Rebecca Hoesli

The Relationship between Jugular Bulb–Vestibular Aqueduct Dehiscence and Hearing Loss in Pediatric Patients

Objective. To determine the prevalence of jugular bulb and vestibular aqueduct dehiscence (JBVAD) in pediatric patients undergoing temporal bone computed tomography (CT) scans and to assess the relationship between JBVAD and hearing loss. Study Design. Cross-sectional study with chart review. Setting. Tertiary academic medical center. Subjects and Methods. All patients 18 years of age or younger who had undergone temporal bone CT scans and audiometric testing between 2004 and 2009 were retrospectively reviewed. JBVAD was determined by blinded review of CT images. Hearing loss was determined by review of audiometric data and was correlated with imaging findings. Results. CT images and audiometric data were available for review in 927 patients (1854 ears). Overall prevalence of JBVAD was 8.6%, with a prevalence of 6.6% in right ears and 3.6% in left ears. JBVAD was present in 8.3% and 7.1% of patients with and without sensorineural or mixed hearing loss, respectively (95% confidence interval [CI], -2.3% to 4.6%; P = .51). Similarly, JBVAD was present in 5.5% of ears with and 4.6% of ears without sensorineural or mixed hearing loss (95% CI, -1.1% to 2.9%; P = .37). Conclusion. The prevalence of JBVAD is 8.6% in pediatric patients undergoing temporal bone CT scans, 65% of which occur in the right ear. We were unable to identify any relationship between JBVAD and hearing loss. A major contribution to pediatric sensorineural hearing loss from JBVAD is therefore extremely unlikely.

Correlation of Crtc1/3-Maml2 fusion status, grade and survival in mucoepidermoid carcinoma

OBJECTIVE Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary glands. Tumor stage and grade have historically been important predictors of survival. An oncogenic CRTC1- or CRTC3-MAML2 gene fusion has been identified in a number of MECs. Historically, these gene fusions have been associated with lower grade tumors and better survival. However, reported gene fusion rates and prognosis varies widely across studies, and have not controlled for tumor grade. We sought to identify gene fusion rates and outcomes in our cohort of MEC patients. MATERIALS AND METHODS An IRB-approved retrospective cohort of patients with MEC was identified at the University of Michigan. Clinical, histologic, and outcome data was collected from medical records. RNA was isolated from formalin fixed paraffin-embedded tumor sections, and qRT-PCR was performed to identify CRTC1/3-MAML2 gene fusions. Sanger sequencing of qRT-PCR products was used to confirm gene fusions. RESULTS Overall, 90 patient MEC tumors were collected (58 low-grade, 25 intermediate-grade, and 7 high-grade). Gene fusions were identified in 59% (53/90) of tumors. On univariate and bivariate analysis, fusion status did not significantly associate with grade or survival. CONCLUSION We have identified a high rate of CRTC1/3-MAML2 gene fusions in a large cohort of MEC. We do not identify any correlation between fusion status with tumor grade or survival. These findings suggest further characterization of MECs is needed before considering the CRTC1/3-MAML2 gene fusion as a prognostic biomarker. Additional genetic drivers may account for survival and grade in MECs.

Surveilling the Potential for Precision Medicine-driven PD-1/PD-L1-targeted Therapy in HNSCC

Immunotherapy is becoming an accepted treatment modality for many patients with cancer and is now approved for use in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Despite these successes, a minority of patients with HNSCC receiving immunotherapy respond to treatment, and few undergo a complete response. Thus, there is a critical need to identify mechanisms regulating immune checkpoints in HNSCC such that one can predict who will benefit, and so novel combination strategies can be developed for non-responders. Here, we review the immunotherapy and molecular genetics literature to describe what is known about immune checkpoints in common genetic subsets of HNSCC. We highlight several highly recurrent genetic lesions that may serve as biomarkers or targets for combination immunotherapy in HNSCC.

Changing the paradigm：the potential for targeted therapy in laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma (LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21st century.

Genomic sequencing and precision medicine in head and neck cancers

Head and neck squamous cell carcinoma (HNSCC) remains a common and deadly disease. Historically, surgical and chemoradiation treatments have been met with modest success, and understanding of genetic drivers of HNSCC has been limited. With recent next generation sequencing studies focused on HNSCC, we are beginning to understand the genetic landscape of HNSCCs and are starting to identify and advance targeted options for patients. In this review, we describe current knowledge and recent advances in sequencing studies of HNSCC, discuss current limitations and future directions for further genomic analysis, and highlight the translational advances being undertaken to treat this important disease.

Eustachian tube duplication: A unique anomaly

Very few eustachian tube anomalies have been published in the literature and have consisted of descriptions of diverticula, hypoplasia/aplasia, fistula, or aberrant associated musculature. We present a girl with a novel anomaly consisting of a eustachian tube duplication that originates in the nasopharynx and exits posterior to a microtic and atretic ear. We review the literature on eustachian tube anomalies and also consider the derivation of this anomaly.

Proportion of CD4 and CD8 tumor infiltrating lymphocytes predicts survival in persistent/recurrent laryngeal squamous cell carcinoma

Tumor infiltrating lymphocytes (TILs) have been shown to be an important prognostic factor in patients with previously untreated head and neck cancer. After organ preservation therapy for laryngeal cancer and subsequent persistence/recurrence, the prognostic value of TILs is unknown. Our goal was to determine if TILs have value as a prognostic biomarker in patients with surgically salvageable persistent/recurrent laryngeal squamous cell carcinoma. Levels of TILs were quantified on tissue microarrays from 183 patients undergoing salvage total laryngectomy for persistent/recurrent laryngeal cancer after radiation or chemoradiation between 1997 and 2014. Demographic and clinical data were abstracted. Immunohistology evaluation included CD4, CD8, PDL-1, p16, CD31, Vimentin, EGFR, and p53. Elevated levels of either CD8 or CD4 positive TILs were associated with improved disease specific survival (CD8: HR 0.46, 95% CI 0.24-0.88, CD4: HR 0.43; 95% CI 0.21-0.89) and disease free survival (CD8: HR 0.53, 95% CI 0.29-0.94, CD4: HR 0.52; 95% CI 0.27-0.99). Levels of CD8 (HR 0.74; 95% CI 0.47-1.17) or CD4 (HR 0.66; 95% CI 0.40-1.08) TILs were not significantly associated with overall survival. In bivariate analysis, patients with elevated CD4 and/or CD8 TILs had significantly improved disease specific survival (HR 0.42; 95% CI 0.21-0.83) and disease free survival (HR 0.45; 95% CI 0.24-0.84) compared to patients with low levels of CD4 and CD8. PDL-1, p16, CD31, Vimentin, EGFR, and p53 were not significant prognostic factors. On multivariate analysis, elevated CD8 TILs were associated with improved disease specific survival (HR 0.35; 95% CI 0.14-0.88, p = .02) and disease free survival (HR 0.41; 95% CI 0.17-0.96, p = .04). CD8, and possibly CD4, positive TILs are associated with favorable disease free and disease specific survival for recurrent/persistent laryngeal cancer.

Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma

Total laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal.

Immunotherapy for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma has been found to be an immunosuppressive malignancy, with many defects in the host immune system contributing to the progression of disease. A greater understanding of these defects has lead to the identification and investigation of new therapeutic strategies, targeting immune system dysfunction in an effort to improve the outcomes of this disease. This article provides a brief review of the knowledge regarding the immune defects present in head and neck cancer, as well as a review of the current therapeutic strategies being investigated for use.

Coherent Raman Scattering Microscopy for Evaluation of Head and Neck Carcinoma

Objective We aim to describe a novel, label-free, real-time imaging technique, coherent Raman scattering (CRS) microscopy, for histopathological evaluation of head and neck cancer. We evaluated the ability of CRS microscopy to delineate between tumor and nonneoplastic tissue in tissue samples from patients with head and neck cancer. Study Design Prospective case series. Setting Tertiary care medical center. Subjects and Methods Patients eligible were surgical candidates with biopsy-proven, previously untreated head and neck carcinoma and were consented preoperatively for participation in this study. Tissue was collected from 50 patients, and after confirmation of tumor and normal specimens by hematoxylin and eosin (H&E), there were 42 tumor samples and 42 normal adjacent controls. Results There were 42 confirmed carcinoma specimens on H&E, and CRS microscopy identified 37 as carcinoma. Of the 42 normal specimens, CRS microscopy identified 40 as normal. This resulted in a sensitivity of 88.1% and specificity of 95.2% in distinguishing between neoplastic and nonneoplastic images. Conclusion CRS microscopy is a unique label-free imaging technique that can provide rapid, high-resolution images and can accurately determine the presence of head and neck carcinoma. This holds potential for implementation into standard practice, allowing frozen margin evaluation even at institutions without a histopathology laboratory.