AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Contraindications
• Workup
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Contraindications
• Workup
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

The location of that nasal cavity and the paranasal sinuses make them extremely close to vital structures. They can grow to considerable size before presentation, and aggressive therapy may be needed in areas close to the brain, eyes, facial nerves, and vital blood vessels.

Problem

Although rare, tumors of the nasal cavity and paranasal sinuses are lesions of immense importance. They produce few if any signs while the tumor is in its early stages. This problem is exacerbated by the fact that the initial manifestations (eg, unilateral epistaxis, obstruction) mimic signs of conditions more common and less serious than tumors of the sinuses. Therefore, the patient often ignores these tumors, or the clinician may minimize them, treating early-stage malignancies as infectious diseases.

By the time ominous signs and symptoms (eg, severe intractable headache, visual disturbances) occur, the neoplasms are advanced and require complex management. The anatomy of the nasal cavity and paranasal sinuses cause these tumors to manifest in advanced stages and complicate their treatment. They are located adjacent to important structures such as the brain, orbital contents, cranial nerves, and vital arteries and veins. When tumors invade, encase, or compress any of these structures, they must be included in the therapeutic field. Of course, careful consideration of treatment on an individualized basis is required and ideally accomplished with a team approach.

The team should include at least the surgeon, the radiation oncologist, the medical oncologist, the radiologist, the pathologist, and the patient.

Frequency

Malignant tumors of the nasal cavity and paranasal sinuses are rare. They are more common in Asia and Africa than in the United States, where about 2000 Americans develop these malignancies each year. Men are affected 1.5 times more often than women, and 80% of these tumors occur in people aged 45-85 years.

Approximately 60-70% of malignancies of the nasal cavity and paranasal sinuses occur in the maxillary sinus. About 20-30% of malignancies of the nasal cavity and paranasal sinuses occur in the nasal cavity itself. An estimated 10-15% occur in the ethmoid air cells (sinuses). The remainder occurs in the frontal and sphenoid sinuses.

Etiology

Risk factors for tumors of the nasal cavity and paranasal sinus have been extensively investigated. They are complicated and multifactorial. Many more may still be unknown, but it is fairly well established that squamous cell carcinoma and/or adenocarcinoma in this area are associated with exposure to the following substances: wood dust, nickel dust, mustard gas, thorotrast, isopropyl oil, chromium, or dichlorodiethyl sulfide. Many of these products are found in the furniture making industry, the leather industry and the textile industry. The risk of developing sinonasal carcinoma in those exposed to these substances varies from 21- to >100-fold compared with nonexposed individuals.

Viral infections and their relationship to malignancy is an interesting area that has not received sufficient investigation. Epstein-Barr virus is certainly involved in the development of nasopharyngeal carcinoma, and speculation about the relationship of some premalignant lesions, such as the inverted papilloma in relation to the human papilloma virus, is widespread.

In summary, risk factors for cancers of the nasal cavity and paranasal sinus are multifactorial and include sex, geographic regions, age, and probably several carcinogens and/or oncogenic viruses.

Clinical

Clinical details

The initial manifestations, such as unilateral epistaxis and/or obstruction, mimic signs of conditions more common and less serious than malignant tumors of the sinuses. Therefore, the patient often ignores these tumors, or the clinician may minimize them, treating early-stage malignancies as infectious diseases. By the time ominous signs and symptoms (eg, severe intractable headache, visual disturbances) occur, the neoplasms are advanced and require complex management.

Malignant neoplasms of the nasal cavity and paranasal sinuses

This discussion is limited to malignant neoplasms. In the strict definition according to Dorland's Medical Dictionary, 24th edition, a malignant neoplasm includes all new growth of a lesion that tends to become more virulent than before, to become progressively worse, and to result in death.

The list of conditions is extraordinarily long because many infectious diseases of the sinuses (eg, mucormycosis in diabetes) may grow as a fungal mass and ultimately become pernicious. In addition, certain autoimmune diseases (eg, Wegener granulomatosis) can also manifest with new growth and malignant behavior.

Finally, growths from adjacent areas may lead to aggressive signs and symptoms and a requirement for radical and destructive therapy. Meningiomas may grow into the sinuses, and orbital tumors may extend into adjacent paranasal sinuses. Even benign conditions, such as juvenile angiofibromas or nasal gliomas, may lead to death if not recognized for what they are.

Therefore this article limits itself to malignant neoplasms that arise from host tissues and that fulfill the usually concept of malignancy. That is, tumors that are locally invasive, destructive, and possibly metastatic.

Inverted papilloma

Patients with masses in the nasal cavity or paranasal sinuses can present with any of the symptoms mentioned above. Therefore, a high index of suspicion is necessary when one evaluates nasal obstruction or stuffiness. Patients occasionally have unilateral epistaxis or headaches. However, the diagnosis of inverted papilloma can be made only with the use of imaging studies and, ultimately, biopsy.

Gross examination reveals a red-to-tan mass in the nasal cavity. More than 90% of these masses are attached to the lateral wall. Full extension of the lesion cannot be determined without sufficient imaging studies. These lesions can also arise primarily in the maxillary sinus, frontal sinus, or ethmoid air cells.

Imaging studies depend on the differential diagnosis. Plain radiographs, CT scans and MRIs all provide information. Each has its own advantages and limitations. Plain radiographs demonstrate the location and size of the lesion. Bone erosion suggests the aggressive nature of this lesion. CT scans provide better indicators of bone involvement than those observed on radiographs, and MRI is extremely valuable in demonstrating soft tissue involvement.

Biopsy is ultimately necessary because more than 10% of samples harbor carcinoma. When carcinoma is discovered, it is almost always a squamous cell variant of any grade. On histologic evaluation, the pathologist sees hyperplasia, that is, multilayered squamous-to-columnar epithelium with or without atypia. All mixtures of these types are possible. If the tumor is largely squamous, it should raise suspicion of an accompanying malignancy. These cells are arranged in exophytic and endophytic growth patterns. Microcysts and mucous cells are always admixed in the epithelium. Individual and small clusters of neutrophils are scattered throughout the epithelium. Occasional mitotic figures may be present but should be limited to the basal and parabasal layers.

Malignant transformation has histologic features of any of the squamous cell variants described in later in the article.

The recurrence rate is potentially high (>70% in some studies). Treatment determines the likelihood of the tumor returning. Conservative excision strongly increases the likelihood of this event. Therefore, if feasible in the individual patient's situation, treatment is lateral rhinotomy and complete excision of the mass.

The pathologist should extensively search for malignancy in any inverted papilloma. If surface keratinization is present, atypia or mitotic figures above the parabasal layer the sample should be considered suggestive of malignancy, and additional sectioning is needed.

Squamous cell carcinoma

Squamous cell carcinoma of the sinus is by far the most common type of malignancy arising in the nasal cavity and paranasal sinus. They constitute over 80% of neoplasms of the paranasal sinuses. About 70% of these occur in the maxillary sinus, 12% occur in the nasal cavity, and the remainder are in the remaining sinuses and nasal vestibule.

The presentation is, as with all of the entities described here, extremely varied and includes a mass, obstructive phenomenon, rhinorrhea, epistaxis, and pain. Long-standing lesions may detectably alter the patient's facial features, causing asymmetry or bulging. Visual disturbances and paresthesias are not rarities. On occasion, malocclusive phenomenon occurs with a notable mass effect arising from the floor of the maxilla and noticeable in the hard palate.

Several variants of carcinoma are often considered variants of squamous cell carcinoma of the nasal cavity and paranasal sinuses. These include verrucous carcinoma, basaloid squamous cell carcinoma, spindle cell carcinoma, transitional of cylindrical cell carcinoma. The unqualified term squamous cell carcinoma is used to indicate malignancies that have the standard features widely understood to represent that entity.

On clinical evaluation, the appearance is a function of the stage of the tumor. At first, it may be little more than a mass or small ulcer. With advanced disease, large ulceration, necrosis, heaped edges, and bone and soft-tissue invasion may be observed.

Biopsy is necessary to classify this lesion. Wegener granulomatosis and some nonneoplastic diseases may simulate all the signs, symptoms and appearances described. Histologic examination reveals sheets, ribbons, and individual squamous, polyhedral, or round-to-ovoid cells with various degrees of keratinization. The sheets and festoons demonstrate intercellular bridges connecting the cells. Individual cells display hyperchromasia, irregular nuclear contours, and an increased nuclear-to-cytoplasmic ratio. The degree of mitotic activity is variable, though occasional abnormal (eg, tripolar or multipolar) figures are observed in virtually all cases.

Most squamous cell carcinomas are high grade, and keratin may or may not be difficult to find.

Verrucous carcinoma

Verrucous carcinoma is a type of squamous carcinoma grossly characterized by a fungating appearance with complex papillary infoldings. In other words, it has a warty, exophytic look. These tumors rarely have ulceration. They range from deep red to white. The hue is a function of vascularity, hemorrhage, and surface keratinization.

On histologic examination, this low-grade malignant neoplasm is composed of well-differentiated, keratinized squamous epithelium with a hyperplastic, or abundantly cellular, appearance. No substantial hyperchromasia, irregularity of nuclear outlines or increase in mitotic figures is present. No abnormal mitoses will be observed. The tumor is locally aggressive and invades by means of large, blunt, and wide epithelial pushing invaginations. Virtually always present a tightly hugging cluster of mononuclear inflammatory cells in the adjacent stroma.

An important issue related to verrucous carcinoma is the potential to progress to the more aggressive traditional squamous cell carcinoma. Verrucous carcinomas cause damage by local invasion but do not metastasize unless they contain a component of squamous cell carcinoma. On extensive examination, 20% of these lesions have demonstrated classical squamous cell carcinoma in at least 1 area. The rate of local invasion is also slower than with that usually observed with squamous cell carcinoma.

Radiation was once believed to increase the probability that these tumors undergo aggressive transformation. However, it is now fairly conclusively demonstrated that this apparent malignant degeneration, or anaplastic transformation, occurs with approximately equal frequency in all verrucous carcinomas independent of radiation exposure.

One important and often-overlooked feature of verrucous carcinoma of the head and neck is their frequent association with synchronous or metachronous tumors. These take the form of epithelial malignancies or premalignancies in the upper aerodigestive tract, and the rate is as high as 37%. This association must always be considered during patient follow-up.

Basaloid squamous cell carcinoma

Basaloid squamous carcinoma is extremely rare in the nasal cavity or paranasal sinuses and more frequent in the oral cavity and larynx. Its clinical presentation and gross appearance are identical to those of an ordinary squamous cell carcinoma. However, on biopsy, basaloid squamous carcinoma has distinguishing and often confusing features. The cells are more hyperchromatic and of small than those of conventional squamous cell carcinoma. The peripheral layer of cells should display palisading. The finding of apoptotic (necrotic) cells or foci of necrosis is not unusual. Mitoses are easy to find.

The confusion this tumor causes is due to the often-observed pseudogland formation, which is caused by the dropout of small groupings of necrotic cells that produce a luminal appearance. This finding alone is easily mistaken for a mucoepidermoid carcinoma or an adenocarcinoma. When the deposition of hyalinized, eosinophilic material is admixed with the pseudogland formation, adenoid cystic carcinoma may be misdiagnosed. To avoid an incorrect diagnosis of adenocarcinoma, one often must use mucicarmine, periodic acid-Schiff (PAS) stains to determine if mucous production is truly present in the cells surrounding the pseudogland formations. The finding of mucus in the lumen is not definitive because even pseudoglandular lumina in the sinuses and nasal cavity may trap mucus.

To differentiate the lesion from adenoid cystic carcinoma, a search for in situ carcinoma on the surface is useful. Basaloid carcinoma should have this finding. Squamous differentiation is common in basaloid carcinoma but not in adenoid cystic carcinoma. Finally, adenoid cystic carcinoma lacks the marked atypicality seen in basaloid squamous cell carcinoma.

Although sinonasal basaloid cell carcinomas are extremely rare, the few lesions reported behaved like conventional squamous cell carcinomas of similar stages. In most case reports of this tumor, the lesion was already in stage III or IV; this tumor apparently metastasizes earlier than do usual types of squamous cell carcinomas.

Spindle cell carcinoma

Spindle cell carcinoma has been named and misnamed many times. The etymologic confusion has sometimes led to clinical consequences. Therefore, one must understand that this neoplasm is a variant of squamous cell carcinoma. Although it has a component that resembles spindle mesenchymal cells, these are simply dedifferentiated squamous cells.

The terms sarcomatoid carcinoma and pseudosarcoma are linguistically accurate but not in much use. The terms carcinosarcoma and collision tumor are distinctly incorrect as the designate that there is indeed a real sarcomatous component to this lesion. This is simply untrue.

Ultrastructural and Immunohistochemical studies demonstrate that the cells of this lesion are dedifferentiated squamous cells. Spindle cell carcinoma is most common in the oral cavity and larynx; on rare occasions, it arises in the sinonasal areas. Although the tumor frequently has clinical and gross appearances indistinguishable from those of conventional squamous cell carcinoma, it often has a polypoid appearance.

Biopsy demonstrates that the lesion arises from the surface, and one may find squamous cell carcinoma in situ associated with it. Specimens show areas of conventional squamous cell carcinoma with polyhedral cells, keratinization, and intercellular bridge formation. Unfortunately, with ulcer formation, the entire squamous portion may be eroded and no longer identifiable. Also present are areas of spindle cell morphology, some of which may be bizarre. These may make up the vast majority of the tumor. Some areas may involve an abrupt transition of the squamous cells to the spindle-shaped cells, or the transition may be gradual, with intermediate-shaped cells between the regions.

To make a certain diagnosis, ultrastructural studies may be used. Here, one is searching for the usual markers of squamous epithelial cells in the spindle component. Tonofilaments and desmosomes are particularly useful findings. Immunohistochemistry can be used to view these same spindle cells. Any evidence of keratin (a broad range of molecular weight is the most useful finding) and indicates the true squamous nature of these tumors. However, many or most of these cells may be negative for keratins, and many may be positive for vimentin, a traditional mesenchymal marker. Therefore, exhaustive searching may be necessary.

The behavior and treatment of these lesions should be the same as of other squamous cell carcinomas. In the past, the polypoid nature of these lesions was thought to improve the prognosis. However, history has not borne this out. Batsakis et al (1980) studied lesions including sinonasal spindle cell carcinomas and found that 77% of patients died within 6 months to 2.5 years.

Transitional cell carcinoma, or cylindrical cell carcinoma

This unusual tumor is similar in presentation and gross appearance to conventional squamous cell carcinoma. In addition to the usual keratin- producing, polyhedral, round-to-oval squamous cells connected by intercellular bridges, one sometimes finds intracellular mucous and occasional features that resemble some germ-cell neoplasms. Its behavior and treatment are similar to those of usual squamous cell carcinoma in the same area.

The main point of recognizing this as a distinct tumor type is to avoid confusing it with a benign papilloma because it does have a propensity for subtle invasion. A search through many microscopic fields may be needed to find invasion in these lesions.

Adenocarcinoma and its variants

Adenocarcinomas of the nasal cavity and paranasal sinuses have historically been important. These tumors as associated distinct risk factors, such as exposure to wood dust, lacquers, and other organic compounds.

Adenocarcinomas of the nasal cavity and paranasal sinuses have several distinctive variants. These carry both morphologic and prognostic significance.

The accepted varieties of sinonasal adenocarcinoma include well-differentiated adenocarcinoma, papillary type of adenocarcinoma, solid type of adenocarcinoma, mucinous type of adenocarcinoma, colonic type of adenocarcinoma, and mixed type of adenocarcinoma. All of these neoplasms demonstrate the typical changes seen in adenocarcinoma at other anatomic sites, that is, malignant gland formation. This finding consists of crowded or back-to-back (cribriform) glands with increased mitotic figures, hyperchromatic nuclei, an increased nuclear-to-cytoplasmic ratio, mucin production, and focal necrosis. Stromal invasion should also be demonstrable.

The well-differentiated adenocarcinoma does not have a large degree of anaplasia nor abundant mitotic figures. Still, the glands should be unequivocally malignant to merit use of the term adenocarcinoma. The pathologist may distinguish the type on the basis of the usual criteria for adenocarcinoma and on specific findings that merit subclassification.

The papillary class has fibrovascular cores with malignant lining cells. The solid variant is almost entirely composed of sheets of malignant cells with rare gland formation and no mucin-rich goblet cells. The mucinous variant includes 2 subtypes based on the size of the gland formation. Common to both subtypes is abundant, easy-to-identify mucin. The colonic type of adenocarcinoma of the nasal cavity and paranasal sinuses receives its appellation from the moderately well differentiated glands that closely resemble colonic-type adenocarcinoma. In fact, Paneth type intestinal cells and/or absorptive cells are sometimes frequently found in these tumors. The mixed classification is reserved for tumors with a mixture of any of these patterns.

The ultimate significance of the histologic feature is simply distinguishing the degree of differentiation in any of the subtypes. Low-grade, well-differentiated adenocarcinomas appear relatively early as exophytic structures. The median age at presentation is 54 years, whereas it is 63 years for tumors less-differentiated than these. Both low- and high-grade tumors cause obstructive symptoms and possibly rhinorrhea and epistaxis. However, pain, paresthesias, and oral ulceration are far more common in the high-grade, poorly differentiated adenocarcinomas than in better-differentiated ones. Regardless of grade, local destruction and the orbits and the base of the skull are frequently involved.

Distant metastases are rare. When they do occur, the lung, liver, and bone are the sites involved. Metastases to the cervical lymph nodes are uncommon, even with poorly differentiated tumors.

Treatment is by local excision with wide margins. This is a difficult task to accomplish because a good deal of the specimen contains bone. Because of the difficulty of cutting calcified bone, optimal frozen section control of the margins may be impossible at the time of surgery. The rarity of lymph node metastasis makes elective neck dissections unnecessary. Still, preoperative evaluation of the neck must be meticulous.

Postoperative chemotherapy or radiation therapy is still under investigation, and their final role in the treatment of this neoplasm has yet to be determined.

The prognosis for low-grade adenocarcinoma is far better than that for high-grade adenocarcinoma of the sinonasal area. High-grade adenocarcinomas have a reported survival rate of less than 35% at 3 years. For low-grade adenocarcinoma, the 5-year survival rate is approximately 80%.

Undifferentiated, or anaplastic, carcinoma

Undifferentiated, or anaplastic, carcinoma is an uncommon neoplasm of the sinonasal region. It receives its name from the lack of clear-cut distinguishing architectural features for this lesion.

Undifferentiated, or anaplastic, carcinoma may grow in fascicles, nests, or broad festoons. Invasion can involve single cells or groups of cells of any size. No real gland formation is observed, but the abundant necrosis may cause into the cell drop out to be mistaken for a lumen. This confusion is avoided by obtaining mucin stains, which are always negative.

This tumor is characterized by a short (weeks to months) history of swelling, proptosis, visual disturbances, paresthesias, and cervical adenopathy. Patients are aged 20-80 years, with a slight female predominance.

Given the location and advanced stage of the tumor at presentation, it is rarely treated with resection. Results of chemotherapy and radiation therapy have been less than encouraging to date. The 5-year survival rate is less than 16%, and the median survival is on the order of 8 months.

Small-cell neuroendocrine carcinoma

Small-cell neuroendocrine carcinoma, similar to oat-cell carcinoma of the lungs, is reported to arise in the nasal cavity and paranasal sinuses in patients ranging aged 26-77 years.

Epistaxis, proptosis, and obstructive phenomenon are presenting signs and symptoms. As with lesions elsewhere in the body, small-cell neuroendocrine carcinoma is composed of small cells with hyperchromasia, a high nuclear-to-cytoplasmic ratio, a high mitotic rate, and inconspicuous nucleoli. The molding or interdigitation of nuclei is seen with frequency, as is the smearing of nuclei near the edges.

The fact that the tumor is almost always in an advanced stage by the time it comes to attention reflects it aggressive nature. Several sinuses are nearly always involved. Cervical lymph nodes and pulmonary metastases may also be involved.

Treatment is multimodal and involves various regimens that include surgery, chemotherapy, and radiation therapy in combination. Despite maximal efforts and individualized therapy, the prognosis is poor. Median survival, as extrapolated from several studies, is less than 2 years.

Lymphomas and related conditions

This category of malignant neoplasia of the sinuses and nasal cavity is complicated, poorly understood, evolving, controversial, and extensive. Nevertheless, clinicians, radiologists, and pathologists must all keep these entities in mind when a patient presents with the signs and symptoms of a nasal cavity or paranasal sinus tumor.

These lesions can be grouped in many ways on the basis of what parameters are being measured. For general purposes, the International Working Formulation is used to classify lymphoid or lymphoplasmacytic tumors. As such, the results of an extensive evaluation by the pathologist are needed before a certain diagnosis is rendered.

In general, non-Hodgkin lymphomas manifest in patients in their 60s or 70s and cause symptoms of obstruction. Rhinorrhea and epistaxis may also be present. After the type of tumor is established, treatment is usually radiation therapy and chemotherapy, as established by protocol. The prognosis is in generally poor for patients with non- Hodgkin lymphoma and, depending on the type and stage ranges, median survival ranges from less than 1 year to close to 80% at 5 years.

Another controversial type of aggressive or malignant tumor has had numerous names throughout its history, including lethal midline granuloma, midline malignant reticulosis, lymphomatoid granulomatosis, angiocentric lymphoproliferative lesion, and T-cell/natural killer–cell lymphoma. Given the current state of knowledge, this lesion is probably best categorized as a T-cell/natural killer–cell lymphoma.

The tumor is a destructive sinonasal lesion associated with obstructive symptoms, bone- and soft-tissue destruction, and hemorrhage. It is strongly associated with the Epstein- Barr virus and is most common in Asia and Latin America, with a patient age at presentation of 13-80 years.

After evaluating the biopsy sample, the pathologist makes the final diagnosis on the basis of the morphology and the results of special studies. The histopathology is complicated, but 1 feature of interest is a tendency for the cells to be centered around walls of blood vessels. These distorted small lymphomatoid cells are often admixed with macrophages, plasma cells, neutrophils, and benign lymphocytes. The vessel wall itself may be destroyed and contain microthrombi.

Treatment has included radiation with or without chemotherapy. The chemotherapeutic regimen often includes combinations of cyclophosphamide, doxorubicin, vincristine, and prednisone. Because of past confusion about to how to categorize this disease, scientifically rigid data to ascertain the prognosis are not available. At present, the prognosis must still be considered poor, and the 5-year survival rate is less than 70% at best.

Malignant melanoma

Malignant melanoma is a rare disorder of the nasal cavity and paranasal sinuses. It accounts for less than 1% of all malignant melanomas and less than 3% of nasal malignancies. It is also rare for melanoma to metastasize to this anatomic region. However, a careful clinical search is still indicated to rule out a metastasis as opposed to a primary sinonasal melanoma.

No sex specificity or preference is apparent. Although the age range is broad, the tumor is most frequently found after the age of 40 years. The presentation may be similar to that of any nasal mass, including bloody discharge, obstruction, and rhinorrhea. The clinical appearance of the lesion is that of a firm, gray-white or pink-to-black, ulcerated mass. Black coloration is a rarity, and its absence does not rule out melanoma without biopsy.

On biopsy, the melanoma can be extraordinarily variable in appearance, and pathologists often state, "Melanoma may look like anything; therefore, is in the differential diagnosis of everything." The tumor may entirely be composed of cells ranging from apparently cohesive, polyhedral squamoid cells with no pigment, to spindle-shaped cells infiltrating individually, to round-to-oval cells with abundant pigment and bizarre nuclei with intranuclear cytoplasmic inclusions. Any morphology is possible, and pathologists are sometimes misled by the initial appearance of the lesion. It is fortunate that special studies can now aid definitive diagnosis. These studies include electron microscopy to look for premelanosomes, a lack of tight junctions, and an absence of other features suggesting another diagnosis.

In addition, immunoperoxidase studies are extremely useful and include the use of HMB-45, S100, Melan A, and one of the newest diagnostic markers pigment epithelium–derived factor (PEDF).

After the diagnosis is made, the primary modality of therapy is resection with clear margins. However, even with negative surgical margins malignant melanomas of the sinonasal region can recur. Radiation therapy and/or chemotherapy have been used as palliative measures. Despite optimal therapy, median survival is less than 2 years.

Salivary-type neoplasms

Pleomorphic adenomas, mucoepidermoid carcinoma, adenoid cystic carcinomas, and other salivary gland neoplasms may arise in the nasal cavity and paranasal sinuses. On gross and histologic evaluation, they are similar to the corresponding salivary gland tumors found elsewhere.

Pleomorphic adenomas are excised with wide margins if feasible. Recurrences are reexcised, often to good effect. The behavior of mucoepidermoid carcinoma is a function of the stage, grade, size, and resection margins of the tumor. High-grade mucoepidermoid is treated as if it were made entirely of squamous cells, that is, as if it were a squamous cell carcinoma.

Adenoid cystic carcinoma is not specific to the patient's sex and occurs earlier than most malignancies. The lesion often manifests in the fourth to sixth decades. It has the usual presentation of nasal malignancies and is often accompanied by paresthesias and/or pain. It has a marked propensity for intraneural and perineural invasion.

Therapy is surgical excision and specialized radiation therapy. The tumors are often advanced by the time they are discovered; therefore, resection is often unsuccessful. Study data suggest that patients should be followed-up for 15 years, as opposed to the traditional 5 years, because these tumors may recur late. The survival rate at 15 years is 25%.

Teratomas and related neoplasms

Teratomas and related neoplasms in the sinonasal area are rare, but they are reported with sufficient frequency to merit discussion.

Teratomas are benign tumors composed of all 3 germ-cell layers in varying percentages, with various degrees of maturity. Although normally considered germ-cell tumor of the gonads, teratomas and related neoplasms can affect the head and neck (<2%). This neoplasm in this location most commonly occurs in neonates. The lesions may be grossly visible as a mass causing facial malformations, or they may manifest with obstructive signs and symptoms. On extremely rare occasions, they appear as epignathi. Epignathi are visible at birth and appear as a malformed, parasitic fetus.

Imaging of these lesions is extremely important because surgical planning must account for possible intracranial extension. After the surgeon begins to resect the neoplasm, he or she may encounter a solid, cystic or mixed solid-cystic mass. Calcification may be found with or without bone formation, hair, cartilaginous and soft mucosa, or virtually any combination of tissues.

On histologic examination, these tumors vary as much as they do grossly. The pathologist must look for all 3 germ-cell layers, for the maturity of these layers on several sections, and for germ-cell neoplasms in these tumors. Immaturity of the tissue is a sign of malignant degeneration.

Each case requires careful preoperative consideration. The extent of the disease near crucial anatomic structures and the unusual geometry of this lesion all add to a guarded prognosis. In addition, choriocarcinoma or another malignant component may not be known until extensive pathologic evaluation is one.

At least 1 other entity is in the category of related neoplasms. This is the extremely rare teratocarcinosarcoma of the sinonasal cavity. It occurs in men after the sixth decade and causes obstructive phenomena and epistaxis. Imaging demonstrates bone destruction and probably soft tissue extension as well. The histologic appearance is that of a teratoma with immature elements of epithelium and mesenchyme. Organoid, minigland formation, and rosettes are commonly seen.

Cases in the literature are too few to support any optimal treatment. However, the prognosis is poor regardless of the therapeutic options. The 3-year mortality rate is 60%.

Sarcoma

Sarcomas of the sinonasal tract are rarities. Given that the nasal cavity and paranasal sinuses contain, nerves, blood vessels, lymphatics, smooth and skeletal muscle, fibrous tissue, bone, and fat, malignant mesenchymal tumors occasionally develop. Fibrosarcomas, leiomyosarcomas, rhabdomyosarcomas, liposarcoma, malignant peripheral nerve-sheath tumors, and other lesions have been reported. Of these tumors, rhabdomyosarcoma deserves special consideration because it is one of the more frequent sinonasal malignancies in children, though it has also been reported in adults.

The symptoms are similar to those of other tumors in this area; however, sarcoma is usually in an advanced stage at the time of presentation. Bone and extensive soft-tissue destruction is not unusual.

Rhabdomyosarcoma may be classified into several subtypes. The criteria and interpretation of features for defining the subtypes has been somewhat fluid and subjective. To further complicate matters, therapy is controversial and has included a strong reliance on a combination of radiation therapy and chemotherapy. The current Intergroup Rhabdomyosarcoma Study protocol should be reviewed before definitive therapy is begun. Despite current optimal therapy, 50% of patients die from this disease.

The other mesenchymal tumors listed above are currently being evaluated, and, each year, cases are added to the state of knowledge regarding treatment and prognosis. Therefore, when one deals with sarcomas occurring anywhere, including the head and neck region, it is always best to consult the latest literature and presentations from the available study data.

Metastatic tumors

Metastatic tumors to the nasal cavity and paranasal sinuses are well documented but uncommon. As expected, tumors that most frequently metastasize to this bony region are those that are well known to metastasize to other bones. These are the traditional metastatic tumors that seem to home in on bone. Medical students in the United States memorized these by using the mnemonic PBKTL (pronounced "P.B. Kittle"), which stands for prostate, breast, kidney, lung, and thyroid.

In addition, melanomas, GI adenocarcinoma, and hepatocellular carcinoma are all reported to metastasize to the head and neck region. Whenever one suspects such a malignancy, it is imperative to do an appropriate evaluation to search for a primary.

Of particular importance are 2 metastatic lesions that may cause confusion. The first is the clear-cell variant of renal cell carcinoma. Its appearance can be similar to the clear -ell variant of a mucoepidermoid carcinoma. Although the pathologist should be able to distinguish these lesions, special studies, such as immunohistochemical studies and possible electron microscopy may be required. These may be take time to perform. Therefore, clinical workup may be most effective. The second metastatic neoplasm that may become problematic for the diagnostician is colorectal adenocarcinoma. This lesion may be indistinguishable from the colonic variant of primary sinus adenocarcinoma.

Recognizing the presence of a colonic or intestinal type of primary adenocarcinoma should automatically lead to an intelligent clinical and radiologic evaluation to distinguish a primary sinonasal tumor from a metastatic colorectal neoplasm.

RELEVANT ANATOMY

Section 3 of 9  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Contraindications
• Workup
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

As with all areas of the head and neck, the relevant anatomy is extremely complex, and the various important structures are close to each other. The fine details of the anatomy of the nasal cavity and paranasal sinuses are beyond the scope of this article. However, the most important anatomic and geometric relationships of these regions are discussed below. These regions include the nasal cavity, the frontal sinuses, the sphenoid sinuses, the maxillary sinuses, and the ethmoid sinuses.

Nasal cavity

The cribriform plate of the ethmoid bone forms the superior aspect of the nasal sinus. Through this plate pierce twigs of the olfactory nerves as they enter the nasal cavity. The inferior aspect is the superior surface of the hard palate. Regarding the lateral and medial aspects, the lateral walls are complex structures. They are formed by portions of the ethmoid, maxilla, palatine, lacrimal, and medial pterygoid plates of the sphenoid, nasal, and inferior turbinate bones. The walls are covered with highly vascular pseudoerectile tissue with immense capacity for serious hemorrhage.

The anterior aspect is an ill-defined area artificially separated from the external nose by cartilaginous structures and the nares. The posterior aspect is defined as the posterior choanae, where the soft palate and hard palate join. Anything posterior to this is considered the nasopharynx.

Frontal sinuses

The frontal sinuses are usually paired, but may show focal fusion. In fact, the frontal sinuses are remarkable for their size and shape variations. On average they are each approximately 7 mL in volume and conical to funnel shaped, with the apex oriented in a superior fashion. They are almost always noticeably asymmetrical.

The superior aspect is an ill-defined stopping point of the cavity in the frontal bone. The inferior aspect is variable but almost always covers some portion of the ipsilateral orbital roof. The lateral aspects of the sinus or cavity gradually fade into more or less porous aspects of the frontal bone. The anterior aspect is simply the point at which the sinus reaches the anterior hard (but still diploe type) of bone of the frontal bone. The anterior bony structures of the anterior cranial fossa for the posterior aspect of the frontal sinus.

Sphenoid sinuses

The sphenoid sinuses are unique among the paranasal sinuses in that they do not arise as invaginations of the nasal cavity. Instead, they originate from embryonic rests in the nasal capsule. They are not discernible on imaging studies or autopsy until an individual is aged 2-4 years.The sinuses are full size at the age of 20 years. At this age, they each have a volume of approximately 8 mL. Orientation, geometry, position, and extent of the sinus vary so greatly that any generalization of fixed borders can give a wrong impression. However, it is essential to realize that the sphenoid sinus is in the sphenoid bone and that it is surrounded by vital structures surround it.

The sphenoid sinus lies immediately beneath and often anterior to the sella turcica with its encased pituitary gland. It is adjacent to the carotid arteries, the optic nerve, the maxillary nerve branch of the fifth cranial nerve and the pons.

At times, the bony walls, floor, or ceiling of the sphenoid sinus may be so thin that dehiscence occurs, exposing the optic nerve or carotid arteries.

Maxillary sinuses

These are paired sinuses located anteriorly on either side of the nose just below the eyes. The structure is that of a pyramid with the base located at the nasal wall. They each have a volume of 10-20 mL.

The orbital floor including the infraorbital nerve constitutes the roof or superior aspect of the maxillary sinus. The inferior aspect is fascinating in that it changes over time. The floor of the maxillary sinus is initially at the level of the nasal floor. As time passes and as the sinus undergoes progressive pneumatization, it approaches the apex of the maxillary canine tooth. In fact, extraction of the canine tooth sometimes results in an oroantral window. The nasal cavity is at the most medial aspect of the maxillary sinus. Thin bone with rich vascular turbinate tissue lines the maxillary sinus at the most medial border. The lateral boundary is a more-or-less abrupt termination of the pneumatic portion of the maxilla where is meets bone.

The anterior aspect is the anterior wall of the maxilla is simply the thin bony plate running from the root of the canine to the floor of the orbit. The posterior aspect of the maxillary sinus is where the converging walls of the lateral, inferior, medial, and superior walls meet below the orbits.

Ethmoid sinuses

The ethmoid sinuses are the most variable of all the paranasal sinuses. For this reason, imaging must be performed in any individual before any operation involving this area is undertaken. The ethmoid sinuses are less of a large open sinus than a series of variably interconnected air cells within bone. On average, 10 such air cells compose each of the paired ethmoid sinuses.

Portions of the superior aspect of the ethmoid sinus lie directly below the anterior cranial fossa. Regarding the inferior aspect, the orbits lie directly beneath these structures over much of their extent. They can extend into the superior wall of the maxillary sinus. In terms of the medial aspect, the lateral bone wall of the nasal cavity and the middle turbinate are the medial wall of the ethmoid. When pneumatization extends into the middle turbinate, the structure is called the concha bullosa. The lateral aspect of the ethmoid air cells varies in thickness. It is the medial wall of the orbit; because of its extremely thin dimension, it is called the lamina papyracea (ie, paper plate).

The anterior-most air cells of the ethmoid is actually bone perforated with an opening which is so curved it is called the hiatus semilunaris. This opening drains the frontal sinus and the maxillary sinus. The sphenoid sinus lies posteriorly over the middle most aspect of the ethmoid bone.

CONTRAINDICATIONS

Section 4 of 9  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Contraindications
• Workup
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

Therapy of sinus and nasal cavity malignancy is often multimodal. Radiation therapy, surgery, and chemotherapy are usually administered in combination. The location of the anatomic structures in question may make the outcome of surgery intolerable to some patients. These locations are adjacent and connected to the orbits, the brain, the base of the skull, the hard palate, and the carotid sheath.

Therefore, careful discussion with the patient and family is ideal before any therapeutic procedure is undertaken.

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Contraindications
• Workup
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

Lab Studies

• The usual battery of blood work and pulmonary function tests are always prudent when upper respiratory surgery is planned. However, in the case of a nasal cavity or paranasal sinus mass or erosion, an antineutrophil cytoplasmic antibody (ANCA) test for possible Wegener granulomatosis should be considered.
• This condition often mimics a neoplasm.
• Assessing for a history of diabetes and laboratory tests to rule this out is advised. In patients with diabetes, mucormycosis can falsely suggest to the clinician that the problem is a neoplasm.

Imaging Studies

• Imaging studies depend on the differential diagnosis.
• Plain radiography, CT scanning, and MRI all provide information. Each has its own advantages and limitations.
• Plain radiographs demonstrate the location and size of the lesion. Bone erosion suggests the aggressive nature of this lesion.
• CT scans can depict indicators of bone involvement better than radiographs, and MRI is extremely valuable in demonstrating soft tissue involvement.

Other Tests

• Biopsy is the only 100% accurate means of obtaining a tissue diagnosis.
• Remember that the turbinates and the possibility of a juvenile angiofibroma may both lead to massive hemorrhage.
• The radiologist's and the clinician's opinions should be given careful consideration.

Histologic Findings

The important histologic features are discussed in detail for the individual neoplasms in Clinical details above.

Staging

The staging of cancers of the paranasal sinus and nasal cavity are complicated because the anatomic region is complicated. Staging is always necessary before definite therapy can begin. The treatment and prognostication of malignancy of the sinonasal tract is based on the stage and cell type.

The National Cancer Institute (NCI) divides the anatomic primary areas into cancer of the maxillary sinus and cancer of the nasal cavity and ethmoid sinus. Staging is not established for infrequent primary sites.

The 5 stages of maxillary sinus primary carcinoma are designed 0-IV. Stage IV is divided into stages IVA, IVB, and IVC. The 5 stages of carcinoma of the nasal cavity and ethmoid sinus are identified 0-IV. Stage IV is divided into stages IVA, IVB, and IVC. Both these designation systems are based on whether the tumor is in situ (stage 0) and on whether it involves other structures, contiguous or distant.

Details of staging can be found on the NCI Web site and in the Physicians' Data Query (PDQ) - NCI's Comprehensive Cancer Database.

Proper staging it will be necessary to evaluate the following:

• Bone invasion and the site of that bone invasion
• Posterior of maxillary sinus
• Hard palate
• Eye socket
• Base of skull
• Other sinuses and ethmoid air cells
• Lymph nodes, including size of the lymph node
• Sphenoid sinus
• Facial skin
• Brain
• Nerves
• Upper part of the throat behind the nose

The clinician is ready to discuss treatment options and the prognosis based on staging only after this list is assessed.

Recurrent malignancy is another matter. Simply defined, it is a return of the malignancy at any site in the body after completion of therapy. The treatment of recurrent cancer is a function of the histologic type of cancer, the location and extent, and the initial therapy.

Treatment for recurrence includes surgery, chemotherapy, and/or radiation therapy.

A prudent approach is to constantly review the Physicians' Data Query (PDQ) - NCI's Comprehensive Cancer Database to see if clinical trials should be considered.

COMPLICATIONS

Section 6 of 9  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Contraindications
• Workup
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

Complications

Complications of treating sinus malignancies are related to the surgery and reconstruction. Surgical complications include clinically significant bleeding, CSF leak, infection, and cranial nerve damage.

Bleeding

Bleeding may occur if control of the large vessels is overlooked. This problem may occur if the artery is initially in vasospasm and if no active bleeding is noted. However, hours later, the patient can have a life-threatening hemorrhage. The best management is prevention. The ethmoid and sphenopalatine arteries should be routinely cauterized, clipped, or ligated to prevent bleeding.

CSF leaks

During surgery, CSF leaks may occur near the skull base. Appropriate management starts with identification of the problem.

A washout sign is a clear or dark streak that is seen in the blood coming from the roof of the nose. This signifies a CSF leak. Other tests, such as a test for tau or beta transferrin, may be most specific.

Simple patching with use of a dermal allograft, turbinate bone, nasal mucosa, and nasal packing is usually sufficient to seal the leak. For large leaks, a spinal drain may be necessary.

Reconstruction

Reconstruction is crucial for patients undergoing ablative surgery for sinus malignancies. This is most obvious in cases with orbital exenteration.

In the ideal cases, reconstruction preserves form and function. A free rectus flap or other distant tissue may be required to protect vital structures, or facial prosthetics may be used. Facial prosthesis can be offered to improve cosmetic results, an expert team is needed, as is maintenance on the patient's part.

Facial disfiguration is one of the most important patient concerns and can lead to considerable social and psychological stress. This outcome must be dealt with initially and on an ongoing basis.

OUTCOME AND PROGNOSIS

Section 7 of 9  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Contraindications
• Workup
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

Survival rates for patients with maxillary sinus cancer average about 40% over 5 years. Early-stage tumors have a cure rate of up to 80%. Patients with unresectable tumors treated with radiation have a survival rate of less than 20%. Survival rates for ethmoid tumors have improved slightly because of advances in skull-base surgery. Cure rates of up to 90% are attainable in low-grade adenocarcinomas that are completely excised. High-grade adenocarcinomas have a dismal 5-year survival rate of less than 20%.

FUTURE AND CONTROVERSIES

Section 8 of 9  

• Authors and Editors
• Introduction
• Relevant Anatomy
• Contraindications
• Workup
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

Although intra-arterial chemotherapy was used in the past, it was only recently shown to be consistently effective. With the advent of thiosulfate, a neutralizer of cisplatin, physicians can now deliver large doses of intra-arterial chemotherapy more safely than before. High-dose cisplatin is administered by means of the arterial blood supply of the tumor. A simultaneous infusion of thiosulfate prevents the systemic effects of cisplatin.

Intra-arterial chemotherapy is used with radiation and had promising results in preserving organs and in managing bulky nodal disease.

Given the anatomy of the paranasal sinuses and their blood supply, intra-arterial chemotherapy may be an effective method of treating sinus malignancies.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Relevant Anatomy
• Contraindications
• Workup
• Complications
• Outcome and Prognosis
• Future and Controversies
• References

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Article Last Updated: Feb 14, 2007