autopsy ; COVID-19/pathology ; Lung/pathology ; Netherlands/epidemiology ; Pandemics ; Pregnancy Complications, Infectious/pathology ; SARS-CoV-2 ; Thrombosis/pathology
Language	English
Publishing date	2024-02-27
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-024-03771-2
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Article ; Online: Histopathology and genetic susceptibility in COVID-19 pneumonia.

von der Thüsen, Jan / van der Eerden, Menno

European journal of clinical investigation

2020 Volume 50, Issue 7, Page(s) e13259

Abstract: Background: The clinical features of COVID-19 pneumonia range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission.: Aims: To provide a brief ... ...

Abstract	Background: The clinical features of COVID-19 pneumonia range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. Aims: To provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID-19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease. Materials and method: We assessed the available early literature for histopathological patterns of COVID-19 pneumonia and underlying risk factors. Result: The histopathological spectrum of COVID-19 pneumonia includes variable patterns of epithelial damage, vascular complications, fibrosis and inflammation. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. Discussion: While some risk factors and their potential role in COVID-19 pneumonia are increasingly recognized, little is known about the mechanisms behind episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. Conclusion: The answer to many of the remaining questions regarding COVID-19 pneumonia pathogenesis may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping.
MeSH term(s)	Age Factors ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/genetics ; Coronavirus Infections/immunology ; Coronavirus Infections/pathology ; Cytokine Release Syndrome/immunology ; Diabetes Mellitus/epidemiology ; Edema/pathology ; Fibrosis ; Genetic Predisposition to Disease ; HLA Antigens/genetics ; Humans ; Hypertension/epidemiology ; Inflammation/immunology ; Inflammation/pathology ; Influenza, Human/pathology ; Obesity/epidemiology ; Pandemics ; Peptidyl-Dipeptidase A/genetics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/genetics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/pathology ; Polymorphism, Genetic ; Respiratory Mucosa/immunology ; Respiratory Mucosa/pathology ; Respiratory System/pathology ; Risk Factors ; SARS-CoV-2 ; Serine Endopeptidases/genetics ; Severe Acute Respiratory Syndrome/pathology ; Thrombosis/pathology
Chemical Substances	HLA Antigens ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2020-06-27
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.13259
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Zs.A 677: Show issues

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Article ; Online: Systematic review and meta-analysis of the prognostic impact of lymph node micrometastasis and isolated tumour cells in patients with stage I-IIIA non-small cell lung cancer.

Hüyük, Melek / Fiocco, Marta / Postmus, Pieter E / Cohen, Danielle / von der Thüsen, Jan H

Histopathology

2022 Volume 82, Issue 5, Page(s) 650–663

Abstract: Lymph node micrometastases could be one of the reasons for the high recurrence rate after complete surgical resection in stage I-IIIA non-small cell lung cancer (NSCLC). The standard evaluation of a single haematoxylin and eosin (H&E) slide of a paraffin- ...

Abstract	Lymph node micrometastases could be one of the reasons for the high recurrence rate after complete surgical resection in stage I-IIIA non-small cell lung cancer (NSCLC). The standard evaluation of a single haematoxylin and eosin (H&E) slide of a paraffin-embedded section of a lymph node is insufficient for the detection of micrometastases, and there is a need for additional histopathological evaluation. The association of lymph node micrometastases with survival remains as yet unresolved. The aim of this systematic review and meta-analysis is to investigate if lymph node micrometastases and isolated tumour cells in patients with stage I-IIIA NSCLC, detected with multiple sectioning and/or immunohistochemistry (IHC) and/or reverse transcriptase polymerase chain reaction (RT-PCR), are associated with overall survival (OS) and disease-free survival (DFS) after surgical resection. We performed a meta-analysis of time-to-event outcomes based on 15 articles using ancillary techniques to detect micrometastases. We extracted the OS and DFS every 3-6 months after surgery, for patients with and without occult lymph node micrometastasis, from the survival curves published in each article. These data were used to reconstruct OS and DFS for 'micrometastasis' and 'no micrometastasis' groups. Based on all included studies that used IHC, serial sectioning, or RT-PCR, we found a 5-year OS of 55% (micrometastasis) vs. 75% (no micrometastasis), and a 5-year DFS of 53% (micrometastasis) vs. 75% (no micrometastasis). Patients with stage I-IIIA NSCLC with lymph node micrometastases detected by ancillary histopathological and molecular techniques have a significantly poorer OS and DFS compared to patients without lymph node micrometastases.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/pathology ; Prognosis ; Lung Neoplasms/pathology ; Neoplasm Micrometastasis/pathology ; Neoplasm Staging ; Lymph Nodes/pathology
Language	English
Publishing date	2022-11-09
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.14831
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Article ; Online: Predominance of M2 macrophages in organized thrombi in chronic thromboembolic pulmonary hypertension patients.

Koudstaal, Thomas / van den Bosch, Thierry / Bergen, Ingrid / Lila, Karishma / Bresser, Paul / Bogaard, Harm Jan / Boomars, Karin / Hendriks, Rudi / von der Thüsen, Jan

European journal of immunology

2024 , Page(s) e2350670

Abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. ... ...

Abstract	Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. Thrombotic lesions in CTEPH contain CD68
Language	English
Publishing date	2024-04-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202350670
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Increase in venous thromboembolism in SARS-CoV-2 infected lung tissue: proteome analysis of lung parenchyma, isolated endothelium, and thrombi.

Lopuhaä, Boaz V / Guzel, Coşkun / van der Lee, Anabel / van den Bosch, Thierry P P / van Kemenade, Folkert J / Huisman, Menno V / Kruip, Marieke J H A / Luider, Theo M / von der Thüsen, Jan H

Histopathology

2024 Volume 84, Issue 6, Page(s) 967–982

Abstract: Aims: COVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed proteomics analysis on SARS-CoV-2 infected lung tissue.! ...

Abstract	Aims: COVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed proteomics analysis on SARS-CoV-2 infected lung tissue. Methods: Liquid chromatography mass spectrometry was performed on SARS-CoV-2 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID-19 versus influenza) and thrombus morphology (embolism versus in situ). Influenza autopsy cases with pulmonary thrombi were used as controls. Results: Compared to influenza controls, both analyses of COVID-19 whole-tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID-19 lung tissue. Analysis of isolated COVID-19 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that in situ thrombi have significant upregulation of coronavirus pathogenesis proteins. Conclusions: The decrease in platelet activation pathways in severe COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, in situ thrombi show upregulation of various proteins related to SARS-CoV-2 pathogenesis compared to thromboemboli, which may indicate increased in situ pulmonary thrombosis in COVID-19. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of in situ thrombosis in severe COVID-19.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/complications ; COVID-19/pathology ; Proteome ; Venous Thromboembolism/complications ; Venous Thromboembolism/pathology ; Influenza, Human/complications ; Influenza, Human/pathology ; Lung/pathology ; Pulmonary Embolism/complications ; Pulmonary Embolism/pathology ; Thrombosis/pathology
Chemical Substances	Proteome
Language	English
Publishing date	2024-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.15143
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Article ; Online: Genomic characterization and detection of potential therapeutic targets for peritoneal mesothelioma in current practice.

van Kooten, Job P / Dietz, Michelle V / Dubbink, Hendrikus Jan / Verhoef, Cornelis / Aerts, Joachim G J V / Madsen, Eva V E / von der Thüsen, Jan H

Clinical and experimental medicine

2024 Volume 24, Issue 1, Page(s) 80

Abstract: Peritoneal mesothelioma (PeM) is an aggressive tumor with limited treatment options. The current study aimed to evaluate the value of next generation sequencing (NGS) of PeM samples in current practice. Foundation Medicine F1CDx NGS was performed on 20 ... ...

Abstract	Peritoneal mesothelioma (PeM) is an aggressive tumor with limited treatment options. The current study aimed to evaluate the value of next generation sequencing (NGS) of PeM samples in current practice. Foundation Medicine F1CDx NGS was performed on 20 tumor samples. This platform assesses 360 commonly somatically mutated genes in solid tumors and provides a genomic signature. Based on the detected mutations, potentially effective targeted therapies were identified. NGS was successful in 19 cases. Tumor mutational burden (TMB) was low in 10 cases, and 11 cases were microsatellite stable. In the other cases, TMB and microsatellite status could not be determined. BRCA1 associated protein 1 (BAP1) mutations were found in 32% of cases, cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) and neurofibromin 2 (NF2) mutations in 16%, and ataxia-telangiectasia mutated serine/threonine kinase (ATM) in 11%. Based on mutations in the latter two genes, potential targeted therapies are available for approximately a quarter of cases (i.e., protein kinase inhibitors for three NF2 mutated tumors, and polyADP-ribose polymerase inhibitors for two ATM mutated tumors). Extensive NGS analysis of PeM samples resulted in the identification of potentially effective targeted therapies for about one in four patients. Although these therapies are currently not available for patients with PeM, ongoing developments might result in new treatment options in the future.
MeSH term(s)	Humans ; Mesothelioma/diagnosis ; Mesothelioma/drug therapy ; Mesothelioma/genetics ; Lung Neoplasms/genetics ; Mesothelioma, Malignant ; Mutation ; Genomics ; Biomarkers, Tumor/genetics ; Peritoneal Neoplasms/diagnosis ; Peritoneal Neoplasms/drug therapy ; Peritoneal Neoplasms/genetics
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2024-04-20
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2053018-3
ISSN	1591-9528 ; 1591-8890
ISSN (online)	1591-9528
ISSN	1591-8890
DOI	10.1007/s10238-024-01342-y
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Article ; Online: ALK in Mesothelioma: To FISH or Not to FISH?

Cornelissen, Robin / Dubbink, Hendrikus J / von der Thüsen, Jan H

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2020 Volume 15, Issue 10, Page(s) e168–e169

MeSH term(s)	Anaplastic Lymphoma Kinase/genetics ; Child ; Gene Rearrangement ; Humans ; Lung Neoplasms/genetics ; Mesothelioma/genetics ; Mesothelioma, Malignant ; Young Adult
Chemical Substances	Anaplastic Lymphoma Kinase (EC 2.7.10.1)
Language	English
Publishing date	2020-09-28
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2020.05.025
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Article ; Online: In Response to "Intratumor Distribution of Ki-67 Antigen Beyond Labeling Index for Clinical Decision Making: A New Way of Counting".

Belderbos, Robert A / Aerts, Joachim G J V / von der Thüsen, Jan H

JTO clinical and research reports

2021 Volume 2, Issue 9, Page(s) 100215

Language	English
Publishing date	2021-09-24
Publishing country	United States
Document type	Journal Article
ISSN	2666-3643
ISSN (online)	2666-3643
DOI	10.1016/j.jtocrr.2021.100215
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