Molecular and cellular biomarkers for field cancerization and multistep process in head and neck tumorigenesis

One way to explain the development of head and neck cancer is through the theories of field cancerization, i.e., the exposure of an entire field of tissue to repeated carcinogenic insult, and multistep process, i.e., development of multiple cancers in a predisposed filed through a series of recognizable stages. Recent molecular genetic studies of histologically normal and premalignant epithelia of high-risk subjects and studies of malignant tumors in aerodigestive tract epithelia have identified a continuum of accumulated specific genetic alterations that possibly occur during the clonal evolution of tumors, namely, during the multistep process. Second primary or multiple primary tumors arise in the same fields as independent clones, with similar but unique molecular genetic and/or cellular alterations. Consequently, the assessment of these genetic and phenotypic alterations has been integrated into clinical chemoprevention trials in an effort to identify biomarkers that are also risk predictors and intermediate end points. This review covers candidate biomarkers of the processes of field cancerization and multistep tumor development in aerodigestive tract epithelia, including general and specific genetic markers, proliferation markers, and squamous differentiation markers.     

Pretherapy dental decisions in patients with head and neck cancer. A proposed model for dental decision support

OBJECTIVE: Sensory and motor abnormalities are common among patients with complex regional pain syndrome (CRPS). The purpose of the present study was to define and characterize these abnormalities and to develop a hypothesis regarding the area of the central nervous system from which they derive. DESIGN: Data were acquired from study subjects using clinical examination and quantitative assessment of neurological function. Subjects were divided into four groups. CRPS patients were differentiated into two groups based on the presence or absence of sensory deficit on the face to clinical examination. The other two groups were composed of patients with other chronic pain syndromes and normal individuals without chronic pain or disability. Clinical and quantitative data were compared between groups. PATIENTS: One hundred forty-five CRPS patients, 69 patients with other pain conditions, and 26 normal individuals were studied. RESULTS: A high incidence of trigeminal hypoesthesia was observed in CRPS patients. CRPS patients with trigeminal hypoesthesia manifested bilateral deficits of sensory function, with a predominant hemilateral pattern. These patients also manifested bilateral motor weakness with a more prominent hemiparetic pattern. Both sensory and motor deficits were greatest ipsilateral to the painful side of the body. These features differed significantly from those of CRPS patients lacking clinical trigeminal deficit, other pain patients, and normals. A lower cranial nerve abnormality (sternocleidomastoid weakness) and a myelopathic feature (Hoffman's reflex) were more common in CRPS patients with trigeminal hypoesthesia. CONCLUSIONS: Nearly half of CRPS patients had abnormalities of spinothalamic, trigeminothalamic, and corticospinal function that may represent dysfunction of the medulla. One-third of the remaining CRPS patients had neuroimaging evidence of spinal cord or brain pathology. The majority of CRPS patients in this study have measurable abnormalities of the sensory and motor systems or neuroimaging evidence of spinal cord or brain dysfunction.     

Management of the clinically positive neck in organ preservation for advanced head and neck cancer

An 82-year-old man was treated with isoniazid (INH) because of a low-grade fever. On the 9th day of treatment, dry coughing and general malaise developed. On the 30th day, he was admitted to our hospital. A chest-X ray film showed infiltrative shadows in the right middle and lower lung fields, but a chest CT scan showed an abnormal lung density in the right lower lobe. Abnormal laboratory findings included leucocytosis, liver dysfunction, hypoxemia, low vital capacity, low diffusing capacity and a high level of C-reactive protein. A differential cell count of the bronchoalveolar lavage fluid (BALF) showed many neutrophils and lymphocytes; examination of a specimen obtained by transbronchial lung biopsy (TBLB) revealed edema of alveolar walls, lymphocyte infiltration, and proliferation of type II alveolar epithelial cells. A drug lymphocyte stimulation test (DLST) against INH was positive. After discontinuation of INH, symptoms resolved, laboratory findings became normal, and the infiltrative shadows in the right middle and lower lung fields disappeared. The clinical course and the findings of BALF, TBLB, and DLST suggested the diagnosis of pneumonitis caused by INH.     

Plasmacytomas of the head and neck

Plasmacytomas are rare tumors that often appear in the head and neck region and are characterized by a monoclonal proliferation of plasma cells. On both clinical presentation and pathologic examination these tumors may be confused with more common tumors of the head and neck. The purpose of this article is to review our experience with these rare neoplasms, with emphasis on clinical, pathologic, and therapeutic features. On retrospective chart review, we identified 20 patients with the diagnosis of plasmacytoma of the head and neck region at the Cleveland Clinic Foundation between 1976 and 1993. Records were reviewed with regard to initial symptoms, location of the neoplasm, diagnostic evaluation, treatment modalities, and survival. Of the 20 cases we identified, the tumor arose in the sinonasal/nasopharyngeal region in 11 (55%). Two cases (10%) represented medullary plasmacytomas, arising in the clavicle and presenting as supraclavicular masses. The mean follow-up was 60.2 months (range 6 to 131 months). In 15 of the 20 cases, immunohistochemistry staining for immunoglobulin light chain production was conducted. One of the two cases (50%) classified as medullary plasmacytoma demonstrated conversion to multiple myeloma, whereas only 2 of 18 cases of extramedullary plasmacytoma (11%) converted to multiple myeloma. The primary modality of treatment was radiation therapy with typical doses of 4500 to 6000 cGy. Kaplan-Meier survival estimates demonstrated 95% survival at 1 year, 82% survival at 5 years, and 10-year estimated survival of 72%. Plasmacytomas of the head and neck region are rare and on initial evaluation must be distinguished from multiple myeloma. The diagnostic evaluation includes appropriate radiologic and pathologic studies including immunohistochemistry. Despite the typical presentation as a locally destructive tumor, plasmacytomas are highly radiosensitive, and 70% to 80% survival may be obtained with the use of radiotherapy. Patients with plasmacytomas require long-term follow-up to detect conversion to multiple myeloma.     

Reconstruction of the head and neck

The collaboration of surgeons, radiation oncologists, chemotherapists, dentists, oral surgeons, prosthodontists, and speech therapists has led to major advances in the management of the difficult cancers of the head and neck area. The advent of myocutaneous flaps and the facilitation of microsurgical free flaps have ushered in an era of one-stage reconstructions to shorten the hospital stay and improve the overall therapeutic, functional, and cosmetic results.     

Melanomas of the head and neck

Melanomas of the skin and mucous membranes of the head and neck region are an uncommon problem for most clinicians. The article emphasizes the differences in terms of biological aggressiveness and treatment between lentigo maligna (LM) and lentigo maligna melanoma (LMM), superficial spreading melanoma (SSM), and nodular melanoma de novo. The results of radiotherapy in the treatment of melanoma of the head and neck are reviewed, and indications are suggested for the use of irradiation in the management of patients with this tumor. A brief discussion of the results of treatment of mucosal melanomas is given.     

Multifocal accumulation of p53 protein in esophageal carcinoma: evidence for field cancerization

A dispersed, rye-specific element has been used to isolate clones of rye origin from wheat plants containing only a single rye chromosome arm or segment. In this way a set of 23 YAC clones has been isolated from the short arm of rye chromosome 1 (1RS). This technique was extended to isolate clones from a small region of 1RS that contains a large number of agronomically important genes. The targeted cloning method allowed the isolation of 26 classes of lambda clones representing about 5% of the region. Ten of the lambda clones could be mapped to segments within this region. A third example of the application of this technique involved the isolation of clones from a very small but fully functional rye chromosome, the midget chromosome. These clones have allowed the confirmation of the origin of the midget from 1RL, and may provide a tool for the isolation of structural elements of cereal chromosomes. This technique allows the identification of clone libraries for any rye chromosome or chromosome arm, since substitution, addition and translocation lines are available for all rye chromosomes. Furthermore, the technique allows isolation of clones derived from segments of the rye genome recombined into wheat. The method is technically simple and both lambda and YAC libraries can be constructed. Synteny between the genomes of the cereals allows region-specific libraries from rye to be used to target regions of the wheat and barley genomes.     

Myofibrosarcoma of the head and neck in children

We have identified a distinctive malignant soft tissue neoplasm that occurred in the head and neck region of six children. Histologically, these neoplasms presented an array of features ranging from low-grade spindle cell to high-grade fibrohistiocytic histologies and often had myoid characteristics. Ultrastructural and immunohistochemical studies indicated that they contained neoplastic myofibroblasts that were variably positive for vimentin (4 positive/4 tested), alpha-smooth muscle actin (4/5), muscle-specific actin (5/5), desmin (2/5), and v-src protein substrate p80/85 (4/5). Three patients died of rapidly progressive unresectable local disease, one died of metastatic and local disease, and two are alive 13 months and 8 years after wide resection. We conclude that these neoplasms form a distinctive subset of pediatric soft tissue sarcomas that display an aggressive clinical behavior, typically with local recurrence, and exhibit features of myofibroblastic differentiation.     

Bite injuries in the head and neck area

In Germany about 8500 dog-bite injuries in the face occur every year; more than 50% of the victims are infants and schoolchildren. Besides dogs, other animals such as cats or horses may be responsible for these accidents. Even human bites are reported. The predominant areas are the nose and the auricles. The tissue defects may be superficial, but they can even cause amputations, including severe vascular and nerve or bony destruction. Systemic antibiotic therapy is needed when the wound is infected. The surgical approach to bite injuries includes local wound cleansing, careful excision of necrotic tissue and primary closure of the wound whenever possible. Regarding the importance of surgery in the head and neck area plastic-reconstructive techniques including autologous transplantations and various local or regional flaps should be used at the time the wound is first repaired.     

Critical care for the severely ill head and neck patient

BACKGROUND: Acne scars cannot be effectively corrected by a single treatment modality because of their widely varied depth and width. OBJECTIVE: We assessed the effectiveness of staged combinations of several surgical modalities in the treatment of acne scars. METHODS: Focal chemical peeling, carbon dioxide (CO2) laser, scar excision, punch grafting, and dermabrasion were used. Initially, focal chemical peeling was performed on all patients and then CO2 laser, scar excision, and punch grafts were used for deep scars. Finally, dermabrasion was done for the remaining scars. RESULTS: Seventy-five percent of patients showed excellent or good results. The degree of improvement increased as the follow-up periods and number of focal chemical peeling procedures increased and as the 3-staged operation progressed. CONCLUSION: A 3-staged operation is effective in the treatment of patients with various types of acne scars.     

Symptom management for incurable head and neck cancer

The overall cure rate for cancer of the head and neck is about 50%. For those patients who will die of their disease, active palliative care is needed. This article seeks to present a practical approach to managing the symptoms, especially pain, suffered by patients with incurable malignancy. (See related article, Using Opioids to Control Suffering: A Painstaking Approach, on page 20 of the February, 1997 WMJ.) While the focus is on head and neck cancer, the principles and much of the information contained herein is applicable to patients dying from other types of malignant disease.     

MR angiography of the head and neck

A review of the basic physics and techniques for acquiring and evaluating magnetic resonance angiograms is provided, including time-of-flight and phase contrast techniques. Magnetic resonance (MR) angiography is becoming a routine method of evaluating carotid bifurcation atherosclerotic disease in both a screening and diagnostic capacity. The expanding clinical utility of MR angiography in the detection of intracranial aneurysms, characterization of arteriovenous malformations, and evaluation of intracranial atherosclerotic disease are also reviewed. Furthermore, MR angiography allows for the noninvasive diagnosis of arterial dissection. Magnetic resonance venography also allows the confirmation of the previously elusive and likely underdiagnosed entity of cerebral venous thrombosis.     

Mucosal melanomas of the head and neck

PURPOSE: To determine the effect of epidural analgesia on biochemical markers of stress, plasma oxytocin concentrations and frequency of uterine contractions during the first stage of labour. METHODS: Nine nulliparous women, in spontaneous labour, with a singleton fetus and cervical dilatation < or = 5 cm were enrolled. Epidural bupivacaine 0.25% (range 10-14 ml) was administered and bilateral sensory blockade to ice (T8-L4) achieved. Blood samples were collected before the epidermal block and every 10 min for one hour after the block was achieved for the measurement of plasma beta-endorphin, cortical, glucose, lactate and oxytocin concentrations. No exogenous oxytocin was given. Intensity of pain was assessed at the time of the blood sampling using a 10 cm visual analogue scale (VAS). The frequency of uterine contractions was recorded for 60 min before and after the epidural block. RESULTS: There was a decrease in plasma beta-endorphin and cortisol concentrations after epidural block (P < 0.01). There were no changes in plasma glucose and lactate concentrations. The mean VAS for pain decreased 10 min after epidural block was achieved and remained < 2 throughout the study period (P < 0.001). Mean plasma oxytocin concentrations did not change. The frequency of uterine contractions before and after the epidural block was similar. CONCLUSIONS: The metabolic stress response to the pain of labour was attenuated by epidural analgesia. In contrast, plasma oxytocin concentration and frequency of uterine contractions were unaffected by the attenuation of metabolic stress response.     

Skin cancer of the head and neck

The incidence of skin cancers is increasing at a rate greater than any other cancer occurring in humans. In this era of managed care, patients with a suspicious skin lesion may first present to their primary care physician for evaluation. Therefore, it is important for the primary care physician to be able to distinguish between benign and malignant pigmented lesions, to know how to evaluate such a patient, and to appreciate the importance of appropriate interdisciplinary management of these patients.     

Expanded flaps on the head and neck

The authors study the practical aspects of head and neck expansion: choice of material, choice of flaps obtained by skin expansion. They then examine the specific features of expansion in this anatomical region, where it is frequently used, with emphasis on preservation of aesthetic units and the specificities of skin hair and natural orifices. Scalp expansion in the context of baldness is discussed in a separate article.     

Nonnasopharyngeal lymphoepithelioma of the head and neck

BACKGROUND: Lymphoepithelioma (squamous cell carcinoma with associated lymphoid stroma) commonly occurs in the nasopharynx, rarely at other sites. As a result, the clinical course and optimal treatment of nonnasopharyngeal lymphoepithelioma of the head and neck have not been well described. This retrospective study was undertaken to analyze the clinical course of the disease in patients treated at a single institution and to formulate recommendations for treatment based on that experience as well as results reported in the literature. METHODS: Between 1950 and 1994, 34 patients with nonnasopharyngeal lymphoepithelioma of the head and neck were treated at the University of Texas M. D. Anderson Cancer Center. The patients' medical records were reviewed and their pathologic specimens evaluated. The primary tumor sites were: oropharynx (24 patients), salivary gland (4), laryngohypopharynx (4), and the maxillary sinus/nasal cavity (2). Assessed in accordance with the 1992 American Joint Committee Against Cancer TNM staging system, T classifications were TX-2, T1-7, T2-8, T3-10, and T4-7, and N classifications were N0-8, N1-5, N2-15, and N3-6. Treatment consisted of radiotherapy for 24 patients, excisional biopsy of the primary tumor followed by radiotherapy for 7 patients, and surgery for 3 patients. Of the patients treated with radiotherapy, neck dissections were performed on only two, both of whom had persistent lymph node masses after completing radiotherapy. The median dose delivered to the primary tumor was 65 gray (Gy) (range, 46-78 Gy). The median fraction size was 2.1 Gy (range, 1.6-3.2 Gy). RESULTS: The 5-year actuarial disease specific survival and overall survival rates were 59% and 39%, respectively. The 5-year actuarial local control rate for all patients was 94%. For the irradiated patients, the 5-year regional control rates were 77% overall and 83% within the radiation field. The 5-year actuarial rate of distant metastasis for all patients was 30%. For patients who presented with and without regional adenopathy, the 5-year rates of distant metastasis were 36% and 12%, respectively (P = 0.27). CONCLUSIONS: Nonnasopharygeal lymphoepithelioma is a radiosensitive disease. High rates of locoregional tumor control were achieved with radiotherapy at all head and neck sites. The main cause of treatment failure was distant metastasis, which occurred more frequently in patients with lymph node involvement. Radiotherapy is appropriate initial locoregional therapy for patients with this disease. Surgery should be reserved for patients who have persistent disease after completing radiotherapy. Systemic therapy is a reasonable approach for patients who present with regional adenopathy because they have a relatively high rate of distant metastasis.     

Traumatic neuromas of the head and neck

An interesting case of a traumatic neuroma of the greater auricular nerve provides the impetus for a discussion of head and neck neuromas. Traumatic neuromas of the head and neck are relatively rare. Division of the greater auricular nerve during parotidectomy occasionally results in a traumatic neuroma. We report a case of a 73-year-old woman who presented with a traumatic neuroma nine years after undergoing superficial parotidectomy with dissection of the facial nerve for a mixed tumor. The patient had a 1.5 cm x 1.0 cm mass located below the old surgical site over the anteromedial border of the sternocleidomastoid muscle. The patient's past history was significant for Frey's syndrome, which is the result of abnormal neurologic growth. On first impression, the tumor was thought to be a recurrence of neoplastic disease; however, because of the evaluation, traumatic neuroma was suspected. An attempt at fine-needle aspiration of the mass was too painful to be carried out. At surgery, a whitish tumor was excised which, on final pathologic examination, revealed traumatic neuroma. The surgical literature is reviewed and the subject of head and neck neuromas, including their evaluation and management, is thoroughly discussed. Knowledge of this possible diagnosis may spare the patient and the surgeon needless worry, as well as unnecessary procedures, once tumor recurrence has been ruled out.     

Pediatric rhabdomyosarcoma of the head and neck

PURPOSE: Survival for pediatric rhabdomyosarcoma has improved with the use of multidrug chemotherapy and external beam radiotherapy. This study was performed to determine survival in a cohort of patients treated on one of three multidrug treatment protocols for head and neck rhabdomyosarcoma and to identify factors that place patients at risk for treatment failure. METHODS: Pertinent prognostic variables including age, sex, subsite of origin, resectability, and TNM stage were analyzed by the Kaplan-Meier methods with comparisons between variables performed using the Prentice-Wilcoxon test statistic. RESULTS: Overall 5-year survival was 74% (95% confidence interval 64% to 84%). Local failure accounted for the cause of death in 10 patients, and 8 died of disseminated disease. On univariate analysis, each variable contributing to the TNM staging system was significant in determining survival; invasiveness (P = 0.01), size (P = 0.02), nodal metastases (P <0.01), and distant disease (P <0.01). CONCLUSION: Survival has improved for head and neck rhabdomyosarcoma treated with multimodality therapy. Patients with advanced-stage disease are at greatest risk for treatment failure and require the most aggressive therapy.