You are in: eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > HEAD AND NECK ONCOLOGY Malignant Tumors of the LarynxArticle Last Updated: Feb 14, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Gerard Domanowski, MD †, Former Associate Chair, Former Associate Professor in Pathology, Former Associate Professor of Otolaryngology and Oral Surgery, Department of Pathology, McGill University Health Center Editors: Jack A Coleman, MD, Assistant Clinical Professor, Department of Otolaryngology, Middle Tennessee Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Karen Hall Calhoun, MD, Chair, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Missouri; Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders; Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine Author and Editor Disclosure Synonyms and related keywords: malignant tumors of the larynx, laryngeal cancer, cancer of the larynx, neck metastases, lymph node metastases, subglottic cancer, glottic cancer, supraglottic cancer, neck cancer, laryngectomy, neck tumor, subglottic tumor, glottic tumor, supraglottic tumor, transglottic tumor, tumors of the transglottic larynx, vocal cord cancer, vocal cord tumor, laryngeal malignancy, squamous cell carcinoma of the larynx, INTRODUCTIONSection 2 of 10
  Definition of the problem The larynx is an essential organ that is responsible for the following vital functions:
Loss of the larynx and its resulting potential disfigurement leads to psychological and sociologic consequences. FrequencyAccording to the National Cancer Institute and the American Cancer Institute, 9880 new cases of laryngeal cancer and 3770 deaths from laryngeal cancer occurred in the United States in 2005. EtiologyUntil the complex molecular interactions of all associated etiologic agents for any cancer can be understood, it is always best to think about these interactions as associations. Thinking of intrinsic (eg, genetic) factors and/or extrinsic (eg, smoking) factors as causes is too simple. To most people, a cause implies a condition that is both necessary and sufficient to produce a prespecified result. Laryngeal carcinomas have multiple associations. The most widely accepted risk factors or associations for laryngeal cancer are listed below. Not everyone who has these risk factors develops laryngeal cancer, and not everyone who develops laryngeal carcinoma has these risk factors.
ClinicalGiven the functions of the larynx mentioned above, one can easily imagine the consequences of a carcinoma destroying and/or obstructing the laryngeal structures and their mechanisms (eg, vocal-cord movement). Symptoms vary with the structures involved by malignancy and its accompanying inflammatory reaction. Although the particular tumor, the site, and the patient's constitution play key roles in any given individual, laryngeal cancers as a whole can cause any of the following findings, alone or in combination:
History As in all clinical evaluations, the history is the first step in gathering the facts. Assess or inquire about the following:
In the author's experience, a patient presented with a 0.7 x 0.3 x 0.4-cm tan-white mass of tissue that was coughed up and preserved in vodka for 3 days. It turned out to be a subglottic squamous cell carcinoma. The patient had preserved it well. Physical examination Carefully listen to the patient's voice. With practice, this sound will reveal a great deal, including the likely location of the tumor and the benignity versus malignancy of the process. On general physical examination, compare current findings with previous ones, such as those documented on patient's chart to detect changes (eg, weight loss). Note breath odors during the process. Thorough head and neck examination should include evaluations of neck mobility, neck masses, direct examination of the oral pharynx and epiglottic tip without the aid of instrumentation, and examination of the cranial nerves. Also useful is indirect (mirror) laryngoscopy. INDICATIONSSection 3 of 10
Many laryngeal tumors may appear late with distant metastasis and near-total destruction of some neck structures. Others may appear early. Treatment is necessary for all tumors. Although supplying comfort may be only palliative, it should still be addressed because tumors of the larynx can cause severe misery for the patient and his or her loved ones. Treatment may include single therapy or combinations of surgery, radiation therapy, and/or chemotherapy. Variations of gene therapy and special photosensitizing or photodynamic therapy are being actively explored. Use of vitamin A analogs holds promise and is an area of interest. To select proper therapy, all of the necessary information must first be obtained before available options are discussed with the patient. The anatomy of the larynx is complex and difficult to visualize. Nevertheless, the team caring for each patient must understand it. Specialists in the areas of surgery, pathology, radiation oncology, and radiology understand this anatomy well. For family members, patients, and clinicians who do not deal with anatomic detail in their daily practice, this is a complicated arena. It is the duty of the entire team to effectively understand each other and communicate with the family. RELEVANT ANATOMYSection 4 of 10
Entire books are written about gross and microscopic laryngeal anatomy. The discussion below is an abbreviated version of the relevant anatomy. It should provide the information any clinician needs to understand this anatomic region, and it should explain why different procedures are indicated in different areas. It also helps in clarifying the consequences of each procedure. The larynx and its tumor locations may be divided in several ways. The simplest description of laryngeal tumors is to divide them into intrinsic tumors, or those that arise in the larynx itself and that are still confined to that structure at presentation, and extrinsic tumors, either those that arise outside the larynx and extend into it or those that arise in the larynx and extend outside it. The extrinsic lesions are usually more advanced and more difficult to treat than the intrinsic ones. Another method of classification, based on anatomic location, is more informative but also more complex than the former system. In this scheme, the larynx is divided into the supraglottic larynx, the glottis or glottic larynx, or the subglottic larynx. The supraglottic larynx includes the epiglottis, the preepiglottic space, the aryepiglottic folds, the false vocal cords, the arytenoids, and the ventricles. The glottis consists of the true vocal cords extending to roughly 1 cm below the true cords, the paraglottic space, and the anterior and posterior commissures extending inferiorly between about 5 cm posteriorly and 1 cm anteriorly. The subglottic larynx has its superior border at the inferior border of the glottis, that is, approximately 1 cm below the true vocal cords and extending inferiorly to the trachea. WORKUPSection 5 of 10
Lab Studies
Imaging Studies
Other Tests
Diagnostic Procedures
Histologic FindingsThe vast majority of laryngeal cancers are of the squamous cell carcinoma variety. Variations include standard squamous cell carcinoma (in situ or invasive, well, moderately or poorly differentiated), verrucous carcinoma, spindle cell carcinoma, basaloid-squamous cell carcinoma, and papillary squamous cell carcinoma. Other types of carcinoma are neuroendocrine carcinoma, lymphepitheliomatous carcinoma, adenocarcinoma, and rare tumors (including sarcomas, lymphomas, adenocarcinomas, and metastases). Because 96% of laryngeal carcinomas in the United States are squamous cell carcinomas, the following discussion is limited to this neoplasm. Laryngeal squamous cell carcinoma histologically is similar in many ways to squamous cell carcinoma found elsewhere in the body. It arises in stages from hyperplasia, dysplasia of various degrees, in situ carcinoma, and invasive squamous cell carcinoma. At times, these stages cannot be observed in an invasive carcinoma. In addition, some squamous cell carcinomas of the larynx arise de novo without an in situ stage. This process was demonstrated for oral tumors, and some indications suggest that this may be true in laryngeal tumors as well. About 5-7 cell layers line the normal larynx. In some regions, this lining is stratified squamous epithelium, and in others (eg, ventricle, false cord, and subglottis), this is pseudostratified respiratory epithelium. The nuclei at the base are elongated, with their long axis perpendicular to the basement membrane. Normal mitotic figures are present in the basal layer, which is 1 layer above the parabasal layer. Mitotic figures should be absent above this second layer. As the cells move toward the surface, the nuclei become oval then full circles. By the fourth to fifth layer from the bottom, all of the squamous cells should have circular nuclei. The nuclei then continue upward and elongate again, first to ovals then to flattened variants. However, this time, the elongated nuclei have their long axis parallel to the surface and therefore parallel to the basement membrane. Surface keratinization may or may not be present. In situ carcinoma is simply full-thickness atypia of the squamous cells. The basal nuclei have round, oval, and elongated forms. The long axes of the elongated forms are haphazardly arranged and not perpendicular to the basement membrane except by occasional chance. Typical and atypical mitotic figures are observed throughout the epithelial surface, with some at the surface or 1 layer below. These figures are usually but not always abundant. The individual cells themselves are bizarre in appearance, with angulated nuclei, multipoled mitotic figures, apoptotic cells (individually necrotic cells), hyperchromasia, and high nuclear-to-cytoplasmic ratios. Invasive squamous cell carcinoma simply means that the wild-appearing squamous cells, and often keratin, are beneath the area where the usual basement membrane lies. The cells may extend deeply into soft tissue, and they may invade cartilage, nerves, blood vessels, and lymphatics. They may invade as nests, broad and pushing fronts, as individual cells, or as any combination of these. The pathologists classify the degree of atypicality as follows: well, moderately, or poorly differentiated or undifferentiated. Use of the undifferentiated classification is best avoided. The term undifferentiated carcinoma is an oxymoron in that an undifferentiated neoplasm cannot show any morphologic features of epithelium (ie, carcinoma). In addition, the pathologist may subtype the tumor according to the types of tumors listed at the beginning of this section (eg, papillary carcinoma or verrucous carcinoma). StagingSquamous cell carcinoma of the larynx is divided into 4 major stages, I-IV. Each of these major stages is divided by location: supraglottis, glottis, or subglottis. In addition, stage IV is subdivided into 3 groups, A, B, and C. To stage a squamous cell carcinoma of the larynx, one must pay attention to the following list:
TREATMENTSection 6 of 10
Medical therapyTreatment of patients with laryngeal carcinoma is extremely complicated because the area contains numerous vital structures near each other. Many therapeutic modalities can damage or destroy these structures. Current treatment of all stages of laryngeal cancer is evolving. For instance, new chemotherapeutic regimens are undergoing clinical trials. Surgical techniques are changing to decrease the morbidity of total laryngectomy. With irradiation, simulations are increasing in sophistication, portals are shrinking, and new techniques (eg, brachytherapy in addition to external-beam irradiation, and intraluminal irradiation) are being used. Experimentation continues for potential gene therapy with antisense cyclin D1, recombinant adenovirus p53 injection has potential, and the combination of adenovirus p16 (INK4A) gene therapy and ionizing radiation holds promise. Experimental investigations are being conducted in China, in several European countries, and in the United States. Therapy is predicated on histologic type, grade, tumoral stage, and overall health of the patient. However, treatment should be individualized to each patient and his or her social circumstances. What is tolerable to one patient may be unthinkable to another. Total laryngectomy is a life-altering procedure that, in a real sense, never heals. Postoperative and peritherapeutic care is also a consideration. One patient may have a supportive family who lives close enough to the patient and to the radiation and chemotherapy center, whereas another may be minimally mobile, living alone in a rural area far from the hospital. These issues are best considered with the patient and the head and neck tumor board as a team. The present author has been a part of a tumor board that met with the patient on one day and then gave the family and patient 3 days to consider the options before reconvening. This approach was extremely effective. That being said, standard treatments have been recognized as a baseline for consideration at each stage of laryngeal cancer. Details and updates about these treatments can be obtained on the Head and Neck Cancer Web site maintained by the National Cancer Institute. Careful consideration and continual monitoring of data from clinical trials and published results should be a priority when therapy, including the addition of neck dissection or partial neck dissection to any procedure or irradiation of the neck or tumor bed, is planned. Surgical therapySurgical therapy is a function of the type and stage of the neoplasm; the patient's health, function, family support mechanisms; and the surgeon's and patient's comfort levels and trust in any procedure. The surgical procedure may vary from something as simple as a vocal-cord stripping to total laryngectomy with glossectomy and partial pharyngectomy. Between these extremes, options include palliative care, vertical hemilaryngectomy, horizontal hemilaryngectomy, and other modifications and new developments. The treatment team and patient must consider these options. Postoperative detailsRecovery from laryngeal surgery is a difficult process on which to put time limits. Depending on the surgery, the process may be long and arduous, involving prostheses, mechanical vocal mechanisms, and severe respiratory problems. The main point is that one must arrange for substantial follow-up care before any laryngeal surgery is performed. The extent of that care depends on the procedure and on the patient. Follow-upFollow-up care is necessary because second primary cancers, recurrences, and late metastases are all strong possibilities. The assistance of speech therapists, occupational therapists, and physical therapists with experience in swallowing or secretion control should also be considered. COMPLICATIONSSection 7 of 10
The complications and consequences of surgery, radiation therapy, and chemotherapy are well known. However, in the larynx, unique or at least unusual complications must be considered. These are listed below.
OUTCOME AND PROGNOSISSection 8 of 10
Many factors influence the outcome and exact therapy for an individual patient. These factors make prognostication in an individual impossible. The survival data described below are for groups. One must be extremely careful not to extrapolate that information to any given patient. That said, data for the patient population in the United States in 1980-1985 are known.
FUTURE AND CONTROVERSIESSection 9 of 10
Gene therapy using adenovirus and other molecular mechanisms aimed at improving the host's immune response and overall handling of the neoplasm is rapidly growing. Photosensitizing agents to work as an adjunct to other therapy, eg, irradiation or laser therapy, are showing initial promise. Retinoids or other vitamin analogs offer great promise, but the adverse effects add complications for which potential solutions are currently being explored. In addition, animal studies have been ongoing. Nothing in the near future of laryngeal cancer can be as exciting and controversial as the current investigations into laryngeal transplants. In Cleveland, Ohio, an area well known for its outstanding medical care, the first laryngeal transplantation was preformed in 1998. As of 2005, the graft continued to function well. Although the patient population is small, given this promising result, research areas worldwide will most likely continue to strive forward in this field. REFERENCESSection 10 of 10
Malignant Tumors of the Larynx excerpt Article Last Updated: Feb 14, 2007 |
