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Choroid plexus carcinoma in a dog
J. Comp.
Path.
1989 \‘ol.
100
SHORT
Choroid
Plexus
R. B. Wilson,*
PAPERS
Carcinoma
M. A. Holschert
in a Dog and W. R. West:
*C. E. Kord Animal Disease Laboratory, P. 0. Box 40627, Melrose Station, .,~ashoille, Tennessee 37204, U.S.A. tnepartment OJ Pathology. Vanderbilt Medical Center, Nashville. Tennessee 37232. lT.S.d. $821 Montuale Road, Ma@lle. Tennessee 37801, I ‘S.A.
Summary Choroid plexus carcinoma was diagnosed in a ii-year-old female mixed breed dog which was euthanized due to progressive ncurologic disease.Diagnosisof
the tumour was based on gross and light microscopic findings following a complete necropsy. The chemical staining patterns in the case are compared with human choroid plexus tumours. The criteria for the distinction betwrcn benign
and malignant
variants
of choroid
plexus
tumours
are discussed.
Introduction Neoplasms of the choroid plexus are rare in both man (Rubinstein, 1972; Carpenter, Michelsen and Hays, 1982: McComb and Burger, 1983; Coffin, With, Braun and Dehner, 1986) and dogs (Cotchin, 1953; Kurtz and Hanlon. 1971; Zaki and Nafe, 1980; Patnaik, Erlandson, Lieberman, Fenner and Prata, 1980; Chenier, Gosselin, Teuscher and Breton, 1983). The limited number of’ reports of choroid plexus tumours indicate that choroid plexus carcinomas are even more uncommon than the benign variant of choroid plexus papilloma (Zaki and Nafe, 1980; Patnaik et al., 1980). Likewise, in man, choroid plexus papilloma is more common than its malignant counterpart (Rubinstein, 1972; McComb and Burger, 1983). We report the clinical, pathological and immunohistochemical findings of a choroid plexus carcinoma in a dog. Case Report A 5-year-old female mixed breed dog was examined because of the recent onset of left-sided head tilt. Physical examination revealed no other abnormalities; the dog was treated with antibiotics and a non-steroidal anti-inflammatory drug. Approximately 1 month later the dog was returned to the veterinarian for evaluation of seizures and a more pronoun.ced head tilt. Clinical laborator) data and survey radiographs were norm&. An anti-convulsant was added to the previously prescribed treatment regimen. No response was noted and the seizures increased in frequency. The dog was destroyed and a complete necropsy was performed. No significant gross lesions were evident. The entire brain was removed from the calvarium, placed in an adequate volume of neutral buffered 10 per cent formalin and submitted to the C. E. Kord Animal Disease Laboratory for histological evaluation. 002 IL9975/x9/030323
+ 04 $03.00/cl
(c: 1989 Academic
Prrss Limited
324
FL B. Wilson
et al.
Sectioning of the brain revealed a 5 mm diameter yellow and red mottled, friable mass located within the fourth ventricle. Expansile growth of the tumour had resulted in focal compression and malacia of the subjacent medulla. Internal hydrocephalus was characterized by dilated lateral ventricles, with lossof the surrounding white matter; in several areas only a narrow 1 to 2 mm rim of white matter remained. Histologically, the tumour was arising within the fourth ventricle and consisted of a marked papillary proliferation of cells with small, round! basophilic nuclei with indistinct nucleoli and moderate amounts of lightly basophilic cytoplasm (Fig. 1). Neoplastic cells covered a delicate to moderate fibrovascular stroma which was infiltrated by numerous lymphocytes, plasma cells and occasional siderophages. Dispersed throughout the stroma were small, round, often laminated foci of mineralization. The subjacent brain was characterized by multiple vacuoles in the white matter accompanied by hypertrophied astrocytes; dilated capillaries were lined by a hypertrophied endothelium. Perivascular spaces near the tumour were sometimes widened by cells with nuclei similar to those of the neoplasm, but with scanty cytoplasm. Accompanying the neoplastic cells were moderate numbers of lymphoid cells. Areas of tumour necrosis with eosinophilic debris were noted. A focal area of tumour was composed of sheets of cells with minimal papillary differentiation, frequently with a vacuolated cytoplasm. Sections of cerebral cortex at the level of the hippocampus revealed a focal cluster of cells located within the leptomeninges which were similar to those seen in the choroid plexus tumour (Fig. 2). Hydrocephalus was evidenced by an attenuated, often mildly vacuolated, internal capsule. Cilia were not seen despite multiple sectioning of
Fig. 1.
Papillary
prolifrration
of nroplastk
wlls accompanied
by compact
cellular
area. HE
x 270.
Choroid
Fig. 2.
Mctastatic
plexus
carcinoma
focus in cerebral
pia-arachnoid
325
space. HE
x 425
the tumour; blepharoplasts (basal bodies) were not demonstrated by phosphotungstic-acid haematoxylin (PTAH) staining. Immunohistochemistry was performed with reagents directed against glial fibrillary acidic protein (GFAP), alpha-cytokeratin, neuron specific enolase (NSE), neurofilament and S-100 proteins. The adjacent normal neuropil served as a positive control. The staining of cells interpreted as positive varied, depending upon the cellular component which was being examined. Cells interpreted as positive for alpha-cytokeratin had a light brown, finely granular cytoplasm. In contrast, cells positive for S-100 protein contained cytoplasmic aggregates of dark brown, coarse granules. Approximately 50 per cent of tumour cells were positive for alpha-cytokeratin, while 35 to 45 per cent of the neoplastic cell population were positive for S-100 protein. Neoplastic cells were negative for GFAP, NSE and neurofilament proteins. Discussion The choroid plexus epithelium has its origin from the differentiation of the primitive medullary epithelium (Rubinstein, 1972). Tumours of the choroid plexus must be differentiated from metastatic carcinomas and ependymomas. A complete necropsy should be performed to exclude the presence of a carcinoma with choroid plexus metastasis. Ependymomas usually have ciliated cells in which blepharoplasts are present (Kurtz and Hanlon, 197 1; Zaki and Nafe, 1980; Carpenter et al., 1982). However, ultrastructural examination of choroid plexus carcinomas in man has revealed the presence of cilia (Rubinstein, 1972; McComb and Burger, 1983; Coffin et al., 1986). The normal
326
R. B. Wilson
et
al.
human choroid plexus is highly ciliated in early fetal life and cilia may persist into adult life (McComb and Burger, 1983). Criteria for the distinction between benign and malignant variants of choroid plexus tumours in man are well defined and include: (1) infiltrative and destructive growth, (2) abundant cellularity, (3) pleomorphic nuclei and cell type, (4) mitotic figures, (5) proliferation of vascular structures, i6) necrosis and (7) loss of boundaries between stroma and parenchyma (McComb and Burger, 1983; Broad and Allen, 1984). Recently, immunohistochemical studies have suggested staining patterns which may be helpful in determining malignant potential (Coffin et al., 1986). Statistical analyses indicated that choroid plexus carcinomas stained positive for carcinoembryonit antigen and negative for S-100 protein; any other staining pattern was indicative of a choroid plexus papilloma. Other work has confirmed that S- 100 protein immunoreactivity is not confined to benign choroid plexus tumours, and these tumours express a complex antigenic profile (Doglioni, Dell Orto, Coggi, Iuzzolino, Bontempini and Viale, 1987). The malignant designation in this dog was based on leptomeningeal metastasis and locally infiltrative growth along perivascular spaces. Many of the neoplastic cells were positive for S-100 protein. These results suggest that, like its human counterpart, choroid plexus tumour immunoreactivity may he complex and preclude accurate classification based solely on staining patterns. References
Broad, R. W. and Allen, P. B. R. (19843. Third ventricle choroid plexus carcinoma. Canadian Journal of .Neurological Sciences, 11, 46 1-465. Carpenter, D. B., Michelsen, W. J. and Hays, A. P. ( 1982). Carcinoma of the choroid plexus. Journal of Neurosurgery, 56, 722-727. Chenier, M., Gosselin, J., Teuscher, E. and Breton, L. ( 1983). Paradoxic vestibular syndrome associated with choroid plexus papilloma in a dog. Journal of’ the American Veterinary Medical .4ssociation, 182, 66-67. Coffin, C. M., With, M. R., Braun, J. T. and Dehner, L. P. (1986). Choroid plexus neoplasms. Clinicopathologic and immunohistochemical studies. The .-lmerican Journal of Surgical Pathology, 10, 394-404. Cotchin, E. (1953). Primary carcinoma of the choroid plexus of the fourth ventricle in a dog. Journal of Pathology and Bacteriolo,y, 64, 257-258. Doglioni, C., Dell Orto, P., Coggi, G., Iuzzolino, P., Bontempini, I,. and Viale, (S. ( 1987 j. Choroid plexus tumors: an immunocytochemical study with particular reference to the coexpression of intermediate filament proteins. .4merican Journal o/‘ Pathologv, 127, 5 19-529. Kurtz, H. J. and Hanlon, G. F. ( 1971). Choroid plexus papilloma in a dog. IFetrrinay Pathology, 8, 91-95. McComb, R. D. and Burger, P. C. ( 1983). Choroid plexus carcinoma: report of a case with immunohistochemical and ultrastructural observations. Cancer, 51, 470-475. Patnaik, A. K., Erlandson, R. A., Lieberman, P. H., Fenner, W. R. and Prata, R. G. (1980). Choroid plexus carcinoma with meningeal carcinomatosis in a dog. Veterinary Pathology, 17, 381-385. Rubinstein, J. J. (1972). Tumors of the central nervous system, fast. 6, Atlas of Tumor Pathology, Washington, D.C. pp. 257-267. Zaki, F. A. and Nafe, L. A. (1980). Choroid plexus tumors in the dog. 3ournal of the American Veterinary Medical Association, 176, 328-330. [Receivedfor publication.
&September 1.st, 1987 ]
Path.
1989 \‘ol.
100
SHORT
Choroid
Plexus
R. B. Wilson,*
PAPERS
Carcinoma
M. A. Holschert
in a Dog and W. R. West:
*C. E. Kord Animal Disease Laboratory, P. 0. Box 40627, Melrose Station, .,~ashoille, Tennessee 37204, U.S.A. tnepartment OJ Pathology. Vanderbilt Medical Center, Nashville. Tennessee 37232. lT.S.d. $821 Montuale Road, Ma@lle. Tennessee 37801, I ‘S.A.
Summary Choroid plexus carcinoma was diagnosed in a ii-year-old female mixed breed dog which was euthanized due to progressive ncurologic disease.Diagnosisof
the tumour was based on gross and light microscopic findings following a complete necropsy. The chemical staining patterns in the case are compared with human choroid plexus tumours. The criteria for the distinction betwrcn benign
and malignant
variants
of choroid
plexus
tumours
are discussed.
Introduction Neoplasms of the choroid plexus are rare in both man (Rubinstein, 1972; Carpenter, Michelsen and Hays, 1982: McComb and Burger, 1983; Coffin, With, Braun and Dehner, 1986) and dogs (Cotchin, 1953; Kurtz and Hanlon. 1971; Zaki and Nafe, 1980; Patnaik, Erlandson, Lieberman, Fenner and Prata, 1980; Chenier, Gosselin, Teuscher and Breton, 1983). The limited number of’ reports of choroid plexus tumours indicate that choroid plexus carcinomas are even more uncommon than the benign variant of choroid plexus papilloma (Zaki and Nafe, 1980; Patnaik et al., 1980). Likewise, in man, choroid plexus papilloma is more common than its malignant counterpart (Rubinstein, 1972; McComb and Burger, 1983). We report the clinical, pathological and immunohistochemical findings of a choroid plexus carcinoma in a dog. Case Report A 5-year-old female mixed breed dog was examined because of the recent onset of left-sided head tilt. Physical examination revealed no other abnormalities; the dog was treated with antibiotics and a non-steroidal anti-inflammatory drug. Approximately 1 month later the dog was returned to the veterinarian for evaluation of seizures and a more pronoun.ced head tilt. Clinical laborator) data and survey radiographs were norm&. An anti-convulsant was added to the previously prescribed treatment regimen. No response was noted and the seizures increased in frequency. The dog was destroyed and a complete necropsy was performed. No significant gross lesions were evident. The entire brain was removed from the calvarium, placed in an adequate volume of neutral buffered 10 per cent formalin and submitted to the C. E. Kord Animal Disease Laboratory for histological evaluation. 002 IL9975/x9/030323
+ 04 $03.00/cl
(c: 1989 Academic
Prrss Limited
324
FL B. Wilson
et al.
Sectioning of the brain revealed a 5 mm diameter yellow and red mottled, friable mass located within the fourth ventricle. Expansile growth of the tumour had resulted in focal compression and malacia of the subjacent medulla. Internal hydrocephalus was characterized by dilated lateral ventricles, with lossof the surrounding white matter; in several areas only a narrow 1 to 2 mm rim of white matter remained. Histologically, the tumour was arising within the fourth ventricle and consisted of a marked papillary proliferation of cells with small, round! basophilic nuclei with indistinct nucleoli and moderate amounts of lightly basophilic cytoplasm (Fig. 1). Neoplastic cells covered a delicate to moderate fibrovascular stroma which was infiltrated by numerous lymphocytes, plasma cells and occasional siderophages. Dispersed throughout the stroma were small, round, often laminated foci of mineralization. The subjacent brain was characterized by multiple vacuoles in the white matter accompanied by hypertrophied astrocytes; dilated capillaries were lined by a hypertrophied endothelium. Perivascular spaces near the tumour were sometimes widened by cells with nuclei similar to those of the neoplasm, but with scanty cytoplasm. Accompanying the neoplastic cells were moderate numbers of lymphoid cells. Areas of tumour necrosis with eosinophilic debris were noted. A focal area of tumour was composed of sheets of cells with minimal papillary differentiation, frequently with a vacuolated cytoplasm. Sections of cerebral cortex at the level of the hippocampus revealed a focal cluster of cells located within the leptomeninges which were similar to those seen in the choroid plexus tumour (Fig. 2). Hydrocephalus was evidenced by an attenuated, often mildly vacuolated, internal capsule. Cilia were not seen despite multiple sectioning of
Fig. 1.
Papillary
prolifrration
of nroplastk
wlls accompanied
by compact
cellular
area. HE
x 270.
Choroid
Fig. 2.
Mctastatic
plexus
carcinoma
focus in cerebral
pia-arachnoid
325
space. HE
x 425
the tumour; blepharoplasts (basal bodies) were not demonstrated by phosphotungstic-acid haematoxylin (PTAH) staining. Immunohistochemistry was performed with reagents directed against glial fibrillary acidic protein (GFAP), alpha-cytokeratin, neuron specific enolase (NSE), neurofilament and S-100 proteins. The adjacent normal neuropil served as a positive control. The staining of cells interpreted as positive varied, depending upon the cellular component which was being examined. Cells interpreted as positive for alpha-cytokeratin had a light brown, finely granular cytoplasm. In contrast, cells positive for S-100 protein contained cytoplasmic aggregates of dark brown, coarse granules. Approximately 50 per cent of tumour cells were positive for alpha-cytokeratin, while 35 to 45 per cent of the neoplastic cell population were positive for S-100 protein. Neoplastic cells were negative for GFAP, NSE and neurofilament proteins. Discussion The choroid plexus epithelium has its origin from the differentiation of the primitive medullary epithelium (Rubinstein, 1972). Tumours of the choroid plexus must be differentiated from metastatic carcinomas and ependymomas. A complete necropsy should be performed to exclude the presence of a carcinoma with choroid plexus metastasis. Ependymomas usually have ciliated cells in which blepharoplasts are present (Kurtz and Hanlon, 197 1; Zaki and Nafe, 1980; Carpenter et al., 1982). However, ultrastructural examination of choroid plexus carcinomas in man has revealed the presence of cilia (Rubinstein, 1972; McComb and Burger, 1983; Coffin et al., 1986). The normal
326
R. B. Wilson
et
al.
human choroid plexus is highly ciliated in early fetal life and cilia may persist into adult life (McComb and Burger, 1983). Criteria for the distinction between benign and malignant variants of choroid plexus tumours in man are well defined and include: (1) infiltrative and destructive growth, (2) abundant cellularity, (3) pleomorphic nuclei and cell type, (4) mitotic figures, (5) proliferation of vascular structures, i6) necrosis and (7) loss of boundaries between stroma and parenchyma (McComb and Burger, 1983; Broad and Allen, 1984). Recently, immunohistochemical studies have suggested staining patterns which may be helpful in determining malignant potential (Coffin et al., 1986). Statistical analyses indicated that choroid plexus carcinomas stained positive for carcinoembryonit antigen and negative for S-100 protein; any other staining pattern was indicative of a choroid plexus papilloma. Other work has confirmed that S- 100 protein immunoreactivity is not confined to benign choroid plexus tumours, and these tumours express a complex antigenic profile (Doglioni, Dell Orto, Coggi, Iuzzolino, Bontempini and Viale, 1987). The malignant designation in this dog was based on leptomeningeal metastasis and locally infiltrative growth along perivascular spaces. Many of the neoplastic cells were positive for S-100 protein. These results suggest that, like its human counterpart, choroid plexus tumour immunoreactivity may he complex and preclude accurate classification based solely on staining patterns. References
Broad, R. W. and Allen, P. B. R. (19843. Third ventricle choroid plexus carcinoma. Canadian Journal of .Neurological Sciences, 11, 46 1-465. Carpenter, D. B., Michelsen, W. J. and Hays, A. P. ( 1982). Carcinoma of the choroid plexus. Journal of Neurosurgery, 56, 722-727. Chenier, M., Gosselin, J., Teuscher, E. and Breton, L. ( 1983). Paradoxic vestibular syndrome associated with choroid plexus papilloma in a dog. Journal of’ the American Veterinary Medical .4ssociation, 182, 66-67. Coffin, C. M., With, M. R., Braun, J. T. and Dehner, L. P. (1986). Choroid plexus neoplasms. Clinicopathologic and immunohistochemical studies. The .-lmerican Journal of Surgical Pathology, 10, 394-404. Cotchin, E. (1953). Primary carcinoma of the choroid plexus of the fourth ventricle in a dog. Journal of Pathology and Bacteriolo,y, 64, 257-258. Doglioni, C., Dell Orto, P., Coggi, G., Iuzzolino, P., Bontempini, I,. and Viale, (S. ( 1987 j. Choroid plexus tumors: an immunocytochemical study with particular reference to the coexpression of intermediate filament proteins. .4merican Journal o/‘ Pathologv, 127, 5 19-529. Kurtz, H. J. and Hanlon, G. F. ( 1971). Choroid plexus papilloma in a dog. IFetrrinay Pathology, 8, 91-95. McComb, R. D. and Burger, P. C. ( 1983). Choroid plexus carcinoma: report of a case with immunohistochemical and ultrastructural observations. Cancer, 51, 470-475. Patnaik, A. K., Erlandson, R. A., Lieberman, P. H., Fenner, W. R. and Prata, R. G. (1980). Choroid plexus carcinoma with meningeal carcinomatosis in a dog. Veterinary Pathology, 17, 381-385. Rubinstein, J. J. (1972). Tumors of the central nervous system, fast. 6, Atlas of Tumor Pathology, Washington, D.C. pp. 257-267. Zaki, F. A. and Nafe, L. A. (1980). Choroid plexus tumors in the dog. 3ournal of the American Veterinary Medical Association, 176, 328-330. [Receivedfor publication.
&September 1.st, 1987 ]