Extracapsular spread in head and neck carcinoma: impact of site and human papillomavirus status.

BACKGROUND: Extracapsular spread (ECS) in cervical lymph node metastases from head and neck squamous cell carcinoma (SCC) is regarded as an adverse prognostic factor and is often used to select patients who may benefit from adjuvant therapy. The prognostic value of ECS was evaluated for patients with oropharyngeal SCC (OPC; with known p16/human papillomavirus [HPV] status) and for patients with SCC of the oral cavity (OCC). METHODS: Disease-specific survival (DSS) was assessed among SCC patients with cervical lymph node metastases (n = 347, including 133 patients with OPC and 214 patients with OCC). All patients were treated surgically between 1983 and 2009. ECS status was determined by pathologists at the time of initial pathologic evaluation and confirmed for this study. HPV status of patients with OPC was determined via immunohistochemistry for p16 and in situ hybridization. RESULTS: Among OCC patients, ECS was a significant, independent factor influencing DSS. For OCC patients with ECS, 3-year DSS was 45% (95% confidence interval [CI], 36%-56%); for those without ECS, 3-year DSS was 71% (95% CI, 62%-81%; P = .0018). The effect of ECS was independent of the number of positive lymph nodes as well as other clinical, pathologic, and treatment variables. Of the 133 OPC patients, 76 (57%) were p16-positive and 57 (43%) were p16-negative. ECS status did not correlate with DSS among p16-positive or p16-negative OPC patients. CONCLUSION: ECS was not associated with worse DSS in p16-positive or p16-negative OPC patients. Adverse prognostic value of ECS in OCC patients was confirmed. Cancer 2013;119:3302-8. © 2013 American Cancer Society.

Head and neck oncology--2010, Part I.

This article reviewed the current state of the art in head and neck oncology. These include very important and stimulating new areas of interest including the marked acceptance of chemoradiation in favor of surgery in patients with cancer of the head and neck. The concept of HPV as a cause of cancer of the oropharynx is relatively new and very important in the epidemiology of these tumors. New modalities such as PET CT scanning and robotic surgery are discussed and appear to be very important in management of cancer of the head and neck. Endoscopic endonasal skull base surgery is another new high technology contribution to the field of head and neck surgery as is the use of endoscopic assisted thyroid surgery. These and other new concepts are discussed in this manuscript.

Head and neck oncology--2010, part II.

Part II this article reviewed the current state of the art in head and neck oncology. These include very important and stimulating new areas of interest including the marked acceptance of chemoradiation in favor of surgery in patients with cancer of the head and neck. The concept of HPV as a cause of cancer of the oropharynx is relatively new and very important in the epidemiology of these tumors. New modalities such as PET CT scanning and robotic surgery are discussed and appear to be very important in management of cancer of the head and neck. Endoscopic endonasal skull base surgery is another new high technology contribution to the field of head and neck surgery as is the use of endoscopic assisted thyroid surgery. These and other new concepts are discussed in this manuscript.

Ocular outcomes after gold weight placement and facial nerve resection.

OBJECTIVE: To assess the effectiveness of acute gold weight placement after facial nerve resection and to determine the role of concomitant lower eyelid procedures. STUDY DESIGN: Retrospective review. SUBJECTS AND METHODS: Twenty-two patients who received an upper eyelid gold weight at the time of parotidectomy and facial nerve resection were reviewed to assess ocular outcomes. RESULTS: After gold weight placement, twelve patients (12 of 22, 54.5%) subsequently presented with symptomatic ectropion (n = 9) and/or lagophthalmos (n = 5). Nine patients received a lower eyelid procedure (7 tarsal strips only, 1 tarsal strip combined with a lateral tarsorrhaphy, and 1 lateral tarsorrhaphy only). Six patients, in addition to a gold weight, also underwent a static sling to the midface at the time of facial nerve resection. None of these 6 received a subsequent lower eyelid procedure. Two patients required gold weight upsizing. Two patients required weight removal. CONCLUSIONS: Insertion of 1.2 gm upper eyelid weight with placement of midface sling is recommended at the time of facial nerve resection. Due to the need to tighten the lower eyelid in many of these patients, we now also consider performing a tarsal strip procedure at the time of facial nerve resection in any patient with pre-existing lower lid laxity.

Chromosomal imbalances in oral squamous cell carcinoma: examination of 31 cell lines and review of the literature.

Classical and molecular cytogenetic analysis, including fluorescence in situ hybridization (FISH) and chromosomal comparative genomic hybridization (CGH), were used to examine genetic changes involved in the development and/or progression of oral squamous cell carcinoma (OSCC). Of 31 OSCC cell lines studied, more than one-third expressed clonal structural abnormalities involving chromosomes 3, 7, 8, 9, and 11. Eleven OSCC cell lines were evaluated using CGH to identify novel genome-wide gains, losses, or amplifications. By CGH, more than half of the cell lines showed loss of 3p, gain of 3q, 8q, and 20q. Further, molecular cytogenetic analyses by FISH of primary tumors showed that the karyotypes of cell lines derived from those tumors correlated with specific gains and losses in the tumors from which they were derived. The most frequent nonrandom aberration identified by both karyotype and CGH analyses was amplification of chromosomal band 11q13 in the form of a homogeneously staining region. Our data suggest that loss of 9p and 11q13 amplification may be of prognostic benefit in the management of OSCC, which is consistent with the literature. The results of this study validate the relationship between these OSCC cell lines and the tumors from which they were derived. The results also emphasize the usefulness of these cell lines as in vitro experimental models and provide important genetic information on these OSCC cell lines that were recently reported in this journal.

Workforce Considerations, Training, and Certification of Physicians in Europe.

Following recent geopolitical events and unification of Europe, the European Union (EU) is currently confronted with health care workforce shortage and insufficient uniform access to quality care. Aging population, difficulties with physician retention, and mobility of health care professionals are thought to contribute to this problem. Because of the differences in medical education and residency curriculum across the European countries, there is a need for a standardized training and certification. Current government initiatives are geared toward developing common policies and programs across the EU countries to address health care access.

The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines.

The purpose of this study was to generate stable cell cultures from head and neck squamous cell carcinomas (HNSCC), and retrospectively analyze the factors associated with successful cell line establishment. Fifty-two HNSCC cell lines were isolated from a series of 199 tumors collected between 1992 and 1997 at the University of Pittsburgh Medical Center. Cell lines were characterized at the molecular and cellular level to determine the features associated with cell line formation. Successful cell line formation was dependent on multiple factors, including gene amplification involving chromosomal band 11q13, local and/or regional involvement of lymph nodes, and alcohol usage. The establishment of HNSCC cell lines enriches the resources available for cancer research. Our findings indicate that generation of stable cell lines from HNSCC is biased towards tumors with a poor prognosis. Our 52 stable lines comprise one of the largest series of HNSCC cell lines in the literature, with complete demographic, histopathologic, clinical, and survival data.

Elective and therapeutic selective neck dissection.

Selective neck dissection is a modification of the more comprehensive modified radical or radical neck dissection that is designed to remove only those nodal levels considered to be at risk for harboring nodal metastases. The role of selective neck dissection continues to evolve: while initially designed as a staging and diagnostic procedure for patients without clinical evidence of nodal disease, a growing body of literature suggests that selective neck dissection has a therapeutic role in patients with clinical and histologic evidence of nodal metastases. The rationale behind selective neck dissection, its application in the clinically negative but histologically node-positive neck and the extended application of selective neck dissection in patients with clinical evidence of nodal disease are discussed.

Cervical metastasis from squamous cell carcinoma of the maxillary alveolus and hard palate.

OBJECTIVES: Squamous cell carcinoma has a predilection for regional lymphatic metastasis. The occurrence of occult cervical metastases from squamous cell carcinoma of the hard palate and maxillary alveolar ridge has not been studied systematically. We have observed many patients who have returned after resection of a primary cancer in these sites with a delayed cervical metastasis. Some of these patients have died of regional or distant metastasis despite control of their primary cancer. METHODS: We have studied 26 patients with squamous cell carcinoma of the maxillary alveolar ridge and hard palate to define incidence of cervical metastasis. RESULTS: Overall incidence of cervical metastasis was: clinical 2 of 26 (7.6%) and occult 7 of 26 (27%) for a total of 9 of 26 (34.6%). The 5-year disease-specific survival was 13 of 22 (59%). Surgery for regional failure was successful in 66% (6 of 9). Radiation was administered after surgery in eight of nine patients. CONCLUSION: Cervical metastasis from cancer of the palate and alveolar ridge is significant. Regional surgery for recurrent disease usually requires radical or modified radical neck dissection. Selective elective neck dissection should be offered to patients with cancer of the hard palate and alveolar ridge. It affords the patient and the treatment team valuable histologic information, which may help to guide therapy and reduce the potential need for future hospitalization, chemoradiation, and more radical surgery.

Base of tongue schwannoma: a case report.

Both malignant and benign lesions may be found on the base of the tongue, including metastasis from other sites. Various surgical approaches to the base of tongue have been described. Here, we report a case of a 26-year-old woman with a schwannoma in the base of tongue removed through a suprahyoid pharyngotomy approach. The biology and pathology of schwannoma in the oral cavity are discussed. The advantage of the suprahyoid pharyngotomy approach for complete excision of a mass in the base of tongue is demonstrated.

Reconstruction of the lateral mandibulectomy defect: management based on prognosis and location and volume of soft tissue resection.

OBJECTIVE: To examine how the accompanying soft tissue resection of the oral cavity, oropharynx, neck, or face affects the reconstructive management of the lateral mandibulectomy defect. STUDY DESIGN: Retrospective review of 76 consecutive patients. METHODS: Patient and tumor variables were extracted from the medical records. Outcomes that were examined included method of reconstruction, medical complications, flap complications, and survival. RESULTS: Age greater than 70 years (P = .03), moderate or severe comorbidity (P = .01), and tumor involvement of the base of tongue (P = .03) were significantly associated with decreased use of a free flap and with decreased 3-year survival rates. For choice of free (osteocutaneous radial forearm free flap or fibula vs. rectus abdominis) and regional flaps (pectoralis or cervicodeltopectoral), lateral defects could be classified into one of three types: type 1 (n = 60), lateral defect with a soft tissue resection limited to the oral cavity and oropharynx; type 2 (n = 11), lateral defect with a through and through defect of the lower one third of the face (skin overlying the mandible) or neck; and type 3 (n = 5), lateral defect with an associated large-volume resection of the midface, parotid, or cheek skin. CONCLUSION: When the lateral mandible is resected with an accompanying large soft tissue defect of the neck or face (type 2 or type 3 defect), the reconstructive challenge becomes the determination of how best to cover the planned bony reconstruction or whether to perform only a soft tissue reconstruction. When placed in the context of expected prognosis, the proposed classification system based on the location and volume of the associated soft tissue resection can help guide the reconstructive options for these decisions.

Selective neck dissection in patients with upper aerodigestive tract cancer with clinically positive nodal disease.

OBJECTIVES: We evaluated the efficacy of the application of selective neck dissection to cases of clinically node-positive disease. METHODS: We performed a retrospective review at the University of Pittsburgh Head and Neck Cancer Database. A database of 65 patients was followed for an average of 36 months (range, 2 to 128 months) after they underwent selective neck dissection for clinically node-positive regional disease. RESULTS: Regional failure occurred in 8 patients (12.3%). In-field failure was experienced in 4 patients (6.1%), and failures outside the field of dissection occurred in 4 patients (6.1%). The overall incidence of extracapsular spread was 33.8% (22 of 65). Only 2 of 8 regional recurrences were associated with extracapsular spread at the initial neck dissection; however, both recurrences were in the contralateral, undissected side of the neck. Four regional failures were salvaged with surgery, with eventual overall regional control in the neck of 93.9%. Only 1 of 4 ipsilateral recurrences (25%) was successfully salvaged. In contrast, 3 of 4 contralateral failures (75%) were successfully salvaged. In our study population, 21 of 65 cases (32%) that were initially staged as clinically node-positive had no evidence of nodal metastases on pathologic examination. CONCLUSIONS: The application of selective neck dissection and postoperative irradiation in patients with clinically Nl and limited N2 clinical disease appears to be oncologically efficacious. Clinical overstaging occurred frequently in this sample, and may put patients at risk for more morbid surgical procedures.

Frequencies of tetramer+ T cells specific for the wild-type sequence p53(264-272) peptide in the circulation of patients with head and neck cancer.

Immunization with wild-type sequence (wt) p53 epitopes represents a novel therapeutic strategy for cancer patients with tumors accumulating mutant p53. To evaluate usefulness of p53-derived peptides as future cancer vaccines, frequencies of wt p53(264-272) peptide-specific CD8+ T cells were determined in the peripheral circulation of patients with squamous cell carcinoma of the head and neck (SCCHN). T cells of 30 HLA-A2.1+ patients and 31 HLA-A2.1+ healthy individuals were evaluated by multicolor flow cytometry analysis using peptide-HLA-A2.1 complexes (tetramers). T cells specific for an influenza matrix peptide (a model recall antigen) or an HIV reverse transcriptase peptide (a model novel antigen) were studied in parallel. Patients with SCCHN had a significantly higher mean frequency of CD8+ T cells specific for wt p53(264-272) than normal donors (P = 0.0041). Surprisingly, the frequency of epitope-specific T cells in the circulation of patients did not correlate with p53 accumulation in the tumor. In patients whose tumors had normal p53 expression or had p53 gene mutations preventing presentation of this epitope, high frequencies of wt p53(264-272)-specific CD8+ T cells were found, of which many were memory T cells. In contrast, patients whose tumors accumulated p53 had low frequencies of wt p53(264-272)-specific CD8+ T cells, which predominantly had a naive phenotype and were unable to proliferate ex vivo in response to the epitope, as reported by us previously (T. K. Hoffmann, J. Immunol., 165: 5938-5944, 2000). This seemingly contradictory relationship between the high frequency of epitope-specific T cells and wt p53 expression in the tumor suggests that other factors may contribute to the observed anti-p53 responses. Human papillomavirus-16 E6/E7 expression is common in SCCHN, and E6 is known to promote presentation of wt p53 epitopes. Although human papillomavirus-16 E6/E7 expression was detected in 46% of the tumors, it did not correlate with the frequency of wt p53(264-272)-specific CD8+ T cells or with p53 expression in the tumor. These findings emphasize the complexity of interactions between the tumor and the host immune system, and, thus, have particularly important implications for future p53-based immunization strategies.

Oncologic outcomes of surgically treated early-stage oropharyngeal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to characterize oncologic outcomes in early (T1-T2, N0) and intermediate (T1-T2, N1) oropharyngeal squamous cell carcinoma (SCC) after surgery. METHODS: Patients with oropharyngeal SCC treated with surgery were identified from 2 academic institutions. RESULTS: Of 188 patients, 143 met the inclusion criteria. Eighty-six (60%) had T1 to T2 N0 and 57 (40%) had T1 to T2 N1 disease. Sixty-five patients (45%) underwent a robotic-assisted resection, whereas the remaining had transoral (n = 60; 42%), mandible-splitting (n = 11; 8%), or transhyoid approaches (n = 7; 5%). Human papillomavirus (HPV) status was known for 97 patients (68%), and 54 (55%) were HPV positive. Three-year recurrence-free survival (RFS) was 82% (95% confidence interval [CI] = 0.75-0.89). Since 2008, HPV infection was protective of recurrence (log-rank p = .0334). A single node did not increase the risk of recurrence (p = .467) or chance of a second primary (p = .175). CONCLUSION: Complete surgical resection is effective therapy for early and intermediate oropharyngeal SCC. HPV-negative patients were at increased risk for locoregional recurrence or second primary disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1471, 2016.

Cricoarytenoid rheumatoid arthritis: an important consideration in aggressive lesions of the larynx.

The most frequent cause of an aggressive mass in the larynx is squamous cell carcinoma (SCC). Rheumatoid arthritis is known to affect the larynx but does not usually produce an aggressive mass. We present a case of rheumatoid arthritis in a 63-year-old woman who presented with acute upper airway obstruction. On CT scans, an erosive mass on the right cricoid cartilage with significant destruction of the surrounding structures was presumed to be an aggressive SCC. Surgical biopsies revealed rheumatoid arthritis of the cricoarytenoid joint. When a patient with rheumatoid arthritis presents with a mass in the larynx, cricoarytenoid rheumatoid arthritis should be ruled out even in the face of an aggressive lesion appearance at CT.

Controversial ectopic thyroid: a case report of thyroid tissue in the axilla and benign total thyroidectomy.

A 43-year-old woman presented with a mass in her left axilla, which was surgically excised. Histologically, the tissue was a reactive lymph node with adjacent thyroid follicular tissue. The differential diagnosis included benign ectopic thyroid versus metastatic well-differentiated follicular-derived thyroid carcinoma. Because of the possibility of carcinoma, the patient underwent a diagnostic total thyroidectomy. The thyroid was grossly normal with no histologic evidence of malignancy. Post-operatively, the patient underwent a whole body 131I scan. Aside from an expected residual uptake in the thyroid bed region, there was no extrathyroidal uptake to suggest additional ectopic thyroid tissue or metastatic disease. At the time of this scan, her thyrotropin (TSH) was 92.8 microU/mL, thyroglobulin was less than 0.3 ng/mL, and thyroglobulin antibody was less than 3 IU/mL. Abnormalities in the embryologic development and migration of the thyroid gland can result in ectopic thyroid tissue. The most frequent locations are along the midline from the base of the tongue to the mediastinum. Only rare case reports exist of ectopic thyroid in other locations, including the chest (heart, trachea), abdomen (liver, gallbladder, pancreas), and pelvis (vagina). This case represents the first description of thyroid tissue in the axilla with a histologically benign thyroid gland.

Combined PET-CT in the head and neck: part 2. Diagnostic uses and pitfalls of oncologic imaging.

Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) is effective for monitoring head and neck cancer. However, lack of anatomic landmarks, variable physiologic FDG uptake, and asymmetric FDG distribution in the neck can confound image interpretation. This is particularly true in the treated neck, where distortion of normal tissue planes makes detection of early disease recurrence difficult with conventional computed tomography (CT) and magnetic resonance imaging. Combined PET-CT helps prevent the misinterpretation of FDG PET findings in patients with head and neck cancer. Superior localization of FDG uptake with this technique can improve diagnostic accuracy and help avoid interpretative pitfalls. In the future, development of tumor-specific ligands will enhance the usefulness of PET-CT in the detection of initial tumors and tumor recurrence, in the evaluation of tumors with low FDG avidity, and in treatment targeting. Furthermore, improved scanner resolution will help address the limitations of PET-CT with respect to small lesions and may make this modality more valuable in initial tumor staging.

Immunophenotypic comparison of salivary gland oncocytoma and metastatic renal cell carcinoma.

OBJECTIVES/HYPOTHESIS: The differential diagnosis of oncocytic neoplasms of salivary glands includes both primary and metastatic tumors, one of which is renal cell carcinoma. This study compared immunohistochemical staining characteristics of oncocytomas arising from salivary gland to metastatic renal cell carcinoma using a panel of markers. STUDY DESIGN: Immunohistochemistry for cytokeratin 7 (CK7), cytokeratin 20 (CK20), epithelial membrane antigen (EMA), vimentin, CD10, and renal cell carcinoma marker (RCC) was performed on 10 oncocytomas and compared with ten metastatic renal cell carcinomas. RESULTS: There were overlapping histologic findings in the oncocytomas and metastatic renal cell carcinomas, with oncocytomas displaying clear cell changes in 2 of 10 cases. CK7 was positive in 9 of 10 oncocytomas and CK20 in 8 of 10 (7/10 stained for both), and vimentin was only weakly positive in 4 of 10 oncocytomas. All oncocytomas were EMA positive, with membranous staining, and all were negative for CD10 and RCC. Metastatic renal cell carcinoma was strongly positive for vimentin, EMA, and CD10 in most cases. RCC and CK7 were variably positive in metastatic renal cell carcinomas (4/10), and only 1 of 10 showed weak staining with CK20. CONCLUSIONS: Salivary gland oncocytomas and metastatic renal cell carcinomas share some similar histologic and immunohistochemical characteristics. CD10 and CK20 were the most useful markers to distinguish metastatic renal cell carcinoma from oncocytomas in the salivary gland, whereas RCC, EMA, CK7, and vimentin are not as useful.

Etiopathogenesis and clinical presentation of carotid body tumors.

The carotid body (CB) is a highly specialized small organ located at the bifurcation of the common carotid artery in the neck and plays an important role in acute adaptation to hypoxia. The most common diseased state of the carotid body is its enlargement (i.e., the CB paraganglioma), which can be caused by a genetic predisposition (hereditary paraganglioma, PGL) and by chronic hypoxic stimulation. The CB is the most common tumor site in head and neck paragangliomas. Currently, inactivating germline mutations in the mitochondrial complex II subunits SDHB, SDHC, and SDHD have been identified as genetic risk factors for CB tumors (CBTs). Another locus at chromosome 11q13, identified by linkage analysis in a single family, may harbor a fourth susceptibility gene. Although CBTs are mostly slow-growing and benign, they can cause significant morbidity because of their proximity to major arteries and nerves in the head and neck. Here, we review the etiological factors implicated in the development of CBTs and provide information pertaining to their clinical presentation. Although CBTs are rare, they have the potential to provide unique insights for tumorigenesis and oxygen sensing and signaling mechanisms.

Prognostic significance of microscopic and macroscopic extracapsular spread from metastatic tumor in the cervical lymph nodes.

It has been established that the presence or absence of cervical node metastases in patients with head and neck squamous cell carcinoma (HNSCC) is a powerful prognostic indicator. This report reviews the evolution of thinking over the past 70 years with regard to the import and detection of cervical nodal metastases which exhibit spread of tumor beyond the confines of the original encompassing nodal capsule. In the process, this discussion touches upon clinical examination, gross and microscopic pathologic examination, and radiographic imaging studies. In particular, the distinction between gross nodal extracapsular spread of tumor and microscopic nodal extracapsular spread of tumor has been drawn in recent reports; this raises the possibility that identification of microscopic breaching of the nodc capsule by tumor might provide clinically significant information which is not provided by the gross observation of an intact lymph node capsule. While it remains to be seen whether microscopic extracapsular spread alone will prove to be an important prognostic factor, it is recommended that selective neck dissection continue to be offered even in those patients with clinically negative necks; further studies should aid in defining the import of microscopic extracapsular tumor spread in patients with positive cervical nodes.