Purity Independent Subtyping of Tumors (PurIST) Pancreatic Cancer Classifier: Analytic Validation of a 16-RNA Expression Signature Distinguishing Basal and Classical Subtypes.

The two major molecular subtypes of pancreatic adenocarcinoma reportedly have differential response to FOLFIRINOX-based therapy. To promote rapid assignment of basal versus classical subtypes, an array-based single-sample classifier assay was developed and applied to 74 formalin-fixed, paraffin-embedded biopsy or resection specimens of known subtype based on transcriptomics. The Purity Independent Subtyping of Tumors (PurIST) algorithm assigns subtype based on relative expression of 16 RNAs counted by RNA sequencing (RNAseq) versus more practical array-based NanoString nCounter Elements XT technology.

Increased tryptophan, but not increased glucose metabolism, predict resistance of pembrolizumab in stage III/IV melanoma.

Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1.

Clinical Laboratory Testing Practices in Diffuse Gliomas Prior to Publication of 2021 World Health Organization Classification of Central Nervous System Tumors.

Context.—: Integration of molecular data into glioma classification supports diagnostic, prognostic, and therapeutic decision-making; however, testing practices for these informative biomarkers in clinical laboratories remain unclear.

Objective.

Neoplastic Cellularity Assessment in Molecular Testing.

Context.—: Neoplastic cellularity assessment has become an essential component of molecular oncology testing; however, there are currently no best practice recommendations or guidelines for this potentially variable step in the testing process.

Objective.

The clinical significance of adenomatous polyposis coli (APC) and catenin Beta 1 (CTNNB1) genetic aberrations in patients with melanoma.

Background: Melanoma-intrinsic activated β-catenin pathway, the product of the catenin beta 1 (CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about the association between the adenomatous polyposis coli (APC) and CTNNB1 gene mutations in stage IV melanoma with immunotherapy response and overall survival (OS).

Methods: We examined the prognostic significance of somatic APC/CTNNB1 mutations in the Cancer Genome Atlas Project for Skin Cutaneous Melanoma (TCGA-SKCM) database.

Aberrant Expression and Subcellular Localization of ECT2 Drives Colorectal Cancer Progression and Growth.

ECT2 is an activator of RHO GTPases that is essential for cytokinesis. In addition, ECT2 was identified as an oncoprotein when expressed ectopically in NIH/3T3 fibroblasts. However, oncogenic activation of ECT2 resulted from N-terminal truncation, and such truncated ECT2 proteins have not been found in patients with cancer.

Mebendazole disrupts stromal desmoplasia and tumorigenesis in two models of pancreatic cancer.

The five-year survival rate for metastatic pancreatic cancer is currently only 3%, which increases to 13% with local invasion only and to 39% with localized disease at diagnosis. Here we evaluated repurposed mebendazole, an approved anthelminthic drug, to determine how mebendazole might work at the different stages of pancreatic cancer formation and progression. We asked if mebendazole could prevent initiation of pancreatic intraepithelial neoplasia precursor lesions, interfere with stromal desmoplasia, or suppress tumor growth and liver metastasis.

Melanoma-specific expression of the tumor suppressor proteins p16 and PTEN is a favorable prognostic factor in established melanoma brain metastases.

PTEN and p16 frequently undergo (epi)genetic aberrations in melanoma resulting in decreased, or absent, protein levels. We investigated the prognostic significance of these tumor suppressor genes in melanoma brain metastases (MBMs). Immunohistochemical analysis was performed on archived tissue sections from craniotomies.

Brain Tumor Microenvironment and Angiogenesis in Melanoma Brain Metastases.

Background: High tumor-infiltrating lymphocytes (TILs) and hemorrhage are important prognostic factors in patients who have undergone craniotomy for melanoma brain metastases (MBM) before 2011 at the University of Pittsburgh Medical Center (UPMC). We have investigated the prognostic or predictive role of these histopathologic factors in a more contemporary craniotomy cohort from the University of North Carolina at Chapel Hill (UNC-CH). We have also sought to understand better how various immune cell subsets, angiogenic factors, and blood vessels may be associated with clinical and radiographic features in MBM.

Olfactory neuroblastoma pulmonary metastasis presenting as a solitary pulmonary mass in an adult: A case report with pathologic correlation.

Pulmonary metastasis of an esthesioneuroblastoma is uncommon. In this report, we present a case of an esthesioneuroblastoma pulmonary metastasis in an adult. A 39-year-old man treated with surgical resection of olfactory neuroblastoma was found to have a solitary pulmonary mass on a surveillance computed tomography scan performed 5 years after undergoing primary surgery and radiation treatment.

Long-term Efficacy of Single-agent Vemurafenib for Pleomorphic Xanthoastrocytoma.

Pleomorphic xanthoastrocytoma is a malignant brain tumor that has a good prognosis with complete resection but does not respond well to chemotherapy if there is residual tumor. BRAF V600E mutations are common in pleomorphic xanthoastrocytomas and provide an additional means for treatment when excision is not possible. Monotherapy with the BRAF V600E inhibitor vemurafenib has only been reported in a small number of cases and mostly in adults.

Colonic epithelial miR-31 associates with the development of Crohn's phenotypes.

Background: Crohn's disease (CD) is highly heterogeneous, due in large part to variability in cellular processes that underlie the natural history of CD, thereby confounding effective therapy. There is a critical need to advance understanding of the cellular mechanisms that drive CD heterogeneity.

Methods: We performed small RNA sequencing of adult colon tissue from CD and NIBD controls.

Triple pathological findings in a surgically amenable patient with mesial temporal lobe epilepsy.

Mesial temporal sclerosis (MTS) is a well-recognized cause of intractable epilepsy; however, coexistence with focal cortical dysplasia (FCD) is less common. Middle fossa epidermoid cysts are rare and may involve the temporal lobe. Most epidermoids are clinically silent, slow-growing, and seldom associated with overt symptomatology, including seizures.

MicroRNAs Classify Different Disease Behavior Phenotypes of Crohn's Disease and May Have Prognostic Utility.

Background: There is a dire need for reliable prognostic markers that can guide effective therapeutic intervention in Crohn's disease (CD). We examined whether different phenotypes in CD can be classified based on colonic microRNA (miRNA) expression and whether miRNAs have prognostic utility for CD.

Methods: High-throughput sequencing of small and total RNA isolated from colon tissue from patients with CD and controls without Inflammatory Bowel Disease (non-IBD) was performed.

Metastatic melanoma in an esophagus demonstrating Barrett esophagus with high grade dysplasia.

Background: Metastatic melanoma involving the esophagus is rare; the occurrence of metastatic melanoma in a background of Barrett esophagus is rarer still. We report a case of an 80 year-old male who presented to our institution for workup of Barrett esophagus with high-grade dysplasia and who proved to have metastatic melanoma occurring in the background of Barrett esophagus, the first report of this kind, to our knowledge, in the English literature.

Case Presentation: An 80 year-old Caucasian male was diagnosed at an outside institution with Barrett's esophagus with high grade dysplasia and presented to our institution for therapy.

Endoscopic Endonasal Approach for Resection of Infundibular Granular Cell Tumor: Case Report and Literature Review.

Granular cell tumors of the pituitary and infundibular stalk are rare, slow growing tumors. Although usually asymptomatic, neurological deficits with chiasmatic compression can lead to clinical presentation. We describe a case in which a purely endoscopic endonasal approach was used for complete resection of an infundibular granular cell tumor with skull base reconstruction with a pedicled nasoseptal flap.

A novel small molecule that selectively inhibits glioblastoma cells expressing EGFRvIII.

Background: Mutations of the epidermal growth factor receptor (EGFR) are a possible molecular target for cancer therapy. EGFR is frequently amplified in glioblastomas and 30 to 40% of glioblastomas also express the deletion mutation EGFRvIII. This frequent oncogenic mutation provides an opportunity for identifying new anti-glioblastoma therapies.

Analysis of two translocation breakpoints and identification of a negative regulatory element in patients with Rieger's syndrome.

Background: Rieger's syndrome is an autosomal dominant disorder characterized by eye, tooth, and umbilical anomalies. A gene responsible for Rieger's syndrome, PITX2, has previously been cloned using two patients with balanced translocations, t(4;16) and t(4;11), with breakpoints that lie near the gene, but which do not interrupt it.

Methods: We sequenced both breakpoint regions on chromosome 4 and screened this area for novel genes.

Cytopathology of mesenchymal chondrosarcomas: a report and comparison of four patients.

Background: Mesenchymal chondrosarcoma (MC) is an infrequent neoplasm, representing approximately 1% of all chondrosarcomas. Cytologic descriptions of MCs have been confined to rare case reports. In the current report, the authors describe their experience with the cytologic features of four MCs: two primary tumors and two metastatic lesions.

Possible maternal inheritance of a common obstructive urinary tract anomaly. Report of a case of a woman with multiple urinary tract infections and two sons with posterior urethral valves.

Background: Posterior urethral valves (PUVs) are the most common cause of lower urinary tract obstruction in boys. Several prior reports have described PUV in siblings and twins, often with a variable phenotype.

Case: PUVs were found in two brothers.