Publications by authors named "Glenn Broeckx"

10 Publications

  • Page 1 of 1

An Incidental Finding of Congenital Pulmonary Airway Malformation Type 3 During a Forensic Autopsy for a Sudden Infant Death: A Case Report With a Brief Literature Review.

Am J Forensic Med Pathol 2021 Apr 7. Epub 2021 Apr 7.

From the Departments of Forensic Pathology Radiology Clinical Pathology, Antwerp University Hospital, Edegem Department of Pathology, Antwerp University, Wilrijk, Belgium.

Abstract: Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic airway malformation, is a developmental disorder of the lower respiratory tract. It is subdivided into 5 types based on clinical and pathologic features. Type 3, an adenomatoid type of CPAM, is the second rarest form of CPAM, occurring in approximately 5% of all CPAM cases. This article reports an autopsy of a nearly 11-week-old male infant, found unresponsive in bed with his mother. She had fallen asleep after breastfeeding a few hours prior. Although the autopsy and additional technical examinations did not uncover the exact cause of death, CPAM type 3 was eventually identified on histological examination. Taking into account the context of this case, in which accidental asphyxia/neglect could not be ruled out, it is thought that the presence of CPAM might have contributed to the demise of the infant. As CPAM is a rare congenital disorder, the diagnosis could easily be missed. Therefore, this article aims to raise awareness of this diagnosis and points out the clinical and pathologic features of this disorder.
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http://dx.doi.org/10.1097/PAF.0000000000000676DOI Listing
April 2021

The immunologic aspects in hormone receptor positive breast cancer.

Cancer Treat Res Commun 2020 29;25:100207. Epub 2020 Aug 29.

Multidisciplinary Oncologic Centre Antwerp [(MOCA)], Antwerp University Hospital, Edegem, Belgium; Center for Oncological Research (CORE), University of Antwerp, Wilrijk, Belgium.

Background:  Although hormone receptor positive/HER2-negative (HR +/HER2-) breast cancer is the most diagnosed breast cancer type, the immunologic aspects HR positive breast cancer (BC) has been neglected until recently.  The purpose of this paper is to review the current knowledge of the immune environment in HR positive BC and the potential use of immunotherapy in these patients.

Method: A computer-based literature research was carried out using PubMed, American Society of Clinical Oncology Annual Meeting (ASCO) and San Antonio Breast Cancer Symposium (SABCS).

Results: The tumour microenvironment (TME), with infiltrating immune cells, plays an important role in HR positive BC. However, the effects of these immune cells are different in the luminal cancers compared to the other breast cancer types. Even though PD-1 and PD-L1 are less expressed in HR positive BC, pathological complete response (pCR) was more often seen after PD-1 inhibitor treatment in patients with an increased expression. The studies support the assertion that endocrine therapy has immunomodulatory effect.

Conclusion: The reviewed literature indicates that immune cells play an important role in HR positive BC. Considerably more research is needed to determine the real effect of the TME in this patient group.
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http://dx.doi.org/10.1016/j.ctarc.2020.100207DOI Listing
August 2020

Cholesterol granuloma mimicking an anterior mediastinal tumor - a case report.

Acta Chir Belg 2020 Sep 9:1-2. Epub 2020 Sep 9.

Department of Thoracic- and Vascular surgery, Antwerp University Hospital, Antwerp, Belgium.

There are many different types of mediastinal masses, which makes it challenging to diagnose them. Furthermore, the clinical presentation can range from asymptomatic to life-threatening. We present the case of a 68-year-old male with an incidental finding of a tumor located in the anterior mediastinum. A computed tomography (CT) of the thorax and an 18-Fluorodeoxyglucose positron emission tomography (PET) suggested a thymoma, which is the most common primary tumor of the anterior mediastinum. The patient was scheduled for a robotic-assisted thoracoscopy (RATS) thymectomy. Both this procedure and the postoperative course were uneventful. The pathology report showed multiple cholesterol granulomas in the mediastinal fat. Furthermore, no malignancy (e.g. a thymoma) could be found. A cholesterol granuloma mimicking an anterior mediastinal tumor is extremely rare.
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http://dx.doi.org/10.1080/00015458.2020.1816672DOI Listing
September 2020

Cervicovaginal cellular angiofibroma.

BMJ Case Rep 2020 Jul 16;13(7). Epub 2020 Jul 16.

Department of Obstetrics and Gynecology, University Hospital Antwerp, Edegem, Antwerp, Belgium

Cellular angiofibroma is a rare type of benign mesenchymal tumour that arises mostly in middle-aged women. It needs to be distinguished from other neoplasms and has a predilection for the vulvovaginal region. To our knowledge, this is the first case of a cervical cellular angiofibroma. A 34-year-old nulligravid woman was referred with a large mass bulging in the fornix posterior. Ultrasound scanning and MRI showed a large solid mass projecting in the pouch of Douglas. Laparoscopic surgical excision was performed. Histopathological examination showed a well-demarcated, unencapsulated tumour, consisting of short fascicles of spindle cells in-between thick-walled medium-sized vessels. On immunohistochemistry, there was strong reactivity with antibodies against CD34 and oestrogen receptor. Angiofibromas are benign mesenchymal tumours mostly occurring in middle-aged women. They can cause abnormal swelling and uterine bleeding and need to be distinguished from other (malignant) neoplasms.
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http://dx.doi.org/10.1136/bcr-2020-235241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368490PMC
July 2020

Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients.

Cancers (Basel) 2020 Apr 2;12(4). Epub 2020 Apr 2.

Centre for Proteomics, University of Antwerp, 2020 Antwerpen, Belgium.

(1) Background: Therapeutic blocking of the interaction between programmed death-1 (PD-1) with its ligand PD-L1, an immune checkpoint, is a promising approach to restore the antitumor immune response. Improved clinical outcomes have been shown in different human cancers, including non-small cell lung cancer (NSCLC). Unfortunately, still a high number of NSCLC patients are treated with immunotherapy without obtaining any clinical benefit, due to the limitations of PD-L1 protein expression as the currently sole predictive biomarker for clinical use; (2) Methods: In this study, we applied mass spectrometry imaging (MSI) to discover new protein biomarkers, and to assess the possible correlation between candidate biomarkers and a positive immunotherapy response by matrix-assisted laser desorption/ionization (MALDI) MSI in 25 formalin-fixed paraffin-embedded (FFPE) pretreatment tumor biopsies (Biobank@UZA); (3) Results: Using MALDI MSI, we revealed that the addition of neutrophil defensin 1, 2 and 3 as pretreatment biomarkers may more accurately predict the outcome of immunotherapy treatment in NSCLC. These results were verified and confirmed with immunohistochemical analyses. In addition, we provide in-vitro evidence of the immune stimulatory effect of neutrophil defensins towards cancer cells; and (4) Conclusions: With proteomic approaches, we have discovered neutrophil defensins as additional prospective biomarkers for an anti-PD-(L)1 immunotherapy response. Thereby, we also demonstrated that the neutrophil defensins contribute in the activation of the immune response towards cancer cells, which could provide a new lead towards an anticancer therapy.
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http://dx.doi.org/10.3390/cancers12040863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225984PMC
April 2020

The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice.

J Pathol 2020 04 9;250(5):667-684. Epub 2020 Apr 9.

Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, TN, USA.

Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5406DOI Listing
April 2020

Clinical Performance of the Idylla MSI Test for a Rapid Assessment of the DNA Microsatellite Status in Human Colorectal Cancer.

J Mol Diagn 2020 03 24;22(3):386-395. Epub 2019 Dec 24.

Laboratory of Pathological Anatomy, Antwerp University Hospital (UZA), Edegem, Belgium; Center for Oncological Research Antwerp (CORE), University of Antwerp, Wilrijk, Belgium.

In this study, the clinical performance of the Idylla MSI test (investigational use only) was evaluated in 330 colorectal carcinoma samples (all stages). This test is fully automated, from formalin-fixed, paraffin-embedded slide to result, and gives a result in <2.5 hours. Compared with the Promega MSI Analysis System version 1.2, an overall agreement, sensitivity, and specificity of 99.7%, 98.7%, and 100%, respectively, was reached. Whereas seven samples were invalid with the Promega MSI Analysis System, only two were invalid with the Idylla MSI test. Compared with the historical immunohistochemistry (IHC) data, overall agreement, sensitivity, and specificity of 98.7%, 94.4%, and 100%, respectively, were observed. Tumor mutation burden analysis of the discordant IHC cases was in favor of the Idylla MSI test result in three of the four samples. Furthermore, for those cases where the IHC data were invalid or hard to interpret because sole loss of one DNA mismatch repair deficiency marker was observed, Idylla MSI test results were always valid and accurate. Herein, the Idylla MSI test has been shown to be an accurate, fast screening assay for the detection of microsatellite status in colorectal cancer patients, with a low number of invalid results.
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http://dx.doi.org/10.1016/j.jmoldx.2019.12.002DOI Listing
March 2020

Determination of the Potential Tumor-Suppressive Effects of in a Chemically Induced and in a Genetically Modified Intestinal Cancer Mouse Model.

Cancers (Basel) 2019 Aug 20;11(8). Epub 2019 Aug 20.

Center of Medical Genetics, University of Antwerp, Prins Boudewijnlaan 43/6, Edegem, BE-2650 Antwerp, Belgium.

(), also known as () and previously identified to be an inducer of regulated cell death, is frequently epigenetically inactivated in different cancer types, suggesting that is a tumor suppressor gene. In this study, we aimed to evaluate the tumor-suppressive effects of GSDME in two intestinal cancer mouse models. To mimic the silencing of by methylation as observed in human cancers, a knockout (KO) mouse was developed. The effect of GSDME on tumorigenesis was studied both in a chemically induced and in a genetic intestinal cancer mouse model, as strong evidence shows that GSDME plays a role in human colorectal cancer and representative mouse models for intestinal cancer are available. Azoxymethane (AOM) was used to induce colorectal tumors in the chemically induced intestinal cancer model ( = 100). For the genetic intestinal cancer model, mice were used ( = 37). In both experiments, the number of mice bearing microscopic proliferative lesions, the number and type of lesions per mouse and the histopathological features of the adenocarcinomas were compared between KO and wild type (WT) mice. Unfortunately, we found no major differences between KO and WT mice, neither for the number of affected mice nor for the multiplicity of proliferative lesions in the mice. However, recent breakthroughs on gasdermin function indicate that GSDME is an executioner of necrotic cell death. Therefore, it is possible that GSDME may be important for creating an inflammatory microenvironment around the tumor. This is in line with the trend towards more severe inflammation in WT compared to KO mice, that we observed in our study. We conclude that the effect of GSDME in tumor biology is probably more subtle than previously thought.
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http://dx.doi.org/10.3390/cancers11081214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721630PMC
August 2019

Next-generation protein analysis in the pathology department.

J Clin Pathol 2020 Jan 15;73(1):1-6. Epub 2019 Jul 15.

Department of Pathology, University Hospital of Antwerp, Antwerp, Belgium

Traditionally, immunohistochemistry (IHC) is used by pathologists to localise specific proteins or peptides in tissue slides. In the era of personalised medicine, however, molecular tissue analysis becomes indispensable for correct diagnosis, prognosis and therapeutic decision, not only on the DNA or mRNA level but also on the protein level. Combining molecular information with imaging presents many advantages. Therefore, matrix-assisted laser desorption/ionisation imaging mass spectrometry (MALDI IMS) is a promising technique to be added to the armamentarium of the pathologist. Here, we focus on the workflow, advantages and drawbacks of both MALDI IMS and IHC. We also briefly discuss a few other protein imaging modalities and give examples of applications.
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http://dx.doi.org/10.1136/jclinpath-2019-205864DOI Listing
January 2020

Malignant peritoneal mesothelioma: a review.

Transl Lung Cancer Res 2018 Oct;7(5):537-542

Department of Pathology, University Hospital of Antwerp, Edegem, Belgium.

Malignant peritoneal mesothelioma (MPM) is a very rare malignancy of the peritoneum and has a poor prognosis. Of all mesotheliomas, pleural mesothelioma is more common than MPM. In comparison to pleural mesothelioma, the link with asbestos exposure is weaker (33-50% >80%), but it is still the best-defined risk factor. MPM spreads predominantly expansive rather than infiltrative and symptoms are related to tumor spread within the abdominal cavity. Often, MPM is encountered incidentally by diagnostic imaging or by surgery. Computed tomography scan is widely accepted as a first line modality in diagnostic imaging. In diagnostic histopathology, MPM presents some challenges. Firstly, adequate clinical information is of utmost importance to consider the possibility of the diagnosis of MPM. Furthermore, a few morphological subtypes and variants exist. The most sensitive immunohistochemical markers are calretinin (100%), WT1 (94%) and CK5/6 (89%). The malignant character of immunohistochemically demonstrated mesothelial cells is not always obvious. This paradigm somewhat changed with the advent of immunohistochemical demonstration of BAP1 (BRCA-1 associated protein 1). Loss of BAP1 expression supports a diagnosis of malignancy. The gold standard in treatment remains cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Targetable molecular pathways in MPM are being identified. An exciting finding was the demonstration of ALK rearrangements in a small subset of patients with MPM and it is hoped for that at least this small subgroup of patients could benefit from treatment with ALK inhibitors. First-generation tyrosine kinase inhibitors against epidermal growth factor receptor (EGFR) did not show any significant activity in MPM. In contrast, nintedanib, an angiokinase inhibitor, improved progression-free survival and bevacizumab, a humanized anti-VEGF antibody increased overall survival in patients with MPM, when administered in combination with cisplatin and pemetrexed. Ongoing immunotherapy trials will offer a possible new treatment.
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http://dx.doi.org/10.21037/tlcr.2018.10.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204422PMC
October 2018