Novel HMGA2::COL14A1 Fusion Identified in Xanthogranulomatous Epithelial Tumor/Keratin-Positive Giant Cell Tumor.

Xanthogranulomatous epithelial tumor (XGET)/Keratin-positive giant cell tumor (KP-GCT) represents a spectrum of recently described neoplasms characterized by a proliferation of distinctive mononuclear cells expressing keratin within a background of osteoclast-like giant cells, mixed inflammatory cells, and a variably prominent xanthogranulomatous component. Recent studies demonstrated a recurrent HMGA2::NCOR2 fusion in many cases. We herein describe a case of XGET/KP-GCT arising in the right femoral head of a 19-year-old male harboring a rare novel HMGA2::COL14A1 fusion.

SARCP, a Clinical Next-Generation Sequencing Assay for the Detection of Gene Fusions in Sarcomas: A Description of the First 652 Cases.

An amplicon-based targeted next-generation sequencing (NGS) assay for the detection of gene fusions in sarcomas was developed, validated, and implemented. This assay can detect fusions in targeted regions of 138 genes and BCOR internal tandem duplications. This study reviews our experience with testing on the first 652 patients analyzed.

Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients.

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease.

Sarcomas Harboring EWSR1::PATZ1 Fusions: A Clinicopathologic Study of 17 Cases.

Soft tissue sarcomas harboring EWSR1::PATZ1 are a recently recognized entity with variable morphology and a heterogeneous immunohistochemical profile. We studied 17 such tumors. The tumors occurred in 12 men and 5 women (median age, 50 years; range, 15-71 years), involved the thoracoabdominal soft tissues (14 cases; 82%), lower extremities (2 cases; 12%), and tongue (1 case; 6%), and ranged from 0.

EWSR1::POU2AF3(COLCA2) Sarcoma: An Aggressive, Polyphenotypic Sarcoma With a Head and Neck Predilection.

EWSR1::POU2AF3 (COLCA2) sarcomas are a recently identified group of undifferentiated round/spindle cell neoplasms with a predilection for the head and neck region. Herein, we report our experience with 8 cases, occurring in 5 men and 3 women (age range, 37-74 years; median, 60 years). Tumors involved the head/neck (4 cases), and one each the thigh, thoracic wall, fibula, and lung.

Fusion-driven Spindle Cell Rhabdomyosarcomas of Bone and Soft Tissue: A Clinicopathologic and Molecular Genetic Study of 25 Cases.

The evolving classification of rhabdomyosarcoma (RMS) now includes spindle cell RMS (SRMS). Bone/soft tissue SRMS often harbor TFCP2, or less often MEIS1 rearrangements. We studied 25 fusion-driven SRMS involving bone (n = 19) and soft tissue (n = 6).

Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile.

Objective: To identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.

Methods: We searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of and expression and sequence variations in , , or (ECPPF) to prognostically stratify MSI-H/NSMP ECs.

Transcriptomic and immunophenotypic characterization of two cases of adamantinoma-like Ewing sarcoma of the thyroid gland.

Introduction: Adamantinoma-like Ewing sarcoma (ALES) is a rare aggressive malignancy occasionally diagnosed in the thyroid gland. ALES shows basaloid cytomorphology, expresses keratins, p63, p40, frequently CD99, and harbours the t(11;22) EWSR1::FLI1 translocation. There is debate on whether ALES resembles more sarcoma or carcinoma.

Extraenteric Malignant Gastrointestinal Neuroectodermal Tumor-A Clinicopathologic and Molecular Genetic Study of 11 Cases.

Malignant gastrointestinal neuroectodermal tumors (MGNETs), also known as "gastrointestinal clear cell sarcoma-like tumors", are very rare, aggressive sarcomas characterized by enteric location, distinctive pathologic features, and EWSR1/FUS::ATF1/CREB1 fusions. Despite identical genetics, the clinicopathologic features of MGNET are otherwise quite different from those of clear cell sarcoma of soft parts. Only exceptional extraenteric MGNET (E-MGNET) has been reported.

ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification: Profiling high-risk subtypes of histomorphologically low-risk and treatment-insensitive endometrioid endometrial cancer.

In endometrial cancer, occult high-risk subtypes (rooted in histomorphologically low-risk disease) with insensitivity to adjuvant therapies impede improvements in therapeutic efficacy. Therefore, we aimed to assess the ability of molecular high-risk (MHR) and low-risk (MLR) ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification to profile recurrence in early, low-risk endometrioid endometrial cancer (EEC) and insensitivity to platinum-based chemotherapy or radiotherapy (or both) in high-risk EEC. Using The Cancer Genome Atlas endometrial cancer database, we identified 192 EEC cases with available DNA sequencing and RNA expression data.

Molecular and Immunophenotypic Correlates of Metastatic Epithelioid Angiomyolipoma Include Alterations of TP53, RB1, and ATRX.

Context.—: Epithelioid angiomyolipomas (eAMLs) are rare tumors of the kidney that occur in patients with tuberous sclerosis complex or in a sporadic setting; a subset of these tumors exhibit metastatic behavior.

Objective.

Evaluating the Significance of Pancreatobiliary Fluorescence In Situ Hybridization Polysomy on Prognosis in De Novo Cholangiocarcinoma.

Introduction: We recently developed a fluorescence in situ hybridization probe set for evaluating suspicious biliary and pancreatic duct strictures (PB-FISH). We aimed to determine whether PB-FISH results in biliary brush cytology specimens are associated with outcomes of patients with cholangiocarcinoma (CCA).

Methods: We performed a retrospective study of patients with CCA tested by PB-FISH from January 2015 to August 2018.

A novel WWTR1::AFF2 fusion in an intra-abdominal soft tissue sarcoma with associated endometriosis.

Application of molecular testing in clinical practice has led to significant advances in the classification of soft tissue sarcomas. Despite remarkable progress, there are still challenging cases that remain unclassified. In this study, we present an unusual spindle cell sarcoma arising in the abdominal cavity of a 37-year-old female.

Gene fusions in gastrointestinal tract cancers.

Fusion genes have been identified in a wide array of human neoplasms including hematologic and solid tumors, including gastrointestinal tract neoplasia. A fusion gene is the product of parts of two genes that are joined together following a deletion, translocation, or chromosomal inversion. Together with single nucleotide variants, insertions, deletions, and amplification, fusion genes represent one of the key genomic mechanisms for tumor development.

Automation of hybridization and capture based next generation sequencing library preparation requires reduction of on-deck bead binding and heated wash temperatures.

Capture-based library preparation for next generation sequencing (NGS) offers a balance between sequencing depth and bioinformatics cost of analysis. Liquid handling automation enhances the reliability of the library preparation process by reducing sample-to-sample variation and substantially enhances throughput, particularly when it can be employed in a 'walk-away' fashion with limited hands-on interaction. This requires complex series of mixing and heating steps like those utilized in capture chemistries to happen on the liquid handler.

Assessment of Risk of Hereditary Predisposition in Patients With Melanoma and/or Mesothelioma and Renal Neoplasia.

Importance: In BAP1 tumor predisposition syndrome, clear cell renal cell carcinoma (RCC) is frequently associated with melanoma and/or mesothelioma, while germline MITF p.E318K alterations are being increasingly reported in melanoma/RCC. Limited data exist on the co-occurrence of melanoma and/or mesothelioma with renal neoplasia and the prevalence of associated germline alterations.

Polymorphous Low-Grade Neuroepithelial Tumor of the Young (PLNTY): Molecular Profiling Confirms Frequent MAPK Pathway Activation.

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and frequent mitogen-activated protein kinase (MAPK) pathway activation. We molecularly profiled 13 cases with diagnostic histopathological features of PLNTY (10 female; median age, 16 years; range, 5-52). Patients frequently presented with seizures (9 of 12 with available history) and temporal lobe tumors (9 of 13).