Malignancies of the Paranasal Sinus

Squamous Cell Carcinoma

The most common of the sinonasal malignancies (40% to 50% incidence), SCC arises from the respiratory epithelium with varying squamous keratinization. Substantial evidence supports the hypothesis that smoking is a predominant risk factor, much as it is for other aerodigestive tract sites. Other risk factors linked to SCC include aflatoxin, chromium, nickel, and arsenic, among others. In terms of increased risk from exposure, a meta-analysis of 12 case-control studies identified an odds ratio of 13.9 for workers in the food preservation industry. A viral etiology is also associated with sinonasal SCC: HPV subtypes 6 and 11 are associated with inverted papilloma, of which approximately 10% degenerate into squamous cell malignancy.

SCCs tend to recur more quickly than other sinonasal subtypes, with mean recurrence reported to be 2 to 3 years. The incidence of regional neck metastasis may be relatively higher at 20% to 25%, which is suggestive of the possible need for elective neck dissection.

Adenocarcinoma

Adenocarcinomas make up between 13% and 19% of paranasal sinus malignancies, and their glandular architecture implies they arise from surface epithelium or seromucous glands. Besides those arising from minor salivary origin, adenocarcinomas are typically divided into non-intestinal and intestinal types. Non-intestinal adenocarcinomas convey a relatively good prognosis. Intestinal-type adenocarcinomas, which are histologically similar to colorectal adenocarcinomas, by contrast are locally aggressive with a high rate of spread to neck lymph nodes. The 5-year overall survival has been reported to be approximately 50%.

Among the known occupational hazards associated with paranasal sinus malignancies, the most indisputable causative connection has been with wood dusts, which have been described to convey up to a 900-fold increased risk in developing adenocarcinoma, specifically the intestinal type. Other pooled analyses have suggested an odds ratio for exposed males in wood-related occupations to be 13.5, increasing to 45.5 for longer duration of exposures. It appears that exposure for as little as 5 years can place workers at risk, whereby the latency before diagnosis is approximately 40 years. Leather-related dust exposure also appears associated with adenocarcinoma development, but to a lesser degree.

Adenoid Cystic Carcinoma

ACCs comprise 6% to 10% of paranasal sinus malignancies and are the most common sinonasal tumors of minor salivary gland origin. They are often classified by their tubular, cribriform, or solid growth pattern, with solid ACCs displaying the most aggressive biology. Of significant interest is ACC's high rate of perineural invasion and distant metastases over time, though its biologic behavior requires further investigation. While 5-year survival ranges from 73% to 90%, 15-year disease-specific survival falls to as low as 40%. Unlike SCC, the high recurrence rate takes many years to manifest.

Esthesioneuroblastoma

Esthesioneuroblastomas make up less than 5% of paranasal sinus malignancies and are of neuroectodermal origin derived from olfactory epithelium. They are characterized by a lobular appearance with neuroblasts and neurofibrils embedded among highly vascular fibrous stroma. The Kadish staging system has been the most widely accepted as an effective means to predict disease-free survival; group A tumors are limited to the nasal cavity, group B tumors extend only to the paranasal sinus, and group C tumors extend beyond the nasal cavity and sinuses. A modified Kadish system includes group D tumors, which have cervical lymphadenopathy or distant metastasis. Of note, esthesioneuroblastomas are typically radiosensitive but eventually develop cervical neck metastases in 20% to 25% of patients. This has prompted controversy about the utility of elective neck dissections or elective neck irradiation in patients with esthesioneuroblastoma. Approximately 50% of esthesioneuroblastomas are first discovered as Kadish group C, and these patients have reported 5-year survival rates of 50% to 70%.

Sinonasal Undifferentiated Neoplasm

SNUCs are aggressive, high-grade malignancies without clear squamous or glandular differentiation. The cells of origin remain unclear but potentially arise from Schneiderian epithelium or nasal ectoderm. Histologically solid sheets and nests of high-grade pleomorphic cells are identified with profuse mitotic figures and necrosis. Immunohistochemistry for SNUCs is nonspecific, lacking reactivity for neuroendocrine markers, but is useful to exclude similar entities such as esthesioneuroblastoma, with which it was originally classified. The clinical presentation of SNUCs is often rapid growth and extensive disease, with more than 80% of patients demonstrating T4 lesions at presentation. Trimodality treatment including surgery, radiation, and chemotherapy is typically recommended if able to be tolerated. Many patients have disease that is unresectable, and for those who are surgical candidates, the appropriate order of treatment (neoadjuvant versus postoperative chemoradiation) remains unclear. Nodal disease has been reported at 26% to 27%, meriting consideration of elective treatment of the bilateral necks. The 5-year overall survival is 22% to 43%, with as many as 65% of patients developing distant metastases.

Mucosal Melanoma

While it is comparatively less common in the paranasal sinuses than the other tumor types discussed here, the sinonasal cavities are the most frequent site for mucosal melanomas in the head and neck. Mucosal melanomas comprise less than 1% of all melanomas and are commonly less pigmented than cutaneous lesions, though they similarly stain positive for S-100, HMB-45, and melanin A. They also behave differently enough to merit their own staging system, as cutaneous predictors such as lactate dehydrogenase (LDH) or Breslow depth have not been historically shown to affect survival. Mucosal melanomas are extremely aggressive, with all lesions classified as T3 and Stage 3 at minimum. While surgical resection remains the standard of care, the majority of patients ultimately develop distant metastases, with the most common sites being lung, liver, and bone. The 5-year overall survival has been reported to be between 25% and 42%.

Rhabdomyosarcoma

Among pediatric patients, rhabdomyosarcomas are the most common paranasal sinus malignancy, with the orbit being the most common subsite overall. Rhabdomyosarcomas are derived from primitive mesenchymal tissue with myogenic differentiation and are among the tumors with small round blue cells found on histology. Current histologic classification subdivides rhabdomyosarcoma into four categories. The embryonal type is the most common variant (55% to 65% incidence) and typically affects infants and younger children. Within the embryonal classification are botryoid and spindle cell subtypes, generally considered to have the most favorable prognosis. The alveolar type (20% to 30% incidence) more often occurs in teens and has poorer prognostic potential, usually requiring more intensive multimodality treatment. The anaplastic type (previously termed pleomorphic type) largely affects adults, while the undifferentiated type is ill-defined with no obvious histologic myogenesis or differentiation. Both of these types harbor poor prognoses due to rapid growth and high rate of distant spread.

In the head and neck, biopsy only is typically performed given the presence of critical structures nearby, as recurrence can be high despite aggressive resection. Some protocols advocate neoadjuvant chemoradiation to make tumors more amenable to resection. Overall, 5-year overall survival is high, especially for orbital rhabdomyosarcoma at 95%, while for parameningeal sites it is 74%.