Publications by authors named "Kyle Mannion"

30 Publications

  • Page 1 of 1

Neuroendocrine carcinomas of the head and neck: A small case series.

Am J Otolaryngol 2021 Feb 17;42(4):102992. Epub 2021 Feb 17.

Department of Otolaryngology - Head and Neck Surgery, Vanderbilt University Medical Center, 1215 21st Ave S, Nashville, TN 37232, United States of America. Electronic address:

Introduction: Neuroendocrine tumors of the head and neck are rare and arise either from epithelial or neuronal origin. Debate continues over the classification systems and appropriate management of these pathologies.

Objective: By investigating a small set of cases of high grade epithelial-derived neuroendocrine tumors of the head and neck (neuroendocrine carcinomas or NEC) from one institution, we compare survival rates of NEC of the head and neck to pulmonary NEC.

Methods: We identified patients from pathology records with neuroendocrine carcinomas of the head and neck and retrospectively collected clinical data as well as immunohistochemical (IHC) staining data.

Results: We identified 14 patients with NEC, arising from the parotid (n = 5), nasal cavity (n = 4), larynx (n = 2), and other regions (n = 2). One additional patient had NEC arising in two sites simultaneously (parotid and nasal). Staining patterns using IHC were relatively consistent across specimens, showing reactivity to chromogranin and synaptophysin in 73% and 100% of specimens, respectively. Treatment courses varied across patients and included combinations of surgery, chemotherapy, and/or radiation. The overall survival rate at 1, 2, and 5 years of these patients was 56%, 56%, and 43% with a mean follow-up time of 2.12 years.

Conclusion: Compared to NEC arising in the lung, this subset of patients had better survival rates, but worse survival rates than the more common squamous cell carcinoma of the head and neck.
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http://dx.doi.org/10.1016/j.amjoto.2021.102992DOI Listing
February 2021

Association of Social Determinants of Health with Time to Diagnosis and Treatment Outcomes in Idiopathic Subglottic Stenosis.

Ann Otol Rhinol Laryngol 2021 Feb 25:3489421995283. Epub 2021 Feb 25.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Objectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients.

Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence.

Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression.

Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.
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http://dx.doi.org/10.1177/0003489421995283DOI Listing
February 2021

Application of the Milan System for Reporting Pediatric Salivary Gland Cytopathology: Analysis of histologic follow-up, risk of malignancy, and diagnostic accuracy.

Cancer Cytopathol 2021 Feb 17. Epub 2021 Feb 17.

Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: The diagnosis and management of salivary gland tumors in pediatric patients can be challenging. The utility of fine-needle aspiration (FNA) cytopathology and the performance of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) in this age group have not been systematically assessed. The paucity of data has contributed to the controversial role of FNA cytopathology in the presurgical management of these patients.

Methods: The authors retrospectively analyzed 104 pediatric salivary gland FNAs (2000-2020). A correlation with the available histopathologic follow-up (n = 54) was performed. The distribution percentages, the risk of neoplasm (RON), and the risk of malignancy (ROM) were assessed for each category of the MSRSGC.

Results: The overall sensitivity, specificity, negative predictive value, and positive predictive value of pediatric salivary gland FNAs were 80%, 97%, and 92%, respectively. The RON values for the nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories were 60%, 11%, 100%, 100%, 100%, 100%, and 100%, respectively, whereas the ROM values were 0%, 11%, 100%, 6%, 67%, 100%, and 100%, respectively. The percentage of nonneoplastic FNAs was greater in comparison with the adult population (52% vs 8%). All neoplasms in patients aged 0 to 10 years were malignant, whereas benign neoplasms occurred only in patients aged ≥11 years; this supported an inverse correlation between age and malignancy rate in salivary gland neoplasms.

Conclusions: FNA cytopathology demonstrates excellent diagnostic performance in differentiating malignant and benign pediatric salivary gland lesions. The MSRSGC is a valuable tool for standardization of the reporting and preoperative risk stratification of these lesions.
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http://dx.doi.org/10.1002/cncy.22415DOI Listing
February 2021

Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect.

Front Oncol 2020 2;10:566315. Epub 2020 Dec 2.

Department of Otolaryngology - Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, United States.

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.

Patients And Methods: Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent change in tumor volume from pretreatment to posttreatment CT scan. Responders were defined as those with a 10% reduction in the volume of the primary tumor or lymph nodes (LN). Pathologic treatment effect (PTE) was defined as the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor area.

Results: Sixteen of 32 patients (50%) with pathologic evidence of LN involvement exhibited discordant PTE between primary sites and LN. In four patients with widely discordant adjacent LN, increased PTE was associated with increased infiltration of tumor CD8 T cells and CD163 macrophages, whereas stromal regulatory T cells were associated with low nodal PTE. RVR correlated with PTE at both primary tumor (slope = 0.55, < 0.001) and in LN (slope = 0.62, < 0.05). 89% (16/18) of radiographic non-responders with T1-T3 primary sites had no (n = 7) or minimal PTE (n = 9), whereas 15/17 (88%) of radiographic responders had moderate (n = 12) or complete (n = 3) PTE.

Conclusion: Nivolumab often induces discordant treatment effects between primary tumor sites and metastatic lymph nodes within subjects. This treatment discordance was also demonstrated in adjacent lymph nodes, which may correlate with local immune cell makeup. Finally, although these data were generated by a relatively small population size, our data support the use of early radiographic response to assess immunotherapy treatment effect in HNSCC.
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http://dx.doi.org/10.3389/fonc.2020.566315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738605PMC
December 2020

Ultrasound Training for Head and Neck Surgeons in Rural Kenya: A Feasibility Study.

J Surg Educ 2020 Jul - Aug;77(4):866-872. Epub 2020 Mar 4.

Department of Otolaryngology - Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.

Objective: To determine the feasibility of training otolaryngologists to perform head and neck ultrasound in low- and middle-income countries over a short timeframe.

Design: Prospective cohort evaluating an ultrasound training course for otolaryngologists in low- and middle-income countries.

Setting: Surgical training camp for otolaryngologists in semirural Kenya.

Methods: Participants were prospectively recruited to participate in an ultrasound training course during a 2-week surgical training camp. They performed baseline ultrasound exams (9-item test, 5-point scale) with no assistance, followed by didactic sessions teaching ultrasound techniques. Participating surgeons then performed head and neck ultrasound exams on patients in clinic or in the operating room with direct supervision. Postcourse ultrasounds were performed, and the results of these tests were compared to baseline exams.

Results: Eight surgeons were enrolled out of a total of 13 (62%). Three were attending surgeons (37.5%), 1 enrollee was a head and neck surgery fellow, and 4 were senior residents (50%). Six of 8 surgeons were from Kenya. The mean precourse test score was 25 (range 21-30) compared to a mean postcourse test score of 40 (range 37-45, p < 0.005). All participants significantly improved their scores, with a mean improvement of 16 points (range 10-23).

Discussion: Otolaryngologists are uniquely equipped to learn head and neck ultrasound given their familiarity with the anatomy and pathology in this region. Training physicians without prior experience can be done even over short timeframes. Early training should focus on ultrasound, with later stages of training focusing on pathology.
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http://dx.doi.org/10.1016/j.jsurg.2020.02.005DOI Listing
March 2020

Transcervical sonography and human papillomavirus 16 E6 antibodies are sensitive for the detection of oropharyngeal cancer.

Cancer 2020 06 4;126(11):2658-2665. Epub 2020 Mar 4.

Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Human papillomavirus 16 (HPV-16) E6 seropositivity is a promising early marker of human papillomavirus-driven oropharyngeal cancer (HPV-OPC), yet more sensitive imaging modalities are needed before screening is considered. The objective of this study was to determine the sensitivity of transcervical sonography (TCS) for detecting clinically apparent HPV-OPC in comparison with computed tomography (CT) and positron emission tomography (PET)/CT.

Methods: Fifty-one patients with known or suspected HPV-OPC without prior treatment underwent oropharyngeal TCS and blood collection (for HPV multiplex serology testing). Eight standard sonographic images were collected; primary-site tumors were measured in 3 dimensions if identified. Each patient underwent a full diagnostic workup as part of standard clinical care. The pathologic details, HPV status, final staging, and imaging findings were abstracted from the medical record. The sensitivity of each imaging modality was compared with the final clinical diagnosis (the gold standard).

Results: Twenty-four base of tongue cancers (47%), 22 tonsillar cancers (43%), and 2 unknown primary cancers (4%) were diagnosed; 3 patients (6%) had no tumors. All p16-tested patients were positive (n = 47). Primary-site tumors were correctly identified in 90.2% (95% confidence interval [CI], 78.6%-96.7%) with TCS, in 69.4% (95% CI, 54.6%-81.7%) with CT, and in 83.3% (95% CI, 68.6%-93.0%) with PET/CT. TCS identified tumors in 10 of 14 cases missed by CT and recognized the absence of tumors in 3 cases for which CT or PET/CT was falsely positive. The smallest sonographically identified primary-site tumor was 0.5 cm in its greatest dimension; the average size was 2.3 cm. Among p16-positive patients, 76.1% (95% CI, 61.2%-87.4%) were seropositive for HPV-16 E6.

Conclusions: TCS and HPV-16 E6 antibodies are sensitive for the diagnosis of HPV-OPC.
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http://dx.doi.org/10.1002/cncr.32799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829679PMC
June 2020

Incidence of pedicle ossification in osseous free flap reconstruction in the head and neck.

Oral Oncol 2020 Apr 28;103:104611. Epub 2020 Feb 28.

University of Nevada - Las Vegas, Department of Otolaryngology - Head and Neck Surgery, Las Vegas, NV, USA.

Background: There are several reports of ossification occurring along the pedicle of fibular free flaps in head and neck microvascular reconstruction, but the incidence of pedicle ossification of other osseous flaps in head and neck surgery has never been investigated.

Methods: A retrospective chart review was conducted for all patients undergoing free flap reconstruction in the head and neck between 2005 and 2016. Patients were included if they had reconstruction with an osseous free flap and if they had computed tomography (CT) scans at least 1 month post-operatively. Available CT images were reviewed for each patient.

Results: Three-hundred thirty four osteocutaneous free flaps were performed. The average age was 64 years (range 8-89). There was slight male predominance with 63.5% of the cohort being male (n = 212). One hundred fifty-five patients had fibular flaps (45%), 108 had radial forearm flaps (34%) and 71 had scapular flaps (21%). One hundred fibulas had available imaging, 73 forearms had available imaging, and 44 scapulas had imaging post-operatively. Of the images reviewed, pedicle ossification was identified in 21 fibular flaps (21%). None of the radial forearm or scapular flaps developed pedicle ossification.

Discussion: Pedicle ossification is relatively common in osteocutaneous free flap reconstruction and is uniquely associated with fibular. The presence of pedicle ossification is benign and does not compromise the flap, though it can create concern in cancer surveillance as the lesion is often identified as a new neck mass. As such, head and neck surgeons should be aware of this relatively frequent finding.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104611DOI Listing
April 2020

Spontaneous Rupture of the Internal Carotid Artery Owing to an Aberrant Styloid Process in an Identical Twin.

JAMA Otolaryngol Head Neck Surg 2020 04;146(4):385-386

Division of Head and Neck, Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.

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http://dx.doi.org/10.1001/jamaoto.2019.4790DOI Listing
April 2020

Salivary Gland NUT Carcinoma with Prolonged Survival in Children: Case Illustration and Systematic Review of Literature.

Head Neck Pathol 2021 Mar 19;15(1):236-243. Epub 2020 Feb 19.

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, USA.

NUT (midline) carcinoma is a rare, highly aggressive, poorly differentiated carcinoma that characteristically harbors a rearrangement of the NUTM1 gene. Most of these tumors occur in adolescents and young adults, arise from the midline structures of the thorax, head, and neck, and are associated with extremely poor outcomes. Rare cases originating from salivary glands have been reported with clinicopathologic features comparable to NUT carcinoma of other sites. Outcome studies regarding this subgroup are currently lacking. We report a case of NUT carcinoma arising in a submandibular gland of a 12-year-old boy. Diagnosis was confirmed by fluorescence in situ hybridization demonstrating fusion of the BRD4 (19p13.12) and NUTM1 (15q14) gene loci. A systematic review of all previously reported salivary gland NUT carcinomas (n = 15) showed exclusive occurrence of pediatric cases (n = 6) in males compared to adult patients (n = 9, male: female = 1:2; p < 0.05). The median survival was 24 and 4 months for pediatric and adult patients, respectively (95% confidence interval was 8-24 and 1-7 months, respectively; p < 0.01). The 1-year overall survival was 67% for pediatric and 11% for adult patients. Among all NUT carcinomas, pediatric salivary gland tumors may represent a distinct clinical subset associated with male predilection and comparatively prolonged survival.
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http://dx.doi.org/10.1007/s12105-020-01141-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010040PMC
March 2021

Comparative Treatment Outcomes for Patients With Idiopathic Subglottic Stenosis.

JAMA Otolaryngol Head Neck Surg 2020 01;146(1):20-29

Department of Otolaryngology-Head and Neck Surgery, Head and Neck Institute, Cleveland Clinic, Cleveland, Ohio.

Importance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research.

Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease.

Design, Setting, And Participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook.

Main Outcomes And Measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications.

Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk.

Conclusions And Relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.
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http://dx.doi.org/10.1001/jamaoto.2019.3022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824232PMC
January 2020

Tissue Fixation Conditions for p16 Immunohistochemistry and Human Papillomavirus RNA In Situ Hybridization in Oropharyngeal Squamous Cell Carcinoma.

Head Neck Pathol 2020 Sep 18;14(3):637-644. Epub 2019 Oct 18.

Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, 3020D Vanderbilt University Hospital, Nashville, TN, 37232-7415, USA.

Human papillomavirus (HPV) has become a critical prognostic biomarker in oropharyngeal squamous cell carcinoma (OPSCC). While retrospective studies suggest that p16 immunohistochemistry and even HPV RNA in situ hybridization work well on tissues and tumors from a variety of labs and various fixation conditions, no formal study of fixation conditions has been performed to date. We took surgically resected specimens from three p16 and HPV RNA in situ hybridization positive OPSCC patients, divided their fresh tumors into small pieces, and varied the time to formalin fixation as 1, 3, 6, 24, and 48 h. Tumors were either held moistened at room temperature or were refrigerated. After fixation and processing, routine hematoxylin and eosin slides were generated and p16 immunohistochemistry and RNA in situ hybridization performed. All three tumors were nonkeratinizing and had strong and diffuse p16 expression at immediate fixation, which, surprisingly, remained positive for all fixation times and conditions and despite significant degeneration at the later points for two of the patients while for one, the nuclear signal dropped out of most cells at early and mid time points, particularly at room temperature, causing false negatives. HPV RNA in situ hybridization stayed positive in all specimens up to 48 h of cold ischemic time refrigerated and even at room temperature, except for overtly autolyzed tumor regions. These findings help to establish that, at least for standard nonkeratinizing, p16 and HPV RNA strongly positive OPSCC patients, and using the most common tests in clinical practice, relatively lenient time to fixation may be acceptable if it cannot be avoided. However, for some patients, p16 immunohistochemistry may be sensitive to signal loss with autolysis. HPV RNA in situ hybridization, in particular, seems remarkably resistant to pretest cold ischemic times.
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http://dx.doi.org/10.1007/s12105-019-01090-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413959PMC
September 2020

Head and Neck Ultrasound in Otolaryngology Surgical Missions.

Ear Nose Throat J 2019 Oct-Nov;98(9):535-536. Epub 2019 Sep 25.

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

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http://dx.doi.org/10.1177/0145561319864553DOI Listing
April 2020

Color Doppler Ultrasonography for Monitoring a Free Flap Anastomosis During a Head and Neck Surgical Camp.

Ear Nose Throat J 2021 Mar 23;100(3):160-161. Epub 2019 Sep 23.

Department of Otolaryngology-Head and Neck Surgery, 12328Vanderbilt University Medical Center, Nashville, TN, USA.

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http://dx.doi.org/10.1177/0145561319864556DOI Listing
March 2021

Hypopharyngeal Skin Cancer Following Total Laryngectomy and Pectoralis Flap Reconstruction: Case Report and Literature Review.

Head Neck Pathol 2019 Dec 19;13(4):643-647. Epub 2019 Mar 19.

Department of Otolaryngology - Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Although early complications of microvascular free flaps and regional pedicled flaps of the head and neck are well described in the literature, there is relatively limited knowledge regarding their long-term complications. We describe the case of a 62-year-old gentleman who underwent primary resection and adjuvant radiation therapy for supraglottic squamous cell carcinoma who subsequently underwent salvage total laryngectomy with pectoralis major muscle flap reconstruction. During a later esophageal dilation for complaints of dysphagia, a new exophytic lesion of the hypopharynx was biopsied on endoscopy. The lesion was excised via transoral robotic surgery with final pathology revealing squamous cell carcinoma completely confined to the skin paddle of the pectoralis flap and arising from the epidermis of the skin flap. No further therapy was undertaken and there has been no evidence of recurrence 2 years after resection. Synchronous cutaneous malignancy is a rare complication of free and pedicled flap reconstruction, however its diagnosis is increasing. Given the concern for recurrent mucosal tumors arising in the upper aerodigestive tract which may require extensive resection with or without adjuvant therapy, it is important to determine the etiology of the underlying malignancy to guide appropriate treatment.
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http://dx.doi.org/10.1007/s12105-019-01029-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854126PMC
December 2019

Early onset oral tongue squamous cell carcinoma: Associated factors and patient outcomes.

Head Neck 2019 06 11;41(6):1952-1960. Epub 2019 Jan 11.

Vanderbilt University Medical Center, Department of Otolaryngology, Nashville, Tennessee, USA.

Background: Incidence of oral tongue squamous cell carcinoma (OTC) is rising among those under age 50 years. The etiology is unknown.

Methods: A total of 395 cases of OTC diagnosed and/or treated at Vanderbilt University Medical Center between 2000 and 2017 were identified. Of those, 113 (28.6%) were early onset (age < 50 years). Logistic regression was used to identify factors associated with early onset OTC. Cox proportional hazards models evaluated survival and recurrence.

Results: Compared to typical onset patients, patients with early onset OTC were more likely to receive multimodality treatment (surgery and radiation; adjusted odds ratio [aOR], 2.7; 95% confidence interval [CI], 1.2-6.3) and report a history of snuff use (aOR, 5.4; 95% CI, 1.8-15.8) and were less likely to report a history of cigarette use (aOR, 0.5; 95% CI, 0.2-0.9). Early onset patients had better overall survival (adjusted hazard ratio, 0.6).

Conclusions: This is the largest study to evaluate factors associated with early onset OTC and the first to report an association with snuff.
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http://dx.doi.org/10.1002/hed.25650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010313PMC
June 2019

Survival Outcomes in T4aN0M0 Mandibular Gingival Squamous Cell Carcinoma Treated with Surgery Alone.

Otolaryngol Head Neck Surg 2019 05 1;160(5):870-875. Epub 2019 Jan 1.

1 Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Objectives: To measure disease-free, disease-specific, and overall survival among patients with T4aN0M0 mandibular gingival squamous cell carcinoma who were treated with surgery alone.

Study Design: Case series with chart review.

Setting: Tertiary care center.

Subjects And Methods: A retrospective chart review was performed of all adult patients treated surgically with an oral cavity composite resection between January 2005 and March 2017. Among other data, patient preoperative characteristics were recorded (eg, age, sex, smoking history, alcohol use, and clinical stage); operative notes were reviewed to determine tumor subsite involvement, reconstruction method, and intraoperative surgical complications; and pathology reports were evaluated for various pathologic findings. Survival outcomes were determined with Kaplan-Meier analysis.

Results: The mean follow-up was 18.5 months (range, 0.1-100). The 1- and 5-year disease-free survival rates were 90.5% and 84.5%, respectively, while the 1- and 5-year disease-specific survival rates were 87.8% and 81.9%. The 1- and 5-year overall survival rates were 86.4% and 80.6%.

Conclusions: Patients with T4aN0M0 squamous cell carcinoma of the mandibular gingiva treated with surgery alone have a 5-year overall survival of 80.6%. Treatment with surgery alone obviates morbidities associated with adjuvant therapy while upholding survival outcomes.
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http://dx.doi.org/10.1177/0194599818821892DOI Listing
May 2019

Cumulative incidence of neck recurrence with increasing depth of invasion.

Oral Oncol 2018 12 20;87:36-42. Epub 2018 Oct 20.

Department of Otolaryngology, Vanderbilt University Medical Center, 7209 Medical Center East - South Tower, 1215 21st Avenue South, Nashville, TN 37232-8605, USA; Division of Head and Neck Surgery, Vanderbilt Bill Wilkerson Center, 1215 21st Ave South, Nashville, TN 37232, USA.

Objective: To determine if there is a critical depth of invasion that predicts micrometastasis in early oral tongue cancer.

Methods: Retrospective series identifying patients undergoing primary surgical resection of T1 or T2 oral tongue cancer who elected against neck treatment between 2000 and 2015. Cox proportional-hazard model compared the relative hazard and cumulative incidence of recurrence to depth of invasion. The model used a 2 parameter quadratic effect for depth that was chosen based on Akaike's information criterion.

Results: Ninety-three patients were identified with T1 or T2 oral tongue squamous cell carcinoma and clinically N0 neck undergoing glossectomy without elective neck treatment. 61% were male and median age was 60 years. Median follow up was 45 months, and 76 patients had at least two years of follow up. Thirty-six of 76 patients recurred (47.4%), with 15 recurring in the oral cavity (19.7%) and 21 developing nodal metastasis (27.6%). Cox proportional-hazards quadratic polynomial showed increasing hazard of recurrence with depth of invasion and the cumulative incidence increased sharply within the range of data from 2 to 6 mm depth of invasion.

Conclusions: Depth of invasion is significantly associated with nodal metastasis and has been added to the 8th AJCC staging guidelines. Variable depths of invasion have been associated with regional metastasis; however, there is likely not a critical depth that predicts neck recurrence due to progressive hazards and cumulative risk of occult metastasis. The risk of regional metastasis is likely much greater than previously believed and increases progressively with increasing depth.
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http://dx.doi.org/10.1016/j.oraloncology.2018.10.015DOI Listing
December 2018

Early onset oral tongue cancer in the United States: A literature review.

Oral Oncol 2018 12 14;87:1-7. Epub 2018 Oct 14.

Vanderbilt University Medical Center, Department of Otolaryngology, 1215 21st Ave S, Nashville, TN 37232, USA; Vanderbilt University Medical Center, 2525 West End Ave, Suite 300, Nashville, TN, 37203, USA. Electronic address:

The incidence of early onset oral tongue squamous cell carcinoma (OTC) has been increasing in the United States, and no clear etiology has been identified. Studies on this topic have generally been small and presented varied results. The goal of this review is to analyze and synthesize the literature regarding early onset OTC risk factors, outcomes, and molecular analyses within the US. To date, studies suggest that early onset OTC patients tend to have less heavy cigarette use than typical onset patients, but there may be an association between early onset OTC and smokeless tobacco (chewing tobacco and snuff) use. Early onset OTC is associated with similar or possibly improved survival compared to typical onset OTC. There has been no evidence to support a significant role for human papillomavirus in development of early onset OTC. Further research with larger cohorts of these patients is needed to better characterize this disease entity.
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http://dx.doi.org/10.1016/j.oraloncology.2018.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039330PMC
December 2018

Surgical outreach and microvascular surgery in developing countries.

Oral Oncol 2018 06 30;81:69-74. Epub 2018 Apr 30.

Vanderbilt University Medical Center, Department of Otolaryngology - Head and Neck Surgery, 1211 Medical Center Drive, Nashville, TN 37232, United States.

Due to the discrepancy between surgical demand and resources in Low-Middle Income Countries (LMIC), surgical outreach programs (SOP) have increased in popularity. In these resource-constrained healthcare environments, the resources necessary to perform basic head and neck procedures are often lacking, and offering microvascular reconstruction adds yet another level of complexity. Here we discuss the difficulties and challenges in establishing a SOP abroad and more specifically some of the challenges specific to microvascular reconstruction - including patient selection, burden of cost, lack of infrastructure and equipment, and patient follow up and outcomes. Although challenges certainly exist, we present the feasibility and the benefit for patient care as well as the role it can play in the foundation development of a low-resource region. The goals of the SOP must be well-defined, and incorporating microvascular surgery can be used as an adjunct to enhance the development of many aspects of the LMIC healthcare system. We present a model of care in which the initial focus is centered on providing safe care to these patients undergoing complex procedures, but after the development of a strong foundation, the focus can begin to include program sustainability and education.
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http://dx.doi.org/10.1016/j.oraloncology.2018.04.004DOI Listing
June 2018

Evaluation of CT Changes in the Head and Neck After Cancer Treatment: Development of a Measurement Tool.

Lymphat Res Biol 2018 Feb;16(1):69-74

2 Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee.

Background: The late effect continuum of lymphedema and fibrosis (LEF) affects more than 70% of patients after treatment for head and neck cancer (HNC). LEF is associated with symptom burden and decreased function and quality of life. Although surveillance imaging is common posttreatment, objective assessment of soft tissues is not, likely due to the lack of objective evaluation methods and understanding of the significance of LEF. We undertook the development of a tool to measure LEF using CT scans in HNC patients.

Methods And Results: We developed a CT measurement tool assessing sites of soft tissue damage secondary to tumor, surgery, or radiation. The tool was applied to pre- and posttreatment CT scans for 10 HNC patients. The data were reviewed, and the initial tool was modified. Ten additional patients' scans were assessed using the revised tool. The tool was modified further after data review by an expert panel and was then applied to scans from all 20 patients. The final tool included 11 items as follows: grading of fat stranding at 6 sites (axial reconstruction images, scale 0-2), measurement of epiglottic thickness (sagittal images, scale mm), and measurement of prevertebral soft tissue thickness at C3 (sagittal images, scale mm). A total of 176 CT scans were evaluated from 20 patients (range 4-14 examinations/patient). Preliminary data demonstrated face validity.

Conclusions: The final LEF assessment tool (CT-LEFAT) provides a standardized method for assessing critical sites that are involved by LEF. Studies to assess reliability and validity are ongoing.
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http://dx.doi.org/10.1089/lrb.2017.0024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810430PMC
February 2018

The expanding role of scapular free-flaps.

Curr Opin Otolaryngol Head Neck Surg 2017 Oct;25(5):411-415

Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Purpose Of Review: The review evaluates the expanding role of scapular free flaps and its application in various complex head and neck defects.

Recent Findings: The recent literature published focuses on the use of three-dimensional modeling for maxillectomy defects, expanded uses in both the megaflap, the various application of the scapular tip flap, and the feasibility of osseointegrated implants.

Summary: The subscapular system of flaps remains a versatile option in head and neck reconstruction. It continues to be one of the best options for large defects requiring generous soft tissue, muscle, and bone. Three-dimensional modeling is currently being applied to complex maxillary defects resulting in increased accuracy and efficiency of reconstruction. Expanded uses have also adopted the latissimus dorsi muscle in conjunction with the scapular bony flap to be used in large defects with resulting decreased fistula rates. Finally, there is sufficient evidence that supports the use of dental implantation into the scapula bone with successful retention rates.
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http://dx.doi.org/10.1097/MOO.0000000000000393DOI Listing
October 2017

Assessment of musculoskeletal impairment in head and neck cancer patients.

Support Care Cancer 2017 07 13;25(7):2085-2092. Epub 2017 Feb 13.

Division of Hematology Oncology, Department of Medicine, Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN, 37232, USA.

Purpose: This study aims to describe the types of musculoskeletal impairment in head and neck cancer survivors and to evaluate objective and subjective measures of musculoskeletal impairment and identify areas of need in future studies.

Methods: This is a cross-sectional pilot study of 29 head and neck cancer patients who were treated with resection and reconstruction. Subjective measures of musculoskeletal impairment (Neck Disability Index, Shoulder Pain and Disability Index, Vanderbilt Head and Neck Symptom Survey, General Symptom Survey) were collected and compared to objective measures (Cervical Range of Motion Device, Inter-incisal Distance). Digital photography was used to assess the severity of postural abnormalities. Findings were summarized using descriptive statistical and graphical methods.

Results: The majority of patients in this cohort suffered from neck disability (69%). Thirty-five percent of patients had shoulder pain and disability. Cervical range of motion deficits were observed in all directions. Inter-incisal distance averaged 33.4 mm and inversely correlated with self-reported jaw and trismus symptoms. Digital photography identified shoulder misalignment in 93% of subjects, head tilt in 89% of subjects, and postural deviation in 68% of subjects.

Conclusion: Musculoskeletal impairment is a significant side effect in head and neck cancer survivors that results in chronic neck pain, shoulder disability, trismus, and postural deficits. Tools to describe postural deficits are needed.
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http://dx.doi.org/10.1007/s00520-017-3603-1DOI Listing
July 2017

A Prospective Study of the Lymphedema and Fibrosis Continuum in Patients with Head and Neck Cancer.

Lymphat Res Biol 2016 12 15;14(4):198-205. Epub 2016 Jun 15.

2 School of Medicine, Vanderbilt University , Nashville, Tennessee.

Background: The purpose of this study was to determine the prevalence and nature of internal, external, and combined lymphedema and fibrosis in patients with head and neck cancer (HNC).

Materials And Methods: We obtained consent from 100 patients newly diagnosed with having cancer of the head and neck for a 4-year, prospective, longitudinal descriptive study. Recruitment began in August 23, 2010, and the study was completed in April 24, 2014. Eighty-three were evaluated at regular intervals from preradiation therapy to 18 months post-treatment. Percentage developing external, internal, or both types of lymphedema and/or fibrosis and trajectories of the severity of external, internal, or both types of lymphedema and/or fibrosis were determined.

Results: Before treatment, lymphedema rates were the following: external: 62.7%, internal: 41.7%, or combined: 29.2%, and/or fibrosis: 42.2%. Ranges of lymphedema late-effect rates were even higher: external: 81.9%-90.1%, internal: 80.4%-89.4%, combined: 70.6%-80.9%, and fibrosis: 66.7%-77.4%. Approximately 75% had a late-effect trajectory characterized by moderate to severe external or internal lymphedema; ∼47% had moderate to severe fibrosis.

Conclusion: Lymphatic and soft tissue complications of HNC occur not only post-treatment but also before treatment. They are ubiquitous throughout the first 18 months post-treatment, with greater than 90% of patients in our study experiencing some form of internal, external, or combined lymphedema, and over half of those patients developing fibrosis. Further research regarding these conditions is indicated.
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http://dx.doi.org/10.1089/lrb.2016.0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178009PMC
December 2016

Internal Lymphedema Correlates with Subjective and Objective Measures of Dysphagia in Head and Neck Cancer Patients.

J Palliat Med 2016 09 26;19(9):949-56. Epub 2016 May 26.

1 Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee.

Background: Tumor/treatment-related internal lymphedema (IL) and/or external lymphedema (EL) are associated with functional deficits and increased symptom burden in head and neck cancer patients (HNCP). Previously, we noted association between EL/IL and patient-reported dysphagia using the Vanderbilt Head and Neck Symptom Survey (VHNSS) version 1.0.

Objective: To determine the relationship between IL/EL and subjective and objective measures of swallowing function.

Methods: Eighty-one HNCP completed: (1) VHNSS version 2.0, including 13 swallowing/nutrition-related questions grouped into three clusters: swallow solids (ss), swallow liquids (sl), and nutrition(nt); (2) physical assessment of EL using Foldi scale; (3) endoscopic assessment of IL using Patterson scale (n = 56); and (4) modified barium swallow study rated by dysphagia outcome and severity scale (DOSS) and in conjunction with a swallow evaluation by National Outcomes Measurement System (NOMS). Examinations were performed at varied time points to assess lymphedema spectrum, from baseline (n = 15, 18.1%) to 18 months post-therapy (n = 20, 24.1%).

Results: VHNSS swallow/nutrition items scores correlated with NOMS/DOSS ratings (p < 0.001). Highest correlation was with NOMS: ss (-0.73); sl (-0.61); nt (-0.56). VHNSS swallow/nutrition scores correlated with maximum grade of swelling for any single structure on Patterson scale: ss (0.43; p = 0.001); sl (0.38; p = 0.004); nt (0.41; p = 0.002). IL of aryepiglottic/pharyngoepiglottic folds, epiglottis, and pyriform sinus were most strongly correlated with VHNSS and NOMS ratings. NOMS/DOSS ratings correlated with EL (> = -0.34; p < 0.01). No meaningful correlations exist between VHNSS swallow/nutrition items and EL (< ± 0.15, p > 0.20).

Conclusions: IL correlated with subjective and objective measures of swallow dysfunction. Longitudinal analysis of trajectory and impact of IL/EL on dysphagia is ongoing.
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http://dx.doi.org/10.1089/jpm.2016.0018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011629PMC
September 2016

Differences of symptoms in head and neck cancer patients with and without lymphedema.

Support Care Cancer 2016 Mar 29;24(3):1305-16. Epub 2015 Aug 29.

School of Nursing, Vanderbilt University, 461 21st Ave. South, GH 516, Nashville, TN, 37240, USA.

Purpose: Head and neck cancer (HNC) patients are at risk for developing external and internal lymphedema. Currently, no documentation of symptom differences between individuals with and without head and neck lymphedema is available. The purpose of this analysis was to examine symptom differences among HNC patients with and without lymphedema.

Methods: Data were drawn from three cross-sectional studies of HNC patients >3 months post-cancer treatment (total N = 163; 128 patients with lymphedema, 35 without lymphedema). External lymphedema was evaluated via physical examination; internal lymphedema was identified through endoscopic examination. Participant's head and neck lymphedema status was categorized into two groups: no indication of external or internal lymphedema and at least some indication of external or internal lymphedema. Lymphedema Symptom Intensity and Distress Survey-Head and Neck (LSIDS-H&N) was used to assess symptom burden. Descriptive statistics, McNemar, chi-squared, Wilcoxon signed-ranks, and Mann-Whitney tests were used.

Results: Twenty-three pairs of patients were identified and matched on the age, primary tumor site, tumor stage, and time since end of cancer treatment. Relative to patients without lymphedema, matched patients with lymphedema reported either increased symptom prevalence or severity or distress level for the following symptoms (prevalence differences of at least 15 % between the matched groups and p < 0.05): (1) numbness; (2) tightness; (3) heaviness; (4) warmth; (5) pain without head/neck movement; (6) problems swallowing mashed or pureed foods; (7) trouble breathing; (8) blurred vision; (9) feel worse when flying in an airplane; and (10) swelling.

Conclusions: Findings suggest that HNC-related lymphedema may be associated with substantial symptom burden. Studies with larger sample sizes are needed to replicate the findings.
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http://dx.doi.org/10.1007/s00520-015-2893-4DOI Listing
March 2016

The value of a collaborative course for advanced head and neck surgery in East Africa.

Laryngoscope 2015 Apr 21;125(4):883-7. Epub 2014 Nov 21.

Department of Otolaryngology-Head & Neck Surgery, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, U.S.A.; Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, U.S.A.

Objectives/hypothesis: To determine the value of a collaborative course for advanced head and neck surgery in East Africa.

Study Design: Survey of participants.

Methods: A 3-day course in head and neck surgery was designed for otolaryngologists and trainees from Kenya and surrounding countries through a collaborative effort between Kenyatta National Hospital, the University of Nairobi, and the Head and Neck Divisions from the Vanderbilt Bill Wilkerson Center and the Massachusetts Eye and Ear Infirmary. Topics included neck dissection, parotidectomy, total laryngectomy, parapharyngeal space tumors excision, and pectoralis myocutaneous flaps. A pre- and postcourse self-evaluation survey was administered to measure course impact.

Results: Eighteen otolaryngologists and trainees participated in the course, with 17 completing course surveys. The majority of participants (72%) were from Kenya. Prior to the start of the course, 41%, 71%, 23%, 12%, and 0% of participants indicated they could complete a neck dissection, parotidectomy, parapharyngeal space mass excision, total laryngectomy, and pectoralis myocutaneous flap, respectively. Following the course, 50%, 94%, 69%, 25%, and 38% of participants indicated they could complete a neck dissection, parotidectomy, total laryngectomy, parapharyngeal space tumors excision, respectively, with a statistically significant increase identified for pectoralis myocutaneous flaps (P < .001) and total laryngectomy (P = .009). There was also a trend toward an increase in the number of participants indicating an ability to complete parotidectomy following the course (P = .085).

Conclusions: This survey demonstrates the potential value of a collaborative course in advanced head and neck surgery as one useful model for increasing the number of well-trained head and neck surgeons in East Africa.
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http://dx.doi.org/10.1002/lary.25028DOI Listing
April 2015

Viable biobanking of primary head and neck squamous cell carcinoma.

Laryngoscope 2013 Mar 8;123(3):641-5. Epub 2013 Jan 8.

Department of Otolaryngology,Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

Objectives/hypothesis: To determine the feasibility of viable storage of head and neck squamous cell carcinoma (HNSCC) for regrowth of cells in culture.

Study Design: Laboratory-based translational study.

Methods: Methods for intermediate-term frozen storage of viable HNSCC were explored using small pieces of primary tumor and dissociated HNSCC cells after short-term culture. Viable cells after freezing were confirmed by adherence to tissue culture plates, cell morphology, and increased cell or colony density. Two cultures were immunostained for cytokeratin to confirm epithelial origin of viable cultured cells after freezing.

Results: Six primary HNSCCs (two oral cavity, three larynx, one oropharynx) and two HNSCCs that had been passaged through a xenograft (two oral cavity) were dissociated to single cells and grown in short-term cell culture for 0 to 12 passages. After short-term culture, cells were frozen for up to 8 months, thawed, and replated. Frozen cells derived from all tumors (six primary and two xenografts) were successfully replated with cultures lasting >7 days with seven of eight tumors presenting increased colony or cell density over 1 week of growth after freezing. In total, 15 of 15 tested samples derived from six primary and two xenografted HNSCCs were viable after freezing.

Conclusions: In the current study, we show that biopreservation of primary or xenografted HNSCC using short-term cell culture is feasible. Initial short-term cell culture was required for successful storage and viability of frozen cells. These proof-of-principle studies, if more widely implemented, could improve preclinical testing of new therapies for HNSCC.
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http://dx.doi.org/10.1002/lary.23674DOI Listing
March 2013

Otolaryngology and radiology: partners in diagnosing and managing head and neck disease.

Otolaryngol Clin North Am 2012 Dec;45(6):xi-xii

Department of Radiology and Neurology, Penn State University and Hershey Medical Center, Hershey, PA 17033, USA.

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http://dx.doi.org/10.1016/j.otc.2012.09.002DOI Listing
December 2012

Imaging of the carotid space.

Otolaryngol Clin North Am 2012 Dec;45(6):1273-92

Department of Otolaryngology/Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-8605, USA.

The most common of the lesions in the carotid space are discussed in relation to their radiographic diagnosis and clinical implications. The appearance of tumors and lesions on computed tomography or magnetic resonance imaging is presented, and their differential diagnosis is discussed. The image of each carotid disease is presented, and the discussion concludes with treatment recommendations and considerations.
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http://dx.doi.org/10.1016/j.otc.2012.08.012DOI Listing
December 2012

Parotid space: anatomic imaging.

Otolaryngol Clin North Am 2012 Dec;45(6):1253-72

Department of Radiology, Penn State University and Hershey Medical Center, Hershey, PA 17033, USA.

The authors present imaging anatomy of the parotid space and discuss non-neoplastic lesions, autoimmune disorders, cysts, neoplastic lesions, epithelial tumors, and nonepithelial lesions. They describe the diseases and their appearance on imaging, describing how the differential diagnoses appear, along with presenting examples of the images, primarily computed tomography and magnetic resonance imaging.
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http://dx.doi.org/10.1016/j.otc.2012.08.011DOI Listing
December 2012