Benign Neoplasms of the Larynx, Hypopharynx, and Trachea

Clinical Features

Patients may present with dysphonia, hoarseness, and breathing difficulties. Symptoms are generally more severe in children, possibly in part because of the smaller diameter of their airways. On clinical examination, papillomas appear as friable, exophytic masses projecting into the airway ( Fig. 5.1 ). They tend to involve metaplastic areas where ciliated columnar transforms into squamous epithelium (squamocolumnar junction), for example, the true and false vocal cords, ventricles, and subglottis. As disease progresses, the papillomas may extend into the epiglottis and hypopharynx. Rarely (~5% of cases) papillomas can extend into the lower airway (bronchus and lung).

Pathologic Features

Microscopic Findings

Squamous papillomas are characterized histologically by a complex proliferation of fingerlike growths consisting of delicate fibrovascular cores lined by squamous epithelium ( Fig. 5.2 ). There is typically little or no keratinization. Uncommonly there may also be a component of ciliated, respiratory-type epithelium. The lining epithelium is typically hyperplastic (i.e., thickened) and often exhibits mild atypia in the form of parabasal cell hyperplasia with mitotic figures elevated slightly above the basal zone ( Fig. 5.3 ). In addition, koilocytic changes such as nuclear hyperchromasia, irregular (raisinoid) nuclear membranes, and perinuclear haloes are often identified in the superficial epithelial layers ( Fig. 5.3 ). These types of changes should not be overinterpreted as squamous dysplasia. With that being said, in very rare instances, squamous papillomas can undergo malignant transformation into squamous cell carcinoma ( Fig. 5.4 ).

Ancillary Studies

Squamous papillomas are usually diagnostically straightforward and ancillary studies are rarely required. Low-risk HPV types (especially 6 or 11) can be demonstrated by HPV testing techniques, most often RNA or DNA in situ hybridization in more than 90% of cases. The signals are diffuse, nuclear, and usually confined to the most superficial layers of the epithelium ( Fig. 5.3 ). This testing is occasionally diagnostically useful (see Differential Diagnosis later) or may be requested by clinicians (e.g., for enrollment into specific clinical trials). p16 immunohistochemistry is not a useful surrogate for low-risk HPV.

Differential Diagnosis

Adult-onset squamous papillomas may be difficult to distinguish from squamous dysplasia (typically induced by smoking), which can sometimes exhibit papillary or exophytic architecture. As described previously, cellular changes that would be consistent with squamous dysplasia in some settings (e.g., parabasal hyperplasia, mitotic figures above the basal layer) are acceptable in benign squamous papillomas. In this setting, HPV 6/11 testing may be diagnostically useful, as a positive result is reassuring that the process is viral and likely not truly dysplastic. Similarly, the papillary variant of squamous cell carcinoma may be architecturally identical to squamous papilloma ( Fig. 5.5A ). However, this carcinoma variant exhibits overtly malignant cellular findings that are unlikely to be confused with a benign process ( Fig. 5.5B ). Verrucoid lesions such as verrucous hyperplasia, verruca vulgaris, or verrucous carcinoma may be considerations because there are also exophytic squamous lesions; however, these proliferations are broad based, lack papillary fronds with fibrovascular cores, and by definition demonstrate considerable surface keratosis.

Prognosis and Therapy

The clinical course of patients with squamous papillomas is rather unpredictable and is often marked by alternating periods of active disease and remissions, with longitudinal studies showing viral persistence in greater than 95% (same strain at the beginning and in follow-up). Although papillomas are technically benign neoplasms, they can cause considerable morbidity due to airway obstruction and result in death in a small subset (2% to 14%) of patients. The aggressiveness of RRP is associated with age of onset, with disease presenting earlier in life being more progressive and more likely to undergo malignant transformation. The rare examples of malignant transformation tend to be associated with some other risk factor, such as smoking or radiation exposure, and are more often seen in RRP-induced by HPV type 11.

Patients with RRP are treated with multiple conventional or laser surgeries, often with injection of antiviral agents (e.g., cidofovir). It is hoped that widespread use of the HPV vaccine will reduce the incidence of RRP, but the vaccine effects are not yet known.

Clinical Features

Granular cell tumor can be seen in a wide age range but most commonly affects patients in their 3rd to 5th decades. There is no predilection for either sex for laryngeal tumors, but tracheal granular cell tumors are seen more often in women. There is a predilection for black patients. In the head and neck, it is most frequently encountered in the skin, oral cavity (especially tongue), and larynx. Patients with laryngeal granular cell tumor tend to present with hoarseness, dysphagia, cough, or hemoptysis, and a small, nontender posterior vocal fold nodule is seen on laryngoscopic examination. Tracheal tumors generally occur in the cervical region of the trachea ( Fig. 5.6 ). Approximately 10% of patients have more than one tumor.