Atypical spindle cell/pleomorphic lipomatous tumour: a clinicopathologic, immunohistochemical and molecular study of 55 cases, highlighting TP53 gene alterations as a genetic hallmark of atypical pleomorphic lipomatous tumour.

Aims: Atypical spindle cell lipomatous tumour (ASLT) and atypical pleomorphic lipomatous tumour (APLT) have been grouped together under the umbrella designation atypical spindle cell/pleomorphic lipomatous tumour (ASPLT) in the 2020 edition of the World Health Organization (WHO) Classification of Soft Tissue and Bone Tumours. They are thought to exist on a morphologic spectrum and share similar clinicopathologic and biological characteristics. The aim of this study was to further explore the genetic background of ASLTs and APLTs by employing DNA-based next-generation sequencing and immunohistochemistry, with a specific focus on the TP53 gene.

Prospective, multicenter validation of a platform for rapid molecular profiling of central nervous system tumors.

Molecular data integration plays a central role in central nervous system (CNS) tumor diagnostics but currently used assays pose limitations due to technical complexity, equipment and reagent costs, as well as lengthy turnaround times. We previously reported the development of Rapid-CNS, an adaptive-sampling-based nanopore sequencing workflow. Here we comprehensively validated and further developed Rapid-CNS for intraoperative use.

A nationwide comprehensive genomic profiling and molecular tumor board platform for patients with advanced cancer.

The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) study assessed the feasibility of using comprehensive genomic profiling (CGP) in clinical decision-making for patients with advanced cancers. This multi-center study enrolled 872 patients from 12 Belgian hospitals. CGP was performed on tumor tissues using a standardized CGP panel (523 genes) across nine laboratories with success in 93% of patients and a median turnaround time of 29 days.

Clinical, Morphologic, and Genomic Findings in Spitz Tumors With RET Fusion: A Series of 31 Cases.

RET-fused Spitz neoplasms represent a rare and poorly characterized category of Spitz tumors. Here we describe the clinical, histologic, and molecular findings of 31 Spitz neoplasms with RET fusion diagnosed as Spitz nevus (n = 16), atypical Spitz tumors (n = 13), and Spitz melanoma (n = 2). The lesions mainly occurred in children and young adults of both sexes with a predilection for the extremities.

Analysis of comprehensive genomic profiling of solid tumors with a novel assay for broad analysis in clinical diagnostics.

Somatic multigene analysis by next-generation sequencing (NGS) is routinely integrated in medical oncology for clinical decision-making. However, with the fast-growing number of recommended and required genes as well as pan-cancer biomarkers, small panels have become vastly insufficient. Comprehensive genomic profiling (CGP) is, thus, required to screen for clinically relevant markers.

Identification of potentially actionable genetic variants in epithelial ovarian cancer: a retrospective cohort study.

Ovarian cancer is the most lethal gynecologic malignancy, mainly due to late-stage diagnosis, frequent recurrences, and eventually therapy resistance. To identify potentially actionable genetic variants, sequencing data of 351 Belgian ovarian cancer patients were retrospectively captured from electronic health records. The cohort included 286 (81%) patients with high-grade serous ovarian cancer, 17 (5%) with low-grade serous ovarian cancer, and 48 (14%) with other histotypes.

Revealing loss in an emerging entity: report of two cases of PRRX1-rearranged mesenchymal tumours.

Aims: -rearranged mesenchymal tumours are a recently identified and rare subgroup of soft tissue neoplasms with distinct morphological features and genetic alterations. This study aims to further investigate the immunohistochemical profile and underlying genetic alterations in these tumours in order to get more insight on their underlying biology and the unique profile of these tumours.

Methods: Two new molecular confirmed cases of -rearranged mesenchymal tumours were thoroughly studied with immunohistochemical stainings (RB1, CD34, ALK and pan-TRK), fluorescence in situ hybridisation (FISH) and RNA-based next-generation sequencing.

Formalin-Fixed, Paraffin-Embedded-Targeted Locus Capture: A Next-Generation Sequencing Technology for Accurate DNA-Based Gene Fusion Detection in Bone and Soft Tissue Tumors.

Chromosomal rearrangements are important drivers in cancer, and their robust detection is essential for diagnosis, prognosis, and treatment selection, particularly for bone and soft tissue tumors. Current diagnostic methods are hindered by limitations, including difficulties with multiplexing targets and poor quality of RNA. A novel targeted DNA-based next-generation sequencing method, formalin-fixed, paraffin-embedded-targeted locus capture (FFPE-TLC), has shown advantages over current diagnostic methods when applied on FFPE lymphomas, including the ability to detect novel rearrangements.

High-grade endometrial stromal sarcoma-like' sarcoma in male: Does it exist? A case report and review of the literature.

We report an exceptional case of an undifferentiated round and spindle cell sarcoma, occurring in the periprostatic region of a 54-year-old male, with a 'high-grade endometrial stromal sarcoma-like' (HG-ESS) morphology and harboring a ZC3H7B::BCOR gene fusion identified by RNA-based next-generation sequencing. In this report, we describe the striking overlap of morphologic, immunohistochemical and molecular features of this current case and previously reported similar cases with ZC3H7B::BCOR fusion-positive HG-ESS, and discuss the differential diagnosis and possible pathogenesis of this unusual entity.

mRNA Capture Sequencing and RT-qPCR for the Detection of Pathognomonic, Novel, and Secondary Fusion Transcripts in FFPE Tissue: A Sarcoma Showcase.

We assess the performance of mRNA capture sequencing to identify fusion transcripts in FFPE tissue of different sarcoma types, followed by RT-qPCR confirmation. To validate our workflow, six positive control tumors with a specific chromosomal rearrangement were analyzed using the TruSight RNA Pan-Cancer Panel. Fusion transcript calling by FusionCatcher confirmed these aberrations and enabled the identification of both fusion gene partners and breakpoints.

Application of an Ultrasensitive NGS-Based Blood Test for the Diagnosis of Early-Stage Lung Cancer: Sensitivity, a Hurdle Still Difficult to Overcome.

Diagnosis of lung cancer requires histological examination of a tissue sample, which in turn requires an invasive procedure that cannot always be obtained. Circulating tumor DNA can be reliably detected in blood samples of advanced-stage lung cancer patients and might also be a minimally invasive alternative for early-stage lung cancer detection. We wanted to explore the potential of targeted deep sequencing as a test for the diagnosis of early-stage lung cancer in combination with imaging.

Malignant pleural mesothelioma with an EML4-ALK fusion: Expect the unexpected!

Case report of malignant pleural mesothelioma with an ALK gene rearrangement, detected by FISH and confirmed by RNA-based next-generation sequencing. The co-occurrence of ALK gene fusions with the more common genetic alterations in CDKN2A, NF2 and BAP1 has, to our best knowledge, not yet been described in malignant mesothelioma. Furthermore, this unexpected finding could suggest a potential target for therapy in this subset of malignant mesotheliomas.

Primary Cutaneous Epithelioid Inflammatory Myofibroblastic Sarcoma Harboring RANBP2-ALK Fusion: Report of an Exceptional Case.

Inflammatory myofibroblastic tumors are rare soft tissue neoplasms with an uncertain biological behavior, derived from fibroblastic and myofibroblastic cells. In rare cases, a peculiar epithelioid phenotypic variant of this tumor is encountered, named epithelioid inflammatory myofibroblastic sarcoma (EIMS). EIMS has overlapping features with inflammatory myofibroblastic tumor but has been correlated with a more aggressive clinical course, a characteristic nuclear membrane or perinuclear anaplastic lymphoma kinase (ALK) immunostaining pattern and a very specific RANBP2-ALK fusion.

Undifferentiated sarcoma of bone with a round to epithelioid cell phenotype harboring a novel EWSR1-SSX2 fusion identified by RNA-based next-generation sequencing.

Due to the increased application of RNA-based next-generation sequencing techniques on bone and soft tissue round cell sarcomas new fusions are frequently found, thereby expanding the molecular landscape of these tumors. In this report, we describe and discuss the finding of an undifferentiated sarcoma of the bone with a round to epithelioid cell phenotype harboring a novel EWSR1-SSX2 fusion. Treatment of this new bone tumor entity according to the Euro Ewing 2012 protocol led to complete pathologic response.

MYCN-induced nucleolar stress drives an early senescence-like transcriptional program in hTERT-immortalized RPE cells.

MYCN is an oncogenic driver in neural crest-derived neuroblastoma and medulloblastoma. To better understand the early effects of MYCN activation in a neural-crest lineage context, we profiled the transcriptome of immortalized human retina pigment epithelial cells with inducible MYCN activation. Gene signatures associated with elevated MYC/MYCN activity were induced after 24 h of MYCN activation, which attenuated but sustained at later time points.

Extrauterine Mesonephric-like Neoplasms: Expanding the Morphologic Spectrum.

Mesonephric-like adenocarcinomas (MLA) are rare neoplasms arising in the uterine corpus and ovary which have been added to the recent 2020 World Health Organization Classification of Female Genital Tumors. They have similar morphology and immunophenotype and exhibit molecular aberrations similar to cervical mesonephric adenocarcinomas. It is debated as to whether they are of mesonephric or Mullerian origin.

Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer.

DNA mismatch repair deficiency (dMMR) testing is crucial for diagnosing Lynch syndrome and detection of microsatellite unstable (MSI) tumors eligible for immunotherapy. The aim of this study was to compare the relative diagnostic performance of three molecular MSI assays: polymerase chain reaction (PCR), MSI testing by Idylla and next-generation-sequencing (NGS) on 49 tumor samples (28 colorectal and 21 endometrial adenocarcinomas) versus immunohistochemistry (IHC). Discrepancies were investigated by MLH1 methylation analysis and integrated with germline results if available.

Intracranial myxoid mesenchymal tumor with EWSR1-CREB1 fusion.

Myxoid mesenchymal tumor with predilection for intracranial location harboring EWSR1 fusions with CREB family transcription factors is a recently described and exceedingly rare neoplasm. While some debate still exists whether this is a true separate entity or a myxoid variant of angiomatoid fibrous histiocytoma, these tumors still deserve separate attention due to localization, fairly distinct histology and higher incidence in the pediatric population. Data regarding outcome of these neoplasms are still sparse in medical literature.

Myxoid hepatocellular adenoma, a rare variant of hepatocellular adenoma with distinct imaging features: A case report with immunohistochemical and molecular analysis and literature review.

Preoperative imaging and histopathology, immunohistochemistry and molecular analysis after resection of 2 hepatocellular adenomas (HCAs) (20 and 2cm) in a 53-year-old female patient were performed. On imaging, the large lesion resembled a myxoid HCA, while the small lesion resembled a more conventional HCA with a small myxoid/fluid area. On microscopy, the large lesion showed cords and nests of hepatocytes embedded in abundant myxoid matrix, while the small lesion resembled a conventional HCA with small foci of myxoid change and serosities; both consistent with a myxoid HCA.

Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma.

Peritoneal spread indicates poor prognosis in patients with serous ovarian carcinoma (SOC) and is generally treated by surgical cytoreduction and chemotherapy. Novel treatment options are urgently needed to improve patient outcome. Clinically relevant cell lines and patient-derived xenograft (PDX) models are of critical importance to therapeutic regimen evaluation.