Veterinary Clinical Pathology ISSN 0275-6382
What is your diagnosis? Cerebrospinal fluid from a dog F. Cian1, V. Palus2, G.B. Cherubini2, J. Archer1, E. Villiers2 1
Department of Veterinary Medicine, University of Cambridge, Cambridge, UK and 2Dick White Referrals, Six Mile Bottom, UK
Correspondence Francesco Cian, Animal Health Trust, Lanwades Park, Newmarket, Suffolk CB8 7UU, UK E-mail: [email protected] DOI:10.1111/vcp.12120
A
Case Presentation An 8-year-old female neutered Springer Spaniel dog was presented as an emergency case for investigation of progressive ataxia of all 4 limbs, staggering and behavioral changes. Neurologic signs started 2 weeks before referral with further acute deterioration. The dog had a solid mammary carcinoma surgically removed one year previously, which recurred 6 months later and was also resected. On physical examination, the dog was tachypneic with hyperemic mucous membranes. The dog was obtunded, nonambulatory tetraparetic with decreased postural reactions and increased spinal cord segmental reflexes in all 4 limbs. The neurologic examination was indicative of multifocal brain localization. Hematology, biochemistry, electrolytes, and urinalysis were unremarkable and there were no abnormalities on thoracic radiographs and in an abdominal ultrasound examination. Magnetic resonance imaging (MRI) revealed a mass lesion with perilesional edema in the left temporal lobe that was hyperintense on the T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. The mass was enhanced after contrast administration. A cerebrospinal fluid (CSF) sample was collected aseptically from the cisterna magna immediately after the MRI study (Figure 1).
B
Figure 1. Cytocentrifuged preparation of cerebrospinal fluid from a Springer Spaniel. Wright–Giemsa (A) 950 and (B) 9100 objective.
Vet Clin Pathol 43/1 (2014) 115–116 ©2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology
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CSF from a dog
Cian et al
Interpretation: Neoplastic pleocytosis of undetermined origin. Cerebrospinal fluid findings included a total nucleated cell count of 30 cells/lL (reference interval [RI] 0–5 cells/lL), the majority being atypical discrete cells (82%) with a lower proportion of neutrophils (13%) and lymphocytes (5%). The RBC count was 90 cells/lL and the protein concentration was 0.25 g/L (RI < 0.35 g/L). The pleomorphic cells were large with moderate amounts of lightly granular basophilic cytoplasm and well-defined borders. Nuclei were round, central to paracentral, with a diameter of 20–25 lm, granular chromatin and small round multiple nucleoli. Anisocytosis and anisokaryosis were marked. A few binucleated and trinucleated cells were seen, and frequent atypical mitotic figures were noted (Figure 2). The cytologic interpretation was malignant neoplasia of unknown origin. The main differentials were primary CNS neoplasia, metastatic tumors, lymphoma, and histiocytic neoplasia. Immunocytochemistry was performed and cells strongly expressed cytokeratin (antibody clone MNF116, broad anti-human keratin reagent, Dako, Glostrup, Denmark), but not vimentin, CD3, CD18, or CD79a (Figure 3). A diagnosis of carcinoma was made. A primary carcinoma of the CNS was considered unlikely, based on the localization of the lesion, the MRI findings, and the results of cytology and immunocytochemistry. With the prior history of mammary carcinoma, this was assumed to be a metastatic mammary carcinoma. The dog was treated with chemotherapy, but did not improve and was euthanized after 6 days.
Discussion Nonhemic neoplasias rarely exfoliate cells into CSF in dogs.1 This is likely due to their location, often arising in a site remote from the ventricles, and their poorly exfoliative nature. In this case, the overall findings were suggestive of a metastatic mammary carcinoma. Primary epithelial CNS neoplasia was considered unlikely. The location was considered unusual for a choroid plexus tumor and ependymoma; the
Figure 3. Immunocytochemical staining of a cytocentrifuged preparation of cerebrospinal fluid from a Springer Spaniel with a presumed metastatic carcinoma. Strong cytoplasmic expression of cytokeratin (MNF116, broad anti-human keratin reagent, Dako, Glostrup, Denmark) by malignant epithelial cells. Diamino-benzidine chromogen.950 objective.
latter was also considered unlikely, given the immunocytochemistry results, as it is usually cytokeratin negative and vimentin positive.2 Metastatic mammary carcinomas are characterized by extensive diffuse meningeal involvement, although focal involvement has been described, in both cases as a likely consequence of hematogenous dissemination.3,4 Epithelial tumors usually exfoliate in cohesive sheets because cells adhere to each other by desmosomes. However, metastatic carcinomas in CSF with a discrete appearance have been described. The reason is unclear, but downregulation of cellular junctions and adhesion molecules on the cell membranes of neoplastic cells are a possibility.3,5 Given the lack of clustering of epithelial tumor cells in CSF, immunostaining is considered a useful diagnostic tool for the identification of the cellular lineage.
Key Words: Immunocytochemistry, mammary carcinoma, pleocytosis
References 1. De Lorenzi D, Mandara MT. The central nervous system. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology. 2nd ed. St. Louis, MO: Elsevier Saunders; 2010:345–347. 2. Koestner A, Higgins RJ. Tumours of the nervous system. In: Meuten DJ, ed. Tumours in Domestic Animals. 4th ed. Ames, IA: Iowa State Press; 2002:707–712. 3. Behling-Kelly E, Petersen S, Muthuswamy A, et al. Neoplastic pleocytosis in a dog with metastatic mammary carcinoma and meningeal carcinomatosis. Vet Clin Pathol. 2010;39:247–252. Figure 2. Cytocentrifuged preparation of cerebrospinal fluid from a Springer Spaniel with a presumed metastatic carcinoma. Pleomorphic large round cells with vacuolated cytoplasm suggesting a possible secretory origin. Two atypical mitotic figures are also seen. Wright Giemsa. 9100 objective.
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4. Pumarola M, Balasch M. Meningeal carcinomatosis in a dog. Vet Rec. 1996;25:523–524. 5. Chidgey M, Dawson C. Desmosomes: a role in cancer? Br J Cancer. 2008;96:1783–1787.
Vet Clin Pathol 43/1 (2014) 115–116 ©2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology
What is your diagnosis? Cerebrospinal fluid from a dog F. Cian1, V. Palus2, G.B. Cherubini2, J. Archer1, E. Villiers2 1
Department of Veterinary Medicine, University of Cambridge, Cambridge, UK and 2Dick White Referrals, Six Mile Bottom, UK
Correspondence Francesco Cian, Animal Health Trust, Lanwades Park, Newmarket, Suffolk CB8 7UU, UK E-mail: [email protected] DOI:10.1111/vcp.12120
A
Case Presentation An 8-year-old female neutered Springer Spaniel dog was presented as an emergency case for investigation of progressive ataxia of all 4 limbs, staggering and behavioral changes. Neurologic signs started 2 weeks before referral with further acute deterioration. The dog had a solid mammary carcinoma surgically removed one year previously, which recurred 6 months later and was also resected. On physical examination, the dog was tachypneic with hyperemic mucous membranes. The dog was obtunded, nonambulatory tetraparetic with decreased postural reactions and increased spinal cord segmental reflexes in all 4 limbs. The neurologic examination was indicative of multifocal brain localization. Hematology, biochemistry, electrolytes, and urinalysis were unremarkable and there were no abnormalities on thoracic radiographs and in an abdominal ultrasound examination. Magnetic resonance imaging (MRI) revealed a mass lesion with perilesional edema in the left temporal lobe that was hyperintense on the T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. The mass was enhanced after contrast administration. A cerebrospinal fluid (CSF) sample was collected aseptically from the cisterna magna immediately after the MRI study (Figure 1).
B
Figure 1. Cytocentrifuged preparation of cerebrospinal fluid from a Springer Spaniel. Wright–Giemsa (A) 950 and (B) 9100 objective.
Vet Clin Pathol 43/1 (2014) 115–116 ©2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology
115
CSF from a dog
Cian et al
Interpretation: Neoplastic pleocytosis of undetermined origin. Cerebrospinal fluid findings included a total nucleated cell count of 30 cells/lL (reference interval [RI] 0–5 cells/lL), the majority being atypical discrete cells (82%) with a lower proportion of neutrophils (13%) and lymphocytes (5%). The RBC count was 90 cells/lL and the protein concentration was 0.25 g/L (RI < 0.35 g/L). The pleomorphic cells were large with moderate amounts of lightly granular basophilic cytoplasm and well-defined borders. Nuclei were round, central to paracentral, with a diameter of 20–25 lm, granular chromatin and small round multiple nucleoli. Anisocytosis and anisokaryosis were marked. A few binucleated and trinucleated cells were seen, and frequent atypical mitotic figures were noted (Figure 2). The cytologic interpretation was malignant neoplasia of unknown origin. The main differentials were primary CNS neoplasia, metastatic tumors, lymphoma, and histiocytic neoplasia. Immunocytochemistry was performed and cells strongly expressed cytokeratin (antibody clone MNF116, broad anti-human keratin reagent, Dako, Glostrup, Denmark), but not vimentin, CD3, CD18, or CD79a (Figure 3). A diagnosis of carcinoma was made. A primary carcinoma of the CNS was considered unlikely, based on the localization of the lesion, the MRI findings, and the results of cytology and immunocytochemistry. With the prior history of mammary carcinoma, this was assumed to be a metastatic mammary carcinoma. The dog was treated with chemotherapy, but did not improve and was euthanized after 6 days.
Discussion Nonhemic neoplasias rarely exfoliate cells into CSF in dogs.1 This is likely due to their location, often arising in a site remote from the ventricles, and their poorly exfoliative nature. In this case, the overall findings were suggestive of a metastatic mammary carcinoma. Primary epithelial CNS neoplasia was considered unlikely. The location was considered unusual for a choroid plexus tumor and ependymoma; the
Figure 3. Immunocytochemical staining of a cytocentrifuged preparation of cerebrospinal fluid from a Springer Spaniel with a presumed metastatic carcinoma. Strong cytoplasmic expression of cytokeratin (MNF116, broad anti-human keratin reagent, Dako, Glostrup, Denmark) by malignant epithelial cells. Diamino-benzidine chromogen.950 objective.
latter was also considered unlikely, given the immunocytochemistry results, as it is usually cytokeratin negative and vimentin positive.2 Metastatic mammary carcinomas are characterized by extensive diffuse meningeal involvement, although focal involvement has been described, in both cases as a likely consequence of hematogenous dissemination.3,4 Epithelial tumors usually exfoliate in cohesive sheets because cells adhere to each other by desmosomes. However, metastatic carcinomas in CSF with a discrete appearance have been described. The reason is unclear, but downregulation of cellular junctions and adhesion molecules on the cell membranes of neoplastic cells are a possibility.3,5 Given the lack of clustering of epithelial tumor cells in CSF, immunostaining is considered a useful diagnostic tool for the identification of the cellular lineage.
Key Words: Immunocytochemistry, mammary carcinoma, pleocytosis
References 1. De Lorenzi D, Mandara MT. The central nervous system. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology. 2nd ed. St. Louis, MO: Elsevier Saunders; 2010:345–347. 2. Koestner A, Higgins RJ. Tumours of the nervous system. In: Meuten DJ, ed. Tumours in Domestic Animals. 4th ed. Ames, IA: Iowa State Press; 2002:707–712. 3. Behling-Kelly E, Petersen S, Muthuswamy A, et al. Neoplastic pleocytosis in a dog with metastatic mammary carcinoma and meningeal carcinomatosis. Vet Clin Pathol. 2010;39:247–252. Figure 2. Cytocentrifuged preparation of cerebrospinal fluid from a Springer Spaniel with a presumed metastatic carcinoma. Pleomorphic large round cells with vacuolated cytoplasm suggesting a possible secretory origin. Two atypical mitotic figures are also seen. Wright Giemsa. 9100 objective.
116
4. Pumarola M, Balasch M. Meningeal carcinomatosis in a dog. Vet Rec. 1996;25:523–524. 5. Chidgey M, Dawson C. Desmosomes: a role in cancer? Br J Cancer. 2008;96:1783–1787.
Vet Clin Pathol 43/1 (2014) 115–116 ©2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology
