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Choroid Plexus Carcinoma in a Goat
ARTICLE IN PRESS J. Comp. Path. 2006,Vol. 135, 42^46
www.elsevier.com/locate/jcpa
SHORT PAPER
Choroid Plexus Carcinoma in a Goat R. Klopfleisch, D. Beier* and J. P. Teifke Friedrich-Loe¥er-Institut, Federal Research Institute forAnimal Health, 17493 Greifswald-InselRiems, and *Wusterhausen, Germany
Summary A15-year-old female goat suddenly developed right-sided head tilting with anorexia and depression. Post-mortem examination of the brain revealed a large, unilateral, well-demarcated, intraventricular neoplasm which was diagnosed as a choroid plexus carcinoma. The neoplasm, which occupied about 75% of the left lateral ventricle, led to unilateral obstructive hydrocephalus and invaded the white and grey matter of the left piriform lobe, with focal subarachnoid spread and meningeal implantation. Histopathological examination revealed loss of branching papillary architecture, invasive growth, a high mitotic index and marked necrosis in the undi¡erentiated areas of the tumour. Neoplastic cells expressed vimentin and, multifocally, broad spectrum cytokeratins, but were negative for GFAP, NSE and Sl00 antigen. This is the ¢rst report of a choroid plexus carcinoma in a goat. r 2006 Elsevier Ltd. All rights reserved. Keywords: brain; choroid plexus carcinoma; goat; tumour
Choroid plexus tumours are rare neuroepithelial neoplasms derived from the choroid plexus epithelium. On the basis of cellular di¡erentiation, numbers of mitoses and invasive growth with ventricular and subarachnoid spread they can be classi¢ed as choroid plexus papillomas (CPPs) or choroid plexus carcinomas (CPCs) (Koestner et al.,1999). They occur, albeit infrequently, in dogs, cats, horses and cattle and must be distinguished from papillary ependymomas and metastatic adenocarcinomas (Hays et al., 1975; Summers et al., 1995; Koestner et al., 1999). In the dog, in which middle-aged male animals are a¡ected in particular (Summers et al.,1995), these neoplasms are found predominantly adjacent to and within the fourth ventricle, but occur also in the third and lateral ventricles (Zaki and Nafe, 1980). Tumours of the nervous system are uncommon in goats, but ventricular epithelioma, ¢brillary astrocytoma, pituitary adenoma, oligodendrocytic glioma, neuroblastoma and malignant schwannoma have been reported ( Martin de las Mulas et al.,1991,1996; Veazey et al.,1993; Marshall et al.,1995; Wicks and Oglesbee, 1995; Miller et al., 1997). Choroid plexus tumours, however, have not previously been deCorrespondence to: J. P. Teifke (e-mail: jens.teifke@£i.bund.de). 0021-9975/$ - see front matter
doi:10.1016/j.jcpa.2006.02.006
scribed in this species. This paper describes the clinical signs and the gross, microscopical and immunohistochemical features of a CPC in a German Improved White goat. A 15-year-old female goat was added as a sentinel lamb to a £ock of goats experimentally infected with caprine arthritis encephalitis virus (CAEV), a lentivirus known to induce leucoencephalomyelitis in young kids and proliferative arthritis and bursitis, lymphohistiocytic mastitis and interstitial pneumonia in adult goats (Al-Ani and Vestweber, 1984). Except for seroconversion this animal showed no clinical signs speci¢c for CAE. During the 10-day period that preceded presentation for clinical examination the goat developed central nervous system (CNS) signs of head tilting to the right side, loss of orientation, and ataxia. Anorexia, weakness and moderate depression also developed. The goat was humanely killed and submitted for complete necropsy. No gross lesions were observed in organs other than the brain, in which there was a focal, sharply demarcated, ¢rm adhesion (1 5 cm in diameter) of the left basal piriform lobe and its adjacent meninges to the cranial cavity; the lobe was asymmetrically and di¡usely enlarged. The brain could be detached from the r 2006 Elsevier Ltd. All rights reserved.
ARTICLE IN PRESS Choroid Plexus Carcinoma in a Goat
calvarium only with partial loss of the neuropil (Fig.1). Coronal sections of the cerebrum and midbrain revealed an irregularly shaped, well circumscribed but nonencapsulated mass (1 2 cm) which occupied about 75% of the moderately dilated left lateral ventricle.The tumour stroma was grey-white, centrally red to pink, and friable. It compressed the subjacent hippocampus and in¢ltrated the surrounding cortical white matter, resulting in deviation of the cerebral midline to the right. Similarly, the basal part of the piriform lobe was in¢ltrated by a poorly demarcated neoplasm, l cm in diameter, with a granular appearance (Fig. 2). The brain was removed, ¢xed in 10% neutral buffered formalin, processed by routine methods and embedded in para⁄n wax; sections (4 mm) were then cut and stained with haematoxylin and eosin (HE). Micro-
43
scopical examination revealed a cell-rich, nonencapsulated neoplasm invading the left lateral ventricle, compressing the adjacent hippocampus and spreading into the white matter of the left dorsomedial cerebrum, basal cortex and adjacent meninges (Fig. 3). It had an arborizing papillary structure with histological features resembling those of normal choroid plexus epithelium (Fig. 4). Arranged in layers one to three cells thick and supported by a moderate ¢brovascular stroma, the cuboidal to columnar neoplastic cells had moderate amounts of pale eosinophilic cytoplasm and regular central oval nuclei with one or two small nucleoli. Multiple foci of neoplastic cells in¢ltrating the neuropil and, more centrally, extensive areas of oedema, necrosis and haemorrhage were present. Mitotic ¢gures were observed at the rate of one per 10
Fig. 1. Midbrain, goat. Basal view demonstrates asymmetrical enlargement of the left piriform lobe with focal loss of neuropil.
Fig. 2. Cerebrum, midbrain, goat, coronal section. Sharply demarcated intraventricular neoplasm compressing and in¢ltrating the adjacent cerebrum with dilatation of the left ventricle and invasion of the left piriform lobe.
ARTICLE IN PRESS 44
R. Klopfleisch et al.
Fig. 3. Piriform lobe, goat, choroid plexus carcinoma. Neoplastic cells invade and replace the neuropil and the meninges of the basal cortex. HE. Bar,180 mm.
Fig. 4. Lateral ventricle, goat, choroid plexus carcinoma. Intraventricular well-di¡erentiated neoplastic choroid plexus cells growing in an arborizing papillary pattern and in¢ltrating the cerebral white matter. Note area of necrosis at the upper right corner. HE. Bar, 180 mm.
microscopical ¢elds (x40). In contrast, the piriform lobe, including the adjacent subarachnoidea, was extensively in¢ltrated by neoplastic cells which, in places, had lost their papillary arrangement, being present in solid cellular sheets supported by a ¢brovascular stroma. The closely packed cells had moderate amounts of eosinophilic cytoplasm and medium-sized, mildly pleomorphic, round to oval nuclei with scant, coarsely stippled heterochromatin.Two to three mitoses per x40 ¢eld were observed (Fig. 5). There were multiple small to extensive areas of necrosis with focal haemorrhages, ¢brinous exudate, cellular debris and occasional in¢ltrates of small numbers of neutrophils. For immunohistochemistry (IHC), ¢xed tissues were embedded in Histosecs (Merck, Darmstadt, Ger-
many) and sections (4^5 mm) were cut and mounted on Super-frost-plus glass slides (Menzel-Glser, Braunschweig, Germany). With the avidin^biotincomplex (ABC) method, the antibodies used were those speci¢c for glial ¢brillary acidic protein (GFAP) (DakoCytomation GmbH, Hamburg, Germany; diluted 1 in 150), vimentin (DakoCytomation; diluted 1 in 40), S100 (DakoCytomation; diluted1in 50), cytokeratins 1^8, 10, 13^16, 19 (AE1, AE3 and Ks13.2; Histoprime ready-to-use; Linaris Biological Products, Wertheim-Bettingen, Germany), and neuron-speci¢c enolase (NSE) (DakoCytomation, diluted 1 in 100). In brief, sections were dewaxed and rehydrated, and endogenous peroxidases were blocked with H2O2 10% in methanol for 10 min. An additional blocking step
ARTICLE IN PRESS Choroid Plexus Carcinoma in a Goat
45
Fig. 5. Piriform lobe, goat, choroid plexus carcinoma. Neoplastic cells with mildly pleomorphic nuclei and frequent mitotic ¢gures, orientated in rosettes around a vascular core. HE. Bar, 40 mm.
Fig. 6. Lateral ventricle, goat, choroid plexus carcinoma. Numerous neoplastic cells exhibit strong cytoplasmic labelling for pancytokeratin. IHC. Bar, 30 mm.
consisted of treatment with normal goat serum for 30 min. Each section was then incubated for 1h with the appropriate primary antibody diluted in Tris-bu¡ered saline (TBS). AEC-Substrate (Dako) was used as chromogen. The sections were counterstained with Mayer’s haematoxylin and mounted with Aquatexs (Merck). Neoplastic cells were positive for vimentin and cytokeratin, but negative for GFAP, NSE and S100 (Fig. 6). On the basis of location, intraventricular and subarachnoid spread, histopathology and immunohistochemical ¢ndings, the neoplasm was diagnosed as a choroid plexus carcinoma. Histological distinction between CPPs and CPCs, which depends mainly on cellular di¡erentiation and
dissemination within the subarachnoid space, may present di⁄culty. Carcinomas in both dogs and man exhibit characteristic features of malignancy, such as nuclear atypia, high mitotic rate, marked necrosis and partly solid growth (Ribas et al., 1989; Waldron and Tihan, 2003). Moreover, the recentWHOInternational Classi¢cation of Tumours of the Nervous System of Domestic Animals proposes invasion and metastasis along the neuraxis as a diagnostic criterion of CPC (Koestner et al., 1999). In dogs particularly, CPCs metastasize within the meninges or the ventricular cavity (Cantile et al., 2002). In the present case, the increased mitotic index (2^3 mitoses/high power ¢eld), the cellular pleomorphism, the marked necrosis and the solid growth pattern of the metastases within the piriform
ARTICLE IN PRESS 46
R. Klopfleisch et al.
lobe and its meninges led to the diagnosis of malignancy. Local compression of the ventricular lumina or increased synthesis of cerebrospinal £uid may have been responsible for the obstructive hydrocephalus observed. The main di¡erential diagnosis for intraventricular tumours is ependymoma. Choroid plexus tumours can be distinguished from neoplasms of ependymal cells by their intraventricular growth, pseudorosettes and rosettes, cilia, and glial rather than ¢brovascular core. In addition to these criteria, anaplastic (malignant) ependymomas display cellular atypia, a high mitotic index, and in¢ltration. Moreover, choroid plexus tumours di¡er from ependymomas in their expression of intermediate ¢laments. Choroid plexus tumour cells in human patients habitually express cytokeratins, to a lesser extent vimentin, and rarely GFAP; in canine choroid plexus tumours, however, expression of cytokeratins, vimentin and GFAP has been described as variable (Baumgrtner and Peixota,1987; Ribas et al.,1989; Wilson et al.,1989; Cantile et al., 2002;Waldron andTihan, 2003). In contrast to these ¢ndings, human ependymomas are regularly positive for GFAP and vimentin (Rubinstein and Brucher, 1981). To the best of the authors’ knowledge, GFAP expression in normal or neoplastic caprine choroid plexus and ependymal cells has not yet been investigated. It is unlikely that the infection with CAEVcontributed to the development of this neoplasm, since postmortem examination and histopathological assessment revealed no speci¢c signs of CAE in this animal.To our knowledge, this is the ¢rst report of a choroid plexus carcinoma in a goat. This type of neoplasm should be included in the di¡erential diagnosis of CNS space-occupying lesions in the goat.
Acknowledgments We thank Gabriele Czerwinski for excellent technical assistance.
References Al-Ani, F. K. and Vestweber, J. G. (1984). Caprine arthritisencephalitis syndrome (CAE): a review.Veterinary Research Communications, 8, 243^253. Baumgrtner, W. and Peixota, P. V. (1987). Immunohistochemical demonstration of keratin in canine neuroepithelioma.Veterinary Pathology, 24, 500^503. Cantile, C., Campani, D., Menicagli, M. and Arispici, M. (2002). Pathological and immunohistochemical studies of choroid plexus carcinoma of the dog. Journal of Comparative Pathology, 126,183^193.
Hays, H. M., Priester,W. A. and Pendergras,T.W. (1975). Occurrence of nervous tissue tumors in cattle, horses, cats, and dogs. InternationalJournal of Cancer, 15, 39^47. Koestner, A., Bilzer, T., Fatzer, R., Schulmann, F.Y., Summers, B.A. and VanWinkle, T.J. (1999). Tumors of neuroepithelial tissue. In: Histological Classi¢cation of Tumors of the Nervous System of Domestic Animals, 2nd series,Vol. 5, Armed Forces Institute of Pathology,Washington, DC, pp. 13^38. Marshall, C. L., Weinstock, D., Krarner, R. W. and Bagley, R. S. (1995). Glioma in a goat. Journal of the AmericanVeterinary Medical Association, 206,1572^1574. Martin de las Mulas, J., Bautista, M. J., de Lara, F. C. and Carrasco, L. (1996). Fibrillary astrocytoma in a goat: pathologic, immunohistochemical, and ultrastructural study. Journal of Veterinary Diagnostic Investigation, 8, 387^389. Martin de las Mulas, J., Vos, J. H., Fernandez, A., Carrasco, L., Mozos, E. and Sierra, M. A. (1991). Caprine peripheral neuroblastomas: structural and ultrastructural features, intermediate ¢laments pro¢le and neuro-endocrine characterization. Journal of Comparative Pathology, 105,175^184. Miller, C. C., Williamson, L. H., Miller-Liebl, D. M. and Thompson, F. N. (1997). Lactation associated with acidophilic pituitary adenoma, pheochromocytoma, and cystic endometrial hyperplasia in two goats. Journal of the AmericanVeterinary Medical Association, 210, 378^381. Ribas, J. L., Mena, H., Braund, K. G., Sesterhenn, I. A. and Toivo-Kinnucan, M. (1989). A histologic and immunohistochemical study of choroid plexus tumours of the dog. Veterinary Pathology, 26, 55^64. Rubinstein, L. J. and Brucher, J. M. (1981). Focal ependymal di¡erentiation in choroid plexus papillomas. Acta Neuropathologica, 53, 29^33. Summers, B.A., Cummings, J.F. and de Lahunta, A. (1995). Tumors of the central nervous system. In:Veterinary Neuropathology, B.A. Summers, J.F. Cummings and A. de Lahunta, Eds, Mosby, St Louis, MO, pp. 373^375. Veazey, R. S., Angel, K. L., Snider, T. G. 3rd., Lopez, M. K. and Taylor, H. W. (1993). Malignant schwannoma in a goat. Journal of Veterinary Diagnostic Investigation, 5, 454^458. Waldron, J. S. and Tihan, T. (2003). Epidemiology and pathology of intraventricular tumors. Neurosurgery Clinics of North America, 14, 469^482. Wicks, J. R. and Oglesbee, M. J. (1995). Epithelioma of the fourth ventricle in a goat.Veterinary Pathology, 32, 429^433. Wilson, R. B., Holscher, M. A. and West, W. R. (1989). Choroid plexus carcinoma in a dog. Journal of Comparative Pathology, 100, 323^326. Zaki, F. A. and Nafe, L. A. (1980). Choroid plexus tumors in the dog. Journal of theAmericanVeterinary Medical Association, 176, 328^330.
Received, September 2nd, 2005 Accepted, February 20th, 2006
www.elsevier.com/locate/jcpa
SHORT PAPER
Choroid Plexus Carcinoma in a Goat R. Klopfleisch, D. Beier* and J. P. Teifke Friedrich-Loe¥er-Institut, Federal Research Institute forAnimal Health, 17493 Greifswald-InselRiems, and *Wusterhausen, Germany
Summary A15-year-old female goat suddenly developed right-sided head tilting with anorexia and depression. Post-mortem examination of the brain revealed a large, unilateral, well-demarcated, intraventricular neoplasm which was diagnosed as a choroid plexus carcinoma. The neoplasm, which occupied about 75% of the left lateral ventricle, led to unilateral obstructive hydrocephalus and invaded the white and grey matter of the left piriform lobe, with focal subarachnoid spread and meningeal implantation. Histopathological examination revealed loss of branching papillary architecture, invasive growth, a high mitotic index and marked necrosis in the undi¡erentiated areas of the tumour. Neoplastic cells expressed vimentin and, multifocally, broad spectrum cytokeratins, but were negative for GFAP, NSE and Sl00 antigen. This is the ¢rst report of a choroid plexus carcinoma in a goat. r 2006 Elsevier Ltd. All rights reserved. Keywords: brain; choroid plexus carcinoma; goat; tumour
Choroid plexus tumours are rare neuroepithelial neoplasms derived from the choroid plexus epithelium. On the basis of cellular di¡erentiation, numbers of mitoses and invasive growth with ventricular and subarachnoid spread they can be classi¢ed as choroid plexus papillomas (CPPs) or choroid plexus carcinomas (CPCs) (Koestner et al.,1999). They occur, albeit infrequently, in dogs, cats, horses and cattle and must be distinguished from papillary ependymomas and metastatic adenocarcinomas (Hays et al., 1975; Summers et al., 1995; Koestner et al., 1999). In the dog, in which middle-aged male animals are a¡ected in particular (Summers et al.,1995), these neoplasms are found predominantly adjacent to and within the fourth ventricle, but occur also in the third and lateral ventricles (Zaki and Nafe, 1980). Tumours of the nervous system are uncommon in goats, but ventricular epithelioma, ¢brillary astrocytoma, pituitary adenoma, oligodendrocytic glioma, neuroblastoma and malignant schwannoma have been reported ( Martin de las Mulas et al.,1991,1996; Veazey et al.,1993; Marshall et al.,1995; Wicks and Oglesbee, 1995; Miller et al., 1997). Choroid plexus tumours, however, have not previously been deCorrespondence to: J. P. Teifke (e-mail: jens.teifke@£i.bund.de). 0021-9975/$ - see front matter
doi:10.1016/j.jcpa.2006.02.006
scribed in this species. This paper describes the clinical signs and the gross, microscopical and immunohistochemical features of a CPC in a German Improved White goat. A 15-year-old female goat was added as a sentinel lamb to a £ock of goats experimentally infected with caprine arthritis encephalitis virus (CAEV), a lentivirus known to induce leucoencephalomyelitis in young kids and proliferative arthritis and bursitis, lymphohistiocytic mastitis and interstitial pneumonia in adult goats (Al-Ani and Vestweber, 1984). Except for seroconversion this animal showed no clinical signs speci¢c for CAE. During the 10-day period that preceded presentation for clinical examination the goat developed central nervous system (CNS) signs of head tilting to the right side, loss of orientation, and ataxia. Anorexia, weakness and moderate depression also developed. The goat was humanely killed and submitted for complete necropsy. No gross lesions were observed in organs other than the brain, in which there was a focal, sharply demarcated, ¢rm adhesion (1 5 cm in diameter) of the left basal piriform lobe and its adjacent meninges to the cranial cavity; the lobe was asymmetrically and di¡usely enlarged. The brain could be detached from the r 2006 Elsevier Ltd. All rights reserved.
ARTICLE IN PRESS Choroid Plexus Carcinoma in a Goat
calvarium only with partial loss of the neuropil (Fig.1). Coronal sections of the cerebrum and midbrain revealed an irregularly shaped, well circumscribed but nonencapsulated mass (1 2 cm) which occupied about 75% of the moderately dilated left lateral ventricle.The tumour stroma was grey-white, centrally red to pink, and friable. It compressed the subjacent hippocampus and in¢ltrated the surrounding cortical white matter, resulting in deviation of the cerebral midline to the right. Similarly, the basal part of the piriform lobe was in¢ltrated by a poorly demarcated neoplasm, l cm in diameter, with a granular appearance (Fig. 2). The brain was removed, ¢xed in 10% neutral buffered formalin, processed by routine methods and embedded in para⁄n wax; sections (4 mm) were then cut and stained with haematoxylin and eosin (HE). Micro-
43
scopical examination revealed a cell-rich, nonencapsulated neoplasm invading the left lateral ventricle, compressing the adjacent hippocampus and spreading into the white matter of the left dorsomedial cerebrum, basal cortex and adjacent meninges (Fig. 3). It had an arborizing papillary structure with histological features resembling those of normal choroid plexus epithelium (Fig. 4). Arranged in layers one to three cells thick and supported by a moderate ¢brovascular stroma, the cuboidal to columnar neoplastic cells had moderate amounts of pale eosinophilic cytoplasm and regular central oval nuclei with one or two small nucleoli. Multiple foci of neoplastic cells in¢ltrating the neuropil and, more centrally, extensive areas of oedema, necrosis and haemorrhage were present. Mitotic ¢gures were observed at the rate of one per 10
Fig. 1. Midbrain, goat. Basal view demonstrates asymmetrical enlargement of the left piriform lobe with focal loss of neuropil.
Fig. 2. Cerebrum, midbrain, goat, coronal section. Sharply demarcated intraventricular neoplasm compressing and in¢ltrating the adjacent cerebrum with dilatation of the left ventricle and invasion of the left piriform lobe.
ARTICLE IN PRESS 44
R. Klopfleisch et al.
Fig. 3. Piriform lobe, goat, choroid plexus carcinoma. Neoplastic cells invade and replace the neuropil and the meninges of the basal cortex. HE. Bar,180 mm.
Fig. 4. Lateral ventricle, goat, choroid plexus carcinoma. Intraventricular well-di¡erentiated neoplastic choroid plexus cells growing in an arborizing papillary pattern and in¢ltrating the cerebral white matter. Note area of necrosis at the upper right corner. HE. Bar, 180 mm.
microscopical ¢elds (x40). In contrast, the piriform lobe, including the adjacent subarachnoidea, was extensively in¢ltrated by neoplastic cells which, in places, had lost their papillary arrangement, being present in solid cellular sheets supported by a ¢brovascular stroma. The closely packed cells had moderate amounts of eosinophilic cytoplasm and medium-sized, mildly pleomorphic, round to oval nuclei with scant, coarsely stippled heterochromatin.Two to three mitoses per x40 ¢eld were observed (Fig. 5). There were multiple small to extensive areas of necrosis with focal haemorrhages, ¢brinous exudate, cellular debris and occasional in¢ltrates of small numbers of neutrophils. For immunohistochemistry (IHC), ¢xed tissues were embedded in Histosecs (Merck, Darmstadt, Ger-
many) and sections (4^5 mm) were cut and mounted on Super-frost-plus glass slides (Menzel-Glser, Braunschweig, Germany). With the avidin^biotincomplex (ABC) method, the antibodies used were those speci¢c for glial ¢brillary acidic protein (GFAP) (DakoCytomation GmbH, Hamburg, Germany; diluted 1 in 150), vimentin (DakoCytomation; diluted 1 in 40), S100 (DakoCytomation; diluted1in 50), cytokeratins 1^8, 10, 13^16, 19 (AE1, AE3 and Ks13.2; Histoprime ready-to-use; Linaris Biological Products, Wertheim-Bettingen, Germany), and neuron-speci¢c enolase (NSE) (DakoCytomation, diluted 1 in 100). In brief, sections were dewaxed and rehydrated, and endogenous peroxidases were blocked with H2O2 10% in methanol for 10 min. An additional blocking step
ARTICLE IN PRESS Choroid Plexus Carcinoma in a Goat
45
Fig. 5. Piriform lobe, goat, choroid plexus carcinoma. Neoplastic cells with mildly pleomorphic nuclei and frequent mitotic ¢gures, orientated in rosettes around a vascular core. HE. Bar, 40 mm.
Fig. 6. Lateral ventricle, goat, choroid plexus carcinoma. Numerous neoplastic cells exhibit strong cytoplasmic labelling for pancytokeratin. IHC. Bar, 30 mm.
consisted of treatment with normal goat serum for 30 min. Each section was then incubated for 1h with the appropriate primary antibody diluted in Tris-bu¡ered saline (TBS). AEC-Substrate (Dako) was used as chromogen. The sections were counterstained with Mayer’s haematoxylin and mounted with Aquatexs (Merck). Neoplastic cells were positive for vimentin and cytokeratin, but negative for GFAP, NSE and S100 (Fig. 6). On the basis of location, intraventricular and subarachnoid spread, histopathology and immunohistochemical ¢ndings, the neoplasm was diagnosed as a choroid plexus carcinoma. Histological distinction between CPPs and CPCs, which depends mainly on cellular di¡erentiation and
dissemination within the subarachnoid space, may present di⁄culty. Carcinomas in both dogs and man exhibit characteristic features of malignancy, such as nuclear atypia, high mitotic rate, marked necrosis and partly solid growth (Ribas et al., 1989; Waldron and Tihan, 2003). Moreover, the recentWHOInternational Classi¢cation of Tumours of the Nervous System of Domestic Animals proposes invasion and metastasis along the neuraxis as a diagnostic criterion of CPC (Koestner et al., 1999). In dogs particularly, CPCs metastasize within the meninges or the ventricular cavity (Cantile et al., 2002). In the present case, the increased mitotic index (2^3 mitoses/high power ¢eld), the cellular pleomorphism, the marked necrosis and the solid growth pattern of the metastases within the piriform
ARTICLE IN PRESS 46
R. Klopfleisch et al.
lobe and its meninges led to the diagnosis of malignancy. Local compression of the ventricular lumina or increased synthesis of cerebrospinal £uid may have been responsible for the obstructive hydrocephalus observed. The main di¡erential diagnosis for intraventricular tumours is ependymoma. Choroid plexus tumours can be distinguished from neoplasms of ependymal cells by their intraventricular growth, pseudorosettes and rosettes, cilia, and glial rather than ¢brovascular core. In addition to these criteria, anaplastic (malignant) ependymomas display cellular atypia, a high mitotic index, and in¢ltration. Moreover, choroid plexus tumours di¡er from ependymomas in their expression of intermediate ¢laments. Choroid plexus tumour cells in human patients habitually express cytokeratins, to a lesser extent vimentin, and rarely GFAP; in canine choroid plexus tumours, however, expression of cytokeratins, vimentin and GFAP has been described as variable (Baumgrtner and Peixota,1987; Ribas et al.,1989; Wilson et al.,1989; Cantile et al., 2002;Waldron andTihan, 2003). In contrast to these ¢ndings, human ependymomas are regularly positive for GFAP and vimentin (Rubinstein and Brucher, 1981). To the best of the authors’ knowledge, GFAP expression in normal or neoplastic caprine choroid plexus and ependymal cells has not yet been investigated. It is unlikely that the infection with CAEVcontributed to the development of this neoplasm, since postmortem examination and histopathological assessment revealed no speci¢c signs of CAE in this animal.To our knowledge, this is the ¢rst report of a choroid plexus carcinoma in a goat. This type of neoplasm should be included in the di¡erential diagnosis of CNS space-occupying lesions in the goat.
Acknowledgments We thank Gabriele Czerwinski for excellent technical assistance.
References Al-Ani, F. K. and Vestweber, J. G. (1984). Caprine arthritisencephalitis syndrome (CAE): a review.Veterinary Research Communications, 8, 243^253. Baumgrtner, W. and Peixota, P. V. (1987). Immunohistochemical demonstration of keratin in canine neuroepithelioma.Veterinary Pathology, 24, 500^503. Cantile, C., Campani, D., Menicagli, M. and Arispici, M. (2002). Pathological and immunohistochemical studies of choroid plexus carcinoma of the dog. Journal of Comparative Pathology, 126,183^193.
Hays, H. M., Priester,W. A. and Pendergras,T.W. (1975). Occurrence of nervous tissue tumors in cattle, horses, cats, and dogs. InternationalJournal of Cancer, 15, 39^47. Koestner, A., Bilzer, T., Fatzer, R., Schulmann, F.Y., Summers, B.A. and VanWinkle, T.J. (1999). Tumors of neuroepithelial tissue. In: Histological Classi¢cation of Tumors of the Nervous System of Domestic Animals, 2nd series,Vol. 5, Armed Forces Institute of Pathology,Washington, DC, pp. 13^38. Marshall, C. L., Weinstock, D., Krarner, R. W. and Bagley, R. S. (1995). Glioma in a goat. Journal of the AmericanVeterinary Medical Association, 206,1572^1574. Martin de las Mulas, J., Bautista, M. J., de Lara, F. C. and Carrasco, L. (1996). Fibrillary astrocytoma in a goat: pathologic, immunohistochemical, and ultrastructural study. Journal of Veterinary Diagnostic Investigation, 8, 387^389. Martin de las Mulas, J., Vos, J. H., Fernandez, A., Carrasco, L., Mozos, E. and Sierra, M. A. (1991). Caprine peripheral neuroblastomas: structural and ultrastructural features, intermediate ¢laments pro¢le and neuro-endocrine characterization. Journal of Comparative Pathology, 105,175^184. Miller, C. C., Williamson, L. H., Miller-Liebl, D. M. and Thompson, F. N. (1997). Lactation associated with acidophilic pituitary adenoma, pheochromocytoma, and cystic endometrial hyperplasia in two goats. Journal of the AmericanVeterinary Medical Association, 210, 378^381. Ribas, J. L., Mena, H., Braund, K. G., Sesterhenn, I. A. and Toivo-Kinnucan, M. (1989). A histologic and immunohistochemical study of choroid plexus tumours of the dog. Veterinary Pathology, 26, 55^64. Rubinstein, L. J. and Brucher, J. M. (1981). Focal ependymal di¡erentiation in choroid plexus papillomas. Acta Neuropathologica, 53, 29^33. Summers, B.A., Cummings, J.F. and de Lahunta, A. (1995). Tumors of the central nervous system. In:Veterinary Neuropathology, B.A. Summers, J.F. Cummings and A. de Lahunta, Eds, Mosby, St Louis, MO, pp. 373^375. Veazey, R. S., Angel, K. L., Snider, T. G. 3rd., Lopez, M. K. and Taylor, H. W. (1993). Malignant schwannoma in a goat. Journal of Veterinary Diagnostic Investigation, 5, 454^458. Waldron, J. S. and Tihan, T. (2003). Epidemiology and pathology of intraventricular tumors. Neurosurgery Clinics of North America, 14, 469^482. Wicks, J. R. and Oglesbee, M. J. (1995). Epithelioma of the fourth ventricle in a goat.Veterinary Pathology, 32, 429^433. Wilson, R. B., Holscher, M. A. and West, W. R. (1989). Choroid plexus carcinoma in a dog. Journal of Comparative Pathology, 100, 323^326. Zaki, F. A. and Nafe, L. A. (1980). Choroid plexus tumors in the dog. Journal of theAmericanVeterinary Medical Association, 176, 328^330.
Received, September 2nd, 2005 Accepted, February 20th, 2006