Regulation of Head and Neck Squamous Cancer Stem Cells by PI3K and SOX2.

Background: We have an incomplete understanding of the differences between cancer stem cells (CSCs) in human papillomavirus-positive (HPV-positive) and -negative (HPV-negative) head and neck squamous cell cancer (HNSCC). The PI3K pathway has the most frequent activating genetic events in HNSCC (especially HPV-positive driven), but the differential signaling between CSCs and non-CSCs is also unknown.

Methods: We addressed these unresolved questions using CSCs identified from 10 HNSCC patient-derived xenografts (PDXs).

Profiling of 149 Salivary Duct Carcinomas, Carcinoma Ex Pleomorphic Adenomas, and Adenocarcinomas, Not Otherwise Specified Reveals Actionable Genomic Alterations.

Purpose: We sought to identify genomic alterations (GA) in salivary gland adenocarcinomas, not otherwise specified (NOS), salivary duct carcinomas (SDC), carcinoma ex pleomorphic adenoma (ca ex PA), and salivary carcinoma, NOS.

Experimental Design: DNA was extracted from 149 tumors. Comprehensive genomic profiling (CGP) was performed on hybridization-captured adaptor ligation-based libraries of 182 or 315 cancer-related genes plus introns from 14 or 28 genes frequently rearranged for cancer and evaluated for all classes of GAs.

Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer.

Context: Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3-5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases.

Survival outcomes with concurrent chemoradiation for elderly patients with locally advanced head and neck cancer according to the National Cancer Data Base.

Background: The overall survival (OS) benefit of concurrent chemoradiotherapy (CRT) for head and neck squamous cell carcinoma patients older than 70 years is debated. This study examines the outcomes of elderly patients receiving CRT versus radiotherapy (RT) alone.

Methods: The National Cancer Data Base was queried for patients older than 70 years with nonmetastatic oropharyngeal, laryngeal, or hypopharyngeal cancer (T3-4 or N(+)).

Sphenoid Wing Meningioma With Extraocular Muscle Involvement Mimicking Idiopathic Orbital Inflammation.

Meningiomas are slow growing, typically benign, tumors originating from arachnoid cap cells. Specifically, sphenoid wing or spheno-orbital meningiomas infiltrate the lesser wing of the sphenoid, lateral orbital wall, and orbital roof with occasional extension to the superior orbital fissure, optic canal, anterior clinoid process, and middle cranial fossa where neurologic and ophthalmologic functions are impaired by compressive injury. The extraocular muscles are rarely involved.

A pilot study of cetuximab and the hedgehog inhibitor IPI-926 in recurrent/metastatic head and neck squamous cell carcinoma.

Background: This phase 1, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), antitumor activity, and molecular correlates of IPI-926, a Hedgehog pathway (HhP) inhibitor, combined with cetuximab in patients with relapsed/metastatic squamous cell carcinoma of the head and neck.

Patients And Methods: Cetuximab was given with a 400mg/m(2) loading dose followed by 250mg/m(2) weekly. IPI-926 was given daily starting two weeks after cetuximab initiation.

PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer.

Regional metastatic differentiated thyroid cancer (mDTC) provides a unique model in which to study the tumor-immune interface. These lymph node metastases persist for years, generally without progression to distant metastases. Although the immune system likely impedes disease progression, it is unsuccessful in eliminating disease.

Skull invaders: when surgical pathology and neuropathology worlds collide.

Skull and dura serve as effective barriers to penetration by most tumors, often preventing masses originating intracranially from extending into the contiguous bone and soft tissues, or those arising in head and neck regions from extending into the dura and brain tissue. We review our 15-year experience with extracranial tumors that had sufficiently invaded adjacent skull, dura, or brain from the "outside-in" to require a neurosurgeon to participate in the surgical resection and discuss our 40 cases in context with the literature. Sinonasal-origin tumors (n = 17) and cutaneous tumors (n = 10) were the most frequent skull-invaders.

Hedgehog signaling alters reliance on EGF receptor signaling and mediates anti-EGFR therapeutic resistance in head and neck cancer.

The EGF receptor (EGFR)-directed monoclonal antibody cetuximab is the only targeted therapy approved for the treatment of squamous cell carcinoma of the head and neck (HNSCC) but is only effective in a minority of patients. Epithelial-to-mesenchymal transition (EMT) has been implicated as a drug resistance mechanism in multiple cancers, and the EGFR and Hedgehog pathways (HhP) are relevant to this process, but the interplay between the two pathways has not been defined in HNSCC. Here, we show that HNSCC cells that were naturally sensitive to EGFR inhibition over time developed increased expression of the HhP transcription factor GLI1 as they became resistant after long-term EGFR inhibitor exposure.

Molecular Pathology of Non-Small Cell Lung Cancer.

This review offers an overview of the molecular pathology of lung cancer, with a focus on analyses that are most commonly part of the current clinical testing paradigm. Molecular testing of lung cancer has proved integral to the success of new targeted therapies, and their use is now commonplace in treatment selection. Traditional pathologic evaluation, however, plays a major role in these advances and serves an equally critical role to aid in determining optimal therapy.

Genetic characterization of gliomas arising in patients with multiple sclerosis.

The co-occurrence of gliomas and multiple sclerosis (MS) in the same patient is uncommon, but a well-reported phenomenon. Most have been high grade astrocytic tumors that developed after the diagnosis of MS, leading authors to postulate that chronic gliosis in demyelinative plaques might be the underlying substrate for secondary induction of a glial neoplasm. Until recently, however, genetic tools have not been available to test the hypothesis that high grade gliomas might arise from longstanding chronic gliosis, with transformation to low grade glioma, and eventually GBM, i.