Molecular Subtypes of Head and Neck Cancer in Patients of African Ancestry.

PURPOSE: The purpose of this study was to better understand the complex molecular biomarkers and signatures of head and neck cancer (HNC) among Black patients and identify possible molecular changes associated with HNC disparities. EXPERIMENTAL DESIGN: Molecular subtypes and genomic changes in HNC samples from patients of African and European ancestry in The Cancer Genome Atlas, Memorial Sloan Kettering Cancer Center, Broad Institute, MD Anderson Cancer Center, and John Hopkins University were identified. Molecular features (genomic, proteomic, transcriptomic) associated with race and genomic alterations associated with clinical outcomes were determined. An independent cohort of HNC tumor specimens was used to validate the primary findings using IHC. RESULTS: Black patients were found to have a younger age at diagnosis, more aggressive tumor types, higher rates of metastasis, and worse survival compared with White patients. Black patients had fewer human papillomavirus-positive tumor types and higher frequencies of laryngeal subtype tumors. Higher frequencies of TP53, MYO18B, KMT2D, and UNC13C mutations and a lower frequency of PIK3CA mutations were observed in Black patients. Tumors of Black patients showed significant enrichment of c-MYC and RET-tyrosine signaling and amplifications. A significant increase in tumor expression of c-MYC in Black patients was observed and was associated with poor survival outcomes in the independent cohort. CONCLUSIONS: Novel genomic modifications and molecular signatures may be related to environmental, social, and behavioral factors associated with racial disparities in HNC. Unique tumor mutations and biological pathways have potential clinical utility in providing more targeted and individualized screening, diagnostic, and treatment modalities to improve health outcomes.

MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma.

We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into "early-stage" by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only (p < 0.001); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2-0.6; p=0.0005). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls (p < 0.0005). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients.

Diagnostic dilemma - sinonasal organizing hematoma.

Sinonasal organizing hematomas are benign lesions often mistaken for malignancy due to their aggressive appearance on diagnostic imaging and endoscopic findings that favor advanced disease. The destructive nature of this pathology paired with the rarity of the presentation often results in diagnostic deception that may escalate intervention planning and affect discussion of prognosis with patients. Herein, we present a case of a 56-year-old male with left-sided nasal obstruction and daily epistaxis, where computed tomography imaging revealed heterogeneous opacification of the left maxillary sinus, erosion of the left inferior orbital wall and extension into the nasal cavity. Although clinical and radiographic presentations of sinonasal organizing hematomas can be managed definitively with endoscopic intervention, there is a need to increase awareness of this entity among clinicians to improve our prognostic counseling with patients.

Oral Pseudomyogenic Hemangioendothelioma: Case Report and Review of the Literature.

Pseduomyogenic hemangioendothelioma (PMH) is a vascular neoplasm of intermediate biological potential first described by Hornick and Fletcher (Am J Surg Pathol 35:190-201, 2011). Despite its initial categorization as a malignant entity, PMH often demonstrates an indolent behavior profile, and thus was classified as a rarely metastasizing endothelial neoplasm in the 2013 WHO Classification of Tumors of Soft Tissue and Bone. It is a tumor primarily of skin and soft tissue, with most reported cases involving the trunk or extremities. To date, only one case of PMH involving the oral cavity has been reported. Herein, we present a case of PMH involving the mandibular gingiva and vestibule of a 33-year-old female and discuss the salient features of this entity.