Tussen schijn en werkelijkheid

Het gebeurt niet vaak dat een patholoog contact heeft met patiënten of familie van patiënten. Enige tijd geleden werd ik gebeld door de vader van een baby die was geboren met een grote hersentumor die de hersenkamers voor een deel innam. Op het door de neurochirurg verwijderde weefsel stelde ik de diagnose carcinoom uitgaande van de plexus chorioideus. De plexus chorioideus is een structuur die in de hersenkamers thuishoort en het hersenvocht, ook wel de liquor geheten, produceert. Mijn diagnose was gebaseerd op enige gelijkenis van het tumorweefsel met die plexus chorioideus. Carcinomen van de plexus chorioideus zijn uitermate zeldzaam. Hoog in het lijstje van alternatieve diagnoses stond de zogenaamde AT/RT (afkorting van atypical teratoid/rhabdoid tumor), een tumor die onduidelijk is gedefi nieerd en waarvan het microscopisch beeld zeer variabel is. Ik had echter, afgezien van genoemde gelijkenis van het tumorweefsel met de plexus, nog een aantal argumenten om de tumor niet als een AT/RT te beschouwen. Omdat de chemotherapie, die wordt gegeven nadat chirurgische verwijdering heeft plaatsgevonden, anders is in het geval van een plexuscarcinoom dan van AT/RT begon de druk vanuit de kinderkliniek toe te nemen om een zekere diagnose te stellen.Rede, in verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar in de Neuropathologie aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 2 oktober 200

Tumor characteristics and biological behavior of oligodendroglioma

Whereas in astrocytomas grading results yielded satisfying clinico-pathological correlations, grading procedures were without acclaim in the oligodendroglia! tumor group. The reason for this might be that only small series of this uncommon neoplasm were studied, and delineation of oligodendroglia! tumors from mixed gliomas or astrocytic tumors was hampered with difficulties. In order to study the relationship between tumor size and survival, as well as tumor size and histopathologic grade, tumor volumes were calculated from the CT-scans of 43 oligodendrogliomas (paper 1). Although a good correlation between grade and survival was shown, no correlation between tumor size and survival or histopathologic grade was obtained. In paper 2 a comparison was made between the traditional grading system of Kernahan, and the recently developed grading system for oligodendrogliomas of Smith. In a retrospective study on 72 patients the grading results of both systems were related to the survival times of the patients. It was found that grading according to both systems yielded three groups of patients with significant differences in survival. Nevertheless, the grading system of Smith is preferred because of its lower inter-observer error. The prognostic value of DNA-flow cytometry and mitotic count was tested retrospectively on the paraffin-embedded material of 85 oligodendrogliomas (paper 3). The results of the DNA-flow cytometry neither correlated with survival, nor with the histopathological grades. The mitotic count, however, had relevance for the prognosis. Thus, the mitotic count is a valid parameter for grading oligodendrogliomas

Approved CAR T cell therapies

Two autologous chimeric antigen receptor (CAR) T cell therapies (Kymriah™ and Yescarta™) were recently approved by the FDA. Kymriah™ is for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute ly

The pleomorphic xanthoastrocytoma and its differential diagnosis: A study of five cases

__Abstract__ Five brain tumors with the histopathologic features of pleomorphic xanthoastrocytomas (PXAs) are presented. Computed tomography scans showed a remarkable homology. Two cases had atypical localizations for a PXA, while one 46-year-old patient did not conform to the normal age distribution of this tumor. Nevertheless, in these cases, the histopathology was always characteristic for PXA, a remarkable pleomorphism, in addition to simultaneous expression of glial fibrillary acidic protein and histiocytic markers in the various tumor cells. In one of the presented tumors, however, clusters of neoplastic neuronal cells were also found. In this particular case, differential diagnostic criteria to distinguish between a PXA and a desmoplastic infantile ganglioglioma are lacking

Unlocking molecular mechanisms and identifying druggable targets in matched-paired brain metastasis of breast and lung cancers

Introduction: The incidence of brain metastases in cancer patients is increasing, with lung and breast cancer being the most common sources. Despite advancements in targeted therapies, the prognosis remains poor, highlighting the importance to investigate the underlying mechanisms in brain metastases. The aim of this study was to investigate the differences in the molecular mechanisms involved in brain metastasis of breast and lung cancers. In addition, we aimed to identify cancer lineage-specific druggable targets in the brain metastasis. Methods: To that aim, a cohort of 44 FFPE tissue samples, including 22 breast cancer and 22 lung adenocarcinoma (LUAD) and their matched-paired brain metastases were collected. Targeted gene expression profiles of primary tumors were compared to their matched-paired brain metastases samples using nCounter PanCancer IO 360™ Panel of NanoString technologies. Pathway analysis was performed using gene set analysis (GSA) and gene set enrichment analysis (GSEA). The validation was performed by using Immunohistochemistry (IHC) to confirm the expression of immune checkpoint inhibitors. Results:Our results revealed the significant upregulation of cancer-related genes in primary tumors compared to their matched-paired brain metastases (adj. p ≤ 0.05). We found that upregulated differentially expressed genes in breast cancer brain metastasis (BM-BC) and brain metastasis from lung adenocarcinoma (BM-LUAD) were associated with the metabolic stress pathway, particularly related to the glycolysis. Additionally, we found that the upregulated genes in BM-BC and BM-LUAD played roles in immune response regulation, tumor growth, and proliferation. Importantly, we identified high expression of the immune checkpoint VTCN1 in BM-BC, and VISTA, IDO1, NT5E, and HDAC3 in BM-LUAD. Validation using immunohistochemistry further supported these findings. Conclusion: In conclusion, the findings highlight the significance of using matched-paired samples to identify cancer lineage-specific therapies that may improve brain metastasis patients outcomes.</p

Unlocking molecular mechanisms and identifying druggable targets in matched-paired brain metastasis of breast and lung cancers

Introduction: The incidence of brain metastases in cancer patients is increasing, with lung and breast cancer being the most common sources. Despite advancements in targeted therapies, the prognosis remains poor, highlighting the importance to investigate the underlying mechanisms in brain metastases. The aim of this study was to investigate the differences in the molecular mechanisms involved in brain metastasis of breast and lung cancers. In addition, we aimed to identify cancer lineage-specific druggable targets in the brain metastasis. Methods: To that aim, a cohort of 44 FFPE tissue samples, including 22 breast cancer and 22 lung adenocarcinoma (LUAD) and their matched-paired brain metastases were collected. Targeted gene expression profiles of primary tumors were compared to their matched-paired brain metastases samples using nCounter PanCancer IO 360™ Panel of NanoString technologies. Pathway analysis was performed using gene set analysis (GSA) and gene set enrichment analysis (GSEA). The validation was performed by using Immunohistochemistry (IHC) to confirm the expression of immune checkpoint inhibitors. Results:Our results revealed the significant upregulation of cancer-related genes in primary tumors compared to their matched-paired brain metastases (adj. p ≤ 0.05). We found that upregulated differentially expressed genes in breast cancer brain metastasis (BM-BC) and brain metastasis from lung adenocarcinoma (BM-LUAD) were associated with the metabolic stress pathway, particularly related to the glycolysis. Additionally, we found that the upregulated genes in BM-BC and BM-LUAD played roles in immune response regulation, tumor growth, and proliferation. Importantly, we identified high expression of the immune checkpoint VTCN1 in BM-BC, and VISTA, IDO1, NT5E, and HDAC3 in BM-LUAD. Validation using immunohistochemistry further supported these findings. Conclusion: In conclusion, the findings highlight the significance of using matched-paired samples to identify cancer lineage-specific therapies that may improve brain metastasis patients outcomes.</p

Overexpression of Colligin 2 in Glioma Vasculature is Associated with Overexpression of Heat Shock Factor 2

In previous studies we found expression of the protein colligin 2 (heat shock protein 47 (HSP47), SERPINH1) in glioma neovasculature while not in normal brain tissue. Generally, the regulation of heat shock gene expression in eukaryotes is mediated by heat shock factors (HSF). In mammals, three heat shock transcription factors, HSF-1, -2, and -4, have been isolated. Here we investigated the relation between the expression of colligin 2 and these heat shock factors at the mRNA level using real-time reverse transcriptase PCR (qRT-PCR) in different grades of astrocytic tumorigenesis, viz., low-grade glioma and glioblastoma. Endometrium samples, representing physiological angiogenesis, were included as controls. Since colligin 2 is a chaperon for collagens, the gene expression of collagen I (COL1A1) was also investigated. The blood vessel density of the samples was monitored by expression of the endothelial marker CD31 (PECAM1). Because NG2-immunopositive pericytic cells are involved in glioma neovascularization, the expression of NG2 (CSPG4) was also measured

Non-Small Cell Lung Cancer Brain Metastasis: The Link between Molecular Mechanisms and Novel Therapeutic Approaches

The prognosis of patients suffering from non-small cell lung carcinomas (NSCLC) worsens significantly when brain metastasis occurs. Seeding to the brain usually happens relatively early in the course of disease and therefore, new therapies anticipating this complication would result in considerable improvement in outcomes. In this review, we address recent molecular data of NSCLC with a focus on the risk of the formation of brain metastasis. Included is new data on the involvement of miRNAs and lncRNAs in the rise of the cerebral seeding of NSCLC. We summarize novel therapeutic approaches developed in the light of these recent molecular discoveries