• View in gallery
    Figure 1

    Postcontrast transverse T1-weighted (A), transverse T2-weighted (B), and postcontrast dorsal T1-weighted (C) MRI images of the calvarium at the level of the olfactory bulb and transverse T2-weighted MRI image at the level of the left medial retropharyngeal lymph node (D) of a 7-year-old male castrated Golden Retriever evaluated for worsening signs of dull mentation, frequent sneezing, and left-sided epistaxis.

  • View in gallery
    Figure 2

    Same images as in Figure 1. A—A mass (arrows) has marked heterogenous contrast enhancement, contact with meninges, and substantial rightward midline shift, supporting extra-axial origin. B—Minimal peritumoral edema surrounds the mass (arrow). C—There is bilateral extension of the mass (arrows) into the nasal cavities, worse on the left. D—The left medial retropharyngeal lymph node (arrows) is markedly enlarged.

  • 1.

    Weishaar KM, Thamm DH, Worley DR, Kamstock DA. Correlation of nodal mast cells with clinical outcome in dogs with mast cell tumour and a proposed classification system for the evaluation of node metastasis. J Comp Pathol. 2014;151:329338.

    • Search Google Scholar
    • Export Citation
  • 2.

    Moore TW, Bentley RT, Moore SA, et al. Spinal mast cell tumors in dogs: imaging features and clinical outcome of four cases. Vet Radiol Ultrasound. 2017;58:4452.

    • Search Google Scholar
    • Export Citation
  • 3.

    Moore LE, Garrett LD, Debey B, Biller DS. Spinal mast cell tumor in a dog. J Am Anim Hosp Assoc. 2002;38:6770.

  • 4.

    Kitagawa M, Okada M, Yamamura H, Kanayama K, Sakai T. Diagnosis of olfactory neuroblastoma in a dog by magnetic resonance imaging. Vet Rec. 2006;159:288289.

    • Search Google Scholar
    • Export Citation
  • 5.

    Khoo A, Lane A, Wyatt K. Intranasal mast cell tumor in the dog: a case series. Can Vet J. 2017;58:851854.

  • 6.

    Matsuda A, Tanaka A, Muto S, et al. A novel NF-kappaB inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors. Res Vet Sci. 2010;89: 378382.

    • Search Google Scholar
    • Export Citation
  • 7.

    Matsuda A, Tanaka A, Amagai Y, et al. Glucocorticoid sensitivity depends on expression levels of glucocorticoid receptors in canine neoplastic mast cells. Vet Immunol Immunopathol. 2011;144:321328.

    • Search Google Scholar
    • Export Citation
  • 8.

    Dos Santos Horta R, Eunice Lavalle G, Narducci Monteiro L, et al. Evaluation of histological, immunohistochemical, clinical and genetic prognostic factors associated with the response of canine mast cell tumours to glucocorticotherapy. J Comp Pathol. 2018;165:7281.

    • Search Google Scholar
    • Export Citation
  • 9.

    Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet Pathol. 1984;21:469474.

    • Search Google Scholar
    • Export Citation

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Nicole S. YangDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO

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Lynn R. GriffinDepartment of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO

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Chad B. FrankDepartment of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO

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Lisa R. BartnerDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO

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Abstract

In collaboration with the American College of Veterinary Radiology

Abstract

In collaboration with the American College of Veterinary Radiology

History

A 7-year-old 33.7-kg castrated male Golden Retriever was evaluated for a 6-week history of generalized cluster seizures and subsequently had mucoid nasal discharge and sneezing that occurred several weeks later. Prior to referral, a brain MRI was performed, revealing a mass occupying the left nasal cavity with extension to the left olfactory bulb and frontal lobe (Supplementary Figure 1S Supplementary materials are posted online at the journal website: avmajournals.avma.org/doi/suppl/10.2460/javma.20.10.0592). Evaluation of rhinoscopy-acquired biopsy samples of the nasal mass revealed severe eosinophilic and lymphoplasmacytic rhinitis with turbinate erosion. Cytologic findings for fine-needle aspirate samples of an enlarged left retropharyngeal lymph node likely represented a poorly differentiated mast cell tumor (MCT). The dog’s clinical signs resolved with the initiation of prednisolone (0.3 mg/kg, PO, q 12 h) and potassium bromide (26.5 mg/kg, PO, q 24 h).

Findings of a CBC and biochemical analyses showed no clinically important abnormalities, and findings on thoracic radiography were unremarkable. A skull CT and an MRI with limited sequences were performed for radiation planning; however, remarkably, the imaging revealed no grossly visible disease aside from mild meningeal contrast enhancement over the left olfactory bulb (Supplementary Figure 2S Supplementary materials are posted online at the journal website: avmajournals.avma.org/doi/suppl/10.2460/javma.20.10.0592).

The client selected palliative treatment, consisting of a 4-week of tapering prednisolone dosage. Seven weeks after discontinuing steroids, the dog developed dull mentation, mild pelvic limb ataxia, frequent sneezing, and left-sided epistaxis; all signs improved after restarting prednisolone. Restaging revealed marked eosinophilia (3.0 X 103 eosinophils/µL; reference range, 0.1 X 103 to 1.2 X 103 eosinophils/µL) on a CBC and a newly identified solitary pulmonary nodule in the right caudal lung lobe on orthogonal thoracic radiography (not shown).

Based on the worsened clinical signs, the dog underwent general anesthesia for repeated CT and MRI fusion for radiation planning (Figure 1). A CSF sample was also collected.

Figure 1
Figure 1
Figure 1
Figure 1
Figure 1

Postcontrast transverse T1-weighted (A), transverse T2-weighted (B), and postcontrast dorsal T1-weighted (C) MRI images of the calvarium at the level of the olfactory bulb and transverse T2-weighted MRI image at the level of the left medial retropharyngeal lymph node (D) of a 7-year-old male castrated Golden Retriever evaluated for worsening signs of dull mentation, frequent sneezing, and left-sided epistaxis.

Citation: Journal of the American Veterinary Medical Association 259, S1; 10.2460/javma.20.10.0592

Formulate differential diagnoses, then continue reading.

Diagnostic Imaging Findings and Interpretation

On MRI, there was a left-sided heterogeneously T2 hyperintense, T1 isointense extra-axial mass with marked heterogeneous contrast enhancement that extended rostrally from the frontal lobe and olfactory bulb into the left nasal cavity through the cribriform plate, causing a rightward midline shift and deviation of the falx (Figure 2). In the nasal cavity, the mass occupied the ventral half of the caudal nasal cavity and caused incomplete lysis of the nasal turbinates. The left medial retropharyngeal lymph node was still markedly enlarged, rounded, and heterogeneously T2 hyperintense and heterogeneously T1 iso- to hyperintense, compared to the gray matter.

Figure 2
Figure 2
Figure 2
Figure 2
Figure 2

Same images as in Figure 1. A—A mass (arrows) has marked heterogenous contrast enhancement, contact with meninges, and substantial rightward midline shift, supporting extra-axial origin. B—Minimal peritumoral edema surrounds the mass (arrow). C—There is bilateral extension of the mass (arrows) into the nasal cavities, worse on the left. D—The left medial retropharyngeal lymph node (arrows) is markedly enlarged.

Citation: Journal of the American Veterinary Medical Association 259, S1; 10.2460/javma.20.10.0592

Treatment and Outcome

Based on prior regression followed by recurrence of the mass, which coincided with corticosteroid administration, steroid-responsive conditions such as round-cell tumors (eg, lymphoma, MCT) or meningoencephalitis (eg, infectious, noninfectious) were considered, and CSF was collected from the cerebellomedullary cistern. On cytologic evaluation, there was an eosinophilic pleocytosis (protein 194.35 mg/dL [reference range, < 30 mg/dL]; WBCs 40 cells/µL [reference range < 5 cells/µL] composed of 90% eosinophils, 5% large mononuclear cells, and 5% small mononuclear cells) with minimal blood contamination (2 RBCs/µL). Results for infectious agent testing were negative for Anaplasma phagocytophilum, A platys, Ehrlichia canis, E ewingii, Dirofilaria immitis, Borrelia burgdorferi, Neospora caninum, Toxoplasma gondii, Rickettsia rickettsii, Bartonella spp, Anaplasma spp, Neorickettsia spp, Wolbachia, Aspergillus spp, Blastomyces spp, Coccidioides spp, Histoplasmosis spp, and Cryptococcus spp. Therefore, an infectious etiology was unlikely for this dog’s eosinophilic pleocytosis.

The left medial retropharyngeal lymph node and 2 left mandibular lymph nodes were surgically excised. Histopathologic examination revealed poorly differentiated neoplastic mast cells. Histologic classification was most consistent with histologic nodal status (HN) of 3 (HN3; on a scale1 of HN0 [no evidence of metastatic disease] to HN3 [overtly metastatic disease]) for the left retropharyngeal lymph node and HN2 (early metastasis) of the left mandibular lymph node.

The differential diagnoses for an extra-axial, strongly contrast-enhancing mass with nasal involvement and a cystic component would normally include an invasive meningioma or a nasal tumor that has eroded the cribriform plate. Other less common neoplasias such as olfactory neuroblastoma (esthesioneuroblastoma), histiocytic sarcoma, and lymphoma have also been described in this location. However, though never reported intracranially, given the definitive diagnosis of metastatic MCT in the lymph node, the dramatic response to prednisone administration, peripheral eosinophilia, and eosinophilic pleocytosis, MCT became our primary differential diagnosis.

Chemotherapy and radiation therapy were declined by the client, so prednisolone was continued (0.3 mg/kg, PO, q 24 h), and the dog remained clinically static until 2 months later when another generalized seizure occurred. At that time, the owner elected euthanasia and necropsy.

Gross postmortem examination revealed a 2 X 1.5 X 1.5-cm, tan, variably soft to moderately firm mass arising from the surface of the most proximal aspect of the left olfactory bulb and extending along the olfactory peduncle to the left caudal nasal cavity. The left retropharyngeal and tracheobronchial lymph nodes were severely enlarged, firm, and diffusely effaced by tumor. A well-demarcated, firm, white to tan 4 X 3 X 3-cm mass expanded the right caudal lung lobe. All other organs were grossly normal. Microscopic examination of the tumor was consistent with disseminated MCT affecting the left telencephalon (frontal lobe and olfactory bulb), left nasal cavity, left retropharyngeal lymph node, tracheobronchial lymph nodes, and right caudal lung lobe.

Comments

To the authors’ knowledge, this is the first case describing an intracranial MCT. Mast cell tumors have been reported in the CNS but only occurring as extradural spinal cord lesions.2,3

Given the initial appearance of an extra-axial mass located within the nasal cavity and cranial fossa having features of marked contrast enhancement, the list of differential diagnoses would include a primary nasal tumor (nasal adenocarcinoma, squamous cell carcinoma), a primary CNS tumor (meningioma, less likely olfactory neuroblastoma [esthesioneuroblastoma]), a round-cell tumor [lymphoma, histiocytic sarcoma, less likely granular cell tumor], metastatic neoplasia, or meningoencephalitis (idiopathic/granulomatous, eosinophilic, and infectious).

Nasal tumors have been reported to invade the calvarium in up to 27.7% of cases.4 However, there are no previously reported confirmed cases of a MCTs progressing in that manner. A case study of 4 dogs with intranasal MCTs reported 1 dog having a history of excessive sneezing and open-mouthed breathing.5 Eventually, the dog developed seizures, which were suspected to have been due to tumor extension into the brain. However, a necropsy was not performed to confirm this.5 For the dog of the present report, prosencephalic signs of seizures and abnormal mentation were noted first, followed by sneezing and mucoid nasal discharge several weeks later, and epistaxis 5 months later, suggesting that cerebral involvement may have preceded nasal involvement.

Upon repeating an MRI for purposes of radiation planning, the gross disease was no longer evident. The only treatment initiated was corticosteroids. However, once steroids were discontinued, the mass reappeared in the same location with similar MRI characteristics as previous. This striking response to prednisolone was an important feature to support round-cell neoplasia in this case. Furthermore, the findings of eosinophilic pleocytosis, peripheral eosinophilia, and lymphadenopathy supported mast cell neoplasia or possibly eosinophilic proliferative diseases. It is established that neoplastic lymphoid cells undergo induction of apoptosis by glucocorticoid treatment.6 Mast cell tumors have more varied responses to glucocorticoids that appear to be dependent on the degree of glucocorticoid receptor expression. In 1 study, 11 of 15 dogs with mast cell tumors partially or completely responded to prednisolone. Their tissues had higher glucocorticoid receptor expression, compared to those with glucocorticoid resistant tumors.7 However, studies thus far showed mixed results in determining a relationship between increased glucocorticoid sensitivity and pathological grade of the MCT.7,8 A traditional histologic grade was unable to be assigned for the tumor of the dog of the present report because the MCT was not cutaneous or subcutaneous; however, the poorly differentiated mast cells may indicate more aggressive behavior.9 Ultimately, it is still unknown which patients may benefit from the use of glucocorticoids given that glucocorticoid effects on apoptosis and factors involved in glucocorticoid resistance have yet to be fully determined.9

In conclusion, MCT should be included as a differential diagnosis for an extra-axial contrast-enhancing intracranial mass in dogs, especially when other supporting evidence is present, such as confirmed mast cell disease elsewhere, eosinophilic pleocytosis, peripheral eosinophilia, lymphadenopathy, or improvement on steroids.

Acknowledgments

The authors have no conflicts of interest to declare.

The authors thank Susan Lana DVM, MS, DACVIM (Oncology) for her contributions.

References

  • 1.

    Weishaar KM, Thamm DH, Worley DR, Kamstock DA. Correlation of nodal mast cells with clinical outcome in dogs with mast cell tumour and a proposed classification system for the evaluation of node metastasis. J Comp Pathol. 2014;151:329338.

    • Search Google Scholar
    • Export Citation
  • 2.

    Moore TW, Bentley RT, Moore SA, et al. Spinal mast cell tumors in dogs: imaging features and clinical outcome of four cases. Vet Radiol Ultrasound. 2017;58:4452.

    • Search Google Scholar
    • Export Citation
  • 3.

    Moore LE, Garrett LD, Debey B, Biller DS. Spinal mast cell tumor in a dog. J Am Anim Hosp Assoc. 2002;38:6770.

  • 4.

    Kitagawa M, Okada M, Yamamura H, Kanayama K, Sakai T. Diagnosis of olfactory neuroblastoma in a dog by magnetic resonance imaging. Vet Rec. 2006;159:288289.

    • Search Google Scholar
    • Export Citation
  • 5.

    Khoo A, Lane A, Wyatt K. Intranasal mast cell tumor in the dog: a case series. Can Vet J. 2017;58:851854.

  • 6.

    Matsuda A, Tanaka A, Muto S, et al. A novel NF-kappaB inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors. Res Vet Sci. 2010;89: 378382.

    • Search Google Scholar
    • Export Citation
  • 7.

    Matsuda A, Tanaka A, Amagai Y, et al. Glucocorticoid sensitivity depends on expression levels of glucocorticoid receptors in canine neoplastic mast cells. Vet Immunol Immunopathol. 2011;144:321328.

    • Search Google Scholar
    • Export Citation
  • 8.

    Dos Santos Horta R, Eunice Lavalle G, Narducci Monteiro L, et al. Evaluation of histological, immunohistochemical, clinical and genetic prognostic factors associated with the response of canine mast cell tumours to glucocorticotherapy. J Comp Pathol. 2018;165:7281.

    • Search Google Scholar
    • Export Citation
  • 9.

    Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet Pathol. 1984;21:469474.

    • Search Google Scholar
    • Export Citation

Contributor Notes

Corresponding author: Dr. Bartner (Lisa.Bartner@colostate.edu)