UPDATE ON RESPIRATORY DISEASES
0195-5616/92 $0.00
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CANINE AND FELINE NASAL AND PARANASAL SINUS TUMORS Gregory K. Ogilvie, DVM, and Susan M. LaRue, DVM, PhD
Tumors involving the nasal cavity and nearby sinuses are rare in the dog and cat. Tumors that originate on the nasal planum are common in the cat but are not discussed in this article. The prevalence of tumors of the nasal and paranasal sinuses ranges between 0.3 to 2.4% of tumors surveyed in the dog and 4.2% of all tumors diagnosed in one study in the cat. 2- 4 • 12• 16• 17 In the dog, tumors of the nasal and paranasal sinuses are generally seen in older animals (median, 10 years), with various sex and breed distributions reported. 3· 12• 16· 17 Affected cats are generally older males with a mean age of 8 to 10 years. 4• 6 Although the most common cause of unilateral epistaxis, facial deformity, and epiphora in the aged dog and cat is a malignant nasal or paranasal tumor, other differentials must be considered. 22 Definitive diagnosis is based on the signalment, history, physical examination findings, radiographs, and histologic evidence of malignant neoplasia. Radiation therapy, with or without surgery, has been considered to be the most effective treatment. This article reviews the clinical features and optimum methods for diagnosing nasal tumors in the dog and cat. Therapeutic strategies are also discussed.
This work was supported by grant number 2 POl CA 29582 from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
From the Comparative Oncology Unit, Colorado State University College of Veterinary Medicine and Biomedical Sciences, Fort Collins, Colorado
VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 22 • NUMBER 5 • SEPTEMBER 1992
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HISTORY AND CLINICAL SIGNS
Diseases within the nasal and paranasal sinuses cause many of the same clinical signs. 11. 12• 14 The clinician should have an increased index of suspicion for a nasal tumor in older dogs or cats that exhibit facial deformity, epiphora, and unilateral epistaxis.22 The epistaxis may be bilateral if the disease has progressed. Other, less specific clinical signs include a purulent or mucoid nasal discharge, dyspnea, coughing, sneezing, ocular discharge, prolapse of the third eyelid, and neurologic signs. 11 • 12• 14 In most cases, these clinical signs persist for months. Owners often report that antibiotic therapy alleviates clinical signs transiently, presumably as a result of a decrease in secondary bacterial infection associated with most nasal tumors. The differential diagnoses that must be considered in each case include bacterial or fungal rhinitis, foreign body, nasal parasites, allergic rhinitis, bleeding disorders, and trauma. Aspergillus sp is the most common cause of fungal rhinitis. The authors have observed that fungal rhinitis seems to have a regional distribution. Fungal rhinitis is rarely diagnosed in the Rocky Mountain area but is seen commonly in the Midwest, where the hot, humid weather provides a more favorable environment for the fungal organisms. PATHOLOGY AND BIOLOGIC BEHAVIOR
Approximately 60% of dogs with nasal or sinonasal tumors have carcinomas. 12· 16 Adenocarcinoma and squamous cell carcinoma are common. Sarcomas (fibrosarcoma, chondrosarcoma, osteosarcoma, and undifferentiated sarcoma) are identified less frequently. At the time of initial diagnosis, metastases are rare. 22 Later in the course of the disease, metastases can be seen in approximately 41% of the cases. 16 Metastatic rate appears to be lowest among nonepithelial tumors. 16 Metastases occur most commonly in the brain, lymph node, lung, and liver. 16 The most common histopathologic diagnoses for intranasal and nasal sinus tumors of the cat include adenocarcinoma, undifferentiated carcinoma, olfactory neuroblastoma, lymphoma, fibrosarcoma, chondrosarcoma, and chondroma. 4 • 5 Brain invasion via the cribriform plate has been seen in approximately 25% of the cases reported in one study. 4 Metastatic disease to the regional lymph nodes is reported in a minority of cases.4 The majority of nasal tumors in the dog and cat are located at or near the cribriform plate. Approximately half of the tumors in the dog are bilateral at the time of diagnosis. 16 Extension through the nasal cavity to external sites is common in advanced cases of nasal tumors in either species. DIAGNOSTIC TESTS
The diagnosis of a nasal tumor begins with a good history and physical examination. Most patients with a nasal tumor are older and
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have a chronic history of respiratory problems associated with the nasal cavity. Unilateral epistaxis, epiphora, and facial deformity are highly suggestive of the presence of a nasal tumor, but other differentials must be considered. A definitive diagnosis can only be obtained with a histologic diagnosis. Other supportive data can be obtained with rhinoscopy, plain radiographs, computed tomography (CT) images, and serology or mycotic cultures for fungal rhinitis. Bacterial cultures are rarely of value. Lymph node biopsy or aspirate specimens are positive approximately 10% of the time and should be consid~red in cases in which a regional lymph node is enlarged. 22 In addition, chest radiographs generally are recommended but often fail to identify evidence of metastatic disease. 22 Before rhinoscopy, radiographs, and biopsy procedures are considered, routine screening tests should be performed to eliminate the possibility of bleeding disorders, especially when epistaxis is present. These tests include, but are not limited to, a hemogram and platelet count, biochemical profile, urinalysis, clotting profile, and, if indicated, blood pressure measurements. Serum should be acquired for titers for potential diseases such as ehrlichiosis and aspergillosis.
Radiographs
Nasal radiographs should be made before other diagnostic tests are done to more specifically d etermine the cause of nasal or paranasal disease. 8 These radiographs are essential to determine the extent and location of disease: two important factors for directing- biopsy procedures and for planning treatment. 8 As a general rule, the dorsoventral frontal sinus view (Fig. 1), and the ventrodorsal open mouth view, with high resolution detail screen placed as far caudad in the nasal cavity as possible, are most valuable. The open-mouth view is made to show the caudal nasal cavity and cribriform plate (Fig. 2). The roentgen signs commonly associated with nasal tumors include loss of nasal and trabecular turbinate pattern, increased density in the nasal cavity and frontal sinus, deviation or deformity of the vomer bone, destruction of overlying bone, periosteal new bone formation, and the presence of an external soft tissue mass. 4 · 8• 9 · 12• 14 Computed tomography provides more information about the location of the tumor and extent of destruction than routine radiographic imaging (Figs. 3-5). Thrall et aF0 showed that CT was more accurate than radiographs in identifying unilateral versus bilateral nasal cavity disease and tumor extension into nearby structures such as the hard palate, pterygopalatine fossa, and cranial cavity. He and others have concluded that CT was useful for more accurate tumor staging, predicting possible treatment-related complications, and planning surgery and radiation therapy. 12• 15 When there is suspicion of brain involvement based on the history, physical examination, or radiographic findings, an iodinated contrast agent should be injected intravenously. If the
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Figure 1. Dorsoventral frontal sinus radiograph showing an increased density in the right frontal sinus, which is caused by a tumor or fluid.
""
Figure 2. Ventrodorsal open-mouth radiograph showing alterations in density, loss of the lacey turbinate structures, and bony lysis of larger bony structures in the right side of the nasal cavity due to a nasal adenocarcinoma.
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Figure 3. Contrast enhanced CT scan of an adenocarcinoma of the rostral nasal cavity showing the destruction of the nasal bone and extension of the nasal tumor into soft-tissue structures overlying the nose.
Figure 4. Contrast enhanced CT scan at the level of the eyes and the rostral aspect of the cribriform plate of the same dog imaged in Figure 3. The tumor has destroyed one frontal sinus and has invaded through the bony orbit into the retrobulbar space. Note the displacement of the eye on the side of the tumor.
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Figure 5. This CT scan is from the same dog shown in Figures 3 and 4 but is taken slightly more caudal than the image displayed in Figure 4. The tumor is destroying the bone over the olfactory bulb of the cribriform plate.
blood-brain barrier is broken, the iodinated contrast agent will extend into the brain and surrounding tissue and will be noted on the CT as an area of increased radiodensity (Fig. 5). In the authors' experience, extension into the brain is a poor prognostic sign.
Rhinoscopy
Rhinoscopy allows direct visualization of the nasal cavity and surrounding structures and can be done with a flexible bronchoscope or rigid cystoscope. Biopsy specimens can be taken concurrently through the endoscope; however, it may be prudent to follow with a transnasal core biopsy procedure. Foreign body removal and identification of nasal parasites can be accomplished easily by an experienced operator. To prevent iatrogenic hemorrhage, patience is essential when performing a careful examination and removing or suctioning various exudates within the nasal cavity. When the flexible endoscope is used, the caudal nasopharynx should be examined for any neoplastic tissue by extending the endoscope through the oral cavity and then retroflexing the scope over the soft palate. The scope should then be directed forward toward the front of the patient to locate any tumor or other abnormalities in the most cranial aspect of the nasopharyngeal area.
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Nasal Flushes
Nasal washings or flushes have been reported with mixed results. MacEwen et aP 1 reported a 50% success rate by flushing the nasal cavity and examining the resulting fluid cytologically. n Others feel the yield is much lower. One method of performing this procedure is to place a large Foley catheter into the nasopharyngeal area via the oral cavity so that when the bulb is inflated, large quantities of fluid can be f.lushed out the nares without escape of fluid caudally through the mouth, trachea, or esophagus. The authors have used this technique to lavage the nasal cavity in cases where grass awns or other smaller fragmented foreign bodies are suspected.
Biopsy Techniques
The cornerstone of the diagnosis of a nasal tumor is based on procurement of adequate tissue for histopathology. In most cases, a biopsy procedure can be done while the animal is anesthetized for radiography or other concurrent diagnostic tests. The simplest, cheapest, most accurate method of obtaining adequate tissue in the dog without resorting to surgery is a transnostril core sampling procedure (Fig. 6). 23 A 3- to 5-mm plastic cannula is used to biopsy all but the smallest dogs. The cannula is snugly attached to a syringe via the hub of a needle, as previously described. 23 The location of the tumor is assessed from the radiographs or CT images and the ass~mbled biopsy instrument is passed up the nostril and directed at the tumor. The tumor frequently has extended into the cribriform region, rendering it very susceptible to trauma from the biopsy, which can result in penetration of the brain by the biopsy instrument. To prevent this, the location of the cribriform plate can be estimated by measuring from the tip of the nares to the medial canthus and the biopsy instrument marked with tape or cut off at the appropriate length (Fig. 6). When passing a plastic cannula, slight resistance usually is felt as the tumor is entered. Negative pressure is applied with the syringe as the cannula is redirected in various angles. After the biopsy procedure has been performed, the tissue is expelled onto a gauze sponge to allow separation of tumor from blood and mucus. The specimen should then be placed in 10% neutral buffered formalin for histologic analysis. Hemorrhage will occur but should subside within a few minutes. Severe hemorrhage can be controlled by permanently ligating the ipsilateral carotid. Tumors in cats and small dogs are sometimes accessible to biopsy by transnostril curettage. If nonsurgical approaches do not work, then a rhinotomy may be considered to obtain tissue for a definitive diagnosis. A trephine generally is used to gain entry to the nasal cavity or sinus; then, a curet is used to scoop out the suspected tumor tissue. Although this method grants the greatest exposure, it still may be accompanied by significant
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Figure 6. The skeletal and soft-tissue landmarks involved in a transnostril core biopsy. In this procedure, a 3 to 5-mm plastic cannula is snugly attached to a syringe via the hub of a needle. The biopsy instrument is passed up the nostril and directed at the tumor. Care is taken not to extend the biopsy instrument past the level of the medial canthus of the eye (A) that corresponds anatomically with the cribriform plate and the rostral aspect of the cranium (B) . After the cannula is placed into the tumor, negative suction is applied, and the instrument is removed from the nasal cavity.
hemorrhage. More importantly, it has the great disadvantage of contaminating the biopsy field with tumor. If the dog is to be treated with radiotherapy, this requires a significant alteration in the treatment plan with a higher dose to the skin in the region, which results in more patient discomfort and possibly a sacrifice in tumor control.
THERAPY Surgery
Because nasal tumors rarely metastasize, therapy is directed at controlling localized disease. Surgical excision alone is not considered an effective option for treating nasal tumors in dogs and cats, because bone invasion occurs early in the pathogenesis of the disease and the tumor is often located near the brain and eyes. Indeed, surgery alone has been shown to be associated with a high prevalence of acute and chronic morbidity without a significant extension of life .11 · 12 Therefore, generally surgery is indicated only when combined with radiation therapy. Complications relating directly to rhinotomy include subcutaneous emphysema, hemorrhage, and infection.
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Cryosurgery
Cryosurgery has been used to treat canine nasal tumors following nasal curettage or radiation therapy. 21 The use of liquid nitrogen resulted in significant complications, including destruction of the hard palate resulting in oronasal fistulas and generalized tissue destruction. In a limited clinical trial, survival times were not increased when cryosurgery was added to standard debulking procedures or radiation therapy. 21 Radiation Therapy
Radiation therapy, with or without surgical debulking, is the only treatment modality that has been shown to be effective for increasing the survival time of dogs and cats with nasal tumors. 3 • 7• 11 • 13• 14• 19 With orthovoltage radiotherapy, surgical debulking is necessary owing to tumor volume. (Lack of penetration by orthovoltage radiation generally precludes orthovoltage radiation alone.) Forty to 50 Gy, delivered in 10 to 12 fractions, is administered to the skin surface overlying the cytoreduced surgical field. The reported median survival of 16 to 23 months is slightly better than megavoltage alone. 7• 13• 19 The 1- and 2year survival rates were 54 to 57% and 43 to 47%, respectively. 7• 19 Although the previously reported median survival for dogs with nasal tumors treated with megaradiation alone was approximately 8 months, 1 a recent paper by McEntee reported a median and mean survival of 12.8 and 20.7 monthsY 1- and 2-year survival rates were 59% and 22%, respectively. Dogs received from 41.8 to 54 Gy on a Monday/Wednesday/Friday schedule, using 10 to 12 fractions over 4 weeks. McEntee et al concluded that the improvement in survival over that of previously published papers was the use of CT for tumor localization and computer-generated treatment plans based on the CT scan in all patients. No prognostic variables were identified, and survival time was not significantly different for carcinomas versus sarcomas. Adding cytoreductive surgery did not significantly alter survival in either series. 1• 13 Megavoltage radiotherapy has adequate penetration to potentially treat nasal tumors without adjuvant surgical intervention. However, the variation in diameter from the tip of the nose to the caudal aspect of the frontal sinus, combined with the typically large tumor volume, makes achieving an even distribution of radiation dose a challenge. Traditionally, parallel opposed portals were used for most patients with nasal tumors. The advent of computerized treatment planners and the availability of CT scans has vastly improved treatment planning and has allowed the radiation oncologist greater flexibility in sparing normal tissue structures. By administering radiation through orthogonal fields (90° hinge), the dose to the contralateral eye can be greatly decreased, minimizing discomfort from the acute effects of irradiation and increasing the likelihood that long-term vision will be maintained.
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Effects of radiation on normal tissues in the field can occur early or late. Early effects generally begin to appear toward the end of therapy and include oral mucositis and rhinitis, keratoconjunctivitis sicca and associated corneal ulceration, and desquamation and alopecia of overlying skin. These changes are seen to some degree in almost every patient and generally resolve within 1 month after completion of therapy. (Keratoconjunctivitis sicca may become a chronic condition, however.) Supportive therapy appropriate to the clinical condition of the patient may be necessary. Severe mucositis may result in dehydration as a result of decreased fluid intake and increased loss from excessive drooling. Subcutaneous or intravenous fluid therapy administration may be indicated. Likewise, some animals will stop eating and need assistance achieving the desired caloric intake. The owner should be advised to avoid foods with high sodium content that would irritate the denuded mucous membranes. Boiled chicken breasts or hamburger will sometimes be more palatable to the animal. Insertion of a nasogastric or stomach tube for feeding is rarely necessary in dogs but can be important for managing cats that have undergone irradiation. Keratoconjunctivitis sicca should be treated with tear substitutes and steroid drops, and the eyes should be closely observed for any evidence of ulceration. Late effects of radiation can be more serious and are dose-limiting. Most radiation protocols are designed to limit the probability of developing these effects to less than 5% of the treated population. Late effects include changes in retinal vessels, which in some cases can affect vision; necrosis of underlying bone, which can result in oronasal fistulas; and brain necrosis. Cataracts will occur in almost all patients; however, they develop very slowly and rarely cause visual deficits. Late effects generally appear no earlier than 6 months after therapy and may manifest years later. Cats with nasal tumors respond well to radiotherapy and in general have a better prognosis than dogs with nasal tumors. With orthovoltage radiation therapy following rhinotomy, mean and median survivals of 27.9 and 20.8 months have been reported. 7 Treatment of six cats with megavoltage radiation alone resulted in a mean survival of 19 months, with two cats still alive. 18 Cases of localized nasal lymphoma in dogs and cats are ideally suited to local radiation therapy. 5
Chemotherapy
Chemotherapy has not been shown to be uniformly effective for the treatment of nonhematopoietic malignancies of the nasal cavity. In one clinical study/0 megavoltage radiation therapy was combined with mitoxantrone chemotherapy; however, the results were not favorable. Cisplatin has been reported as an effective agent for the treatment of nasal tumors in the dog; the drug is contraindicated in cats.
PROGNOSIS
Dogs with nasal tumors can be expected to live for 3 to 5 months if they are not treated, if they receive cryosurgery, immunotherapy, or if the tumor is surgically debulked. 11 • 14• 21 Radiation therapy has been the only treatment shown to be effective for extending the survival time. Indeed, median survival times in treated dogs approach 23 months in some cases; in the cat, approximately 20 months has been reported. 7• 18 Metastases are rare when the animal is initially pr~sented but are seen more commonly as the disease progresses. References 1. Adams WM, Withrow SJ, Walshaw R, et al: Radiotherapy of malignant nasal tumors in 67 dogs. J Am Vet Med Assoc 191:311-315, 1987 2. Bradley PA, Harvey CE: Intranasal tumors in the dog: An evaluation of prognosis. J Small Anim Pract 14:459-467, 1973 3. Brodey RS: Canine and feline neoplasia. Adv Vet Sci Comp Med 14:309-354, 1970 4. Cox NR, Brawner WR, Powers RD, et al: Tumors of the nose and paranasal sinuses in cats: 32 cases with compari~on to a national database (1977 through 1987). J Am Anim Hosp Assoc 27:339-347, 1991 5. Elmslie RE, Ogilvie GK, Gillette EL, et al: Radiotherapy with and without chemotherapy for the control of localized lymphoma in cats: 10 cases (1983-1989). Vet Radio) 32:277-280, 1991 6. Engle CG, Broday RS: A retrospective study of 395 feline neoplasms. J Am Anim Hosp Assoc 5:21-31, 1969 7. Evans SM, Goldschmidt M, McKee LJ, et al: Prognostic factors and survival after radiotherapy for canine intranasal neoplasms: 70 cases (1974- 1985). J Am Vet Med Assoc 194:1460-1463, 1989 8. Gibbs C, Lane JG, Denny HR: Radiographical features of intranasal tumor lesions in the dog: A review of 100 cases. J Small Anim Pract 20:515-535, 1979 9. Harvey CE, Biery ON, Morello J, et al: Chronic nasal disease in the dog: Its radiographic diagnosis. Vet Radio) 20:91-98, 1979 10. LaRue SM, Gillette EL, Ogilvie GK, et al: Irradiation plus mitoxantrone for treatment of canine nasal tumors. In Proceedings of the American College of Veterinary Radiology, Chicago, Ill, Nov 1990 11. MacEwen EG, Withrow SJ, Patnaik AK: Nasal tumors in the dog: Retrospective evaluation of diagnosis, prognosis and treatment. 170:45-48, 1977 12. Madewell BR, Priester WA, Gillette EL, et al: Neoplasms of the nasal passages and paranasal sinuses in domesticated animals as reported by 13 veterinary colleges. Am J Vet Res 37:851-856, 1976 13. McEntee MC, Page RL, Heidner GL, et al: A retrospective study of 27 dogs with intranasal neoplasms treated with cobalt radiation. Vet Radio) 32:135-139, 1991 14. Norris AM: Intranasal neoplasms in the dog. J Am Anim Hosp Assoc 15:231- 236, 1979 15. Park RD, Beck ER, LeCouteur RA: Comparison of computed tomography and radiology for detecting changes produced by malignant neoplasia in dogs. JAm Vet Med Assoc, in press 16. Patnaik AK: Canine sinonasal neoplasms: Clinicopathological study of 285 cases. J Am Anim Hosp Assoc 25:103-114, 1989 17. Priester WA, McKay FW: The occurrence of tumors in domestic animals. Monograph No. 54, Washington, DC, National Institutes of Health, 1980, Nos. 35 and 39 18. Straw RC, Withrow SJ, Gillette EL, et al: Use of radiotherapy for the treatment of intranasal tumors in cats: six cases (1985-1989). J Am Vet Med Assoc 189:927- 929, 1986
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19. Thrall DE, Harvey CE: Radiotherapy of malignant nasal tumors in 21 dogs. JAm Vet Med Assoc 183:663-666, 1983 20. Thrall DE, Robertson ID, McLeod DA, et a!: A comparison of radiographic and computed tomographic findings in 31 dogs with malignant nasal cavity tumors. Vet Radio! 30:59-65, 1989 21. Withrow SJ: Cryosurgical therapy for nasal tumors in the dog. J Am Anim Hosp Assoc 18:585-589, 1982 22. Withrow SJ: Tumors of the respiratory system. In Withrow SJ, MacEwen EG (eds): Clinical Veterinary Oncology. Philadelphia, JB Lippincott, 1989, p 215-233 23. Withrow SJ, Susaneck SJ, Macy DW, et a!: Aspiration and punch biopsy techniques for nasal tumors. JAm Anim Hosp Assoc 21:551-554, 1985
Address reprint requests to Gregory K. Ogilvie, DVM Comparative Oncology Unit Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins, CO 80523
0195-5616/92 $0.00
+ .20
CANINE AND FELINE NASAL AND PARANASAL SINUS TUMORS Gregory K. Ogilvie, DVM, and Susan M. LaRue, DVM, PhD
Tumors involving the nasal cavity and nearby sinuses are rare in the dog and cat. Tumors that originate on the nasal planum are common in the cat but are not discussed in this article. The prevalence of tumors of the nasal and paranasal sinuses ranges between 0.3 to 2.4% of tumors surveyed in the dog and 4.2% of all tumors diagnosed in one study in the cat. 2- 4 • 12• 16• 17 In the dog, tumors of the nasal and paranasal sinuses are generally seen in older animals (median, 10 years), with various sex and breed distributions reported. 3· 12• 16· 17 Affected cats are generally older males with a mean age of 8 to 10 years. 4• 6 Although the most common cause of unilateral epistaxis, facial deformity, and epiphora in the aged dog and cat is a malignant nasal or paranasal tumor, other differentials must be considered. 22 Definitive diagnosis is based on the signalment, history, physical examination findings, radiographs, and histologic evidence of malignant neoplasia. Radiation therapy, with or without surgery, has been considered to be the most effective treatment. This article reviews the clinical features and optimum methods for diagnosing nasal tumors in the dog and cat. Therapeutic strategies are also discussed.
This work was supported by grant number 2 POl CA 29582 from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
From the Comparative Oncology Unit, Colorado State University College of Veterinary Medicine and Biomedical Sciences, Fort Collins, Colorado
VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 22 • NUMBER 5 • SEPTEMBER 1992
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HISTORY AND CLINICAL SIGNS
Diseases within the nasal and paranasal sinuses cause many of the same clinical signs. 11. 12• 14 The clinician should have an increased index of suspicion for a nasal tumor in older dogs or cats that exhibit facial deformity, epiphora, and unilateral epistaxis.22 The epistaxis may be bilateral if the disease has progressed. Other, less specific clinical signs include a purulent or mucoid nasal discharge, dyspnea, coughing, sneezing, ocular discharge, prolapse of the third eyelid, and neurologic signs. 11 • 12• 14 In most cases, these clinical signs persist for months. Owners often report that antibiotic therapy alleviates clinical signs transiently, presumably as a result of a decrease in secondary bacterial infection associated with most nasal tumors. The differential diagnoses that must be considered in each case include bacterial or fungal rhinitis, foreign body, nasal parasites, allergic rhinitis, bleeding disorders, and trauma. Aspergillus sp is the most common cause of fungal rhinitis. The authors have observed that fungal rhinitis seems to have a regional distribution. Fungal rhinitis is rarely diagnosed in the Rocky Mountain area but is seen commonly in the Midwest, where the hot, humid weather provides a more favorable environment for the fungal organisms. PATHOLOGY AND BIOLOGIC BEHAVIOR
Approximately 60% of dogs with nasal or sinonasal tumors have carcinomas. 12· 16 Adenocarcinoma and squamous cell carcinoma are common. Sarcomas (fibrosarcoma, chondrosarcoma, osteosarcoma, and undifferentiated sarcoma) are identified less frequently. At the time of initial diagnosis, metastases are rare. 22 Later in the course of the disease, metastases can be seen in approximately 41% of the cases. 16 Metastatic rate appears to be lowest among nonepithelial tumors. 16 Metastases occur most commonly in the brain, lymph node, lung, and liver. 16 The most common histopathologic diagnoses for intranasal and nasal sinus tumors of the cat include adenocarcinoma, undifferentiated carcinoma, olfactory neuroblastoma, lymphoma, fibrosarcoma, chondrosarcoma, and chondroma. 4 • 5 Brain invasion via the cribriform plate has been seen in approximately 25% of the cases reported in one study. 4 Metastatic disease to the regional lymph nodes is reported in a minority of cases.4 The majority of nasal tumors in the dog and cat are located at or near the cribriform plate. Approximately half of the tumors in the dog are bilateral at the time of diagnosis. 16 Extension through the nasal cavity to external sites is common in advanced cases of nasal tumors in either species. DIAGNOSTIC TESTS
The diagnosis of a nasal tumor begins with a good history and physical examination. Most patients with a nasal tumor are older and
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have a chronic history of respiratory problems associated with the nasal cavity. Unilateral epistaxis, epiphora, and facial deformity are highly suggestive of the presence of a nasal tumor, but other differentials must be considered. A definitive diagnosis can only be obtained with a histologic diagnosis. Other supportive data can be obtained with rhinoscopy, plain radiographs, computed tomography (CT) images, and serology or mycotic cultures for fungal rhinitis. Bacterial cultures are rarely of value. Lymph node biopsy or aspirate specimens are positive approximately 10% of the time and should be consid~red in cases in which a regional lymph node is enlarged. 22 In addition, chest radiographs generally are recommended but often fail to identify evidence of metastatic disease. 22 Before rhinoscopy, radiographs, and biopsy procedures are considered, routine screening tests should be performed to eliminate the possibility of bleeding disorders, especially when epistaxis is present. These tests include, but are not limited to, a hemogram and platelet count, biochemical profile, urinalysis, clotting profile, and, if indicated, blood pressure measurements. Serum should be acquired for titers for potential diseases such as ehrlichiosis and aspergillosis.
Radiographs
Nasal radiographs should be made before other diagnostic tests are done to more specifically d etermine the cause of nasal or paranasal disease. 8 These radiographs are essential to determine the extent and location of disease: two important factors for directing- biopsy procedures and for planning treatment. 8 As a general rule, the dorsoventral frontal sinus view (Fig. 1), and the ventrodorsal open mouth view, with high resolution detail screen placed as far caudad in the nasal cavity as possible, are most valuable. The open-mouth view is made to show the caudal nasal cavity and cribriform plate (Fig. 2). The roentgen signs commonly associated with nasal tumors include loss of nasal and trabecular turbinate pattern, increased density in the nasal cavity and frontal sinus, deviation or deformity of the vomer bone, destruction of overlying bone, periosteal new bone formation, and the presence of an external soft tissue mass. 4 · 8• 9 · 12• 14 Computed tomography provides more information about the location of the tumor and extent of destruction than routine radiographic imaging (Figs. 3-5). Thrall et aF0 showed that CT was more accurate than radiographs in identifying unilateral versus bilateral nasal cavity disease and tumor extension into nearby structures such as the hard palate, pterygopalatine fossa, and cranial cavity. He and others have concluded that CT was useful for more accurate tumor staging, predicting possible treatment-related complications, and planning surgery and radiation therapy. 12• 15 When there is suspicion of brain involvement based on the history, physical examination, or radiographic findings, an iodinated contrast agent should be injected intravenously. If the
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Figure 1. Dorsoventral frontal sinus radiograph showing an increased density in the right frontal sinus, which is caused by a tumor or fluid.
""
Figure 2. Ventrodorsal open-mouth radiograph showing alterations in density, loss of the lacey turbinate structures, and bony lysis of larger bony structures in the right side of the nasal cavity due to a nasal adenocarcinoma.
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Figure 3. Contrast enhanced CT scan of an adenocarcinoma of the rostral nasal cavity showing the destruction of the nasal bone and extension of the nasal tumor into soft-tissue structures overlying the nose.
Figure 4. Contrast enhanced CT scan at the level of the eyes and the rostral aspect of the cribriform plate of the same dog imaged in Figure 3. The tumor has destroyed one frontal sinus and has invaded through the bony orbit into the retrobulbar space. Note the displacement of the eye on the side of the tumor.
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Figure 5. This CT scan is from the same dog shown in Figures 3 and 4 but is taken slightly more caudal than the image displayed in Figure 4. The tumor is destroying the bone over the olfactory bulb of the cribriform plate.
blood-brain barrier is broken, the iodinated contrast agent will extend into the brain and surrounding tissue and will be noted on the CT as an area of increased radiodensity (Fig. 5). In the authors' experience, extension into the brain is a poor prognostic sign.
Rhinoscopy
Rhinoscopy allows direct visualization of the nasal cavity and surrounding structures and can be done with a flexible bronchoscope or rigid cystoscope. Biopsy specimens can be taken concurrently through the endoscope; however, it may be prudent to follow with a transnasal core biopsy procedure. Foreign body removal and identification of nasal parasites can be accomplished easily by an experienced operator. To prevent iatrogenic hemorrhage, patience is essential when performing a careful examination and removing or suctioning various exudates within the nasal cavity. When the flexible endoscope is used, the caudal nasopharynx should be examined for any neoplastic tissue by extending the endoscope through the oral cavity and then retroflexing the scope over the soft palate. The scope should then be directed forward toward the front of the patient to locate any tumor or other abnormalities in the most cranial aspect of the nasopharyngeal area.
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Nasal Flushes
Nasal washings or flushes have been reported with mixed results. MacEwen et aP 1 reported a 50% success rate by flushing the nasal cavity and examining the resulting fluid cytologically. n Others feel the yield is much lower. One method of performing this procedure is to place a large Foley catheter into the nasopharyngeal area via the oral cavity so that when the bulb is inflated, large quantities of fluid can be f.lushed out the nares without escape of fluid caudally through the mouth, trachea, or esophagus. The authors have used this technique to lavage the nasal cavity in cases where grass awns or other smaller fragmented foreign bodies are suspected.
Biopsy Techniques
The cornerstone of the diagnosis of a nasal tumor is based on procurement of adequate tissue for histopathology. In most cases, a biopsy procedure can be done while the animal is anesthetized for radiography or other concurrent diagnostic tests. The simplest, cheapest, most accurate method of obtaining adequate tissue in the dog without resorting to surgery is a transnostril core sampling procedure (Fig. 6). 23 A 3- to 5-mm plastic cannula is used to biopsy all but the smallest dogs. The cannula is snugly attached to a syringe via the hub of a needle, as previously described. 23 The location of the tumor is assessed from the radiographs or CT images and the ass~mbled biopsy instrument is passed up the nostril and directed at the tumor. The tumor frequently has extended into the cribriform region, rendering it very susceptible to trauma from the biopsy, which can result in penetration of the brain by the biopsy instrument. To prevent this, the location of the cribriform plate can be estimated by measuring from the tip of the nares to the medial canthus and the biopsy instrument marked with tape or cut off at the appropriate length (Fig. 6). When passing a plastic cannula, slight resistance usually is felt as the tumor is entered. Negative pressure is applied with the syringe as the cannula is redirected in various angles. After the biopsy procedure has been performed, the tissue is expelled onto a gauze sponge to allow separation of tumor from blood and mucus. The specimen should then be placed in 10% neutral buffered formalin for histologic analysis. Hemorrhage will occur but should subside within a few minutes. Severe hemorrhage can be controlled by permanently ligating the ipsilateral carotid. Tumors in cats and small dogs are sometimes accessible to biopsy by transnostril curettage. If nonsurgical approaches do not work, then a rhinotomy may be considered to obtain tissue for a definitive diagnosis. A trephine generally is used to gain entry to the nasal cavity or sinus; then, a curet is used to scoop out the suspected tumor tissue. Although this method grants the greatest exposure, it still may be accompanied by significant
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Figure 6. The skeletal and soft-tissue landmarks involved in a transnostril core biopsy. In this procedure, a 3 to 5-mm plastic cannula is snugly attached to a syringe via the hub of a needle. The biopsy instrument is passed up the nostril and directed at the tumor. Care is taken not to extend the biopsy instrument past the level of the medial canthus of the eye (A) that corresponds anatomically with the cribriform plate and the rostral aspect of the cranium (B) . After the cannula is placed into the tumor, negative suction is applied, and the instrument is removed from the nasal cavity.
hemorrhage. More importantly, it has the great disadvantage of contaminating the biopsy field with tumor. If the dog is to be treated with radiotherapy, this requires a significant alteration in the treatment plan with a higher dose to the skin in the region, which results in more patient discomfort and possibly a sacrifice in tumor control.
THERAPY Surgery
Because nasal tumors rarely metastasize, therapy is directed at controlling localized disease. Surgical excision alone is not considered an effective option for treating nasal tumors in dogs and cats, because bone invasion occurs early in the pathogenesis of the disease and the tumor is often located near the brain and eyes. Indeed, surgery alone has been shown to be associated with a high prevalence of acute and chronic morbidity without a significant extension of life .11 · 12 Therefore, generally surgery is indicated only when combined with radiation therapy. Complications relating directly to rhinotomy include subcutaneous emphysema, hemorrhage, and infection.
CANINE AND FELINE NASAL AND PARANASAL SINUS TUMORS
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Cryosurgery
Cryosurgery has been used to treat canine nasal tumors following nasal curettage or radiation therapy. 21 The use of liquid nitrogen resulted in significant complications, including destruction of the hard palate resulting in oronasal fistulas and generalized tissue destruction. In a limited clinical trial, survival times were not increased when cryosurgery was added to standard debulking procedures or radiation therapy. 21 Radiation Therapy
Radiation therapy, with or without surgical debulking, is the only treatment modality that has been shown to be effective for increasing the survival time of dogs and cats with nasal tumors. 3 • 7• 11 • 13• 14• 19 With orthovoltage radiotherapy, surgical debulking is necessary owing to tumor volume. (Lack of penetration by orthovoltage radiation generally precludes orthovoltage radiation alone.) Forty to 50 Gy, delivered in 10 to 12 fractions, is administered to the skin surface overlying the cytoreduced surgical field. The reported median survival of 16 to 23 months is slightly better than megavoltage alone. 7• 13• 19 The 1- and 2year survival rates were 54 to 57% and 43 to 47%, respectively. 7• 19 Although the previously reported median survival for dogs with nasal tumors treated with megaradiation alone was approximately 8 months, 1 a recent paper by McEntee reported a median and mean survival of 12.8 and 20.7 monthsY 1- and 2-year survival rates were 59% and 22%, respectively. Dogs received from 41.8 to 54 Gy on a Monday/Wednesday/Friday schedule, using 10 to 12 fractions over 4 weeks. McEntee et al concluded that the improvement in survival over that of previously published papers was the use of CT for tumor localization and computer-generated treatment plans based on the CT scan in all patients. No prognostic variables were identified, and survival time was not significantly different for carcinomas versus sarcomas. Adding cytoreductive surgery did not significantly alter survival in either series. 1• 13 Megavoltage radiotherapy has adequate penetration to potentially treat nasal tumors without adjuvant surgical intervention. However, the variation in diameter from the tip of the nose to the caudal aspect of the frontal sinus, combined with the typically large tumor volume, makes achieving an even distribution of radiation dose a challenge. Traditionally, parallel opposed portals were used for most patients with nasal tumors. The advent of computerized treatment planners and the availability of CT scans has vastly improved treatment planning and has allowed the radiation oncologist greater flexibility in sparing normal tissue structures. By administering radiation through orthogonal fields (90° hinge), the dose to the contralateral eye can be greatly decreased, minimizing discomfort from the acute effects of irradiation and increasing the likelihood that long-term vision will be maintained.
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Effects of radiation on normal tissues in the field can occur early or late. Early effects generally begin to appear toward the end of therapy and include oral mucositis and rhinitis, keratoconjunctivitis sicca and associated corneal ulceration, and desquamation and alopecia of overlying skin. These changes are seen to some degree in almost every patient and generally resolve within 1 month after completion of therapy. (Keratoconjunctivitis sicca may become a chronic condition, however.) Supportive therapy appropriate to the clinical condition of the patient may be necessary. Severe mucositis may result in dehydration as a result of decreased fluid intake and increased loss from excessive drooling. Subcutaneous or intravenous fluid therapy administration may be indicated. Likewise, some animals will stop eating and need assistance achieving the desired caloric intake. The owner should be advised to avoid foods with high sodium content that would irritate the denuded mucous membranes. Boiled chicken breasts or hamburger will sometimes be more palatable to the animal. Insertion of a nasogastric or stomach tube for feeding is rarely necessary in dogs but can be important for managing cats that have undergone irradiation. Keratoconjunctivitis sicca should be treated with tear substitutes and steroid drops, and the eyes should be closely observed for any evidence of ulceration. Late effects of radiation can be more serious and are dose-limiting. Most radiation protocols are designed to limit the probability of developing these effects to less than 5% of the treated population. Late effects include changes in retinal vessels, which in some cases can affect vision; necrosis of underlying bone, which can result in oronasal fistulas; and brain necrosis. Cataracts will occur in almost all patients; however, they develop very slowly and rarely cause visual deficits. Late effects generally appear no earlier than 6 months after therapy and may manifest years later. Cats with nasal tumors respond well to radiotherapy and in general have a better prognosis than dogs with nasal tumors. With orthovoltage radiation therapy following rhinotomy, mean and median survivals of 27.9 and 20.8 months have been reported. 7 Treatment of six cats with megavoltage radiation alone resulted in a mean survival of 19 months, with two cats still alive. 18 Cases of localized nasal lymphoma in dogs and cats are ideally suited to local radiation therapy. 5
Chemotherapy
Chemotherapy has not been shown to be uniformly effective for the treatment of nonhematopoietic malignancies of the nasal cavity. In one clinical study/0 megavoltage radiation therapy was combined with mitoxantrone chemotherapy; however, the results were not favorable. Cisplatin has been reported as an effective agent for the treatment of nasal tumors in the dog; the drug is contraindicated in cats.
PROGNOSIS
Dogs with nasal tumors can be expected to live for 3 to 5 months if they are not treated, if they receive cryosurgery, immunotherapy, or if the tumor is surgically debulked. 11 • 14• 21 Radiation therapy has been the only treatment shown to be effective for extending the survival time. Indeed, median survival times in treated dogs approach 23 months in some cases; in the cat, approximately 20 months has been reported. 7• 18 Metastases are rare when the animal is initially pr~sented but are seen more commonly as the disease progresses. References 1. Adams WM, Withrow SJ, Walshaw R, et al: Radiotherapy of malignant nasal tumors in 67 dogs. J Am Vet Med Assoc 191:311-315, 1987 2. Bradley PA, Harvey CE: Intranasal tumors in the dog: An evaluation of prognosis. J Small Anim Pract 14:459-467, 1973 3. Brodey RS: Canine and feline neoplasia. Adv Vet Sci Comp Med 14:309-354, 1970 4. Cox NR, Brawner WR, Powers RD, et al: Tumors of the nose and paranasal sinuses in cats: 32 cases with compari~on to a national database (1977 through 1987). J Am Anim Hosp Assoc 27:339-347, 1991 5. Elmslie RE, Ogilvie GK, Gillette EL, et al: Radiotherapy with and without chemotherapy for the control of localized lymphoma in cats: 10 cases (1983-1989). Vet Radio) 32:277-280, 1991 6. Engle CG, Broday RS: A retrospective study of 395 feline neoplasms. J Am Anim Hosp Assoc 5:21-31, 1969 7. Evans SM, Goldschmidt M, McKee LJ, et al: Prognostic factors and survival after radiotherapy for canine intranasal neoplasms: 70 cases (1974- 1985). J Am Vet Med Assoc 194:1460-1463, 1989 8. Gibbs C, Lane JG, Denny HR: Radiographical features of intranasal tumor lesions in the dog: A review of 100 cases. J Small Anim Pract 20:515-535, 1979 9. Harvey CE, Biery ON, Morello J, et al: Chronic nasal disease in the dog: Its radiographic diagnosis. Vet Radio) 20:91-98, 1979 10. LaRue SM, Gillette EL, Ogilvie GK, et al: Irradiation plus mitoxantrone for treatment of canine nasal tumors. In Proceedings of the American College of Veterinary Radiology, Chicago, Ill, Nov 1990 11. MacEwen EG, Withrow SJ, Patnaik AK: Nasal tumors in the dog: Retrospective evaluation of diagnosis, prognosis and treatment. 170:45-48, 1977 12. Madewell BR, Priester WA, Gillette EL, et al: Neoplasms of the nasal passages and paranasal sinuses in domesticated animals as reported by 13 veterinary colleges. Am J Vet Res 37:851-856, 1976 13. McEntee MC, Page RL, Heidner GL, et al: A retrospective study of 27 dogs with intranasal neoplasms treated with cobalt radiation. Vet Radio) 32:135-139, 1991 14. Norris AM: Intranasal neoplasms in the dog. J Am Anim Hosp Assoc 15:231- 236, 1979 15. Park RD, Beck ER, LeCouteur RA: Comparison of computed tomography and radiology for detecting changes produced by malignant neoplasia in dogs. JAm Vet Med Assoc, in press 16. Patnaik AK: Canine sinonasal neoplasms: Clinicopathological study of 285 cases. J Am Anim Hosp Assoc 25:103-114, 1989 17. Priester WA, McKay FW: The occurrence of tumors in domestic animals. Monograph No. 54, Washington, DC, National Institutes of Health, 1980, Nos. 35 and 39 18. Straw RC, Withrow SJ, Gillette EL, et al: Use of radiotherapy for the treatment of intranasal tumors in cats: six cases (1985-1989). J Am Vet Med Assoc 189:927- 929, 1986
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19. Thrall DE, Harvey CE: Radiotherapy of malignant nasal tumors in 21 dogs. JAm Vet Med Assoc 183:663-666, 1983 20. Thrall DE, Robertson ID, McLeod DA, et a!: A comparison of radiographic and computed tomographic findings in 31 dogs with malignant nasal cavity tumors. Vet Radio! 30:59-65, 1989 21. Withrow SJ: Cryosurgical therapy for nasal tumors in the dog. J Am Anim Hosp Assoc 18:585-589, 1982 22. Withrow SJ: Tumors of the respiratory system. In Withrow SJ, MacEwen EG (eds): Clinical Veterinary Oncology. Philadelphia, JB Lippincott, 1989, p 215-233 23. Withrow SJ, Susaneck SJ, Macy DW, et a!: Aspiration and punch biopsy techniques for nasal tumors. JAm Anim Hosp Assoc 21:551-554, 1985
Address reprint requests to Gregory K. Ogilvie, DVM Comparative Oncology Unit Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins, CO 80523
