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Background The purpose of this study was to evaluate the long-term outcomes after initial definitive or adjuvant radiotherapy (RT) for T3 laryngeal cancers. Methods We reviewed 412 patients treated for T3 laryngeal squamous cell cancer from 1985 to 2011. Results The 10-year overall survival (OS) was 35%; disease-specific-survival (DSS) was 61%; locoregional control was 76%; and freedom from distant metastasis was 83%. Chemotherapy, age, performance status

BACKGROUND Unexpected malignancy is common in major salivary gland tumors due to variability of workup, creating challenging treatment decisions. The purpose of this study was to define treatment-related outcomes for patients with incompletely treated major salivary gland tumors. METHODS A retrospective cohort study was completed of patients with incompletely treated major salivary gland tumors. Tumor burden at presentation was established and treatment categorized. The Cox Proportional Hazards model was used to determine predictors of survival and failure. RESULTS Of the 440 included patients, patients with gross residual or metastatic disease had a worse overall survival (OS; P < .001). Presentation status was an independent predictor of OS on multivariate analysis (gross residual disease adjusted hazard ratio [HRadjusted ] 2.55; 95% confidence interval [CI] 1.20-5.30; metastatic disease HRadjusted 9.53; 95% CI 3.04-27.06). CONCLUSION Failure to achieve gross total resection during initial surgery resulted in worse OS. Adequate preoperative planning is required for initial surgical management to optimize tumor control and survival.

Background This was a retrospective study of patients with human papillomavirus (HPV)-associated oropharyngeal cancer treated with concurrent systemic therapy and radiation. Methods Data were extracted through chart review, and statistical analyses included frequency tabulation, chi-square, and Kaplan–Meier tests. Results Three hundred thirty-nine patients were analyzed; 166 received neoadjuvant chemotherapy. One hundred thirty-six patients were treated with cisplatin, 123 with cetuximab, and 59 with carboplatin. The 2-, 3-, and 5-year actuarial overall survival rates were 92%, 88%, and 78%, respectively. There were no significant differences in survival or disease control when analyzed by systemic agent. Platin-treated patients had greater hematologic toxicity, and required more intravenous hydration. The incidence of confluent mucositis was highest among patients treated with cetuximab. Conclusion Platin and cetuximab seem to have similar efficacy when delivered concurrently with radiation in our retrospective population study. Although platin did cause greater hematologic toxicity, radiation-specific side effects seemed relatively comparable. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

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

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, 2015

Background Treatment of T4 nasopharyngeal carcinoma (NPC) is challenging because of the proximity of the tumor to the central nervous system. The purpose of this study was to present our evaluation of disease control and toxicity outcomes for patients with T4 NPC treated with intensity-modulated radiation therapy (IMRT) and chemotherapy. Methods The medical records of 66 patients with T4 NPC treated from 2002 to 2012 with IMRT were reviewed. Endpoints included tumor control and toxicity outcomes (Common Terminology Criteria for Adverse Events [CTCAE v4.0]). Results Median follow-up was 38 months. Five-year rates of locoregional control, distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) were 80%, 62%, 57%, and 69%, respectively. Nodal involvement was associated with worse PFS (p = .015). Gross target volume (GTV) volume >100 cm and planning target volume (PTV) volume >400 cm were associated with worse OS (p = .038 and p = .004, respectively). Four patients had significant cognitive impairment, and 9 had MRI evidence of brain necrosis. Conclusion For patients with T4 NPC treated with IMRT and chemotherapy, survival and locoregional disease control rates have improved; however, late treatment toxicity remains a concern. © 2015 Wiley Periodicals, Inc. Head Neck 38: E925–E933, 2016

Background The purpose of this study was to determine the antitumor activity of the epidermal growth factor receptor (EGFR) inhibitor gefitinib in patients with recurrent/metastatic salivary gland cancer. Methods We conducted a phase II study in adenoid cystic carcinoma (ACC) and non-ACC. Gefitinib was administered 250 mg orally daily. The primary endpoint was tumor response. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and disease control rates. EGFR and human epidermal growth factor receptor 2 (HER2) expression were evaluated and correlated with outcomes. Results Thirty-seven patients were enrolled in this study, and 36 were evaluable (18 with ACC and 18 with non-ACC). No responses were observed. Median PFS was 4.3 months and 2.1 months, and median OS was 25.9 months and 16 months for patients with ACC and non-ACC, respectively. The disease control rate at 8 weeks was higher in patients with ACC. No unexpected toxicities occurred. EGFR and HER2 overexpression did not correlate with outcomes. Conclusion We did not observe significant clinical activity of gefitinib in advanced salivary gland cancer. NCT00509002. © 2015 Wiley Periodicals, Inc. Head Neck 37: 644–649, 2015

The majority of conventional leukoplakia remains constant and only a subset progress to high-grade dysplasia or invasive carcinoma. A less recognized form known as proliferative verrucous leukoplakia (PVL) represents a unique progressive and elusive variant. Identifying patients with this form can only be achieved through the keen clinical observation of the temporal gross and histologic progression in individual patients with squamous cell carcinoma. The difficulty in the early diagnosis of PVL stems from the overlapping clinical and pathologic features with conventional multifocal leukoplakia with dysplasia. We present the current view on the clinicopathologic and biological characteristics of PVL and discuss their diagnosis, differential diagnosis, and management.

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. © 2013 Wiley Periodicals, Inc. Head Neck 36: E44–E47, 2014

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. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1094–1102, 2014

Background Esthesioneuroblastoma is a rare cancer of the anterior cranial base that arises in the region of the olfactory rootlets. The purpose of this study was to review the long-term outcomes of patients diagnosed with esthesioneuroblastoma (ENB) treated at a single institution to determine factors associated with improved disease control and survival. Methods A retrospective review of 70 patients with ENB treated at the University of Texas MD Anderson Cancer Center between 1992 and 2007 was undertaken. Survival and recurrence was analyzed and compared using the Kaplan–Meier method and log-rank statistics. Results Seventy patients were reviewed. The majority (77%) had T3 or T4 disease at presentation, 38% identified as modified Kadish stage C or D. Ninety percent of patients received surgical resection as part of their treatment, and 66% received postoperative radiation or chemoradiation. The median follow-up was 91.4 months (7.6 years). Forty-eight percent of patients developed recurrent disease and the median time to recurrence was 6.9 years. Overall and disease-specific median survival was 10.5 and 11.6 years, respectively. Patients who were treated with surgery alone had a median disease-specific survival of 87.9 months, whereas those who were treated with surgery and postoperative radiation had a median disease-specific survival of 218.5 months (p = .047). Conclusion Patients with ENB can achieve favorable long-term survival, even if disease is locally advanced. Survival is improved considerably when surgical resection is followed by postoperative radiation. However, recurrence rates and mortality remain high, and therefore long-term observation in these patients is warranted. © 2013 Wiley Periodicals, Inc. Head Neck 36: 524–530, 2014

Background Mesenchymal malignancies of salivary origin are rare and are histologically diverse. We reviewed our experience with these tumors, as well as the published literature, with an emphasis on treatment modalities and prognosis. Methods We identified 17 patients treated for malignant mesenchymal cell tumors at The University of Texas MD Anderson Cancer Center between 1990 and 2007. We compared our results to the literature from January 1990 to July 2010. Results Tumors were located primarily in the parotid gland and were primarily T1 tumors (

Background Sinonasal undifferentiated carcinoma remains a poorly characterized malignancy at both the clinical and molecular level, and consequently the optimal treatment strategy remains undefined.

Background Minor salivary gland malignancies in children are rare and data on treatment and outcomes are limited. Methods A retrospective chart review of all pediatric patients with the pathologic diagnosis of minor salivary gland malignancy at a tertiary care cancer hospital was used to conduct this review. Results From 1952 to 2006, 35 children with minor salivary gland cancers were treated at The University of Texas MD Anderson Cancer Center. Mean age was 15.2 +/- 2.9 years with a slight female predominance. Recurrence occurred in 4 patients and was significantly associated with positive margins, advanced stage, and high histologic grade. Overall survival (OS) and disease-specific survival (DSS) were 89.3% and 88.4%, respectively, at 5 years. Advanced stage, positive margins, and high grade were associated with adverse survival. Conclusion Minor salivary gland malignancies in children are rare. Surgical resection with clear margins yields excellent outcomes in patients with low-intermediate grade and early stage tumors. Patients with high-grade malignancies do poorly despite multimodality therapy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Background We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. Methods From September 2001 to October 2004, 23 patients aged 18 to 49 years with clinical T2–3 N0–2 M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. Results On final surgical pathology, 9 patients (39%) had a complete/major (2 complete) histologic response at the primary tumor site; 8 patients (35%) had no response or progression. Similarly, 9 patients (39%) had a complete response in the neck or remained node negative; 6 patients (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 patients (43%) developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (p = .029), poor histologic differentiation (p = .012), and multiple adverse features on final surgical pathology (p = .040). Conclusion Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

The expression of miRNA in head and neck squamous cell carcinomas (HNSCCs) that had been classified as high risk by surgical pathologic features and validated by trial outcome for disease recurrence was determined and compared with matched adjacent normal tissues.miRNA and corresponding gene expression were determined using miRNA bioarrays and gene expression arrays.Twenty miRNAs were determined to be differentially regulated in the HNSCC samples when compared with their normal tissue counterparts. Quantitative reverse transcriptase-polymerase chain reaction confirmed differential regulation of miRNA expression, and gene expression analysis on these same-paired samples confirmed the loss of putative mRNA targets including genes such as adenomatous polyposis coli, programmed cell death protein 4, and TGF beta receptor 3 in the tumor samples.These data suggest a role for the upregulation of specific miRNAs in high-risk HNSCC. Furthermore, upregulation of these miRNAs may be responsible for the elimination of mRNAs that lead to the growth and progression of HNSCC.

Aurora kinase A (AURKA) is amplified with varying incidence in multiple human cancers including head and neck squamous cell carcinoma (HNSCC). We investigated whether AURKA is a potential therapeutic target in HNSCC.We conducted an immunohistochemical analysis of AURKA expression in paired normal and tumor samples (n = 63). HNSCC cells treated with siRNA specific for AURKA were assessed for AURKA mRNA and protein expression levels by reverse transcriptase-polymerase chain reaction and Western blot analysis. Tumor cells treated with siRNA and paclitaxel were assessed for cell proliferation by MTT assay and for cell cycle distribution by flow cytometry.AURKA expression was higher in tumor than in adjacent normal in most (85%) of the samples analyzed. HNSCC cells and primary tumors revealed high expression levels of AURKA. Most primary tumors also showed high kinase activity of the enzyme. Targeted AURKA inhibition increased the sub-G1 cell fraction, with a concomitant reduction in the G1 cell population, indicating induction of apoptosis and thus markedly suppressed proliferation of HNSCC cells. Combining siRNA-induced AURKA inhibition with 5 to 10 nM paclitaxel synergistically enhanced apoptosis induction.AURKA is a potential therapeutic target for HNSCC. Further investigation of small-molecule AURKA inhibitors as therapeutic agents is warranted.

Background. c-Met is upregulated in papillary thy- roid carcinoma (PTC) and can be an attractive therapeutic tar- get. We tested the effects of the small molecule c-met inhibitor PHA665752 in blocking c-met-dependent phenotypic effects in PTC cell lines. Methods. PTC patient tissues and cell lines were evaluated for c-met expression. The effect of PHA665752 on c-met phos- phorylation, downstream signaling, hepatocyte growth factor (HGF)-dependent cell growth, and induction of apoptosis was studied. The IC50 of PHA665752 in c-met-expressing PTC cells was determined, and growth curves at 0.13 ,1 3, and 103 IC50 concentrations were obtained. Poly(ADP-ribose) polymerase (PARP) and caspase-9-processing post-PHA665752 treatment were studied as markers of apoptosis, and assays analyzing HGF-dependent cell invasion and migration in the presence and absence of PHA665752 were done. Results. c-Met was upregulated in most of the patient tissues with PTC and in many PTC cell lines. PHA665752 specifically inhibited c-met phosphorylation, c-met-dependent cell growth, signal transduction, cell survival, cell invasion, and migration in PTC cells with high c-met. Conclusions. PHA665752 is an effective and specific inhibi- tor of c-met in PTC cells with high levels of c-met expression. V V C 2008 Wiley Periodicals, Inc. Head Neck 30: 991-1000, 2008

Background. Simultaneous malignancies in the field of radiation for Hodgkin's disease is an extremely rare event. A unique case of concurrent thyroid and neck mass in the postirradiation field of a young patient with Hodgkin's disease is presented. Methods and Results. Thyroidectomy and excision biopsy of the neck mass were performed. A 1.5-cm papillary thyroid carcinoma was identified in thyroidectomy and an initial diagnosis of undifferentiated malignant neoplasm was rendered on the neck mass biopsy. Subsequent surgical excision of the neck mass and immunohistochemical analysis revealed malignant peripheral nerve sheath tumor. Conclusion. Concurrent malignancies in the field of treatment of Hodgkin's disease may occur. Rare malignancies including malignant peripheral nerve sheath tumor may be encountered along with the more common papillary thyroid carcinoma. © 2007 Wiley Periodicals, Inc. Head Neck, 2008

Background. We report a rare case of endodermal sinus tumor (EST) of the paranasal sinus in a 59-year-old man with a 6-week history of nasal obstruction. Methods and Results. High-resolution MRI showed a right nasoethmoid mass with obstructive changes in the sphenoid, frontal, and right maxillary sinuses and orbital and intracranial extension. Histologic analysis showed 2 distinct histologic features: poorly differentiated carcinoma and EST. Immunohistochemical studies showed strong keratin staining in both components and restricted positivity of α-fetoprotein in the endodermal sinus-like component. The patient underwent 3 cycles of neoadjuvant chemotherapy consisting of ifosfamide, paclitaxel, and cisplatin, which resulted in significant regression of the tumor, but after the fourth cycle, the mass showed a slight increase in size. The tumor was excised with clear margins through an anterior craniofacial approach to the skull base. Histologic examination of the resected specimen showed extensive fibrosis with residual areas of viable tumor composed mainly of the poorly differentiated component with only residual microscopic foci of EST. Adjuvant postoperative intensity-modulated radiation therapy was administered. At 1-year follow-up, the patient was tumor free, with normal α-fetoprotein levels. Conclusion. Because of the rarity of this entity, no standardized treatment protocol has been defined. The involvement of the anterior skull base in our case necessitated a radical craniofacial resection, despite a partial response to chemotherapy. © 2007 Wiley Periodicals, Inc. Head Neck, 2008

Background. We describe, for the first time, the occurrence of two pure examples of spindle cell neoplasm with fibrous and smooth muscle differentiation in the larynx. Materials and Method. Tissue sections from both tumors stained with hematoxylin and eosin were reviewed. Immunophenotypic analysis using keratin, S-100 protein, SMA, and h-Caldesmon markers was performed. Results. Tumors were seen as raised submucosal nodules in the glottic region of two elderly male patients. Histopathologically, the lesions were unencapsulated and composed of spindle cells that manifested variable cellular anaplasia and expressed SMA and were negative for keratin, S-100, and h-Caldesmon. Conclusions. We document histologically low-grade malignant myofibroblastic tumors of the larynx. Complete excision is advised. © 2003 Wiley Periodicals, Inc. Head Neck 25: 606–611, 2003

Background Primary intestinal-like adenocarcinoma of the major salivary glands has not previously been reported. Methods The clinical and radiological findings of 2 patients with primary submandibular and sublingual tumors are presented. Histopathologic and immunohistochemical examinations of tumor sections were performed. Metastatic workup for distant occult primary was carried out. Results The light-optic and the immunomarkers revealed intestinal-like adenocarcinoma consistent with upper respiratory tract origin. Metastatic workup of both patients was negative for primary gastro-intestinal primary. Conclusion Primary intestinal-like adenocarcinoma can develop in major salivary glands and should be considered in the differential diagnosis. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

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. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Background The limited studies and the small number of published cases of papillary squamous cell carcinoma have precluded accurate assessment of the biologic characteristics of this lesion. Methods Thirty-eight of the carcinomas were studied. In-situ hybridization and polymerase chain reaction were performed to detect human papilloma virus (HPV) and p53 expression. Results HPV was found in 4 of 14 assessable carcinomas by in-situ hybridization and in 5 of 14 by polymerase chain reaction. The most frequently identified HPVs were HPVs in 6/11 and 16/18 patients. In general, a reciprocal relationship was found between p53 and HPV prevalence. The most lethal site for this tumor was the sinonasal tract, whereas patients with papillary squamous cell carcinomas of the larynx had the best outlook. Eleven of 25 (44%) assessable patients died of disease (mean time interval, 2 year). Conclusions Papillary squamous cell carcinoma of the upper aerodigestive tract is a distinct variant of squamous cell carcinoma. As such and because of its putative association with HPV, papillary squamous cell carcinoma could be an informative model for defining how viral oncogenes cooperate with other factors in genomic instability, carcinogenesis, and tumor development. © 2000 John Wiley & Sons, Inc. Head Neck 22: 360–368, 2000.

Background Restricted presentation of malignancy at both lacrimal and parotid salivary glands are unusual occurrences that may pose clinical and diagnostic difficulties. Methods We applied certain clinicopathological criteria to distinguish between lacrimal and parotid gland primaries in a series of 11 patients with synchronous and/or metachronous tumors of similar histology at both sites. Results Of eight patients with primary lacrimal carcinomas, seven had metachronous metastases to parotid glands. All three patients with primary parotid carcinomas had concurrent metastases to lacrimal glands. Patients with primary lacrimal tumors metastasizing to the parotid gland appear to have better clinical outcome in comparison with those with parotid primary with secondary lacrimal metastases. Conclusion Careful examination of parotid glands in the assessment of any lacrimal gland tumor with high-grade adenocarcinoma morphology is recommended to rule out the possibility of a parotid primary. © 1999 John Wiley & Sons, Inc. Head Neck 21: 512–516, 1999.

Background When to do a neck dissection as part of the surgical treatment for a patient with squamous carcinoma of the oral tongue is controversial, particularly when the primary can be resected without entering the neck. If the patient who is at high risk for having occult nodal disease in the neck can be identified, node dissection with the glossectomy could be justified. To better identify patients for this procedure, we correlated various tumor and patient factors along with preoperative diagnostic studies with the presence or absence of pathologically positive nodes in a group of patients who underwent node dissection. Methods Ninety-one previously untreated patients with biopsy-proved squamous carcinoma of the oral tongue were prospectively studied. All patients had a glossectomy and neck dissection as their initial treatment. The pathology findings (ie, lymph nodes with squamous cancer) were correlated with many preoperative and intraoperative factors, and a statistical analysis was made. Results The use of computed tomography and ultrasound was not better than the clinical examination in determining the presence or absence of nodal metastases. The best predictors were depth of muscle invasion, double DNA aneuploidy, and histologic differentiation of the tumor. Conclusions All patients with stage T2–T4 squamous cancers of the oral tongue should have an elective dissection of the neck. Patients with T1N0 cancer who have a double DNA-aneuploid tumor, depth of muscle invasion >4 mm, or have a poorly differentiated cancer should definitely undergo elective neck dissection. Ultrasound and computed tomography are of little value in predicting which patients have positive nodes. © 1998 John Wiley & Sons, Inc. Head Neck20: 138– 144. 1998.

Background It has been suggested that metastasizing pleomorphic adenomas may represent unrecognized malignancy. Methods The cytologic and clinical characteristics of two metastasizing pleomorphic adenomas diagnosed by fine-needle sampling are reported. Results Both showed malignant evolution: the primary tumors arose from the palate and the parotid salivary glands, respectively. Metastases occurred simultaneously with local recurrence in the first patient and after a second local recurrence in the second patient. Both patients were treated by surgery and radiotherapy but died of disseminated disease 8 and 4 years after initial diagnosis. No histologic evidence of malignancy was observed on cytology smears or histology sections in either case. Conclusion Clinically, our cases support the hypothesis that metastasizing pleomorphic adenomas represent unrecognized malignancy, because the biologic course of two tumors led to unequivocally lethal outcome.

Background Galectins are carbohydrate-binding proteins thought to be important for cell growth and differentiation, whose expression is altered in some tumors with aggressive phenotype. Our objective was to evaluate the expression of galectins in head and neck squamous cell carcinoma (HNSCC). Methods Fourteen HNSCC cell lines and four primary tumor specimens were evaluated using immunoblotting, and immunohistochemical analysis was performed on 35 primary HNSCCs. Results Galectin-1 and galectin-3 were expressed in most HNSCC cell lines and primary tumor specimens. Galectin-1 was detected in the basal layer of normal adjacent mucosa, in connective tissue stroma, and at the periphery of invasive tumor islands. Galectin-3 localized to superficial mucosal layers, and adjacent to keratin pearls is in invasive carcinoma. Conclusions Galectins are manifested in HNSCC tumors and are localized to the cell surface, where they may participate in cellular interactions. The expression pattern of galectins appears to be associated with degree of squamous differentiation, suggesting a potential role for galectins as biologic and differentiation markers in HNSCC. HEAD & NECK 1996;18:422–432 © 1996 John Wiley & Sons, Inc.