Benign Neoplasms of the Nasal Cavity, Paranasal Sinuses, and Nasopharynx

Clinical Features

SPs are a rare disease with an estimated annual incidence of ~2.3 cases per 100,000 population, representing < 5% of all sinonasal tract tumors. Males are affected much more commonly than females (2 to 10 : 1), depending on subtype, with patients presenting over a wide age range (mean, 20 to 70 years), also type dependent. Children are rarely affected. Clinical symptoms are nonspecific and include unilateral nasal obstruction, followed by epistaxis, an asymptomatic mass, polyps, rhinorrhea, facial pressure, and headaches. Symptoms are often present for a long duration. Often, patients report previous intranasal surgery before a diagnosis of SP is firmly established. Physical examination usually demonstrates a unilateral polypoid mass in the nasal cavity. There is well-documented evidence that exophytic papillomas have a strong HPV association (38% to 65%) and a weaker association with IPs but usually low-risk types 6 and 11, with only rare cases of types 16 and 57b. The association is not established for oncocytic type. p16 at this time does not have the same surrogate expression as seen in oropharyngeal carcinoma.

SPs show a remarkable anatomic distribution according to histologic type: EPs arise almost exclusively on the nasal septum (lower anterior); IPs and OPs affect the lateral nasal wall, middle meatus, and the paranasal sinuses (maxillary, ethmoid, sphenoid, frontal sinuses). Rarely, exceptions are noted. Less than 3% of cases are bilateral and usually reflect extension or secondary involvement of the disease from one side to the other. Rarely, cases are seen as primary lesions in nasopharyngeal, lacrimal sac, or middle ear mucosa.

Radiographic Features

Plain x-rays, computed tomography (CT), and magnetic resonance imaging (MRI) routinely show a unilateral polypoid mass filling the nasal cavity, although variable based on the extent of disease ( Fig. 2.1 ). Displacement of the nasal septum and opacification of sinuses are also frequently seen. Pressure erosion of the bone is present in ~45% of cases.

Pathologic Features

Microscopic Findings

Exophytic Papilloma

EPs consist of branching, exophytic proliferations composed of fibrovascular cores lined by well-differentiated multilayered (up to 20 cells thick) squamous epithelium ( Fig. 2.2 ). The epithelium ranges from basal and parabasal cells ( Fig. 2.3 ) to well-differentiated keratinized cells with a granular cell layer and surface keratin with hyperkeratosis ( Figs. 2.4 and 2.5 ). Koilocytic atypia may be seen. Surface keratinization is uncommon. There may be intraepithelial or luminal ciliated or goblet cells. The stroma usually contains variable numbers of seromucous glands. Mitotic figures and atypical mitoses are uncommon. Malignant change is exceptional.

Inverted Papilloma

IP consists of a markedly thick, inverted, or endophytic growth of multiple layers (up to 30 cells thick) of nonkeratinizing transitional cells ( Fig. 2.6 ) associated with transmigrating neutrophils. The inverted areas are surrounded by a well-formed basement membrane and do not show irregular, “invasive” growth ( Fig. 2.7 ). The epithelium in IP undergoes squamous maturation with superficial cells adopting a flattened orientation, but ciliated columnar epithelium is usually seen, whereas surface keratinization and a granular cell layer are uncommon (< 10%). Distinct cell borders and cleared cytoplasm (due to glycogen) are frequent findings. Cellular pleomorphism may be present but is focal and not associated with dyskeratosis or increased mitotic activity. A characteristic feature is the presence of numerous intraepithelial microcysts containing macrophages, neutrophils, mucin, and cellular debris ( Fig. 2.8 ). These microcysts are more numerous close to the luminal surface. Mucous cells may be interspersed. Mitotic activity is variable but usually limited to basal and parabasal cells. The stroma ranges from edematous, myxomatous, to fibrous, usually showing a conspicuous absence of seromucous glands. An inflammatory infiltrate is composed of a variable mixture of neutrophils, eosinophils, and small lymphocytes ( Fig. 2.8 ). Concurrent nasal inflammatory polyps may be present. Malignant transformation may be seen, identified as conventional in situ and invasive carcinomas ( Fig. 2.9 ), developing in ~2% of patients. When carcinoma is present, it is synchronous in the majority of cases, with squamous cell carcinoma the most common tumor type, although mucoepidermoid carcinoma, sinonasal undifferentiated carcinoma, and verrucous carcinoma may be seen.

Oncocytic Cell Papilloma

OPs are characterized by a proliferating multilayered (two to eight cells thick) columnar or oncocytic epithelium ( Fig. 2.10 ) arranged in both exophytic and endophytic patterns, associated with intraepithelial microcysts. Most OPs have an exophytic branching papillary appearance with long delicate fibrous cores. The individual tumor cells show well-defined cell borders with eosinophilic or granular oncocytic cytoplasm. The nuclei are round, centrally located, and uniform. Small to medium nucleoli are readily seen. The surface cells frequently show cilia ( Fig. 2.11 ), although often with regression. Numerous small intraepithelial microabscesses are seen, filled with mucin and/or neutrophils. Mitotic figures are uncommon in OP. Unlike IP, seromucous glands may be seen in the submucosa. Malignant transformation of OP is uncommon but may develop.

Ancillary Studies

Differential Diagnosis

The differential diagnosis depends on the histologic type of papilloma and includes sinonasal polyps, cutaneous squamous papilloma, verruca vulgaris, papillary squamous cell carcinoma, respiratory epithelial adenomatoid hamartoma (REAH), low-grade papillary adenocarcinoma, and rhinosporidiosis. Sinonasal polyps have marked stromal edema and inflammation with a nonproliferative epithelium, lacking intraepithelial microcysts, and usually show minor mucoserous glands in the subepithelial stroma. Verruca vulgaris has prominent keratinization with verrucoid or papillomatous growth, keratohyaline granules, and koilocytes, while lacking intraepithelial mucocytes and transepithelial neutrophils. Origin from skin rather than mucosa is also a helpful finding. Papillary squamous cell carcinomas are characterized by papillae with fibrovascular cores lined by clearly malignant squamous epithelium. It is important to bear in mind the possibility of a carcinoma arising in a sinonasal papilloma. REAH is a rare hamartoma with epithelium arranged in a glandular distribution, usually with a well-developed basement membrane. Low-grade papillary sinonasal adenocarcinoma has an infiltrative growth, with acinar, cystic, or trabecular growth. Rhinosporidiosis has characteristic sporangia and endospores within the stroma, below the epithelium rather than the microcysts within the epithelium of IPs and OPs.

Prognosis and Therapy

The long-term prognosis of SPs without in situ or invasive carcinoma is excellent. However, there is a considerable recurrence rate, often dependent on the extent of the tumor and initial surgical approach used. If inadequately removed, recurrences or persistence develop in up to 50% (more common for inverted than the other types), usually developing within 5 years of initial presentation. Multiple recurrences are not uncommon. Given the anatomic confines, if neglected, significant morbidity may be experienced. There is no correlation between the number of recurrences and the development of carcinoma, if it occurs. Carcinoma is seen in ~2% of cases, although exceptional in the exophytic type, and seems to be synchronous or de novo, rather than developing after many recurrences. Prognosis for carcinoma is similar to primary squamous cell carcinoma.

The treatment of choice is surgery, whether endoscopic, snare avulsion, or by a more radical excision (lateral rhinotomy and medial maxillectomy, Caldwell-Luc procedure, craniofacial resection or midfacial degloving). Meticulous removal is imperative if recurrences are to be averted. Chemotherapy and radiation therapy are not of benefit, although radiation may be used in rare cases to treat unresectable cases.

Clinical Features

Approximately one-third of mucosal LCH arise in the nasal cavity (~60% present in the oral cavity). When in the oral cavity, the gingiva is most frequently affected, whereas in the nasal cavity, the anterior inferior nasal septum (Little area) accounts for ~60% of cases ( Fig. 2.12 ); 20% involve the nasal vestibule and 20% affect the turbinates and/or sinuses. These lesions usually affect boys younger than 15 years, females in their reproductive years and especially during pregnancy, and, less commonly, older adults of either sex. Patients with an inherited syndrome tend to be younger at initial presentation. Overall, females are affected more frequently than males (2 : 1), but in the pediatric group (up to 18 years), males are much more frequently affected than females.

Patients typically present with intermittent, painless episodes of unilateral epistaxis (in ~95% of cases). The lesions tend to bleed easily, often with only slight trauma. Large lesions may cause nasal obstruction (in up to 35% of cases). Tumors may present as a rapidly growing, painless, hemorrhagic mass, with patients experiencing symptoms for a relatively short duration. Rhinoscopy generally shows a well-defined, sessile or polypoid, red to purplish mass. Often, there is mucosal ulceration with a fibrinous exudate. Patients who develop tumors during pregnancy may show spontaneous involution postpartum, as hormone levels return to normal.

Radiographic studies show the anatomic site, extent, and vascular nature of the lesion (intensely enhancing) and identify feeder vessels and allow for presurgical embolization.

Pathologic Features

Gross Findings

LCHs are polypoid ( Figs. 2.12 and 2.13 ), nodular, or sessile masses with pink or gray-tan color. They are often soft and compressible submucosal masses. Frequently, the surgical specimen is ulcerated (~40% of cases) and partially covered with a yellow to white fibrinous exudate. There is a wide range in size (1 to 8 cm), with a mean of ~1.5 cm.

Microscopic Findings

The term “lobular capillary hemangioma” properly describes the microscopic appearance of this benign vascular tumor. At low power the polypoid LCH exhibits a distinct lobular architecture with a mixture of thin and thick blood vessels comprising the center of the lesion ( Fig. 2.14 ). Surface ulceration with fibrinoid material can be seen ( Fig. 2.15 ), sometimes with a collarette of epithelium on either side of the ulcerated area. The lobules are quite cellular and composed of small, closely packed capillaries with slit-like or indistinct lumina ( Fig. 2.16 ). The endothelial cells are plump with bland nuclear findings and scant to moderate eosinophilic cytoplasm ( Fig. 2.17 ). Mitotic activity within the lobules is readily identified. The center and superficial portions of LCH show well-formed capillaries or large angulated vessels with branching lumina. These vessels may have thick walls resembling small arteries or venules. There is usually an intimate association of spindled pericytes within the perivascular spaces. The stroma ranges from edematous to fibrotic, the latter well-developed in older lesions. The inflammatory infiltrate is usually limited, much more prominent at the surface ulceration, where a fibrinous exudate and areas indistinguishable from conventional granulation tissue may be seen ( Fig. 2.15 ).

Ancillary Studies

Although unnecessary in the vast majority of cases, the endothelial cells are positive for vascular markers such as CD31, CD34, FLI1, and FVIIIRAg, as well as variable staining with estrogen and progesterone receptors. Actin stains highlight pericytes and smooth muscle cells. Reticulin will highlight the endothelial cells, whereas elastic stains highlight fibers in the vessel walls. Although not used in diagnosis, a clonal deletion (21)(q21.2q22.12) has been identified.

Differential Diagnosis

This benign tumor must be separated from nasopharyngeal angiofibroma (NPA), glomangiopericytoma (GPC), and angiosarcoma. The lobular architecture is not seen in other vascular tumors. The vascular component of NPA, which develops exclusively in males, is separated by thin to thick collagen fibers and spindle or stellate stromal cells. GPC is a cellular tumor composed of syncytia of oval to spindle cells with a characteristic perivascular hyalinization and interspersed mast cells and eosinophils. Angiosarcoma is widely infiltrative, composed of atypical endothelial cells lining freely anastomosing vascular channels, while showing increased mitoses. Sinonasal polyps have more of a haphazard vascular proliferation but are surrounded by an edematous to fibrotic stroma with mucoserous glands and eosinophils.

Prognosis and Therapy

LCHs are benign tumors that do not recur after complete resection, but recurrences (up to 42%) are usually seen in older patients. Biopsy should be avoided due to potential profound epistaxis. Planning of the resection should include radiographic studies to investigate the extent of the tumor and allow for possible presurgical embolization. Excision is best accomplished by wide endoscopic resection, using yttrium aluminium garnet (YAG) laser to control potential bleeding. The resection should include a rim of normal mucosa/submucosa. Aplasia of the nasal cartilages could result in potential disfigurement in young patients, so caution should be used in choosing between various surgical options.

Clinical Features