Laryngeal Cancer: Diagnosis and Preoperative Work-up

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Laryngeal carcinoma is the eleventh-most common form of cancer among men worldwide and is the second-most common malignancy of the head and neck. The primary functions of the larynx involve phonation, respiration, and deglutition but it also contributes to taste and smell by allowing the movement of air over the special sense organs. Thus, loss of laryngeal function affects speech and swallowing and some of the senses that allow us to enjoy the world. Moreover, total laryngectomy bypasses the critical humidification function of the upper aerodigestive tract that renders pulmonary toiletry problematic for these patients. With relatively little change in mortality since the 1970s, recent research has focused not only on improving survival but on laryngeal preservation modalities.

Section snippets

Biology of laryngeal malignancy

Effective treatment and understanding of laryngeal cancer requires fundamental knowledge of the complex anatomy of this region. Based on its embryologic development, the larynx can be divided into three levels: supraglottic, glottic, and subglottic, with each level containing a number of subsites (Table 1). These divisions have clinical relevance in that they help predict the clinical behavior and pattern of spread of the tumor.

The supraglottis extends from the tip of the epiglottis superiorly

Laryngeal framework

Except for advance stage tumors, most laryngeal cancers tend to remain confined to one anatomic site because of the “pushing” mechanism of tumor growth (Fig. 1). Seminal dye and histologic studies have confirmed this compartmentalization in lymphatics and vasculature [5], [6]. Additionally, cartilaginous and fascial anatomic structures, such as the thyroid and cricoid cartilages with their overlying perichondrium, the ventricle, the conus elasticus, the quadrangular and thyrohyoid membranes,

Office evaluation

The are three major goals to the initial evaluation:

  • (1)

    Determining whether or not the lesion is malignant (tissue diagnosis)

  • (2)

    Staging the lesion in the context of the optimal treatment for the patient

  • (3)

    Mapping both the gross disease and regional nodes as well as potential occult or metastatic disease.

The typical patient is a male in his 50s or 60s with a history of smoking and alcohol use. However, the male predilection for this disease has recently decreased from a male:female ratio of 15:1 to

Tobacco and alcohol abuse

Eighty-five percent of laryngeal cancers can be attributed to tobacco and alcohol use. Smoking is the predominant risk factor for laryngeal carcinoma with alcohol use being an independent and synergistic risk factor [9]. Current smokers have a 10- to 20-fold increased risk of laryngeal cancer compared with nonsmokers [10], [11]. However, these risks decline sharply after smoking cessation—although never to the same level as patients who have never smoked. Ten to 15 years after smoking

Imaging

Imaging serves as a critical adjunct to the physical examination, and not a substitute. It can be useful for staging. Imaging can provide valuable assessment of anatomic spaces difficult to objectively assess on physical examination or by endoscopy (pre-epiglottic space, paraglottic space, thyroid cartilage invasion). Imaging may also supplement clinical examination information as to the tumor volume and extralaryngeal extension. Furthermore, imaging can assist with surgical planning and in the

PET/CT in post-treatment evaluation

While PET/CT has found increased use in the pretreatment period, its greatest utility may be in the setting of detecting recurrent cancer after radiation therapy and/or surgery, where the resultant anatomic changes are difficult to characterize by traditional imaging modalities (CT, MRI) alone. PET/CT already has a track record of high sensitivity and specificity in detection of recurrences of head and neck cancers in general. One of the few studies looking specifically at laryngeal cancer

Metastatic work-up

In the absence of advanced laryngeal carcinoma and cervical metastasis, distant spread of tumor is rare. Spector and colleagues [32] reviewed 1667 patients with primary laryngeal carcinoma and found an overall metastasis incidence of 3.6%, 4.4%, and 14.2% for supraglottic, glottic, and subglottic tumors respectively. The incidence of distant metastasis for supraglottic tumors correlated with the presence of cervical metastasis while the incidence for glottic tumors correlated with T-stage and

Operative assessment

Despite an adequate examination in the office including laryngoscopy and tumor mapping, most patients with laryngeal carcinoma require a trip to the operating room for formal endoscopic examination and biopsy under anesthesia.

Is panendoscopy still indicated?

Panendoscopy including laryngoscopy, esophagoscopy, and bronchoscopy has been the standard for many years. However, with improved preoperative imaging some centers do not consider panendoscopy a standard part of the diagnostic work-up. Others have advocated symptom-directed endoscopies based on the fact that most second primaries are revealed by their specific symptoms [36]. Supporters of continued panendoscopy argue that while the number of simultaneous second primary tumors identified at

Newer/novel diagnostic modalities

Various new techniques have been introduced to improve the diagnostic accuracy of microlaryngoscopy. Autofluorescence diagnosis is based on the ability of oxidized flavin mononucleotide (FMN) in normal cells to emit green fluorescence when exposed to blue light. Neoplastic cells can be distinguished by their significantly lower levels of FMN and consequently do not fluoresce to the same degree. Initial studies have shown some promise with increased accuracy and a tendency toward earlier

Molecular diagnosis

The reader is directed to the article by Loyo and Pai on “The Molecular Genetics of Laryngeal Cancer” in this issue for a more in-depth review of this topic. Squamous cell carcinoma (SCC) accounts for approximately 95% of all laryngeal malignancies. SCC of the head and neck arises from premalignant progenitors followed by growth of clonal populations associated with cumulative genetic alterations and phenotypic progression to invasive malignancy. These genetic changes lead to inactivation of

Staging

The last modification of the AJCC TNM staging protocol occurred in 2002 (Appendix). Although this staging provides prognostic information, it does not stratify the patients into the various treatment modalities to assist the clinicians. To this end, the American Society of Clinical Oncology formed a multidisciplinary Expert Panel to review the current literature available through November of 2005 [49]. One finding was the lack of randomized prospective trials to direct evidence-based treatment

Histology

Squamous cell carcinoma constitutes the overwhelming majority of laryngeal malignancies: 90% to 95%. One note about the histology of laryngeal SCCA is that the grade of the carcinoma is not predictive of prognosis, unlike SCCA in some of the other areas of the head and neck. There are recent reports that the depth of invasion may correlate with its aggressive behavior, but these findings have yet to be corroborated.

Several clinical dilemmas present themselves when leukoplakia is diagnosed with

Follow-up

Although laryngeal cancer patients are treated by a multidisciplinary team, the surgeon should play the leadership role during the follow-up period. Most recurrences occur in the first 2 years after primary treatment, so a complete otolaryngologic history and examination is mandatory within this time frame. The clinical visits are typically spaced every 4 to 6 weeks the first year and every 8 to 12 weeks the second year. Annual visit can be done after the fifth year. There are no serum markers

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