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Infections and Inflammatory Processes
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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.
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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.
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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.
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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.
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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).
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Tumors of the Nose, Sinuses, and Nasopharynx
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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.
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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.
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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.
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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%.
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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.
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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.