Unifocal and multifocal squamous papillomas occur throughout the upper aerodigestive tract, from the nasal vestibule, to the oral cavity, to the larynx. They can develop at any age, but often occur in children and young to middle-aged adults, possibly reflecting a relationship with exposure to human papillomavirus (HPV). Some lesions may be distinguished as condylomas or verruca when they are caused by HPV; however, such distinction is usually not necessary, and unequivocal infection is rarely demonstrated without ancillary testing. It should be noted that although koilocytic change may be helpful for identifying lesions induced by HPV, the appearance of an HPV-associated viral cytopathic effect is also not entirely specific. True HPV-induced lesions are often multiple and are more common in individuals infected with human immunodeficiency virus (HIV) or who are otherwise immunosuppressed. While most papillomas are not considered to be at risk for malignant transformation and do not show dysplastic changes, lesions in immunocompromised patients may show dysplasia and may be at increased risk for malignant transformation.

Grossly, these lesions are exophytic and may vary considerably in size. A rough, warty appearance may be noted. Histologically, the squamous epithelium is thickened and covers papillary cores of stromal tissue (Fig. 2.1, eFigs. 2.1 and 2.2).¹ Keratinization may be present
and the granular cell layer may appear thickened (Fig. 2.2, eFig. 2.3). The stratified squamous epithelium usually shows normal maturation with limited, if any, atypia. Mitotic figures should be located near the basal layer of the epithelium and some degree of chronic inflammation may be present, especially at the bases of the lesions within the stroma
(eFig. 2.4). The stroma of papillomas of the nasal vestibule will contain skin appendages.² Many lesions have broader bases with more rounded surfaces and less keratinization and thus appear similar to condylomata of the cervix, replete with focal, apparent koilocytic change (Fig. 2.3, eFig. 2.5).

Benign squamous papillomas must be distinguished from malignant or potentially premalignant disease such as verrucous carcinoma or verrucous hyperplasia (see Chapters 3 and 4). Patients with verrucous carcinoma or verrucous hyperplasia are older and will usually have long histories of tobacco use. Verrucous carcinoma and verrucous hyperplasia generally do not appear as discrete polypoid masses; verrucous carcinoma is a destructive lesion which infiltrates the underlying stroma in a pushing manner. As mentioned, squamous papillomas of the upper aerodigestive tract appear less verrucoid than typical skin lesions and more like condylomata.

A particular lesion of the oral cavity, focal epithelial hyperplasia, arises more commonly in children and young adults and tends to be more common is certain geographic locations and in certain ethnicities.³ These lesions are benign and regress as patients age. Numerous small, slightly raised, pink lesions are seen grossly which may become confluent. Histologically, the lesions have squamous hyperplasia, usually devoid of papillary architecture. Koilocytes are readily identified and the clumped chromatin may sometimes appear similar to mitotic figures (mitosoid bodies).

Squamous papillomas of the larynx are categorized according to their number (solitary or multiple) and the age of the patient affected (juvenile or adult).⁴,⁵ Most laryngeal papillomatosis occurs in younger patients. The lesions usually are located in the region of the true vocal cords; however, they may be found throughout the larynx and even throughout the oropharynx and trachea.⁴ They often recur after resection and may cause obstruction. The juvenile lesions and some of the adult lesions are etiologically related to infection of the mucosa with HPV types 6 and 11.⁴ In cases of juvenile papillomatosis, it is thought that infection occurs at birth, whereas with adults, it is believed that the infection may occur at a later age.⁴

Grossly, the lesions are variably sized but are usually smaller than a centimeter in greatest dimension. Histologically, these lesions are characterized by a branched fibrovascular core, covered with maturing stratified squamous epithelium (Fig. 2.4, eFigs. 2.6 and 2.7).⁴ Keratosis is generally not seen. Intraepithelial dysplasia is infrequent but has been noted, and severe or full-thickness dysplasia is very uncommon and should suggest a diagnosis of papillary carcinoma (Fig. 2.5, eFig. 2.8).⁶ Koilocytic change may be seen. Rare cases of extremely well-differentiated squamous cell carcinomas arising in patients with laryngeal papillomatosis have been recorded.⁷,⁸

The differential diagnosis includes other squamoproliferative lesions especially squamous cell carcinoma, and some cases of laryngeal papillomas in older individuals may be very difficult to separate from papillary
squamous cell carcinomas or verrucous carcinomas. In general, these other lesions are destructive or will show invasion; however, history may be unknown or unclear and invasion may be difficult to assess with small biopsies. Papillary squamous cell carcinoma should show full-thickness cytologic atypia; however, as was mentioned, laryngeal papillomas may also show cytologic atypia. For this reason, clinical follow-up and complete excision are recommended for any adult with a solitary papillary lesion that shows any degree of atypia. Verrucous carcinomas will not, by definition, show severe cytologic atypia and should show keratinization. They should not be diagnosed if the base of the lesion cannot be assessed on biopsy.

Sinonasal or schneiderian papillomas arise almost exclusively within the nasal cavity and paranasal sinuses from the ectodermally derived ciliated columnar epithelium that lines these surfaces; they arise rarely at other sites such as the middle ear.⁹,¹⁰ They occur in middle-aged patients and are at least twice as common in men.¹⁰,¹¹ They are classified according to their growth pattern (exophytic/fungiform vs. endophytic/inverted) and by their epithelial cell type (squamous vs. oncocytic/cylindrical cell), although some lesions may show combined features.¹⁰,¹¹,¹² Most develop within the nasal cavity proper or maxillary sinus (Table 2.1).