------------------------------------------------------------------------------- TITLE: PARANASAL SINUS NEOPLASMS SOURCE: Dept. of Otolaryngology, UTMB, Grand Rounds DATE: October 13, 1993 RESIDENT PHYSICIAN: Robert D. Hoffman, MD FACULTY: Karen H. Calhoun, MD DATABASE ADMINISTRATOR: Melinda McCracken, M.S. ------------------------------------------------------------------------------- "This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion." Epidemiology: True neoplasms of the paranasal sinuses are uncommon in the general population. Malignant tumors of the sinonasal tract constitute less than l% of all malignancies in the body and about 3% of those arising in the upper respiratory tract. Males are affected by sinonasal tumors twice as often as are females. Caucasians are affected more than blacks with a ratio varying from 1:1 to 15:1. These tumors are most frequently found during the fifth to the seventh decades. Tobacco and alcohol, which are major risk factors for malignant tumors arising in other areas of the upper aerodigestive tract, do not seem to play a role in sinonasal carcinogenesis. Exposure to industrial fumes and wood dust have been associated with an increased incidence of certain types of sinonasal malignant tumors. Nickel-refining processes have been implicated in the development of squamous cell and anaplastic carcinomas. Nickel workers show an incidence 250 times greater than the general population with a latent period of 18 to 36 years. Furniture workers, who are exposed to hardwood dust, suffer an increased incidence of adenocarcinoma of the ethmoid sinus. Other woodworkers, exposed to softwood dust, show an increased incidence of squamous cell, anaplastic, and adenocarcinoma. Workers in the shoe industry, especially those working with the tanning process of leather, show an increased incidence of epithelial malignancies of the sinonasal tract. Other industrial workers associated with an increased incidence of sinonasal cancer include those exposed to mineral oils, chromium and chromium compounds, isopropyl oils, lacquer paint, soldering and welding, and radium dial painting. Evaluation: Symptoms: The most common clinical presentation of tumors of the sinonasal tract includes facial or dental pain, nasal airway obstruction, epistaxis, nasal discharge, or swelling of the cheek. This presents a serious dilemma to the evaluating physician, considering that 2O% to 40% of all visits to a general otolaryngologist are related to nasal or paranasal sinus conditions. Furthermore, it has been reported that 9% to 12% of patients with sinonasal tumors are asymptomatic. Regional and distant metastases are infrequent despite the advanced stage of the primary tumors. The reported incidence of cervical metastases on initial presentation varies from less than 1% to 26%, with most large series reporting less than lO%. Distant metastasis on initial presentation is less common, with most series presenting an incidence of less than 7%. Ten to twenty percent of these patients will develop a second malignancy. As the disease progresses, it infiltrates adjacent structures, giving rise to additional symptoms as follows: 1. Diplopia or vision loss is most often a manifestation of tumor mass compressing or invading the orbit and may also result from direct involvement of the optic or oculomotor nerves at the orbital apex or the cavernous sinus. 2. Epiphora is caused by obstruction or infiltration of the lacrimal duct situated in the anteromedial aspect of the maxilla. 3. Facial swelling and malocclusion result from bone destruction and advancement of the tumor into the soft tissues of the face or mouth 4. Trismus signals far-advanced tumor invading the muscles of mastication, most commonly the pterygoid muscles. 5. Neck mass, palpable metastatic adenopathy in the jugular chain, is another sign of advanced disease, since the first-echelon nodes are located in the parapharyngeal region. 6. Hearing loss usually results from nasopharyngeal extension of the tumor causing serous otitis. 7. Facial numbness is a manifestation of tumor invasion of portions of the trigeminal nerve. Physical Findings: Until the tumor has infiltrated a cranial nerve or facial bones or grown sufficiently to obstruct a sinus ostium, it will silently advance in size and extent. Discovering an asymptomatic sinus tumor at an early stage is truly a rare and fortuitous event. The most common features include the following: 1. Nasal, facial, or intraoral mass. The intranasal mass is often necrotic, but polypoid mucosa may obscure underlying tumor tissue in the nose. Facial swelling results when an antral tumor erodes into the soft tissues of the cheek. The widening of the upper alveolar ridge or development of loose, nonvital teeth may the earliest sign of inferior bony invasion. A palate mass and ulceration are evidence of more advance disease. 2. Proptosis. Mild protrusion of the eye may be consistent with tumor compression of the periorbita without frank invasion, but usually it reflects intraorbital tumor and implies advanced disease. 3. Cranial nerve deficits. The commonly involved cranial nerves are the second (CN II), third (CN III), fourth (CN IV), two branches of the fifth (CN V1 and CN V2), and the sixth (CN VI). Involvement of cranial nerves is a manifestation of advanced disease and indicates a poor prognosis. Paranasal tumors are associated with a high incidence of cranial neuropathies (34%) as compared to inflammatory disease (4% to 8%). Radiologic Assessment: Radiologic imaging is essential during the initial examination. Plain films continue to be an important part of the initial evaluation. They may demonstrate opacification, mass effect, or bone destruction. Plain films demonstrate bone destruction in 60% to 90% of patients with malignant sinonasal tumors. However, 6% of these films will be interpreted as normal. Keep a high index of suspicion for those patients with a history of exposure to the previously discussed carcinogens; those presenting with severe persistent pain, cranial neuropathies, exophthalmos, chemosis, unilateral disease, bone erosion on plain films; or those with persistent symptoms after adequate medical treatment. Patients in these high-risk groups should be imaged by CT scanning or MRI. CT Scan CT scanners that provide high resolution and thin sectioning are helpful in evaluation soft tissue detail and its relationship to bone and the air containing spaces of the sinuses. Its true importance, however, lies in its ability to detect bone erosion. Critical areas to be assessed include the bony orbital walls, the cribriform plate, the fovea ethmoidalis, the posterior wall of the maxillary sinus with its attached pterygoid plates, the pterygopalatine fossa, the confines of the sphenoid sinus, and the posterior wall of the frontal sinus. Despite the significant amount of information that can be gathered from a CT scan, several limitations exist. It cannot always determine whether the tumor has invaded or just approached the periorbita. It is often difficult to differentiate tumor from soft tissue swelling. Consequently, it is difficult to determine the degree of actual tissue invasion. It is also difficult to determine the extent of tumor infiltration into obstructed sinuses because of similar soft tissue attenuation values. MRI Imaging MRI imaging provides excellent delineation of tumor from surrounding soft tissue, inflammatory tissue, and retained secretions within the sinuses. This characteristic, in combination with multiplanar capability and lack of radiation exposure, gives a distinct advantage to MRI over CT. Coronal images are the best for the evaluation of the foramen rotundum, Vidian canal, foramen ovale, and optic canal, allowing a side-to-side comparison. Sagittal images are most useful to demonstrate the replacement of the normal low-intensity signal of Meckel's cave and the high intensity signal of fat in the pterygopalatine fossa by tumor signals similar to brain in echo time images. The ability of MRI imaging to differentiate tumor from benign processes, such as surrounding soft tissues, inflammatory tissue, and retained secretions, is based on differences in proton mobility. In general, the typical appearance of edema or retained secretions within the sinuses or MRI images will be of low intensity on T1-weighted images and high intensity on T2-weighted images, reflecting the high water content associated with the excessive interstitial fluid or retained secretions. However, because of the frequent chronic nature of these benign processes in patients who have a nasal cavity or paranasal sinus tumor, especially in those patients in whom an advanced tumor has been diagnosed, sufficient time has elapsed to allow for the concentration of high water affinity mucoproteins and the absorption of free water. This leads to various degrees of shortening of both the T1 and T2 relaxation times. The areas of almost complete desiccation can have low signal voids, which can be seen adjacent to areas that are still predominantly composed of water. This can produce a wide variety of signal intensities on both the T1 and T2-weighted images. Carcinomas of the nasal cavity and paranasal sinuses share similar gross and microscopic pathologic characteristics: They are highly cellular tumors with little water and, as such, are represented by a homogeneous MRI appearance, with low to intermediate signal intensity on T1 and T2-weighted images. There may be focal, well defined areas of intermediate to high signal intensities on T1 and T2 images that represent subacute or chronic hemorrhage. There may be areas of low to intermediate signal intensity on T1-weighted images and areas of high intensity on T2-weighted images that represent fluid filled sites of necrosis. Once intracranial spread of the tumor usually tends to be broad-based and flat, despite the pattern of destruction below the skull base. Benign processes within the nasal cavity and paranasal sinuses, such as polyps and papillomas, often can be differentiated from malignant lesions by their morphologic appearance and signal intensities on T1 and T2-weighted images. Extension of benign processes intracranially is seen as a highly polypoid, intracranial surface. A gadolinium enhanced study may offer additional information. In most instances, gadolinium enhancement of the tumor is less intense than enhancement of the mucosa. The extent of tumor enhancement with gadolinium appears to correlate with the vascularity of the tumor, with the more vascular tumors having the greater amount of enhancement. Mucosal enhancement, however, may help differentiate an obstructed sinus from tumor. Pathology: The sinonasal tract pathology, with certain important exceptions, parallels the pathology found in other areas of the head and neck. It can be divided into benign and malignant epithelial tumors and benign and malignant nonepithelial tumors. Benign Epithelial Tumors: Papillomas may arise from squamous or schneiderian epithelium. Nasal cavity papillomas, although benign in nature, extend beyond their site of origin, tend to destroy bone, recur when not excised completely, and may be associated with malignant tumors. They are most commonly diagnosed in Caucasian males during the fifth to the seventh decade (mean 50 years). Schneiderian papillomas grow in three architectural patterns; (1) papillary and exophytic, (2) inverted, with an inwardly invaginating epithelial growth into underlying struma, and (3) cylindrical, with proliferating, multilayered columnar cells. Two recent large reviews of inverted papillomas found the most common symptom to be unilateral nasal obstruction. Other symptoms included mass or polyp in the nose, sinusitis, nasal discharge, epistaxis, anosmia, and facial pain. Symptoms such as facial swelling and numbness were much less common and are signals of a possible malignancy. Another common finding was a history of surgical therapy with recurrence of symptoms. The most common site of origin for this lesion is the lateral nasal wall. Malignancy is associated with inverting papilloma in approximately 8% of patients and is nearly always squamous cell carcinoma. Treatment for this lesion is usually lateral rhinotomy and medial maxillectomy. The recurrence rate following this procedure is about 10%. Limited procedures have in the past lead to unacceptably high recurrence rates of between 70% to 100%. However, Waitz and Wigand recently reported on 35 patients who had an endoscopic resection of an inverted papilloma. The procedure entailed macroscopic tumor debulking then endoscopic resection of the remaining tumor. The underlying bone was then burred with a diamond drill in order to eliminate deep reaching tumor infiltration. They reported a recurrence rate of 17% for this procedure. Adenomas of the sinonasal tract are more common in the nasal septum, which is interesting considering the fact that most minor salivary glands are located in the lateral nasal wall. Most are found during the fourth to the seventh decade occurring with an equal sex distribution. The recurrence rate is low following complete removal (10%). Malignant Epithelial Tumors: Squamous cell carcinoma is the most common tumor of the sinonasal tract. The maxillary sinus is involved in 70% of cases, followed by the nasal cavity (20%) and other sinuses (10%). The disease is limited to the maxillary sinus at the time of diagnosis in only 25% of cases. Carcinoma of the maxillary sinus is twice as common in men as in women, and more than 95% of patients are older than 45 years of age. The prognosis is related to the extent of the tumor and the site of origin. Minor Salivary Gland Tumors: Adenoid cystic carcinomas of the sinonasal tract include 20% of all the adenoid cystic carcinomas arising in the head and neck and is the most predominant salivary gland tumor of the paranasal sinuses. High- and low-grade varieties have also been described. Low-grade tumors are defined by a histology with less than 30% solid anaplastic conformation and include the cribriform and tubular patterns. High grade tumors correspond to those with a histologic pattern more than 30% solid. The incidence of perineural invasion seems to be similar for both, but the incidence of local recurrence and metastases is higher in the solid type. The survival rate is significantly better for low-grade tumors. The treatment has been primarily surgical, although combined surgery and postoperative radiation therapy seem to yield better local control. The course of these tumors may be very insidious, and patients may live some years even with the presence of distant metastases. Adenocarcinomas make up 4% to 8% of all sinonasal tumors. They originate most commonly at the ethmoids and nasal cavity. Adenocarcinomas may be divided into low and high grades according to their histologic characteristics and behavior. Low-grade tumors present a uniform glandular architecture and cytologic characteristics, with rare mitoses and seldom perineural invasion or distant metastases. They tend to recur locally. High-grade adenocarcinomas present a solid growth pattern with poorly defined margins, prominent pleomorphism, and large number of mitoses. One third of these patients will present with distant metastases. Mucoepidermoid carcinomas are extremely rare in the sinonasal tract. One paper reported 21 cases out of more than 400 mucoepidermoid carcinomas of the head and neck. They tend to present in very advanced stages and metastasize in more than 25% of cases. It is important to distinguish these tumors from squamous cell carcinoma, since behavior and prognosis seem to differ with well differentiated tumors. The propensity for widespread local invasion makes complete resection difficult, and so surgery as a single modality usually is inadequate. Attempts at en block surgical resection often leaves positive surgical margins. Recent series concluded that combined treatment by surgical resection and radiation therapy offers the best chance of cure for most patients. Melanoma of the sinonasal tract may be primary or metastatic. Although 20% of all melanomas originate in the head and neck, less than 10% arise from the sinonasal tract. They are most commonly found in the nasal cavity, followed by the maxillary sinus, lateral wall, ethmoid sinus, and frontal sinus in descending order. The anterior part of the nasal septum is the single most common location. The hallmark of these tumors is local multicentricity with early metastases. Most patients present with disease confined to the site of origin but show a tendency toward early vascular and lymphatic invasion. This probably explains the high incidence of local recurrence after surgical excision. Malignant melanomas appears as mass lesions on MRI with hyperintense in T1-weighted scans and hypointense in T2-weighted scans. They demonstrate moderate to marked enhancement following gadolinium. Prognosis is related to the extent of disease and completeness of surgical removal. Postoperative radiation therapy may be beneficial, although its impact on survival and local control has not been addressed in scientific trials. The 5-year survival rate seems to be 25% to 30%. The most common cause of failure, in contrast to the cutaneous variety, is local recurrence. Olfactory neuroblastoma or esthesioneuroblastoma is a rare neoplasm of the neuroectodermal origin that arises from the olfactory epithelium in the cribriform region, the upper third of the nasal septum, and along the superior and supreme nasal turbinates. The primary cell type ranges from an immature neuroblast to a benign-appearing neurocyte. The histology may be mistaken for lymphoma, melanoma, undifferentiated carcinoma, extramedullary plasmacytoma, and embryonal rhabdomyosarcoma and other sarcomas. Electron microscopy and histochemical analysis is needed to differentiate these lesions. It has a bimodal frequency at 10 to 20 and 50 to 60 years of age, with a similar incidence in males and females. A metastatic rate of 20% to 57% is reported with the most common site being the cervical lymph nodes. CT and MRI scanning generally demonstrate a homogenous mass with moderate to marked enhancement. These tumors are hypointense to brain on T1-weighted images and appear rather hyperintense to brain on T2-weighted images. At times, the tumor may be inhomogeneous with areas of cystic degeneration. These tumors may show calcifications. Its prognosis is related to the extent of disease and resectability on initial presentation. Since these tumors usually present in an advanced stage, most institutions have adopted combined therapies based on the Kadish staging system. UCLA recently reviewed 26 patients with esthesioneuroblastoma. They also introduced a new staging system in the familiar TNM type of classification style. It uses CT and MRI images to ascertain the extension of disease: T1: Tumor involving the nasal cavity and/or paranasal sinuses (excluding sphenoid), sparing the most superior ethmoidal cells T2: Tumor involving the nasal cavity and/or paranasal sinuses (including the sphenoid) with extension to or erosion of the cribriform plate T3: Tumor extending into the orbit or protruding into the anterior cranial fossa T4: Tumor involving the brain Their treatment recommendation is a craniofacial en bloc tumor resection followed by postoperative radiation therapy. Nevertheless, the need for radiation therapy for resectable tumors has been recently refuted by Biller and co-workers. They found better local control and less distant metastasis when the patients were treated with surgery only. Teratocarcinomas are rare, highly aggressive tumors, showing teratoid, carcinomatous, and sarcomatous components. These tumors are most commonly diagnosed in aging adults, as the median age of this series of patients was 60 years. The tumors grow rapidly and are locally destructive. More than 60% of the patients were dead at 3 years of follow-up, despite the use of surgery and radiation therapy in most cases. Undifferentiated carcinomas are usually composed of small and medium-sized cells and must be differentiated from rhabdomyosarcomas, melanoma, olfactory neuroblastoma, lymphoma, and squamous cell carcinoma. The onset of symptoms is very rapid, and they usually present with very advanced stage involving multiple sinuses. Prognosis is poor, with 80% to 90% of the patients dying of the disease within one year. Benign nonepithelial tumors: Osseous Tumors - Osteomas are slow growing, benign tumors composed of mature bone and are found almost exclusively in the head and neck. They are most commonly found in the frontal sinus followed by the ethmoid sinus and the maxilla. Surgical removal is indicated when the patient becomes symptomatic or a mucocele forms. The surgical approach is a frontal osteoplastic flap or external ethmoidectomy. Ameloblastomas constitute only 1% of all tumors and cysts in the jaws. Eighty percent of these occur in the mandible and 20% occur in the maxilla. Of the maxillary tumors, half are found in the molar area, a third are found adjacent to the antrum, and the remainder occur at other sites. Histologically, the tumor tends to mimic the enamel organ. There are two microscopic patterns: follicular and plexiform. Because of certain recurrence with simple curettage, ameloblastoma of the maxilla must be excised en bloc with good surgical margins. This often requires a radical maxillectomy with preservation of the orbit. Fibrous Dysplasia is characterized by the replacement of normal bone by tissue containing collagen, fibroblasts, and varying amounts of osteoid tissue. It can be either monostotic or polyostotic. The maxilla is the most frequently involved bone in monostotic fibrous dysplasia. Radiographically it is characterized by a mottled or ground glass appearance to the affected bone and there is no discrete border. It is slow growing and tends to stabilize during adulthood. Complete surgical excision is usually impossible and functional and cosmetic considerations steer intervention. Chondromas - Chondrogenic tumors of the head and neck generally arise in cartilaginous tissue such as that of the larynx or in bones that have ossified from cartilage such as the ethmoid and sphenoid. Chondrogenic tumors of the sinonasal cavities are rare and most often malignant. About 60% of the tumors arise in the anterior alveolar region of the maxilla. Early, wide excision may result in a cure. Nerve sheath tumors are divided into schwannomas, neurofibromas, and neurogenic sarcomas. Most of these tumors arise from sensory nerves. In the sinonasal cavities, they arise from the first and second division of the trigeminal nerve and from autonomic nerves. On CT scans, schwannomas appear as well- defined, homogeneous masses, and reveal moderate enhancement after intravenous injection of contrast. However, they may be inhomogeneous as well as cystic. On MRI images, schwannomas reveal a low-to-intermediate signal intensity of T1-weighted and hyperintensity on T2-weighted images. They demonstrate moderate- to-marked enhancement after intravenous injection of gadolinium. Schwannomas are bone pushing and remodeling lesions, and the presence of aggressive bone destruction should be considered as an indication of malignant degeneration. Sinonasal nerve sheath tumors make up 4% of those arising in the head and neck area. Ninety percent of these show a benign histology. Two thirds of the reportedly benign sinonasal tumors are schwannomas and one third neurofibromas. Even with a benign histology they may present a diagnostic dilemma, requiring the use of electron microscopy and immunohistochemical analysis for proper documentation. They may be associated with von Recklinghausen's syndrome. They are best treated by complete surgical excision, although partial removal is recommended for massive neurofibromas involving vital areas. Malignant nonepithelial tumors: Rhabdomyosarcoma - This is the most common soft tissue sarcoma in infants and children. It ranks seventh among the common malignancies of childhood, accounting for 5% to 15% of all neoplasms in children. The peak incidence is in the 2- to 5-year old age group, with a second peak occurring between 15 and 19 years of age. The head and neck is the most common site of origin. Lesions in the orbit, 30% of all head and neck lesions, tend to remain localized without lymphatic spread. Parameningeal sites, 34% of cases, lie adjacent to the meninges at the base of the skull (nasopharynx, middle ear, paranasal sinuses, infratemporal and pharyngopalatine fossae) and exhibit a propensity for regional spread into bone, meninges, and lymph nodes. The remaining 37% of head and neck rhabdomyosarcomas are classified as "non-orbital, non-parameningeal" and include tumors of the larynx, oropharynx, oral cavity, parotid, cheek, and scalp. Rhabdomyosarcomas are pleomorphic tumors, and the cells may be anaplastic. On the basis of their histopathologic characteristics, they are classified into three histologic types: embryonal, differentiated, or alveolar. Differentiated rhabdomyosarcoma is the least frequent type and is rarely misdiagnosed because cells with eosinophilic cytoplasmic fibrils that are usually cross-striated are used to identify the tumor. Embryonal rhabdomyosarcoma, the most common histologic subtype, is believed to arise from the primitive muscle cell, such as would be found in a fetus of 7 to 10 weeks gestation. The histologic diagnosis of embryonal and alveolar type rhabdomysarcoma may be difficult; it has been estimated that up to 50% of the proven cases of rhabdomyosarcoma are incorrectly diagnosed on initial biopsy. They are both aggressive bone destroying and bone pushing lesions. CT and MRI studies should be performed with and without contrast enhancement, with particular attention paid to the detection of bone erosion at the skull base and intracranial extension of the tumor. In 1987 the Intergroup Rhabdomyosarcoma Study reported their experience with the use of intensive radiation and chemotherapy on children with nonorbital parameningeal rhabdomyosarcoma showing cranial nerve deficits or skull or intracranial involvement. This landmark study reported an improvement of the survival rate from 51% to 81%. However, these results have never been confirmed in adults. Adult rhabdomyosarcomas are usually treated by with surgical excision. Radiation is recommended for positive margins or inoperable or recurrent disease. Chemotherapy has a palliative role that must be weighed against its possible morbidity. Leiomyosarcomas originate from smooth muscle. In the sinonasal tract, they are most commonly found in the nasal cavity, followed by the maxillary sinus and then the ethmoid sinus. They are more common in males (2:1) and the average age at diagnosis is 53 years. Their prognosis depends on the completeness of surgical resection. The presence of orbital invasion indicates a worse prognosis. Radiation and chemotherapy are usually reserved for inoperable or recurrent tumors. Half of the patients will be dead within one year and only 20% will survive 5 years. Fibrosarcomas are tumors of fibroblasts. The term encompasses a spectrum of malignancies, including the low grade fibromatosis and higher-grade tumors. Misdiagnosis very common. Radiation and trauma have been implied as possible etiologic factors. Low-grade malignancies respond well to surgical excision, although recurrences are common. Recurrences seem to be responsive to radiation therapy. High-grade or undifferentiated fibrosarcomas behave more aggressively, metastasize more frequently, and are less radioresponsive. The treatment of choice in either is wide surgical excision for previously untreated tumors. Radiation is recommended for involved margins or recurrent or inoperable tumors. Angiosarcomas are slow-growing but locally aggressive tumors characterized by wide horizontal spread with poorly fined margins. Well-differentiated tumors are usually found in children and young adults, while poorly differentiated lesions are a disease of the elderly. Sinonasal angiosarcomas tend to develop at a younger age and are associated with less incidence of metastasis and local recurrences than their cutaneous counterparts. Surgical excision is the treatment of choice. Radiation seems to be an effective adjunct to surgery for the treatment of sinonasal angiosarcomas. Hemangiopericytoma - Sinonasal hemangiopericytomas are rare lesions that usually present with nasal obstruction and epistaxis. The term pericyte was first introduced by Zimmerman in 1923, and refers to a specific cell type lying external to the reticulin sheath of capillaries. They are small, round or spindle-shaped cells with branching cytoplasmic processes that envelop capillaries. They are external to the endothelial cells, are surrounded by the basement membrane, and are thought to regulate the size of capillary lumina through contractile properties and to synthesize collagen. The criteria for distinguishing a benign from a malignant hemangiopericytoma is extremely difficult. In the head and neck, 40% to 60% of the tumors recur locally with a metastatic rate of 5% to 10%. This tumor metastasizes by spreading through lymphatics and blood vessels to the lung, bone, and local nodes. They appear on CT scans as moderate to markedly enhancing masses. They may show some calcification, and the masses may be large and associated with bone erosion. On MRI images they appear as low-to- intermediate signal intensity on T1-weighted and intermediate-to- hyperintense on T2-weighted images. they disclose moderate-to- marked enhancement following infection of gadolinium. Their prognosis relates to the size of the lesion, number of mitoses, and metastases. Higher incidence of metastases has been suggested for the sinonasal tumors. The primary treatment is surgical excision. Radiation and chemotherapy have been used anecdotally with different results. Osteosarcoma is the most common primary neoplasia of bone. Those originating, within the jaws constitute 7% to 10% of all osteosarcomas. Although osteosarcoma of the long bones occurs most frequently in the second decade, primary lesions of the skull and jaw occur most commonly in the third decade. The radiographic appearance of these tumors may vary from a purely lytic to a blastic destructive mass. There may be characteristic tumor bone formation within a large soft tissue destructive mass or a so-called sunburst periosteal reaction and tumor bone formation. The most effective therapy is surgical excision. However, during the past decade several reports have suggested that adjunctive radiation and chemotherapy may lead to improved survival. Chondrosarcomas are slow-growing but locally aggressive tumors that usually arise from cartilaginous structures. Sinonasal chondrosarcomas are more common during the sixth decade of life and usually remain asymptomatic until they reach a large size. These tumors have been graded from I to III on the basis of the rate of mitoses, cellularity, and nuclear size. Size of the tumor and grading correlate with the rate of metastasis, local aggressiveness, and ultimate survival. Surgical removal with wide margins is the treatment of choice. Gross total removal with postoperative radiation is recommended for those involving vital structures. Lymphoma - Lymphomas are commonly classified in Hodgkin's disease and non-Hodgkin's lymphomas. In general, Hodgkin's disease develops within lymph nodes and spreads by involving adjacent nodal groups. Non-Hodgkin's lymphomas may originate within a lymph node group, but in 40% of the cases, they originate in extralymphatic organs or tissue. Lymphomas arising in the nose and paranasal sinuses are of the non-Hodgkin's type and frequently are observed in patients who have disseminated lymphoma. The clinical appearance of lymphomas in the nose and paranasal sinuses may be easily confused with that of an infection or granulomatous or nonlymphomatous neoplastic process. On CT and MRI studies, lymphoma may mimic the much more common entities of sinusitis, polyposis, granulomatous processes and benign and malignant neoplasms. They are often seen as bulky masses and there may be changes to indicate expansion, erosion, or infiltration. The treatment includes radiation therapy for localized lesions and chemotherapy for systemic involvement. The behavior is remarkably different in the pediatric and adult populations. Adults seem to suffer frequent relapses, commonly involving the abdomen, and show a 5-year survival rate of around 45%. In children, complete remissions are more common, involvement of the gastrointestinal tract is rare, and the 5-year survival rate is close to 75%. Plasmacytoma - Plasma cell neoplasms are designated as multiple myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma. Extramedullary plasmacytoma accounts for about 20% of the plasma-cell neoplasms and occurs frequently in the upper airways. Sixty percent of all extramedullary plasmacytomas occur in the nose, nasopharynx, and paranasal sinuses. It is confined to the soft tissues; there is no generalized bone involvement or systemic manifestations. Multiple myeloma and plasmacytoma are part of a continuum of B- cell lymphoproliferative disorders. Plasmacytoma of the sinonasal tract appears on CT scans as a fairly well-defined mass, which often has expansile characteristics and is associated with bone remodeling as well as bone erosion. There well be moderate to marked enhancement after intravenous infusion of contrast material. On T1-weighted MRI images plasmacytoma appears as a mass of low to intermediated signal intensity and is associated with moderate contrast enhancement. It is intermediate to high signal intensity of T2-weighted images. It may have marked enhancement after gadolinium infusion. It tends to spread locally, metastasizing to the cervical nodes in less than 25% of the cases. The prognosis is unpredictable, and a variable number of the patients will be diagnosed with multiple myeloma. It is of utmost importance to rule out this diagnosis on the initial presentation, because the treatment of patients with multiple myeloma differs from that of extramedullary plasmacytoma. Most patients with extramedullary plasmacytoma will respond to radiation therapy in doses of 4000 to 5000 cGy administered over 4 to 5 weeks. Metastatic tumors: Metastatic tumors to the sinonasal tract produce symptoms similar to those of primary tumors. More than 100 cases have been reported, metastasizing to the maxillary, ethmoid, frontal, and sphenoid sinus in descending order. The most common primary sources are hypernephroma and breast and lung carcinomas. The treatment is palliative, with radiation, surgery, or chemotherapy to relieve obstructive and compressive symptoms or pain. Staging: The American Joint Committee on Cancer has formulated standard tumor, nodes, and metastases (TNM) staging for malignant tumors of the maxillary sinus. Ohngren's line is an imaginary line drawn between the medial canthus of the eye and the angle of the mandible. This line divides the maxillary antrum into the infrastructure (anteroinferior) and the suprastructure (posterosuperior). This line gives a rough estimate of the dividing line between tumors that may be resected with a good or poor prognosis. The AJCC staging criteria for primary tumors is as follows: T1: Tumor confined to antral mucosa of infrastructure with no bone erosion or destruction T2: Tumor with erosion or destruction of the infrastructure, including the hard palate and/or the middle nasal meatus T3: Tumor invades any of the following: skin of the cheek, posterior wall of maxillary sinus, floor or medial wall of orbit, anterior ethmoid sinus T4: Tumor invades orbital contents and/or any of the following: cribriform plate, posterior ethmoid or sphenoid sinuses, nasopharynx, soft palate, pterygomaxillary or temporal fossae, or base of skull Management of malignant neoplasms by site of origin: Maxillary sinus: The majority of patients with malignant maxillary neoplasms present with advanced disease. At least 75% of the patients present with stage III or IV, locally advanced disease that has already violated the bony boundaries of the sinus. Treatment of paranasal sinus carcinoma is complicated by the strategic location of the sinus and invasion of adjacent structures at presentation. En bloc resection with healthy margins is difficult to obtain. Delivering a high curative radiation dose required to sterilize tumor cells embedded in compact bone of the skull base is difficult without producing optic nerve, chiasmal, or brain damage. Local recurrence is by far the most common cause of treatment failure and death. Long term survival rates for advanced disease have been historically low. Rates with single modality treatment (surgery or radiation therapy) are approximately 25% to 30%. Most authors agree that combined surgery and radiation therapy offer optimal control. Recently published studies of combined surgery and radiation therapy have five year survival rates from 50% to 70%. Radiation therapy may be given pre- or post-operatively. The rationale for postoperative therapy is that the cancer may have a high potential for radioresistance, radiation therapy is more successful when malignantly involved bone is excised, surgery permits accurate planning of postoperative radiation therapy and there is better tissue healing when surgery precedes radiation therapy. However, Stern recently published a review of 85 patients from M.D. Anderson with squamous cell carcinoma of the maxillary sinus. In comparing patients who were treated by surgery alone with those treated by combined surgery and postoperative radiotherapy, no statistically significant differences were found between these two groups if symptoms, signs, and results of imaging studies were analyzed individually. A multimodality treatment protocol was recently described from the University of Chicago. One stage III patient and 11 stage IV patients were treated with neoadjuvant chemotherapy, surgery and concomitant chemotherapy with radiation therapy. With a median follup of 55 months, 11 of the patients were alive and free of disease. Patients who are not operative candidates or refuse surgery may be treated with a chemotherapy/radiation therapy combination. Choi reported treating 14 such patients with a split-course hyperfractionated radiation and concomitant cisplatin infusion. Eleven of the 12 patients achieved a complete response and 7 of 12 were alive at 35 to 72 months. Ethmoid sinus: Ethmoid sinus lesions represent 5% to 25% of all sinus malignancies. Nineteen patients with primary ethmoid sinus malignancies were recently reviewed by the Cleveland Clinic. Pathologic diagnosis included adenocarcinoma (8), sarcoma (4), squamous cell carcinoma (3), mucoepidermoid carcinoma (2), adenoid cystic carcinoma (1), and undifferentiated carcinoma (1). All had surgical resection and 12 had combined treatment with radiation therapy. Ten patients were alive with no evidence of disease at publication. The mainstay of therapy in this group was craniofacial resection. It provides excellent exposure and improves the chances to achieve negative surgical margins. Radiation therapy was used in patients with positive surgical margins and those with at high risk for tumor recurrence with negative margins due to tumor volume or aggressive histologic findings. Involvement of dura, brain, sphenoid sinus, or nasopharynx are associated with a poor prognosis. Management of advanced tumors: Orbital invasion: Sinonasal tract tumors may extend to the orbit by invasion or erosion of the bony walls, by perineural or perivascular invasion, or following preformed pathways benign tumors usually expand the bony walls and follow preformed pathways, while malignant tumors most commonly erode through the bone. The incidence of or invasion from sinonasal tract malignancies varies with primary site, histology, and aggressiveness of the tumor. Orbital invasion is most commonly associated with a carcinoma, with an incidence as high as 66%. There has been a general trend toward more conservative surgical procedures in regard to orbital preservation. Some feel that orbital preservation could be accomplished in the majority of cases unless frank invasion through the periorbita was demonstrated at the time of surgery. Harrison indicated that ocular preservation could be realistically accomplished only if there was no orbital involvement. He contends that in a disease with such a poor prognosis, local control and quality of life are better accomplished with orbital exenteration at the time of initial surgery. When the orbital floor is resected and the patient undergoes radiation therapy, only about 20% of the eyes retain adequate function. Therefore, when the orbital floor is resected and the radiation field will include the eye, exenteration should be performed, because the chance for good ocular function is extremely low, and ocular complaints may significantly diminish the quality of life for patients. Cervical metastasis: The incidence of nodal metastasis ori initial presentation varies from 3% to 16%, with most series reporting an incidence around lO%. An increased incidence of nodal metastases has been reported in patients with tumors extending to the intraoral mucosa. The presence of cervical metastasis during the course of the disease is higher, varying from 5% to 44%, and is most common during the first 48 months after treatment. Recurrence in the form of cervical metastasis ranks second after local recurrence as a cause for treatment failure. However, isolated recurrence to cervical nodes is rare; usually it is accompanied by recurrent disease at the primary site. It has been reported that elective irradiation to the neck resulted in 100% regional control, but no survival benefit was noted. The low incidence of nodal metastasis from sinonasal malignancies does not justify the use of elective neck dissection or radiation. The presence of cervical node metastasis on initial presentation does not seem to be a contraindication for radical treatment of the primary. ---------------------------------------------------------------------------- BIBLIOGRAPHY Bielamowicz S, Calcaterra TC, Watson D. Inverting papilloma of the head and neck: the UCLA update. Otolaryngology Head Neck Surg 1993;109:71-76. Bridger GP, Mendelsohn MS, Baldwin M, Smee R. Paranasal Sinus Cancer. Aust. N. Z. J. Surg 1991;61:290-294. Carrau RL, Myers EN, Johnson JT. Paranasal Sinus Carcinoma - Diagnosis, Treatment and Prognosis. Oncology 1992;6:43-50. Choi KN, Rotman M, Aziz H, Potters L. 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