- Email: [email protected]
Olfactory neuroblastoma in a cat
C A S E / Olfactory neuroblastoma
CT of the skull revealed a contrast-enhancing 1 cm x 0.5 cm soft tissue mass filling the middle portion of the nasopharynx.
FIG 2 This image of the nasopharyngeal mass was obtained via retroflexion of a bronchoscope dorsally and cranially behind the soft palate. The vomer bone is seen dorsally, the soft palate is seen ventrally and the nasopharynx is seen centrally
On rhinoscopy, a 1 x 0.5 cm pink fleshy soft tissue mass was visualized. FIG 1 Post-contrast computed tomography axial view, showing the nasopharyngeal mass (arrow)
On repeat physical examination later that day, there was severely diminished nasal airflow bilaterally and stertorous respiration. The primary clinical problem was upper respiratory disease. Differential diagnoses included neoplasia and inflammatory or infectious rhinitis/ nasopharyngitis (bacterial, fungal or viral). Computed tomography and rhinoscopy Computed tomography (CT) of the skull was performed, which revealed a contrast-enhancing 1 cm x 0.5 cm soft tissue mass filling the middle portion of the nasopharynx (Fig 1). The mass was centered near the caudal aspect of the hard palate, extending 1 cm craniad and 3 mm caudad to that point. The caudal nasopharynx was open and clear at the level of the caudal soft palate. The lymph nodes of the head were normal and there was no evidence of invasion of the cribriform plate. Rhinoscopy was performed following the CT scan. The oropharynx was normal. The soft palate was retracted and the bronchoscope (Olympus BF-P160, light source CVL 160) was retroflexed into the nasopharynx. A 1 x 0.5 cm pink fleshy soft tissue mass was visualized (Fig 2). Several biopsies were taken and submitted for histologic assessment. Histology Histopathology of the mass revealed an invasive population of polygonal cells forming nests separated by moderate amounts of an arborizing fibrovascular stroma. Neoplastic cells were arranged in peritrabecular pal-
868
JFMS CLINICAL PRACTICE
isades, Homer-Wright rosettes and FlexnerWintersteiner rosettes (Fig 3). Neoplastic cells had basal, hyperchromatic nuclei and moderate amounts of eosinophilic cytoplasm that tapered toward the rosette’s center. Nuclei were moderately sized, round to irregular, hyperchromatic and had multiple small nucleoli. Anisocytosis and anisokaryosis were minimal and mitotic figures were not observed.
FIG 3 Histopathology of the olfactory neuroblastoma showing peritrabecular palisades (arrow-head), HomerWright rosettes (arrows) and (inset picture) a Flexner-Wintersteiner rosette (arrow-head). Magnification 600x
C A S E / Olfactory neuroblastoma
Histologically, instead of having distinct cytoplasmic borders, the nuclei are surrounded by neurofibrillary material, often forming rosette patterns. On immunohistochemical testing, the tumor stained positive for keratin (Fig 4), neuron-specific enolase and vimentin, and negative for glial fibrillary acid protein, neurofilaments and S-100. The final diagnosis was olfactory neuroblastoma (esthesioneuroblastoma). Outcome Treatment options were discussed with the owner, including radiation therapy and chemotherapy. Due to financial constraints, the owner elected to take the cat home. Two weeks later, the owner reported that the cat was still doing well, although he was snorting occasionally. A further 8 days later, the cat presented to his local veterinarian for recurrence of stertorous, open-mouth breathing. At that point, the owner elected humane euthanasia. No necropsy was performed.
Discussion Olfactory neuroblastoma is a rare malignant tumor of the olfactory neuroepithelium. It was first reported in human medicine in 1924.1 It is widely accepted that olfactory neuroblastoma originates from the olfactory membrane of the upper nasal cavity.2 It has also been reported to invade the intracranial cavity via the cribriform plate.3 Reports of this neoplasm are infrequent in the veterinary literature, but cases have been described in several species.4 Tumor frequency and clinical signs Nasal and paranasal sinus tumors have been reported to represent 1–4.2% of all feline neoplasms. The most common feline nasal neoplasms include adenocarcinoma, squamous cell carcinoma and lymphoma, although there is controversy over their relative prevalence.5–7 Over 90% of these tumors are malignant.5,7,8 Historically, older castrated male cats have been predisposed to nasal tumors.5,6,8 Given the low numbers of reported feline olfactory neuroblastomas, it is difficult to say if the same criteria apply. Clinical signs of olfactory neuroblastoma are non-specific. In human patients, the most common presenting complaints are progressive nasal obstruction, epistaxis and hypo/anosmia. In some instances, there are no clinical signs noted at the time of diagno-
FIG 4 Immunohistochemistry. Keratin stain. Magnification 600x
sis.9 Veterinary patients with nasal and paranasal sinus tumors commonly present with sneezing, nasal discharge, dyspnea, facial deformity, stertor and partial to complete anorexia.5,7,8 Alternatively, patients may present for evaluation of seizures and/or neurologic signs.3,10 Histologic diagnosis Diagnosis of olfactory neuroblastoma relies on certain histologic criteria. The tumor must exhibit lobular architecture with a vascular interlobular stroma. Instead of having distinct cytoplasmic borders, the nuclei are surrounded by neurofibrillary material, often forming rosette patterns. A grading system based on histopathology exists – grade I representing the most differentiated tumors, and grade IV the least differentiated. Grade I and II tumors frequently exhibit a pseudorosette pattern (Homer-Wright type), whereas grade III tumors tend to demonstrate true neural rosettes (Flexner-Wintersteiner type). Neither type of rosette is typically seen in grade IV tumors. Grade IV neoplasms are the most difficult to diagnose and are often confused with small cell undifferentiated tumors of the sinonasal tract. Grade III and IV tumors may require further ultrastructural, immunoperoxidase or fume-fluorescence studies to distinguish them from poorly differentiated carcinomas. Immunohistochemistry stains are routinely performed to aid in the diagnosis of olfactory neuroblastoma.2 In human medicine, there is a pre-therapy staging system for olfactory neuroblastoma.11,12 Tumors are staged into one of four groups based on anatomic location. Staging systems for canine nasosinal tumors have been described, focusing on primary tumor location and extent of tumor involvement.13 Most staging systems have not been proven to have prognostic significance. Felinespecific systems have not been described. Treatment protocols and prognostic factors Treatment protocols and success rates have been infrequently reported in the veterinary literature. The only report the authors managed to locate describes successful radiotherapy treatment of a dog with olfactory neuroblastoma.14 Given its rarity in human JFMS CLINICAL PRACTICE
869
C A S E / Olfactory neuroblastoma
Olfactory neuroblastoma most commonly metastasizes to regional lymph nodes. The most commonly affected distant sites are lung, brain and bone. medicine (olfactory neuroblastoma represents 3% of all intranasal neoplasms), the ‘best’ treatment has yet to be established. There seems to be a consensus that aggressive surgical debulking (ie, craniofacial resection) followed by a combination of radiotherapy ± chemotherapy has offered the best long-term survival rates.9,15 Most often, the tumor stage and grade will influence the treatment protocol. Advanced stage tumors are often not amenable to surgery. In these cases, radiation therapy, chemotherapy or chemoradiotherapy is recommended.15 One human study evaluated whether the expression of tumor markers in olfactory neuroblastomas could predict the response to chemotherapy and the prognosis. The authors concluded that the tumor marker bcl-2, a member of the gene family that regulates apoptosis, was prevalent in olfactory neuroblastoma and that expression correlated with a good initial response to chemotherapy. However, studies have demonstrated that overall survival tends to be poorer in patients with tumors expressing bcl-2.16 A few veterinary studies have attempted to characterize the expression of bcl-2 in healthy and neoplastic feline tissue. In one study, bcl-2 was consistently expressed in the basal layers of mucous membrane epithelium in healthy cats. The same study identified bcl-2 expression in intranasal carcinomas.17 Another study evaluated the expression of bcl-2 in cats with lymphoma. No correlation was found between bcl-2 expression and response to chemotherapy.18 Feline olfactory neuroblastomas have not been evaluated for bcl-2 expression. In one veterinary report, numerous type C FeLV retroviral particles were identified via polymerase chain reaction in olfactory neuroblastomas diagnosed in three cats. The retroviral particles were similar in appearance to the neurosecretory granules that are highly characteristic of olfactory neuroblastoma in humans. The authors suggest that there may be a relationship between FeLV and the development of olfactory neuroblastoma, and that
FeLV particles may have been misdiagnosed in other feline olfactory neuroblastoma cases as neurosecretory granules.19 Further investigation is warranted to evaluate the presence of retroviral particles in feline olfactory neuroblastoma and whether a true causal relationship exists. Tumor recurrence is the primary cause of treatment failure is most patients. Several authors agree that higher stage and grade tumors are more likely to recur. Olfactory neuroblastoma most commonly metastasizes to regional lymph nodes. The most commonly affected distant sites are lung, brain and bone.9,15,20,21
Conclusions Olfactory neuroblastoma is a differential for spontaneous intranasal tumors in cats. Clinical signs may be variable and depend on the extent of tumor involvement. If histologic changes are not definitive, special stains may be required to correctly identify the nasal tumor as an olfactory neuroblastoma. Treatment options are varied and somewhat dependent upon surgical skill and the availability of adjuvant chemoradiotherapy. Further investigation into a possible relationship between olfactory neuroblastoma and retroviral oncogenesis is warranted. The prognosis may be related to tumor stage and grade.
References 1
2
3
4
5
Berger L, Luc R. L’esthesioneuroepitheliome olfactif. Bull Assoc Fr Etude Cancer 1924; 13: 410–21. Hyams VJ. Tumors of the upper respiratory tract and ear. In: Atlas of tumor pathology, second series, fascicle 25. Washington, DC: Armed Forces Institute of Pathology, 1988: 240–48. Kitagawa M, Okada M, Yamamura H, Kanayama K, Sakai T. Diagnosis of olfactory neuroblastoma in a dog by magnetic resonance imaging. Vet Rec 2006; 159: 288–89. Koestner A, Higgins, RJ. Tumors of the nervous system. In: Meuten DJ, ed. Tumors in domestic animals. 4th edn. Ames: Iowa State Press, 2002: 713–14. Madewell BR, Priester WA, Gillette EL, Snyder SP. Neoplasms of the nasal passages and paranasal sinuses in domesticated animals as reported by 13 veterinary colleges. Am J Vet Res 1976; 37: 851–56.
Further investigation is warranted to evaluate the presence of retroviral particles in feline olfactory neuroblastoma and whether a true causal relationship exists.
870
JFMS CLINICAL PRACTICE
C A S E / Olfactory neuroblastoma
6
7
8
9
10
11
12
13
Cox NR, Brawner WR, Powers RD, Wright JC. Tumors in the nose and paranasal sinuses in cats: 32 cases with comparison to a national database (1977 through 1987). J Am Anim Hosp Assoc 1991; 27: 339–47. Legendre AM, Krahwinkel DJ, Spaulding KA. Feline nasal and paranasal sinus tumors. J Am Anim Hosp Assoc 1981; 17: 1038–39. Mukaratirwa S, van der Linde-Sipman JS, Gruys E. Feline nasal and paranasal sinus tumors: clinicopathological study, histomorphological description and diagnostic immunohistochemistry of 123 cases. J Feline Med Surg 2001; 3: 235–45. Castelnuovo P, Bignami M, Delu G, Battaglia P, Bignardi M, Dallan I. Endonasal endoscopic resection and radiotherapy in olfactory neuroblastoma: our experience. Head Neck 2007; 29: 845–50. Smith MO, Turrel JM, Bailey CL, Cain GR. Neurologic abnormalities as the predominant signs of neoplasia of the nasal cavity in dogs and cats: seven cases (1973–1986). J Am Vet Med Assoc 1989; 195: 242–45. Kadish S, Goodman M, Wang CC. Olfactory neuroblastoma. A clinical analysis of 17 cases. Cancer 1976; 37: 1571–76. Morita A, Ebersold MJ, Olsen KD, Foote RL, Lewis JE, Quast LM. Esthesioneuroblastoma: prognosis and management. Neurosurgery 1993; 32: 706–15. Turek MM, Lana SE. Canine nasosinal tumors. In: Withrow SJ, Vail DM, eds. Small animal
14
15
16
17
18
19
20
21
clinical oncology. 4th edn. St Louis: Saunders 2001: 525–39. Ueno H, Kobayahi Y, Yamada K. Olfactory esthesioneuroblastoma treated with orthovoltage radiotherapy in a dog. Aust Vet J 2007; 85: 271–75. Kim HJ, Kim CH, Lee BG, et al. Surgical treatment versus concurrent chemoradiotherapy as an initial treatment modality in advanced olfactory neuroblastoma. Auris Nasus Larynx 2007; 34: 493–98. Kim JW, Kong IG, Lee CH, et al. Expression of Bcl-2 in olfactory neuroblastoma and its association with chemotherapy and survival. Otolaryngol Head Neck Surg 2008; 139: 708–12. Madewell BR, Gandour-Edwards R, Edwards BF, Walls, JE, Griffey, SM. Topographic distribution of bcl-2 protein in feline tissues in health and neoplasia. Vet Pathol 1999; 36: 565–73. Dank G, Lucroy MD, Griffey SM, GandourEdwards R, Madewell BR. bcl-2 and MIB-1 labeling indexes in cats with lymphoma. J Vet Intern Med 2002; 16: 720–25. Schrenzel MD, Higgin RJ, Hinrichs SH, Smith MO, Torten M. Type C retroviral expression in spontaneous feline olfactory neuroblastomas. Acta Neuropathol 1990; 80: 547–53. Eriksen JG, Bastholt L, Krogdahl AS, Hansen O, Joergensen EK. Esthesioblastoma: what is the optimal treatment? Acta Oncol 2000; 139: 231–35. Diaz EM, Johnigan RH, Pero C, et al. Olfactory neuroblastoma: the 22-year experience at one comprehensive cancer center. Head Neck 2005; 27: 138–49.
Available online at www.sciencedirect.com
JFMS CLINICAL PRACTICE
871
CT of the skull revealed a contrast-enhancing 1 cm x 0.5 cm soft tissue mass filling the middle portion of the nasopharynx.
FIG 2 This image of the nasopharyngeal mass was obtained via retroflexion of a bronchoscope dorsally and cranially behind the soft palate. The vomer bone is seen dorsally, the soft palate is seen ventrally and the nasopharynx is seen centrally
On rhinoscopy, a 1 x 0.5 cm pink fleshy soft tissue mass was visualized. FIG 1 Post-contrast computed tomography axial view, showing the nasopharyngeal mass (arrow)
On repeat physical examination later that day, there was severely diminished nasal airflow bilaterally and stertorous respiration. The primary clinical problem was upper respiratory disease. Differential diagnoses included neoplasia and inflammatory or infectious rhinitis/ nasopharyngitis (bacterial, fungal or viral). Computed tomography and rhinoscopy Computed tomography (CT) of the skull was performed, which revealed a contrast-enhancing 1 cm x 0.5 cm soft tissue mass filling the middle portion of the nasopharynx (Fig 1). The mass was centered near the caudal aspect of the hard palate, extending 1 cm craniad and 3 mm caudad to that point. The caudal nasopharynx was open and clear at the level of the caudal soft palate. The lymph nodes of the head were normal and there was no evidence of invasion of the cribriform plate. Rhinoscopy was performed following the CT scan. The oropharynx was normal. The soft palate was retracted and the bronchoscope (Olympus BF-P160, light source CVL 160) was retroflexed into the nasopharynx. A 1 x 0.5 cm pink fleshy soft tissue mass was visualized (Fig 2). Several biopsies were taken and submitted for histologic assessment. Histology Histopathology of the mass revealed an invasive population of polygonal cells forming nests separated by moderate amounts of an arborizing fibrovascular stroma. Neoplastic cells were arranged in peritrabecular pal-
868
JFMS CLINICAL PRACTICE
isades, Homer-Wright rosettes and FlexnerWintersteiner rosettes (Fig 3). Neoplastic cells had basal, hyperchromatic nuclei and moderate amounts of eosinophilic cytoplasm that tapered toward the rosette’s center. Nuclei were moderately sized, round to irregular, hyperchromatic and had multiple small nucleoli. Anisocytosis and anisokaryosis were minimal and mitotic figures were not observed.
FIG 3 Histopathology of the olfactory neuroblastoma showing peritrabecular palisades (arrow-head), HomerWright rosettes (arrows) and (inset picture) a Flexner-Wintersteiner rosette (arrow-head). Magnification 600x
C A S E / Olfactory neuroblastoma
Histologically, instead of having distinct cytoplasmic borders, the nuclei are surrounded by neurofibrillary material, often forming rosette patterns. On immunohistochemical testing, the tumor stained positive for keratin (Fig 4), neuron-specific enolase and vimentin, and negative for glial fibrillary acid protein, neurofilaments and S-100. The final diagnosis was olfactory neuroblastoma (esthesioneuroblastoma). Outcome Treatment options were discussed with the owner, including radiation therapy and chemotherapy. Due to financial constraints, the owner elected to take the cat home. Two weeks later, the owner reported that the cat was still doing well, although he was snorting occasionally. A further 8 days later, the cat presented to his local veterinarian for recurrence of stertorous, open-mouth breathing. At that point, the owner elected humane euthanasia. No necropsy was performed.
Discussion Olfactory neuroblastoma is a rare malignant tumor of the olfactory neuroepithelium. It was first reported in human medicine in 1924.1 It is widely accepted that olfactory neuroblastoma originates from the olfactory membrane of the upper nasal cavity.2 It has also been reported to invade the intracranial cavity via the cribriform plate.3 Reports of this neoplasm are infrequent in the veterinary literature, but cases have been described in several species.4 Tumor frequency and clinical signs Nasal and paranasal sinus tumors have been reported to represent 1–4.2% of all feline neoplasms. The most common feline nasal neoplasms include adenocarcinoma, squamous cell carcinoma and lymphoma, although there is controversy over their relative prevalence.5–7 Over 90% of these tumors are malignant.5,7,8 Historically, older castrated male cats have been predisposed to nasal tumors.5,6,8 Given the low numbers of reported feline olfactory neuroblastomas, it is difficult to say if the same criteria apply. Clinical signs of olfactory neuroblastoma are non-specific. In human patients, the most common presenting complaints are progressive nasal obstruction, epistaxis and hypo/anosmia. In some instances, there are no clinical signs noted at the time of diagno-
FIG 4 Immunohistochemistry. Keratin stain. Magnification 600x
sis.9 Veterinary patients with nasal and paranasal sinus tumors commonly present with sneezing, nasal discharge, dyspnea, facial deformity, stertor and partial to complete anorexia.5,7,8 Alternatively, patients may present for evaluation of seizures and/or neurologic signs.3,10 Histologic diagnosis Diagnosis of olfactory neuroblastoma relies on certain histologic criteria. The tumor must exhibit lobular architecture with a vascular interlobular stroma. Instead of having distinct cytoplasmic borders, the nuclei are surrounded by neurofibrillary material, often forming rosette patterns. A grading system based on histopathology exists – grade I representing the most differentiated tumors, and grade IV the least differentiated. Grade I and II tumors frequently exhibit a pseudorosette pattern (Homer-Wright type), whereas grade III tumors tend to demonstrate true neural rosettes (Flexner-Wintersteiner type). Neither type of rosette is typically seen in grade IV tumors. Grade IV neoplasms are the most difficult to diagnose and are often confused with small cell undifferentiated tumors of the sinonasal tract. Grade III and IV tumors may require further ultrastructural, immunoperoxidase or fume-fluorescence studies to distinguish them from poorly differentiated carcinomas. Immunohistochemistry stains are routinely performed to aid in the diagnosis of olfactory neuroblastoma.2 In human medicine, there is a pre-therapy staging system for olfactory neuroblastoma.11,12 Tumors are staged into one of four groups based on anatomic location. Staging systems for canine nasosinal tumors have been described, focusing on primary tumor location and extent of tumor involvement.13 Most staging systems have not been proven to have prognostic significance. Felinespecific systems have not been described. Treatment protocols and prognostic factors Treatment protocols and success rates have been infrequently reported in the veterinary literature. The only report the authors managed to locate describes successful radiotherapy treatment of a dog with olfactory neuroblastoma.14 Given its rarity in human JFMS CLINICAL PRACTICE
869
C A S E / Olfactory neuroblastoma
Olfactory neuroblastoma most commonly metastasizes to regional lymph nodes. The most commonly affected distant sites are lung, brain and bone. medicine (olfactory neuroblastoma represents 3% of all intranasal neoplasms), the ‘best’ treatment has yet to be established. There seems to be a consensus that aggressive surgical debulking (ie, craniofacial resection) followed by a combination of radiotherapy ± chemotherapy has offered the best long-term survival rates.9,15 Most often, the tumor stage and grade will influence the treatment protocol. Advanced stage tumors are often not amenable to surgery. In these cases, radiation therapy, chemotherapy or chemoradiotherapy is recommended.15 One human study evaluated whether the expression of tumor markers in olfactory neuroblastomas could predict the response to chemotherapy and the prognosis. The authors concluded that the tumor marker bcl-2, a member of the gene family that regulates apoptosis, was prevalent in olfactory neuroblastoma and that expression correlated with a good initial response to chemotherapy. However, studies have demonstrated that overall survival tends to be poorer in patients with tumors expressing bcl-2.16 A few veterinary studies have attempted to characterize the expression of bcl-2 in healthy and neoplastic feline tissue. In one study, bcl-2 was consistently expressed in the basal layers of mucous membrane epithelium in healthy cats. The same study identified bcl-2 expression in intranasal carcinomas.17 Another study evaluated the expression of bcl-2 in cats with lymphoma. No correlation was found between bcl-2 expression and response to chemotherapy.18 Feline olfactory neuroblastomas have not been evaluated for bcl-2 expression. In one veterinary report, numerous type C FeLV retroviral particles were identified via polymerase chain reaction in olfactory neuroblastomas diagnosed in three cats. The retroviral particles were similar in appearance to the neurosecretory granules that are highly characteristic of olfactory neuroblastoma in humans. The authors suggest that there may be a relationship between FeLV and the development of olfactory neuroblastoma, and that
FeLV particles may have been misdiagnosed in other feline olfactory neuroblastoma cases as neurosecretory granules.19 Further investigation is warranted to evaluate the presence of retroviral particles in feline olfactory neuroblastoma and whether a true causal relationship exists. Tumor recurrence is the primary cause of treatment failure is most patients. Several authors agree that higher stage and grade tumors are more likely to recur. Olfactory neuroblastoma most commonly metastasizes to regional lymph nodes. The most commonly affected distant sites are lung, brain and bone.9,15,20,21
Conclusions Olfactory neuroblastoma is a differential for spontaneous intranasal tumors in cats. Clinical signs may be variable and depend on the extent of tumor involvement. If histologic changes are not definitive, special stains may be required to correctly identify the nasal tumor as an olfactory neuroblastoma. Treatment options are varied and somewhat dependent upon surgical skill and the availability of adjuvant chemoradiotherapy. Further investigation into a possible relationship between olfactory neuroblastoma and retroviral oncogenesis is warranted. The prognosis may be related to tumor stage and grade.
References 1
2
3
4
5
Berger L, Luc R. L’esthesioneuroepitheliome olfactif. Bull Assoc Fr Etude Cancer 1924; 13: 410–21. Hyams VJ. Tumors of the upper respiratory tract and ear. In: Atlas of tumor pathology, second series, fascicle 25. Washington, DC: Armed Forces Institute of Pathology, 1988: 240–48. Kitagawa M, Okada M, Yamamura H, Kanayama K, Sakai T. Diagnosis of olfactory neuroblastoma in a dog by magnetic resonance imaging. Vet Rec 2006; 159: 288–89. Koestner A, Higgins, RJ. Tumors of the nervous system. In: Meuten DJ, ed. Tumors in domestic animals. 4th edn. Ames: Iowa State Press, 2002: 713–14. Madewell BR, Priester WA, Gillette EL, Snyder SP. Neoplasms of the nasal passages and paranasal sinuses in domesticated animals as reported by 13 veterinary colleges. Am J Vet Res 1976; 37: 851–56.
Further investigation is warranted to evaluate the presence of retroviral particles in feline olfactory neuroblastoma and whether a true causal relationship exists.
870
JFMS CLINICAL PRACTICE
C A S E / Olfactory neuroblastoma
6
7
8
9
10
11
12
13
Cox NR, Brawner WR, Powers RD, Wright JC. Tumors in the nose and paranasal sinuses in cats: 32 cases with comparison to a national database (1977 through 1987). J Am Anim Hosp Assoc 1991; 27: 339–47. Legendre AM, Krahwinkel DJ, Spaulding KA. Feline nasal and paranasal sinus tumors. J Am Anim Hosp Assoc 1981; 17: 1038–39. Mukaratirwa S, van der Linde-Sipman JS, Gruys E. Feline nasal and paranasal sinus tumors: clinicopathological study, histomorphological description and diagnostic immunohistochemistry of 123 cases. J Feline Med Surg 2001; 3: 235–45. Castelnuovo P, Bignami M, Delu G, Battaglia P, Bignardi M, Dallan I. Endonasal endoscopic resection and radiotherapy in olfactory neuroblastoma: our experience. Head Neck 2007; 29: 845–50. Smith MO, Turrel JM, Bailey CL, Cain GR. Neurologic abnormalities as the predominant signs of neoplasia of the nasal cavity in dogs and cats: seven cases (1973–1986). J Am Vet Med Assoc 1989; 195: 242–45. Kadish S, Goodman M, Wang CC. Olfactory neuroblastoma. A clinical analysis of 17 cases. Cancer 1976; 37: 1571–76. Morita A, Ebersold MJ, Olsen KD, Foote RL, Lewis JE, Quast LM. Esthesioneuroblastoma: prognosis and management. Neurosurgery 1993; 32: 706–15. Turek MM, Lana SE. Canine nasosinal tumors. In: Withrow SJ, Vail DM, eds. Small animal
14
15
16
17
18
19
20
21
clinical oncology. 4th edn. St Louis: Saunders 2001: 525–39. Ueno H, Kobayahi Y, Yamada K. Olfactory esthesioneuroblastoma treated with orthovoltage radiotherapy in a dog. Aust Vet J 2007; 85: 271–75. Kim HJ, Kim CH, Lee BG, et al. Surgical treatment versus concurrent chemoradiotherapy as an initial treatment modality in advanced olfactory neuroblastoma. Auris Nasus Larynx 2007; 34: 493–98. Kim JW, Kong IG, Lee CH, et al. Expression of Bcl-2 in olfactory neuroblastoma and its association with chemotherapy and survival. Otolaryngol Head Neck Surg 2008; 139: 708–12. Madewell BR, Gandour-Edwards R, Edwards BF, Walls, JE, Griffey, SM. Topographic distribution of bcl-2 protein in feline tissues in health and neoplasia. Vet Pathol 1999; 36: 565–73. Dank G, Lucroy MD, Griffey SM, GandourEdwards R, Madewell BR. bcl-2 and MIB-1 labeling indexes in cats with lymphoma. J Vet Intern Med 2002; 16: 720–25. Schrenzel MD, Higgin RJ, Hinrichs SH, Smith MO, Torten M. Type C retroviral expression in spontaneous feline olfactory neuroblastomas. Acta Neuropathol 1990; 80: 547–53. Eriksen JG, Bastholt L, Krogdahl AS, Hansen O, Joergensen EK. Esthesioblastoma: what is the optimal treatment? Acta Oncol 2000; 139: 231–35. Diaz EM, Johnigan RH, Pero C, et al. Olfactory neuroblastoma: the 22-year experience at one comprehensive cancer center. Head Neck 2005; 27: 138–49.
Available online at www.sciencedirect.com
JFMS CLINICAL PRACTICE
871