As mentioned previously, the nose and the paranasal sinuses pose a unique set of problems that deserve separate consideration from SCC of the UADT. For instance, while SCC is still the most common histology found there, it accounts for less than 50% of disease. The four most common malignant histologies of the paranasal sinuses are SCC, sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma, and esthesioneuroblastoma (often referred to as olfactory neuroblastoma).

Cancer of the nose and paranasal sinuses is relatively rare. When taken as a whole, these malignancies account for only 0.2% to 0.8% of cancers diagnosed annually, or approximately 3% of cancers of the UADT. The incidence is generally reported as 0.3 to 1 per 100,000 population. These cancers tend to occur most commonly in the fifth decade of life although they can occur in the much younger and much older. Cancer of the nose and paranasal sinuses is rare in children except for some sarcomas, such as rhabdomyosarcoma. While there are numerous environmental factors associated with cancer of the nose and paranasal sinuses, as industry has modernized, these have become somewhat less important. There continues to be a relationship between these malignancies and tobacco exposure, however.

Neoplasms of the nose and paranasal sinuses rarely present early. This is due to the fact that these tumors tend to be asymptomatic and usually contained within either a sinus or the nasal cavity. It is not until the patient develops symptoms from nasal airway obstruction or acute sinusitis that the patient seeks medical attention. Early symptoms usually include nasal airway obstruction, rhinorrhea, sinusitis, and occasionally, dental problems such as dental pain, numbness, and loose teeth. Late symptoms are often epistaxis, cranial nerve deficitis, proptosis, facial pain and swelling, ulceration through the palate, and trismus, all of which are ominous signs.

The diagnosis of nose and paranasal sinus cancers is made by having a high index of suspicion in a patient who presents with nasal airway obstruction and a nasal mass. Key to this is a thorough endoscopic or fiberoptic examination of the entire nasal cavity to rule out benign disease such as nasal polyposis or uncomplicated acute or chronic sinusitis. Biopsy is indicated when a mass is found. However, great care should be taken as these lesions can hemorrhage, especially neuroendocrine carcinoma and esthesioneuroblastoma, which have a propensity toward epistaxis. In fact, a patient who presents with significant epistaxis with an otherwise smaller asymptomatic lesion very commonly has neuroendocrine carcinoma. When taking a patient to the operating room for an endoscopic examination and biopsy, a frozen section should be obtained. While it may not be impossible to determine the exact histology of a particular lesion on frozen section, the pathologist is usually able to make a distinction between benign and malignant histology. This allows the surgeon to terminate the procedure if necessary and avoids an unnecessary or contraindicated operation in a patient with a presumed benign diagnosis who actually has a malignant process.

When evaluating the patient with a sinonasal mass, imaging plays an important part in not only the diagnosis and staging of these lesions but also the surgical planning. CT and MRI both play important roles in the evaluation of sinonasal neoplasms. The combination of CT and MRI provides useful information for surgical planning, especially with regard to skull base involvement. While CT provides more information regarding bony anatomy and helps with surgical planning, MRI is better at assessing perineural involvement and skull base involvement and is better able to distinguish neoplasm from inspissated mucus.

The staging of cancer of the paranasal sinuses is made radiographically. As a result of the fact that these malignancies rarely present as early stage, the commonly accepted staging systems are not commonly used; however, for completeness, they are provided in

Table 90-18 for the maxillary sinuses and Table 90-19 for the ethmoid sinuses. Special note is made of the “Ohngren line,” or the malignant plane. The Ohngren line was an early attempt at the staging of cancers of the paranasal sinuses by using plane x-rays. That system divided tumors of the maxillary sinus into favorable and unfavorable, based on their relationship to this plane. The plane is defined on plane x-rays of the sinus and falls between the medial canthus of the orbit and the angle of the mandible. It was considered that tumors above this line (suprastructure) were unfavorable while those below (infrastructure) were favorable. This is no longer used due to the fact that we rarely get plane x-ray films. However, the distinction between unfavorable (suprastructure) and favorable (infrastructure) remains true. The distribution of the location of malignant carcinomas of the paranasal sinuses is shown in

Table 90-20.

Histology
The histology of neosplasms of the nose and paranasal sinuses is varied and can be divided into benign and malignant disease. The most common sinonasal tumor, by far, is benign allergic nasal polyposis. If this is excluded, then the relationship between benign and malignant disease is approximately one to one. After benign nasal polyposis, inverting papilloma accounts for the majority of noninflammatory pathologies. It is generally felt that inverting papillomas arise from the squamous, or Schneiderian, mucosa. Although inverting papilloma are benign, they can act very aggressive locally, causing destruction of vital structures, invasion of the orbit, diplopia, and significant deformities. Furthermore, these are associated with an approximately 15% incidence of malignancy. As a result of their aggressive nature and risk of malignancy, all inverting papillomas should be excised promptly and completely. Varied approaches exist for the resection of inverting papilloma. These approaches vary in terms of their cosmetic impact on the patient but also in their ability to access different areas of the sinonasal cavities. While cosmesis is important, the surgeon must maintain as his primary goal complete excision of the inverting papilloma. Despite complete excision, these tumors can recur locally (9%) and degenerate into malignant disease.

The more common malignancies of the sinonasal cavity are listed in

Table 90-21. As sarcomas and salivary gland malignancies are covered in separate sections, this section will deal only with SCC, SNUC, neuroendocrine carcinoma, and esthesioneuroblastoma.

Treatment
The treatment of neoplasms of the sinonasal cavity are varied and histology specific. The mainstay of treatment, however, is a multidisciplinary approach to all patients with malignant disease. This includes open communication and cooperation between surgeons, radiotherapists, chemotherapists, speech pathologists, dental practitioners, prosthodontists, and social workers. “Traditional” treatment has been surgery, followed by radiation therapy when indicated. While very effective for smaller tumors of select histologies, this combination provides poor control in many instances. This is due to the fact that these tumors usually present with advanced disease. The shortcomings of traditional treatment have led to the incorporation of new approaches, including chemotherapy.

Surgery alone as treatment for sinonasal malignancy is rarely used. It is most commonly associated with postoperative radiation therapy and, more recently, induction or adjuvant chemotherapy. When surgery is indicated, en bloc resection is indicated, as piecemeal excision has a higher risk or recurrence and should be avoided. The operation used depends on the location of the tumor, the extent of the tumor, the histology, cosmesis, and patient preference. For each operation of the sinonasal cavities, there usually exists more than one option for incision and access to the lesion. For example, lateral rhinotomy is one option. This incision lies along the side of the nose and extends from the medial canthus to the nasal ala. It can extend around the nasal ala into the nasal vestibule and allows excellent visualization of the nasal cavity. The vertical limb along the side of the nose is best situated halfway between nasal dorsum and the nasomalar crease. It allows excellent exposure for medial maxillectomy. Obviously, however, many are uncomfortable with the scar on the face, and thus a midface degloving is often used. This is performed through a complete transfition incision of the membranous septum combined with endonasal endocartilagenous incisions bilaterally, which allows the skin of the nose to be elevated completely to the nasion. This incision is then combined with bilateral gingivobuccal incisions that allow the soft tissue of the midface to be elevated from the maxilla, thus exposing the lower two-thirds of the midface. While this approach allows excellent access to the lower sinonasal cavity, there can be some difficulty in reaching the superiormost aspects of the nasal cavity, ethmoids, and cribiform plate.

For maxillectomies, a variant of the “Weber-Fergusson” incision is often used. Specifically, the Weber-Fergusson incision includes the aforementioned lateral rhinotomy with an extension beneath the eye either through the conjunctiva or in an infraorbital skin crease. There can be an extension lateral to the orbit and the zygoma. This skin incision allows excellent exposure to the maxilla and orbit and allows access to the posterior maxillary tissues, thus facilitating maxillectomy. Cosmesis is a concern, but this incision provides the necessary exposure to the lateral maxilla for performing larger resections.

Endoscopic resection of small tumors, especially inverting papilloma, has gained some favor in recent years. While endoscopic resection is possible in some cases and does provide a valuable tool in biopsy, surveillance, and staging, traditional surgical approaches to the midface are still most commonly used for resection of malignant neoplasms.

The indications for a particular operation are based solely on the extent of the lesion. Medial maxillectomy is best used for benign disease or very limited malignancy that is limited to the medial wall of the maxilla or lateral wall of the nasal cavity. It can be performed through a lateral rhinotomy without a lip split or through midface degloving. This is a very effective operation for inverting papilloma and requires no reconstruction. Meticulous closure of the lateral rhinotomy usually leads to a very favorable cosmetic result as well.

Maxillectomy includes removal of the antral walls of the maxillary sinus but leaves the orbital periosteum and the malar strut. It is indicated for T1 and T2 lesions of the maxillary antrum without erosion beyond the sinus. This operation can be tailored to a particular tumor in order to decrease postoperative morbidity. Specifically, when feasible, rather than making a straight midline incision through the palate, the palatal excision can be curved away from the premaxilla, thus saving the incisors and cuspids. This provides a better functional result postoperatively. In addition, the orbital roof can also be preserved if the tumor is located inferiorly. This prevents diplopia, helps to prevent contracture of the skin, and avoids ectropion. The surgical reconstruction of this defect is usually limited to a split-thickness skin graft and prosthetic rehabilitation.

When tumor extends beyond the maxillary sinus into the orbit, then total or radical orbital maxillectomy is indicated. Orbital exenteration is indicated when the periorbita is involved. There is much controversy with regard to the need for exenteration in that while the orbital contents can be saved when only the orbital periosteum is involved, if orbital fat and especially if extraocular movements are restricted due to muscle involvement, the eye should be sacrificed. Innovations with induction chemotherapy may eventually lead to preservation of the eye in certain situations. Once again, reconstruction is best accomplished through the use of a split-thickness skin graft and prosthesis. Occasionally, a free flap may be required for more extensive resections.

Finally, combined craniofacial resections are indicated when tumors extend to the skull base. While many combined operations can be performed exclusively from below by an experienced head and neck surgeon, combination with neurosurgery allows approach of the tumor from above, and the brain is protected from iatrogenic injury. In this situation, a pericranial flap is usually used to resurface the sinonasal roof and protect intracranial dura and contents. In most cases, a free flap is then used to protect the contents of the cranial vault.

The complications of these operations are varied and depend, obviously, on the particular approach used. The most common problem is dysfunction of the lacrimal apparatus. This is especially important for patients who are likely to receive postoperative radiation therapy. As a result, we recommend dacrocystorhinostomy (DCR)382 in all patients who are having midfacial surgery with disruption of the lacrimal apparatus. In addition, as many as 20% of patients will suffer postoperative diplopia due to loss of support in the bony floor. Despite tethering of the medial canthus along the nasal bones and supporting the eye medially, this problem persists. Early intervention by ophthalmology is beneficial. With combined craniofacial resections, pneumocephalus can also occur. It has previously been felt that tracheostomy should be performed in all craniofacial patients to decrease the risk of pneumocephalus. With meticulous closure of the pericranial flap and the use of free flaps as indicated, however, we have not found this to be the case. Rarely do we feel that tracheostomy is indicated for combined craniofacial resections. Pneumocephalus, however, is an indicator of a persistent leak that can often lead to a high likelihood of meningitis and persistent cerebrospinal fluid (CSF) rhinorrhea.

Radiotherapy plays a large role in the management of sinonasal malignancies. It is used both pre- and postoperatively and can be used in select cases as definitive therapy for small T1 and T2 lesions, especially those limited to the nasal vestibule and anterior nasal fossa.382 In this situation, high locoregional control rates and good cosmetic outcome result. With the increased used of radiotherapy in combination with surgery, ever-improving rates of locoregional control have been achieved. However, this has also lead to higher recognized rates of distant metastasis. Surgery with postoperative radiation therapy remains the standard of care for advanced sinonasal cavity tumors. In select patients that are not felt to be good surgical candidates or when a tumor is inoperable, radiation therapy alone performs effectively in terms of local control and palliation. Preoperative radiation therapy can also be used for select inoperable tumors.

Essentially all patients who receive radiation therapy either as single agent treatment or in combination with surgery and/or chemotherapy will suffer some negative sequelae from the use of the radiation. Most will resolve over time. Acute complications include skin desquamation, nasal dryness, and mucositis. Chronic side effects include nasal dryness, dry eye, visual impairment, and atrophic rhinitis. Dry eye can range from mild dryness alleviated with over-the-counter drops to significant keratitis, corneal ulceration, and even blindness. Enucleation may even be necessary for significant damage. While the retina, like most neural structures, is radioresistant, visual impairment can occur as a result of damage to the microvasculature that supports both the retina and optic nerve.

While chemotherapy is covered more extensively in a separate section, some aspects of chemotherapy deserve special consideration and will be mentioned briefly here. Traditionally, chemotherapy has been used for sinonasal tumors in palliative situations or for patients with recurrent tumors. However, an unwillingness to sacrifice the eye has lead to the use of induction chemotherapy in select patients. In addition, positive results have led to more widespread and mainstream use of chemotherapy in certain situations.

Finally, regimens previously felt to be too toxic to be used regularly have gained more acceptance as supportive care in these patients has improved. While the use of chemotherapy remains experimental and should only be administered as part of controlled protocols, recent prospective trials may suggest that control and overall survival are superior with the incorporation of chemotherapy.

In cases of SCC, surgery remains the treatment of choice when sacrifice of vital structures is not required. However, if a surgeon feels, based on clinical examination and imaging findings, that a tumor is not likely to be resectable with negative margins or that surgery would require sacrifice of vital structures, then induction chemotherapy in addition to surgery with postoperative radiation therapy should be considered. Both Choi and colleagues and investigators at the University of Chicago have used induction chemotherapy with combinations of cis-platinum and infusional 5-fluorouracil (5-FU) to achieve improved rates of locoregional control and preserve the eye. Many studies using intraarterial chemotherapy (usually cis-platinum) followed by surgery and/or radiation therapy exist. While these studies have shown some benefit with regard to locoregional control, the morbidity associated with intraarterial therapy may not justify the intraarterial approach.

SNUC is fortunately rare. It is a lethal cancer typically presenting as advanced disease in elderly patients. Traditional treatment has been surgery followed by postoperative radiation therapy, but this has provided poor long-term control. Scattered reports exists in the literature that describe small series using chemotherapy and/or chemoradiotherapy in association with surgery to achieve some locoregional control. SNUC is rare, and existing series are too small and varied to be able to promote one regimen as better than any other. However, in light of the poor locoregional control achieved with traditional surgery and postoperative radiation therapy, most agree that continued exploration for concomitant chemoradiotherapy is the best avenue for these patients.

Neuroendocrine carcinomas, which occur commonly in the larynx as well, have also been traditionally treated with surgery and postoperative radiation therapy. However, the literature suggests that they should be treated much like neuroendocrine carcinoma at other primary sites. Specifically, the University of Texas M.D. Anderson Cancer Center advocates the use of induction chemotherapy with cis-platinum, carboplatinum, and itoposide. If patients achieve a complete response, then they proceed directly to radiotherapy, and surgery is avoided. If, on the other hand, only a partial response is achieved, then surgery followed by radiation therapy is the treatment of choice. This has lead to increasing locoregional control rates with decreased morbidity from surgery.

Finally, esthesioneuroblastoma, or olfactory neuroblastoma, is a rare neoplasm of the sinonasal cavity; it emanates from the cribiform plate and early on invades the anterior cranial vault and, often, brain parenchyma. These patients usually present with nasal obstruction and epistaxis. Under the microscope, these tumors present as small blue cell tumors and can often be confused with neuroendocrine carcinoma. The distinction between the two is important, however, as while the best approach to treatment for neuroendocrine carcinoma is chemotherapy and/or surgery and radiation therapy, esthesioneuroblastoma is best treated with en bloc resection of the primary and (if indicated) postoperative radiation therapy. Investigators from the University of Virginia reported on 34 consecutively treated patients and the use of preoperative radiation therapy and chemotherapy. They found that patients who responded to induction regimens had decreased disease-specific mortality and had 5- and 10-year survival rates of 81% and 55%, respectively. Finally, a recently published single-institution trial tested carboplatin, lomustine, and vincristine systemically (median 4 cycles) and/or regionally (median 17 cycles) every 2 months in 6 patients with no prior central nervous system involvement with newly identified metastatic esthesioneuroblastoma involving the central nervous system. This study showed that recurrent metastatic disease is treatable with acceptable toxicity and reasonable palliation. Four patients had partial responses; two patients progressed. The median response duration was 9 months (range 2 to 12 months), and median overall survival was 10.2 months (range 3to 13 months).

As one can see, the management of sinonasal carcinoma differs distinctly from that of malignancies of the remainder of the UADT. This is most likely a result of the fact that traditional approaches using surgery followed by postoperative radiation therapy had significant morbidity and were associated with poor locoregional control. As a result of those unsatisfactory results with traditional therapy, numerous institutions have created differing protocols for the management of these patients. However, one defining principal remains true: patients suffering from such malignancies require a multidisciplinary approach to their treatment. Our institution advocates that all patients be presented, before treatment, in a multidisciplinary setting with all indicated specialties. While no one protocol can be advocated over another, we support the continued investigation of chemotherapy in an adjuvant role for the management of these patients but also feel that surgery will continue to play a large role in the control of this disease. Thus, the surgeon should remain at the core of the treatment team.