Chapter 33: Diseases of the Upper Airways and Sinuses

Given their proximity to the environment, it is not surprising that the nasal cavities, sinuses, oropharynx, and trachea are all sites for infectious, inflammatory, and neoplastic diseases. As detailed in Chaps. 2 and 10, much of the lung's conducting zone is well constructed to warm, humidify, and cleanse the inspiratory gas stream while maintaining physical barriers to aspiration events during eating, drinking, and speech. This chapter will focus on diseases that bear directly on respiratory function and pulmonary medicine rather than provide a compendium of all illnesses that might properly be considered the clinical domain of otolaryngology. Students are encouraged to consult adjoining chapters in this book for more specific details regarding anatomical landmarks, histologic configurations, and regional host defense mechanisms.

Infections and Inflammatory Processes

Inflammatory diseases are the most common disorders of the nose and its accessory paranasal sinuses. Rhinitis, or inflammation of the nasal mucosa, may be either infectious or allergic in its etiology. Nasal and sinus infections are usually viral in origin, particularly with adenoviruses, echoviruses, and rhinoviruses. Macroscopically, the affected areas appear red and swollen and may express copious watery exudates, all of which narrow or occlude nasal air passages and increase dynamic upper airway resistance. The histologic presentation is of respiratory mucosal edema, often with inflammatory cell infiltrates. Secondary bacterial infections are common in this setting, in which case neutrophilic influx and purulence are prominent. Uncomplicated cases of acute rhinitis normally resolve in 5-7 days in the immunocompetent host, although sequential infection of deeper airways can occur. As for viral and bacterial infections of the lung parenchyma, treatment options for rhinitis vary from curative to palliative depending upon the pathogen.

Allergic rhinitis, or hay fever, is caused by IgE-mediated reactions to any of the numerous allergens that are known to affect specific individuals. As many as 20% of the American public is affected by such seasonal disease, with the most common irritants as in asthma being plant pollens, fungi, animal dander, and insect droppings (Chap. 21). In such settings, there is also marked mucosal edema and redness of the affected nasal passages, while histologically the inflammatory infiltrates are often distinctly eosinophilic in composition. Nasal polyps are focal, usually non-neoplastic protrusions that commonly arise in the setting of such chronic rhinitis; they may be up to 3-4 cm in greatest dimension. Polyps are often asymptomatic and only found during routine physical exam. Alternatively, they may present with complaints of persistent rhinorrhea (runny nose), noisy breathing, and snoring. Histologically, the polyp is often covered by an intact respiratory epithelium that overlies a markedly edematous connective tissue stroma, usually with mucoid hyperplasia and cyst formation visible, as well as chronic inflammatory cell infiltrates (Fig. 33.1). Persistent polyps can become infected, even as they encroach upon airway lumens and impair sinus drainage. Medical treatment is primarily with nasal or oral corticosteroids, with surgical excision the best option for patients in whom such medical interventions fail.

Acute sinusitis usually results from normal oropharyngeal flora causing inflammation and edema of the sinus mucosa. Obstruction of sinus outflow may cause empyema or lead to formation of a mucocele, a localized mucus accumulation in the absence of bacterial colonization. Indeed, diabetics can develop mucormycosis, often a life-threatening fungal sinusitis. The progression of acute sinusitis to chronic sinusitis is common, particularly with repeated exposure to a causative agent, in the immunosuppressed population, and in patients with anatomical anomalies like deviated nasal septa that block sinus drainage. Such chronic sinusitis (Fig. 33.2) may become superimposed with bacterial infection or become complicated by meningitis, osteomyelitis, orbital cellulitis, or cavernous vein thrombosis. Patients with Wegener's granulomatosis often show nasal as well as intrapulmonary disease, in which there are microscopic findings of vasculitis, geographic necrosis, histiocyte accumulation, granulomatous inflammation, and epithelial ulceration. Chronic sinusitis is a presenting symptom in Kartagener syndrome due to defective ciliary clearance mechanisms, along with bronchiectasis and situs inversus.

Necrotizing lesions of the nasal passages and sinuses may arise from several of the etiologies described above, notably those that reflect actual or potential systemic diseases, like mucormycosis and Wegener's granulomatosis. Focal necrosis of these regions can also occur as a consequence of adjacent superimposed bacterial infection, tumor-related granulomatous inflammation, and some neoplastic processes involving other leukocytes, including natural killer cells.

Inflammation of the oropharynx and its associated lymphoid tissues causes pharyngitis and tonsillitis, respectively. As mentioned above, these often follow chronologically and anatomically from antecedent upper respiratory infections with rhinoviruses, adenoviruses, influenza, and respiratory syncytial virus (RSV). As for the nasal passages and sinuses, the pharynx becomes red and swollen with edematous mucosa and pseudomembranous exudates. Follicular tonsillitis is common and painful, with physical exam showing enlarged reddened tonsils covered with pinpoint exudates that adhere to or appear to be emerging from tonsillar crypts. Superinfection is common with β-hemolytic Streptococci and Staphylococcus aureus, whose late sequelae can produce rheumatic fever and glomerulonephritis (Chaps. 26 and 40).

Tumors of the Nose, Sinuses, and Nasopharynx

Sinonasal papillomas are benign neoplasms that arise from the sinonasal mucosa and most commonly present in adult men whose primary complaint is nasal obstruction. Histologically, they consist of proliferating squamous epithelium among other mucin- positive cells. As such, their cytologic atypia is not impressive, and the cells as a group are usually mature and well-differentiated. The presence of human papilloma virus (HPV) types 6 and 11 is detected in many sinonasal papillomas. Papillomas that originate in the nasal septum are most common; most often these have an exophytic growth pattern, emerging mushroom-shaped from the mucosa with a core of connective tissue [Fig. 33.3(a)]. Papillomas that originate from the middle meatus or middle or inferior turbinates are of an inverted type with an endophytic growth pattern that resembles plant root tubercles penetrating the underlying stroma [Fig. 33.3(b)]. Such inverted papillomas recur at a high rate if not completed excised surgically, and they are also the type most often associated with coexisting or subsequent carcinomas, in 3%-10% of patients.

Nasopharyngeal angiofibromas are relatively uncommon and benign growths that occur almost exclusively in adolescent males, presumably reflecting androgen dependence of the tumor. They arise principally from the posterolateral wall of the nasopharynx, from where they may grow to completely occlude the nares (Fig. 33.4). Histologically, these tumors appear composed mostly of an intricate blend of microvasculature and fibrotic stroma. As a result of this vascular composition, they often bleed profusely during surgical excision.

Olfactory neuroblastomas or esthesioneuroblastomas are uncommon but highly malignant small-cell tumors of neuroendocrine origin. Electron microscopic analysis shows neurosecretory granules, and sections for light microscopy can be stained immunohistochemically for neuron-specific enolase (NSE), neurofilaments, and chromogranin (Fig. 33.5). They arise superiorly and laterally in the nose, where they are often locally invasive and cause distant metastases in ~20% of patients. Overall 5-year survival is relatively poor, although most olfactory neuroblastomas are radiosensitive if treated early or in combination with surgery.

Nasopharyngeal carcinomas are malignant epithelial tumors that are rare in the United States but very common in southeast Asia and parts of Africa. Epidemiological evidence indicates that they most often result from the combined effects of a person's genetic predisposition, local environmental factors, and Epstein-Barr virus (EBV) infection. Histologically, they resemble other squamous cell carcinomas with large cells, prominent nucleoli, and indistinct cell borders. These tumors have a strong tendency to spread to regional lymph nodes, such that cervical lymphadenopathy is a common presenting symptom. By growing silently, these carcinomas often present when already unresectable. In many countries, they are the most common pediatric cancer. Radiotherapy is currently considered the treatment of choice, and 3-year survival ranges from 50% to 70%.

Three major subtypes of nasopharyngeal carcinoma are recognized. Keratinizing squamous cell carcinoma is the most common form in the United States and is not associated with EBV infection [Fig. 33.6 (a)]. It also has the worst prognosis, presumably because it is the least radiosensitive variant. Nonkeratinizing squamous cell carcinoma [Fig. 33.6 (b)] is probably the most common form, at least in the eastern hemisphere. It is clearly associated with EBV infection and shows intermediate radiosensitivity. Finally, the undifferentiated carcinomas [Fig. 33.6 (c)] are also common worldwide, likewise showing association with EBV infection, and are considered the most radiosensitive. Because this variant is often found with an accompanying lymphocytic infiltrate, they are occasionally referred to as lymphoepitheliomas.

A wide variety of other tumors may occur in the sinuses and nasopharynx, and in most cases these resemble histologically their counterparts found at other sites. Notable among these are plasmacytomas that arise in lymphoid structures adjacent to the nose and sinuses; these occasionally can exhibit polypoid growth that resemble polyps described above. In addition, patients may present less commonly with adenocarcinoma, sarcomatoid carcinoma, basaloid carcinoma, malignant lymphoma, malignant melanoma, and some salivary gland tumors including adenoid cystic carcinoma.

Infections and Inflammatory Processes

Like the nasopharynx, the larynx is exposed to a variety of inflammatory and infectious conditions. Collectively these cause laryngitis, the most common laryngeal disorder. Chronic nonspecific laryngitis can result from infection or persistent exposure to tobacco, alcohol, gastric acid, or other toxins. Histologically, the laryngeal wall shows a typical submucosal inflammatory infiltrate with lymphocytes, histiocytes, and plasma cells. The epithelium itself may appear hyperplastic over the affected mucosa. In heavy smokers, such chronic laryngitis is considered an important predisposing condition for squamous epithelial changes and possibly carcinoma. Among the systemic infections that can cause laryngitis, fungi are particularly common and include Histoplasma, Aspergillus, Blastomyces, Candida, and Cryptococcus spp. Mycobacterium tuberculosis may involve the larynx as well. Certain systemic granulomatous diseases, notably sarcoidosis, are rarer but presumably causal agents.

Acute laryngoepiglottitis presents as marked swelling and edema of the epiglottis that can involve the vocal chords sufficiently to produce a medical emergency. It is common in children and can be caused by Haemophilus influenzae or, less often, by some strains of β-hemolytic Streptococcus. Infections with RSV or parainfluenza viruses are common causes of laryngotracheobronchitis or croup. Again, more commonly in children, patients with laryngotracheobronchitis often present with marked respiratory stridor due to significant inflammation and edema in the upper airways (Chaps. 14 and 40). Incidence continues to decline among infants with use of the H. influenzae type B (HIB) vaccine.

Laryngeal nodules, or singer's nodules/polyps, represent a noninflammatory condition that arises from overuse/abuse of the voice. For the most part, these small (usually <5 mm), smoothly rounded, and benign lesions occur on the anterior third of the true vocal chords and are most common in adult males (Fig. 33.7). Histologically, laryngeal nodules are covered by squamous epithelium overlying a core of loose connective tissue that features edema and fibroblast proliferation. Over time the nodules become vascularized and contain hyaline tissue that is the source of one misnomer for these nodules, amyloid tumor. Although laryngeal nodules can lead to progressive hoarseness, they have no known association with cancer. True amyloid deposition can occur in the larynx, but it is not a component of classic laryngeal nodules.

Non-neoplastic conditions that involve the trachea include amyloidosis, rheumatoid nodules, and tracheopathia osteoplastica. The latter is idiopathic and consists of numerous small nodules composed of bone and cartilage that arise in the tracheal submucosa. Of course the trachea can become infected and/or inflamed due to the same types of pathogens and environmental insults that have been described above for the nasopharyngeal regions. However, there is no particular propensity for the trachea to be more sensitive to these conditions than is the remainder of the conducting zone. Serious injuries to the trachea's respiratory mucosa during the course of mechanical ventilation or bronchoscopy are fortunately rare. Like the accidental aspirations of foreign objects, most involve simple abrasions of the tracheal epithelium that heal without incident. Catastrophic hemorrhage into the distal airways is usually attributable to the rupture of blood vessels serving intratracheal masses as these are being inspected or excised. While some of these injuries are clearly medical emergencies, they too resolve spontaneously in most instances.

Precancerous Lesions and Tumors of the Larynx and Trachea

Laryngeal papillomas are benign squamous neoplasms usually found on the true vocal chords, are associated with HPV infection (types 6 and 11), and have differing clinical presentations in the pediatric and adult populations. In children they are often multiple and recur frequently, yielding juvenile laryngeal papillomatosis. These may spread from the child's vocal chords to adjacent regions of the larynx, where they have a small chance of malignant transformation and can occasionally cause airway obstruction and rarely death. In adults, a laryngeal papilloma is usually solitary, rarely spreads or recurs once excised, and has virtually no malignant potential. Grossly, laryngeal papillomas are soft, raspberry-like nodules <1 cm in diameter [Fig. 33.8 (a)]. Histologically, the papilloma in cross section appears with finger-like projections composed of fibrovascular cores, all covered by squamous epithelium (Fig. 33.8). Tracheal papillomas are likewise the most common benign neoplasms in this central airway. These also differ in their complexity and recurrence with patient age and can present as tracheal papillomatosis.

Laryngeal keratosis is a benign epithelial or squamous cell hyperplasia that occurs in smokers and in those who overuse or abuse their voices (Clinical Correlation 33.1). By laryngoscopy, keratosis presents as a thickened white mucosal surface. Microscopically these lesions show hyperkeratosis (excessive keratin synthesis) and acanthosis (thickened hyperplastic epithelium).

Laryngeal dysplasia may occur with keratosis or independently and features cellular atypia and disordered maturation over a wide range of appearances. Dysplasia is graded as mild, moderate, or severe depending on the degree of atypia and extent of involvement through the epithelial layer. Full-thickness atypia (with an intact basal lamina) that does not invade the submucosal layer is termed a carcinoma in situ (CIS). Most CIS forms of dysplasia are considered precursor lesions to invasive carcinoma; the risk of developing malignancy is estimated to be 23%-28% when a biopsy shows both keratosis and severe atypia. More than 75% of patients with invasive carcinomas have CIS in their history. Most CIS cases are found only on the true vocal chords, since they evoke an early symptom of non-resolving hoarseness.

At least 95% of laryngeal malignancies are laryngeal squamous cell carcinomas that are typically graded as well, moderately, or poorly differentiated. Overall, these laryngeal malignancies account for ~2% of all cancers in men and ~0.5% of all cancers in women. As for cancers deeper in the lung (Chaps. 31 and 32), the most important risk factor is tobacco use, followed distantly by alcohol consumption, HPV infection, previous irradiation, metastasis, and laryngeal dysplasia (see above). The laryngeal carcinomas follow distinct patterns of longitudinal spread across specific glottic structures (Fig. 33.9). The occurrence frequencies at each site influence both the likelihood of lymph node metastasis and the expected 5-year survival rate (Table 33.1). Not surprisingly, the most common malignant tumor in the trachea is tracheal squamous cell carcinoma. Most of these malignancies occur in the distal third of the trachea and/or adjacent to the hilum and carry a poor prognosis.

Important considerations regarding laryngeal carcinoma include both the limited lymphatic circulation and the paucity of mucoserous glands in the vicinity of the vocal chords. As a result, glottic carcinomas tend to remain localized for extended periods of time and so are curable if detected and resected early in their course. Nevertheless, invasive glottic carcinomas require a total laryngectomy. Supraglottic tumors may be treatable with a more limited supraglottic laryngectomy, sparing the vocal chords. However, such patients require good pulmonary reserves and intact reflexes to avoid subsequent aspiration events. Infraglottic tumors often will produce a symptom of dyspnea that becomes severe enough to require emergent tracheostomy. In at least 30% of laryngeal carcinoma patients, the lesion crosses the midline (by direct extension or through contralateral lymph node metastasis), which worsens the prognosis. Laryngeal and tracheal carcinomas can be staged using the same International Association of Lung Cancer (IASLC) TNM System as for lung cancer itself (Chap. 32). However, the precise categorizations of laryngeal and tracheal carcinomas into TNM staging subclasses go beyond the intended scope of this book.

There are many rarer and histologically distinguishable laryngeal and tracheal tumors. Clinically, the most aggressive among these in the larynx include small cell carcinoma, basaloid squamous carcinoma, and sarcomatoid (or spindle cell) carcinomas. Verrucous carcinoma is an extremely well-differentiated polypoid type of squamous carcinoma that can show marked local invasion of the larynx but rarely metastasizes. Adenoid cystic carcinoma may involve the larynx or the trachea and is the second most common tracheal malignancy. Larynx and trachea can develop adenocarcinomas, carcinoid tumors, and sarcomas, but collectively these represent a very small percentage of all cases.