Search

Purpose: To report long-term outcomes of modern radiotherapy for sinonasal cancers., Methods and Materials: A retrospective analysis of patients with sinonasal tumors treated with intensity-modulated radiotherapy or proton therapy. Multivariate analysis was used to determine predictive variables of progression free survival (PFS) and overall survival (OS)., Results: Three hundred and eleven patients were included, with median follow-up of 75 months. The most common histologies were squamous cell (42%), adenoid cystic (15%), and sinonasal undifferentiated carcinoma (15%). Induction chemotherapy was administered to 47% of patients; 68% had adjuvant radiotherapy. Ten-year local control, regional control, distant metastasis free survival, PFS, and overall survival rates were 73%, 88%, 47%, 32%, and 51%, respectively. Age, non-nasal cavity tumor site, T3-4 stage, neck dissection, and radiation dose were predictive of PFS, while age, non-nasal cavity tumor site, T3-4 stage, positive margins, neck dissection, and use of neoadjuvant chemotherapy were predictive of OS. There was a 13% rate of late grade ≥3 toxicities., Conclusion: This cohort of patients with sinonasal cancer treated with modern radiotherapy demonstrates favorable disease control rate and acceptable toxicity profile., (© 2023 Wiley Periodicals LLC.)

Background: To describe the clinical presentation, treatment, and overall prognosis in eight patients with primary Ewing's sarcoma (ES) involving the orbit., Methods: A retrospective interventional study of all biopsy-proven cases of primary ES involving the orbit was done., Results: There were seven males and one female with a median age of 14 years. Imaging showed osseous involvement in all eight cases with extraorbital extension in four. Complete tumor resection was done in four, partial resection in three, and biopsy followed by sinus surgery in one. EWSR1 gene rearrangement analysis was done to confirm diagnosis. All patients received multidrug systemic chemotherapy and seven patients received adjuvant radiotherapy. Eye salvage was achieved in all patients. At a mean follow-up duration of 52.63 months, seven patients were doing well with no evidence of disease., Conclusions: ES involving the orbit is sensitive to chemotherapy and radiation. Aggressive multimodality treatment can help salvage the globe and improve overall survival., (© 2021 Wiley Periodicals LLC.)

Background: High-grade neuroendocrine carcinoma of the larynx (HG-NECL) is rare and aggressive with limited data regarding response to systemic therapy. We evaluated clinicopathological features, therapeutic approaches, and outcomes in patients with laryngeal or hypopharyngeal HG-NECL., Methods: Data were retrospectively collected through 1997-2020. Median disease-free (mDFS), progression-free (mPFS), and overall survival (mOS) were estimated using the Kaplan-Meier method., Results: Fifteen patients were identified; most had locoregional (N = 7) or metastatic disease (N = 5). The main curative-intent treatment was chemoradiation concurrent with platinum-based chemotherapy; the rate of complete response was 78%. Most patients (80%) developed recurrence; the mDFS was 13.1 months. For the first-line palliative therapy, the ORR and mPFS were 50% and 3.1 months, respectively. For all patients, the mOS was 17.8 months, and 8.6 months for metastatic disease., Conclusion: Laryngeal HG-NEC is associated with high relapse rates and dismal prognosis for those with recurrent/metastatic disease. Novel therapeutic strategies are needed., (© 2021 Wiley Periodicals LLC.)

Background: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. Recently, biomarker studies found promising targetable alterations. In this study, we provide a descriptive analysis of tumor and immune biomarkers and survival associations., Methods: We extracted clinical data and performed immunohistochemistry for AR, AR-V7, HER-2, PD-L1, LAG-3, and tumor-infiltrating immune cells., Results: We included 17 patients. Age ranged from 42 to 85 years old; HER-2 was overexpressed or amplified in 65%. AR was positive in 88% of patients, while AR-V7 was positive in 13% by IHC. We found low scores of immune infiltration and a PD-L1 expression in 53%. We found no clinically significant association between biomarkers and survival outcomes., Conclusion: In this small series of SDC, biomarkers do not seem to correlate with disease biology, although they provide additional treatment options. SDC may harbor a different immune profile compared to other subtypes, with an indication of T-cell dysfunction., (© 2021 Wiley Periodicals LLC.)

Background: The temporomandibular joint (TMJ) harbors a myriad of pathologic alterations including arthritides and benign and malignant neoplasms., Methods: Herein, we describe our institutional experience of some uncommon and unusual synovial pathologies of the TMJ along with a review of literature. We searched through the archives of department of pathology and institutional electronic medical record for specimens of TMJ between 1999 and 2019. Hematoxylin and eosin slides were reviewed and data (final diagnosis, age, gender, clinical presentation, tumor size, treatment modality, recurrence, and vital status) were collected., Results: A total of seven cases were identified including four cases of synovial chrondromatosis; and one case each of tenosynovial giant cell tumor, localized type, tenosynovial giant cell tumor, diffuse type, and synovial sarcoma., Conclusions: The article emphasizes on the clinical, radiologic, pathologic, and molecular features of these uncommon entities. The differential diagnosis of each entity is also discussed. Current updates in the management are also reviewed., (© 2020 Wiley Periodicals, Inc.)

Background: Sinonasal papilloma has a tendency toward local destruction, recurrence, and malignant transformation. This study aimed to unravel mechanisms in the malignant transformation of sinonasal papillomas using RNA-seq., Methods: The cohort consisted of 37 consecutive patients; tumor histology included a continuum spectrum (sinonasal papillomas/dysplastic/carcinomas-in-situ/invasive squamous cell carcinomas). These were microdissected and RNA was subjected to whole-transcriptome shotgun sequencing., Results: RNA-seq and pathway analysis showed that the highest expressed genes/potential drivers were development- and differentiation-related genes. The protein expression of six highly upregulated genes (HOXA9, EN1, DUX4, CA9, CD1a, and CK5/6) validated the RNA-seq results. HOXA9 and CA9 were found to be expressed in most of the carcinoma samples but were largely negative in papillomas; all of the CA9-negative carcinomas were recurrent., Conclusions: We conclude that sinonasal carcinomas arising from papillomas are mainly defined by overexpressed developmental/homeobox genes, which provide the potential for transformation/plasticity, along with differentiation and proliferation behavior of neoplastic cells. Our results support HOXA9 and CA9 as biomarkers for carcinomas, with CA9 emerging as a predictive marker of recurrence., (© 2019 Wiley Periodicals, Inc.)

Background: Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer. It is often difficult to determine whether SNUC is a distinct pathologic entity with poorly differentiated neuroendocrine features or it represents an undifferentiated tumor of squamous lineage. Also, reliable histopathologic markers that distinguish SNUC from poorly differentiated sinonasal squamous cell carcinoma (SNSCC) are lacking. Therefore, identification of new diagnostic molecular markers for SNUC is needed., Methods: Treatment-naïve tumor specimens obtained from 15 SNUC and 6 SNSCC patients were used. Gene expression analysis was performed using an oncology panel., Results: An unsupervised cluster analysis divided the patients into the one with only SNUCs and the one with mainly SNSCCs. Of 132 differentially expressed genes, 7 genes completely distinguished SNUCs from SNSCCs. SNUCs were enriched in sets of genes related to DNA repair, synthesis/replication, and cell division., Conclusions: Our study identified new diagnostic markers and potential therapeutic targets for SNUC., (© 2019 Wiley Periodicals, Inc.)

Background: The 8th edition of the American Joint Committee on Cancer's (AJCC) staging system for oral cavity cancer incorporates pathological features. We aimed to assess whether these changes results in better risk stratification of patients with early oral tongue squamous cell carcinoma (OTSCC)., Methods: Overall survival (OS) and disease-specific survival (DSS) of 244 patients were calculated using the Kaplan-Meier method. Multivariate analysis with stepwise selection was performed using Cox proportional hazards regression., Results: Sixty-two patients (25%) were upstaged using the 8th edition. Multivariate analysis revealed that overall stage using the 8th edition of the AJCC staging system but not using the 7th edition was a significant predictor for both OS and DSS. The 8th edition had lower Akaike information criterion and improved concordance index values compared with the 7th edition., Conclusion: The 8th edition of AJCC allows better risk stratification and more precise counseling of patients with OTSCC who were previously considered at low risk., (© 2018 Wiley Periodicals, Inc.)

Salivary gland cancers represent a rare group of tumors composed by over 20 histological subtypes. Initially treated as one single disease, its diagnosis, prognosis, and treatment are currently being stratified based on morphology. More recently, insight has been provided on the molecular characterization of each subtype, further improving diagnostic accuracy and paving the way for personalized therapy. In this article, we provide a comprehensive review of recent breakthroughs, preliminary results of novel therapy, and future directions on the treatment of these complex malignancies., (© 2018 Wiley Periodicals, Inc.)

Background: Depth of invasion (DOI) in oral cavity cancer is important in determining prognosis. This study aims to determine optimal cut-points of DOI for detection of occult disease and survival., Methods: A retrospective cohort study was completed of previously untreated early stage lateral oral tongue cancer. DOI cut-points were computed. Multiple logistic regression and multivariate Cox proportional hazards models were used to assess predictors of occult nodal disease and overall survival (OS) and disease-specific survival (DSS)., Results: Occult nodal disease was found in 55 (26%) of the 212 patients. DOI of 7.25 mm was most predictive for occult nodal disease and 8 mm for OS and DSS. DOI was an independent predictor of OS and DSS., Conclusion: The optimal DOI cut-point for detection of occult nodal metastasis was 7.25 and 8 mm for OS and DSS at 5 years. DOI is an independent predictor of OS and DSS., (© 2018 Wiley Periodicals, Inc.)

Background: Optimal treatment and prognostic factors affecting long-term survival in patients with sinonasal adenoid cystic carcinoma (ACC) have yet to be clearly defined., Methods: We conducted a retrospective review of patients treated with curative intent from 1980-2015 at MD Anderson Cancer Center., Results: One hundred sixty patients met inclusion criteria, including 8 who were treated with radiotherapy alone. Median follow-up time was 55 months. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 67.0% and 49.0%, respectively. The 10-year OS and DFS rates were 44.8% and 25.4%, respectively. Factors that portended for poor survival on multivariate analysis were recurrent disease, any solid type histology, epicenter in the sinus cavity, the presence of facial symptoms, or the original disease not treated with surgery. There was no association between surgical margin status or nodal status and survival., Conclusion: In this large cohort of patients with sinonasal ACC with extended follow-up, long-term survival is better than reported in prior literature. Future research should target patients with adverse risk factors., (© 2018 Wiley Periodicals, Inc.)

Background: Patients with metastatic Merkel cell carcinoma are treated similarly to small cell lung cancer (SCLC). Poly ADP-ribose polymerase-1 (PARP1) is overexpressed in SCLC and response to PARP inhibitors have been reported in patients with SCLC. Our study explores PARP as a therapeutic target in Merkel cell carcinoma., Methods: We evaluated PARP1 expression and Merkel cell polyomavirus (MCPyV) in 19 patients with Merkel cell carcinoma. Target exome-sequencing was performed in 14 samples. Sensitivity to olaparib was tested in 4 Merkel cell carcinoma cell lines., Results: Most Merkel cell carcinomas (74%) express PARP1 at high levels. Mutations in DNA-damage repair genes were identified in 9 samples (64%), occurred exclusively in head neck primaries, and correlated with TP53/RB1 mutations. The TP53/RB1 mutations were more frequent in MCPyV-negative tumors. Sensitivity to olaparib was seen in the Merkel cell carcinoma line with highest PARP1 expression., Conclusion: Based on PARP1 overexpression, DNA-damage repair gene mutations, platinum sensitivity, and activity of olaparib in a Merkel cell carcinoma line, clinical trials with PARP inhibitors are warranted in Merkel cell carcinoma., (© 2018 Wiley Periodicals, Inc.)

Background: Oncologic outcomes for induction chemotherapy and its role in patients with advanced olfactory neuroblastoma (ONB) remain unclear., Methods: A retrospective review of 15 consecutive patients with extensive local invasion and/or nodal disease treated with induction chemotherapy with curative intent followed by definitive local therapy., Results: The majority of patients were treated with cisplatin and etoposide. The response to chemotherapy was 68% (10/15). Response was 78% (7/9) in the high Hyams high-grade group and 50% (3/6) in the Hyams low-grade group. Seven patients had complete response (CR) and 3 patients were able to avoid orbital exenteration. The 5-year disease-free survival (DFS) and overall survival (OS) were 71% and 78%, respectively, with a trend toward improved survival in patients with CR., Conclusion: ONB is a chemosensitive tumor and induction chemotherapy is an acceptable strategy for aggressive and locoregional advanced disease. Hyams grade may predict chemosensitivity and CR may be associated with improved survival., (© 2017 Wiley Periodicals, Inc.)

Sebaceous carcinoma (SC) is a rare but aggressive malignancy with frequent recurrence and metastases. Surgery is the mainstay of therapy, but effective systemic therapies are lacking because the molecular alterations driving SC remain poorly understood. To identify these, we performed whole-exome next-generation sequencing of 409 cancer-associated genes on 27 SCs (18 primary/locally recurrent ocular, 5 paired metastatic ocular, and 4 primary extraocular) from 20 patients. In ocular SC, we identified 139 non-synonymous somatic mutations (median/lesion 3; range 0-23). Twenty-five of 139 mutations (18%) occurred in potentially clinically actionable genes in 6 of 16 patients. The most common mutations were mutations in TP53 (n = 9), RB1 (n = 6), PIK3CA (n = 2), PTEN (n = 2), ERBB2 (n = 2), and NF1 (n = 2). TP53 and RB1 mutations were restricted to ocular SC and correlated with aberrant TP53 and RB protein expression. Systematic pathway analyses demonstrated convergence of these mutations to activation of the PI3K signalling cascade, and PI3K pathway activation was confirmed in tumours with PTEN and/or PIK3CA mutations. Considerable inter-tumoural heterogeneity was observed between paired primary and metastatic ocular SCs. In primary extraocular SC, we identified 77 non-synonymous somatic mutations (median/lesion 22.5; range 3-29). This overall higher mutational load was attributed to a microsatellite instability phenotype in three of four patients and somatically acquired mutations in mismatch repair genes in two of four patients. Eighteen of 77 mutations (23%) were in potentially clinically actionable genes in three of four patients, including BTK, FGFR2, PDGFRB, HRAS, and NF1 mutations. Identification of potentially clinically actionable mutations in 9 of 20 SC patients (45%) underscores the importance of next-generation sequencing to expand the spectrum of genotype-matched targeted therapies. Frequent activation of PI3K signalling pathways provides a strong rationale for application of mTOR inhibitors in the management of this disease. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: Parotid adenocarcinoma not otherwise specified (PANOS) is a common parotid cancer, but studies specifically on this subject are limited., Methods: We conducted a retrospective review of the National Cancer Database., Results: Ten percent of all parotid cancers were PANOS (n = 3155). Median age was 67 years. Most patients were men (62.8%) with high-grade histology (67.2%). Regional metastasis was common (35.9%), whereas occult nodal metastasis (20.2% overall) was less frequent in non-high-grade lesions (8.5% vs 31.6%; p < .001). Distant metastasis was rare (7.9%). Five-year overall survival (OS) was 47%. In multivariate analysis, age, regional metastasis, distant metastasis, high-grade, and T classification were predictors of lower survival. Patients with stage III to IV disease receiving surgery and radiotherapy had a better OS than those receiving surgery alone (51% vs 41%; p < .001)., Conclusion: PANOS is an aggressive disease with frequent regional metastasis and low survival. Numerous variables are associated with worse survival. © 2016 Wiley Periodicals, Inc. Head Neck 38:1208-1212, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: We analyzed local control and early ocular toxicity after eye-sparing management of lacrimal gland carcinoma., Methods: For consecutive patients with lacrimal gland carcinoma treated during 2007 to 2014, we reviewed tumor characteristics, treatment details, ocular toxic effects, and recurrence., Results: Twenty patients, median age 55 years, were treated for lacrimal gland carcinoma during the study period; 11 had globe-sparing surgery. Seven patients had adenoid cystic carcinoma, 2 had carcinoma ex pleomorphic adenoma, and 1 each had high-grade and low-grade adenocarcinoma. Ten patients underwent postoperative radiotherapy, median 60 Gy (range, 52-64 Gy), 6 with concurrent chemotherapy. At a median of 30 months after radiation, all patients had dry eye syndrome, and 1 patient had severe corneal and conjunctival damage leading to enucleation. All 11 patients were disease free at last contact, median follow-up after surgery of 33 months., Conclusion: An eye-sparing approach with surgery followed by adjuvant radiotherapy or chemoradiotherapy is feasible for selected patients with lacrimal gland carcinoma and is associated with a reasonable locoregional control and ocular toxicity profile. © 2016 Wiley Periodicals, Inc. Head Neck 38:1258-1262, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: Lacrimal gland carcinomas are rare. Identification of molecular abnormalities underlying lacrimal gland carcinogenesis is critical to the development of new targeted therapies for lacrimal gland carcinomas. The purpose of our study was to look for mutations that can be targeted as new treatments for lacrimal gland carcinomas., Methods: Genomic DNA from patients with lacrimal gland epithelial neoplasms was analyzed. The Sequenom matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass ARRAY platform was used to profile 168 common oncogenic point mutations in 40 genes. Mutation frequency was assessed overall and by histologic diagnosis. These genetic mutations were then correlated with clinical outcomes in the patients., Results: The study included 14 men and 10 women with a median age of 45 years (range, 17-75 years). The histologic diagnoses were as follows: adenoid cystic carcinoma (n = 16), low-grade carcinoma ex pleomorphic adenoma (n = 2), high-grade carcinoma ex pleomorphic adenoma (n = 2), squamous carcinoma (n = 1), and pleomorphic adenoma (n = 3). Analysis revealed 18 oncogenic mutations in 13 patients: KRAS mutations in 10 patients (46%), NRAS mutations in 2 patients (8%), MET mutations in 3 patients (13%), PIK3CA mutation in 1 patient (4%), and BRAF mutation in no patients. About half of the patients with adenoid cystic carcinoma had oncogenic mutations (7 of 16; 44%). Of the 16 patients with adenoid cystic carcinoma, 5 had KRAS mutations, 1 had MET mutations, and 1 had an NRAS mutation., Conclusion: KRAS, NRAS, and MET mutations are frequent in epithelial neoplasms of the lacrimal gland, with the highest rate of mutations found in adenoid cystic carcinoma. Therapies targeting these genes may be effective treatments for lacrimal gland carcinomas. © 2015 Wiley Periodicals, Head Neck 38: E-E, 2016., (© 2015 Wiley Periodicals, Inc.)

Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small-cell and large-cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high-grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2259-E2266, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Mucoepidermoid carcinoma arises from major or minor salivary glands, making up 10% of salivary gland tumors. Intraosseous mucoepidermoid carcinomas are rare, and make up only 2% to 3% of all mucoepidermoid carcinomas. The t(11;19) and its CRTC1-MAML2 fusion gene transcript have been identified in mucoepidermoid carcinoma and are associated with a subset of mucoepidermoid carcinomas. The extent to which the transcript influences disease features and patient survival is unclear., Methods: We conducted a retrospective analysis of records for clinical features, surgical interventions, and prognoses. Reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) used to assess the t(11;19) fusion gene in intraosseous mucoepidermoid carcinoma., Results: Twenty-five patients with intraosseous mucoepidermoid carcinoma treated between 1998 and 2013 were identified. The t(11;19) fusion gene transcript CRTC1-MAML2 manifested in 9 intraosseous mucoepidermoid carcinomas, whereas is was not detected in another 9 intraosseous carcinomas. Although the incidence of this fusion in mucoepidermoid carcinoma varies, it is generally accepted that more than 50% of this entity manifest the CRTC1-MAML2., Conclusion: Intraosseous mucoepidermoid carcinoma diagnosis should be based on clinical and pathologic manifestations and complete resection is the first choice for patient treatment. The need for neck dissection and adjuvant treatment are debatable. Radiotherapy may improve prognosis and may be recommended in the postoperative period. Primary intraosseous mucoepidermoid carcinoma can manifest the fusion transcript in a subset of tumors. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1312-E1317, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite multimodal therapy, the prognosis in SNUC remains poor, and new therapies are needed. Thus, the purpose of this study was to explore potential therapeutic targets in SNUC., Methods: Using the human-derived SNUC MDA8788-6 cell line, we performed whole genome single nucleotide polymorphism (SNP) analysis to identify copy number changes in this line. Protein expression levels were evaluated by Western blotting. Cell growth inhibition was assessed by methylthiazol tetrazolium (MTT) and clonogenic assays. The mouse flank model was used to examine the effect of growth inhibition in vivo., Results: The ERBB2 gene was highly amplified and cell extracts showed human epidermal growth factor receptor 2 (HER2) was overexpressed and phosphorylated in MDA8788-6. Lapatinib effectively inhibited the HER2 signaling pathway in our SNUC cell line. HER2 inhibition successfully suppressed the cell growth of MDA8788-6 cells both in vitro and in vivo., Conclusion: Targeting HER2 may be a promising avenue for the development of novel therapies for SNUC. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1926-E1934, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: Overexpression of p16 is associated with improved outcomes among patients with oropharyngeal carcinoma. However, its role in the outcomes of patients with nasopharyngeal cancer (NPC) remains unclear., Methods: Eighty-six patients with NPC treated at MD Anderson Cancer Center from 2000 to 2014 were identified. Epstein-Barr virus (EBV) and human papillomavirus (HPV) status were determined by in situ hybridization (ISH) and p16 by immunohistochemical staining., Results: EBV positivity was associated with extended overall survival (OS; median, 95.0 vs 44.9 months; p < .004), progression-free survival (PFS; median, 80.4 vs 28.1 months; p < .013), and locoregional control (median, 104.4 vs 65.5 months; p < .043). In patients with EBV-positive tumors, p16 overexpression correlated with improved PFS (median, 106.3 vs 27.1 months; p < .02) and locoregional control (median, 93.6 vs 64.5 months; p < .02)., Conclusion: P16 overexpression is associated with improved PFS and locoregional control in patients with EBV-positive NPC. P16 expression may complement EBV status in predicting treatment outcomes for patients with NPC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1459-E1466, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Primary extradural meningiomas (PEMs) are rare, particularly those involving the paraspinal cervical area, so little is known about them. We identified a new case and compared it with 10 previous cases, addressed the diagnostic challenges, and highlighted the clinical and pathologic characteristics., Methods: We conducted a case report and literature review of PEM cases reported since 1976., Results: A 59-year-old man presented with right neck stiffness and discomfort that was present over the last several months, which is consistent with other cases. CT scan and MRI revealed a paraspinal cervical mass. Fine-needle aspiration (FNA) and core biopsy revealed spindle cells with whorling consistent with meningioma. The patient underwent complete en bloc resection of the tumor. The PEM was histologically benign., Conclusion: Cervical PEMs should be considered in the differential diagnosis of a deep neck mass. These tumors are typically benign and are surgically resected., (© 2014 Wiley Periodicals, Inc.)

Background: Little is known about the molecular signature of the rare tumor sinonasal squamous cell carcinoma (SNSCC). The purpose of this study was to comprehensively assess various molecular biomarkers in SNSCC., Methods: We chose 13 markers for this study, which have been known as prognostic markers in head and neck squamous cell carcinoma. Expression of these markers was examined by either in situ hybridization or immunohistochemical methods on tissue microarrays made from 70 SNSCC specimens and 28 matched-pair normal tissues from patients who underwent surgical resection at our institution. Expression data were correlated with patient clinicopathologic parameters and survival., Results: Of the 13 markers, only epidermal growth factor receptor (EGFR) protein expression was associated with significantly shorter disease-free survival (DFS; p = .01307). EGFR expression was also associated with shorter overall survival (OS), but the difference was not statistically significant., Conclusion: Targeted inhibition of tumor EGFR expression may be a new approach to treating SNSCC., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Primary laryngeal adenocarcinomas are uncommon and typically of salivary or seromucinous glands origin. Similarly, metastatic adenocarcinoma, including intestinal origin to the larynx, is a rare occurrence., Methods: We present a case of a 63-year-old woman with odynophagia and an epiglottic mass of 2 months' duration. Physical examination revealed a large mass involving the entire epiglottis with extension to the preepiglottic space anteriorly and to the right lateral wall of the oropharyngeal/hypopharyngeal junction., Results: Induction chemotherapy was initiated, and, after 4 cycles with no noticeable response, the patient underwent total laryngectomy and bilateral levels II to IV neck dissection. The final pathology diagnosis was primary intestinal-type adenocarcinoma of the larynx., Conclusion: We present a primary high-stage intestinal-type adenocarcinoma of the larynx and discuss its putative origin and the clinicopathologic characteristics., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Schwannomas comprise 8% to 10% of all primary intracranial tumors. Primary intraorbital schwannomas are rare, accounting for 1% to 2% of all intracranial tumors. Schwannomas arise from Schwann cells in the myelin sheaths of sensory and cranial nerves., Methods: We present the case of a 56-year-old white man blind since 1970 who presented to an outside hospital for a painful right eye. Physicians identified no clinical or radiologic features of neurofibromatosis., Results: The patient underwent enucleation; the final pathologic diagnosis was ancient schwannoma., Conclusion: We describe herein a case of intrascleral schwannoma with ancient changes arising within the globe of the right eye occupying the subretinal space and completely replacing the vitreous body., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in frequency. We reviewed patients with advanced-stage OPSCC treated with chemoradiation to assess the impact of residual neck disease on survival., Methods: We reviewed 202 patients with OPSCC between 1990 and 2010 treated with primary chemoradiation followed by neck dissection. Imaging was analyzed using RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria. Survival was evaluated using both univariate and multivariate analyses., Results: Overall survival at 5 years was 89%. Forty-two patients (21%) had residual disease in the neck (pN+). pN+ was associated with greater locoregional recurrence (LRR) and distant metastasis (DM) and decreased survival. No clinicopathologic factors were predictive of pN+. Contrasted posttreatment CT had low sensitivity and specificity., Conclusions: In advanced OPSCC pN+, patients have higher rates of LRR and DM. Neither clinicopathologic factors nor posttreatment imaging was predictive of pN+, although increased use of modern imaging may reduce the rate of negative neck dissections., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Carcinoma ex pleomorphic adenoma (Ca ex-PA) is defined as a carcinoma arising from a primary (de novo) or recurrent benign pleomorphic adenoma (PA)., Methods: We present a parotid myoepithelial carcinoma ex pleomorphic adenoma in a 38-year-old man with a t(3;8)(p21;q13) as the only chromosomal alteration by cytogenetic and spectral karyotypic analysis (SKY)., Results: The finding of this translocation in a subset of PA and in the present case suggests a critical role for this event in the malignant transformation of PA., Conclusions: Collectively, both the cytogenetic and the molecular studies suggest the concept that PA lacking alterations pursue a benign behavior, whereas those with the t(3;8) translocation may progress to carcinoma., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Adenoid cystic carcinoma (ACC) cells with a high level of ALDH1, a known cancer stem cell (CSC) marker, had higher tumorigenic, invasive, and metastatic abilities. We examined the immunohistochemical expression of ALDH1 in ACC and its correlation with survival., Methods: Archival paraffin blocks of ACC were analyzed. A tissue microarray was constructed and immunohistochemical expression of ALDH1 was analyzed using anti-ALDH1 monoclonal antibody. Correlations between ALDH1 expression and clinical and histological parameters were assessed by chi-square tests. Survival was assessed by the Kaplan-Meier method and log-rank test., Results: Most of the tumors (63%) showed stromal staining only, 11% of the tumors showed both epithelial and stromal expression, and 26% of the tumors did not show either epithelial or stromal staining. Statistical analyses did not show any correlation between the pattern of ALDH1 expression and tumor histology, tumor size, or perineural invasion. There were no significant differences in survival among the 3 patterns of ALDH1 expression., Conclusion: Other factors, besides CSCs, may play important roles in tumorigenesis, cell differentiation, and tumor progression in these tumors., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: The local-regional failure of advanced oral squamous cell carcinoma (OSCC) after surgery results from the regrowth of residual tumor cells that may be stimulated by epidermal growth factor receptor (EGFR) ligands during the wound healing process., Methods: The level of EGFR ligands in human drain fluids (DFs) from OSCC resection and remote flap donor site were determined. A mouse model of microscopic residual OSCC was established and treated with cetuximab to measure tumor growth, survival, and cervical lymph node metastases. A mouse model of wound healing was also established to assess the effect of an EGFR antibody on the wound healing process., Results: EGFR ligands are found in sites from OSCC resection. EGFR targeted therapy can delay tumor regrowth in a microscopic residual disease model of OSCC without significant effects on local wound healing., Conclusion: These results provide a strong rationale for clinical evaluation of this approach to treat patients with local-regionally advanced OSCC., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Chondrolipoma is a rare form of a benign mesenchymal tumor containing mature cartilage and fatty tissue. Chondrolipomas may be found in almost any part of the body, particularly in the connective tissue of the breast, head and neck area, and in the skeletal muscle., Methods: We present the case of a 51-year-old woman complaining of 8 to 9 months of intermittent right cheek swelling. Magnetic resonance imaging (MRI) and CT scans showed a 4.0-cm fat-containing mass involving the right masseter muscle., Results: The patient was taken to the operating room for excision of the mass. The final pathologic diagnosis was chondrolipoma., Conclusions: We describe a case of a chondrolipoma in the masseter muscle., (Copyright © 2011 Wiley Periodicals, Inc.)

Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality, and the alleviation thereof requires greater understanding of the pathobiologic behavior of HNSCC. Although the existence of cancer stem cells (CSCs) in most solid tumors has not been formally proven, application of the CSC concept has certainly enhanced understanding of HNSCC heterogeneity and progression. Recent data support the role of ALDH1(+) CD44(+) CSC in HNSCC, since the implantation of a few ALDH1(+) CD44(+) cells consistently gives rise to tumors that can be serially passaged in vivo. In addition to CSC biomarkers, recent explorations of CSC signaling pathways, gene expression, and localization in HNSCC carry significant clinical and therapeutic implications. Identification and characterization of CSC populations that regulate HNSCC growth, metastasis, and treatment resistance will facilitate development of novel diagnostic, therapeutic, and prognostic strategies. Furthermore, advances in multimodal imaging and nanotechnology, in conjunction with CSC models, may better elucidate the regulatory mechanisms that govern CSC biology in vivo, as well as develop platforms for targeted theragnostics. It is hoped that the promising applications of the CSC model in HNSCC will eventually alleviate the morbidity and mortality of this pervasive disease., (Copyright © 2011 Wiley Periodicals, Inc.)