Joseph A. Brennan

Molecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck.

BACKGROUND Surgical oncologists rely heavily on the histopathological assessment of surgical margins to ensure total excision of the tumor in patients with head and neck cancer. However, current techniques may not detect small numbers of cancer cells at the margins of resection or in cervical lymph nodes. METHODS We used molecular techniques to determine whether clonal populations of infiltrating tumor cells harboring mutations of the p53 gene could be detected in histopathologically negative surgical margins and cervical lymph nodes of patients with squamous-cell carcinoma of the head and neck. RESULTS We identified 25 patients with primary squamous-cell carcinoma of the head and neck containing a p53 mutation who appeared to have had complete tumor resection on the basis of a negative histopathological assessment. In 13 of these 25 patients, molecular analysis was positive for a p53 mutation in at least one tumor margin. In 5 of 13 patients with positive margins by this method (38 percent), the carcinoma has recurred locally, as compared with none of 12 patients with negative margins (P = 0.02 by the log-rank test). Furthermore, molecular analysis identified neoplastic cells in 6 of 28 lymph nodes (21 percent) that were initially negative by histopathological assessment. CONCLUSIONS Among specimens initially believed to be negative by light microscopy, a substantial percentage of the surgical margins and lymph nodes from patients with squamous-cell carcinoma of the head and neck contained p53 mutations specific for the primary tumor. Patients with these positive margins appear to have a substantially increased risk of local recurrence. Molecular analysis of surgical margins and lymph nodes can augment standard histopathological assessment and may improve the prediction of local tumor recurrence.

Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck.

BACKGROUND Although epidemiologic studies have long associated tobacco and alcohol use with the development of squamous-cell carcinoma of the head and neck, the molecular targets of these carcinogens have yet to be identified. We performed a molecular analysis to determine the pattern of mutations in the p53 gene in neoplasms from patients with squamous-cell carcinoma of the head and neck and a history of tobacco or alcohol use. METHODS Sequence analysis of the conserved regions of the p53 gene was performed in tumor samples from 129 patients with primary squamous-cell carcinoma of the head and neck. We then used statistical analysis to identify any patient characteristics associated with mutation of the p53 gene. RESULTS We found p53 mutations in 42 percent of the patients (54 of 129). Fifty-eight percent of the patients who smoked cigarettes and used alcohol (37 of 64; 95 percent confidence interval, 45 to 70 percent), 33 percent of the patients who smoked but abstained from alcohol (13 of 39; 95 percent confidence interval, 19 to 50 percent), and 17 percent of the patients who neither smoked nor drank alcohol (4 of 24, 95 percent confidence interval, 5 to 37 percent) had p53 mutations (P = 0.001). (Two patients used alcohol but did not smoke, and neither had a p53 mutation.) Furthermore, 100 percent of the mutations in the patients who neither drank nor smoked occurred at sites containing cytidine phosphate guanosine dinucleotides (potentially representing endogenous mutations) within the p53 gene (5 of 5 mutations; 95 percent confidence interval, 48 to 100 percent), whereas only 23 percent of those in cigarette smokers consisted of such changes (12 of 53 mutations; 95 percent confidence interval, 12 to 36 percent; P = 0.001). CONCLUSIONS In our study, a history of tobacco and alcohol use was associated with a high frequency of p53 mutations in patients with squamous-cell carcinoma of the head and neck. Preliminary evidence linked cigarette smoking to p53 mutations at nonendogenous mutation sites. Our findings suggest a role for tobacco in the molecular progression of squamous-cell carcinoma of the head and neck and support the epidemiologic evidence that abstinence from smoking is important to prevent head and neck cancer.

Gene mutations in saliva as molecular markers for head and neck squamous cell carcinomas.

BACKGROUND Cancer is caused by the accumulation of mutations that activate proto-oncogenes and inactivate tumor suppressor genes. The result is a clonal expansion of genetically identical daughter cells that eventually become clinical malignancies. The specific mutations acquired by the progenitor cell are like a fingerprint carried by each cell of the tumor. These mutations can serve as very specific markers for the presence of tumor cells in a background of normal cells. METHODS Mutations in the p53 gene recovered from head and neck squamous cell carcinomas were sequenced, and these altered DNA sequences were used retrospectively as tumor-specific genetic markers for cancer cells in the patients saliva. Cloned p53 sequences amplified by the polymerase chain reaction from DNA extracted from banked preoperative saliva specimens were screened for the presence of tumor-specific mutations using radiolabeled oligonucleotide probes. RESULTS We identified tumor-specific mutations in preoperative saliva samples of 5 of the 7 patients evaluated (71%). CONCLUSIONS These results suggest a potential for clinical applications of this novel approach to cancer detection using gene mutations as molecular markers for carcinomas.

Elective carotid artery resection for advanced squamous cell carcinoma of the neck

The authors performed a retrospective review of their 10‐year experience of carotid artery resection without revascularization for advanced squamous cell carcinoma of the neck. From 1982 to 1991, seven patients underwent elective carotid artery resection without reconstruction at the University of Colorado Health Sciences Center in Denver. A vascular clamp with gradual carotid occlusion was placed preoperatively on four patients and awake temporary balloon occlusion of the carotid was used on three patients. The primary lesions were three laryngeal carcinomas, two oral cavity carcinomas, and two hypopharyngeal carcinomas. All seven resected specimens showed invasion of the carotid fascia on pathological exam, while five specimens exhibited actual destruction of the arterial wall. Cerebrovascular accidents occurred in two patients (one immediate and one delayed), and the perioperative mortality was 29% (one cerebrovascular accident and one gastrointestinal bleed). The five remaining patients died of locoregional recurrence or metastatic disease within 1 year after their carotid artery resection.

PARATHYROID CARCINOMA IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 WITH A CLASSIC GERMLINE MUTATION

OBJECTIVE To report the case of a patient with multiple endocrine neoplasia type 1 (MEN 1) syndrome with con-comitant parathyroid carcinoma and a classic MEN1 germline mutation. METHODS We present the clinical findings, laboratory results, imaging studies, and surgical histopathologic features in a woman with MEN 1 syndrome and concomitant parathyroid carcinoma. We also review the literature regarding patients with similar clinical entities and the use of adjuvant radiotherapy for parathyroid carcinoma. RESULTS A 53-year-old woman presented with nausea and severe primary hyperparathyroidism. Computed tomography revealed parathyroid masses, shown later to be bilateral parathyroid carcinomas and adenomas. Magnetic resonance imaging demonstrated a pituitary macroadenoma, and gastrinomas were confirmed by computed tomography and a secretin stimulation test. She was successfully treated with total thyroidectomy, subtotal parathyroidectomy, and adjuvant radiotherapy. Genetic analysis revealed a classic MEN1 germline mutation. CONCLUSION This report describes a patient with parathyroid carcinoma occurring in conjunction with MEN 1, further characterizing this rare condition. In contrast to previously described patients, our patient is the first with a classic MEN1 germline mutation, confirming that parathyroid cancer can occur in association with classic MEN 1 genetics.

Traumatic Airway Management in Operation Iraqi Freedom

Objectives. To examine the role of head and neck surgeons in traumatic airway management in Operation Iraqi Freedom and to understand the lessons learned in traumatic airway management to include a simple airway triage classification that will guide surgical management. Study Design. Case series with chart review. Setting. Air Force Theater Hospital at Balad Air Base, Iraq. Subjects and Methods. The traumatic airway experience of 6 otolaryngologists/head and neck surgeons deployed over a 30-month period in Iraq was retrospectively reviewed. Results. One hundred and ninety-six patients presented with airway compromise necessitating either intubation or placement of a surgical airway over the 30-month timeframe. Penetrating face trauma (46%) and penetrating neck trauma (31%) were the most common mechanisms of injury necessitating airway control. The traumatic airways performed include 183 tracheotomies, 3 cricothyroidotomies, 9 complicated intubations, and 1 stoma placement. Red or emergent airways were performed in 10% of patients, yellow or delayed airways in 58% of patients, and green or elective airways in 32% of patients. Lastly, surgical repair of the laryngotracheal complex was performed in 25 patients with 16 thyroid cartilage repairs, 4 cricoid repairs, and 8 tracheal repairs. Conclusions. The role of the deployed otolaryngologist in traumatic airway management was crucial. Potentially lifesaving airways (red/yellow airways) were placed in 68% of the patients. The authors’ recommended treatment classification should optimize future traumatic airway management by stratifying traumatic airways into red (airway less than 5 minutes), yellow (airway less than 12 hours), or green categories (airway greater than 12 hours).

Massive Facial Trauma following Improvised Explosive Device Blasts in Operation Iraqi Freedom

Objective. To investigate the association of massive facial trauma with brain and eye injuries, injury severity scores, and blood transfusion utilization. Study Design. Retrospective study. Setting. Air Force Theater Hospital, Balad, Iraq. Subjects and Methods. Retrospective review of US service members injured by improvised explosive devices and treated at the Air Force Theater Hospital in Iraq from October 2004 to September 2007. Massive facial trauma was defined as any injury to the face involving 3 or more facial aesthetic units. The anatomic injury patterns, injury severity scores, and blood transfusion rates of simple and massive facial trauma were compared. Results. One hundred four patients who sustained facial trauma from improvised explosive device blasts were reviewed, including 29 patients with massive facial trauma. The average injury severity score was 13.9 in the simple facial trauma group and 21.7 in the massive facial trauma group (P = .006). Sixteen (55%) of the patients in the massive facial trauma group received transfusions compared with only 21 (28%) in the simple facial trauma group (P = .009). The rate of associated eye injury was 55% in the massive facial trauma group and 27% in the simple facial trauma group (P = .006). Brain injuries occurred in 48% of the patients with massive facial trauma and 28% of the patients with simple facial trauma (P = .05). Conclusion. There is an association between massive facial trauma higher injury severity scores, higher transfusion rates, and an increased risk for eye and brain injuries.

Tracheal paraganglioma presenting with acute airway obstruction.

p a m w c s S aragangliomas of the larynx are rare lesions that are ften confused with other primary and secondary layngeal neoplasms. Location in the subglottis is excepionally rare. These lesions are often misinterpreted as edullary thyroid carcinoma (MTC). Accurate microcopic and immunohistochemical analysis combined ith clinical and radiographic examinations are critical or proper diagnosis. In this report, we describe a case f a recurrent tracheal paraganglioma presenting with cute airway obstruction and hemorrhage following riginal misdiagnosis and treatment as MTC.

Primary hyperparathyroidism secondary to supernumerary intravagal parathyroid adenoma

Abstract Objectives: The goal of this report is to discuss a rare case of primary hyperparathyroidism secondary to a supernumerary ectopic intra-vagal parathyroid adenoma. Methods: Case report with discussion of current literature. Results: A 30-year-old female with primary hyperparathyroidism initially underwent neck exploration to resect a suspected adenoma based on the preoperative localization scan. Despite extensive neck exploration no adenoma was identified. Repeat localization scans and surgical re-exploration successfully identified a high cervical ectopic intravagal parathyroid adenoma. The adenoma was completely resected with a subsequent decrease in the patient’s calcium and parathyroid levels. Conclusion: This unusual case of primary hyperparathyroidism is only the seventh case reported in the English-language literature and highlights the challenges faced by head and neck surgeons when evaluating and treating this disease process. The variability inherent to parathyroid gland anatomy continues to create treatment dilemmas. Though rare, exploration of the vagus nerve should be considered as a possible location of a suspected ectopic adenoma.

The head and neck manifestations of mycosis fungoides

Mycosis fungoides (MF) is a cutaneous T‐cell lymphoma that may progress to involve lymph nodes, the spleen, and other visceral organs. We have retrospectively reviewed our 10‐year experience with MF at the Johns Hopkins Hospital. Forty‐five patients received treatment for MF between 1983 and 1992. Approximately 70% of the patients with MF presented with cutaneous or extracutaneous lesions of the head and neck. The head and neck manifestations, clinical assessment, and treatment of our patient population are presented. Mycosis fungoides is a potentially lethal disease that frequently involves the head and neck region and should be included in the differential diagnosis of cutaneous head and neck lesions.