V e t . Pathol. 15: 525-530 (1978)
Intracranial Teratoma in a Domestic Rabbit L. BISHOP
Division of Comparative Medicine and Department of Pathology, T h e Johns Hopkins Medical Institutions, Baltimore, Md.
Abstract. A solid and cystic suprasellar teratoma was found in a rabbit killed because of incoordination. The tumor consisted of neural cells, cysts lined by various types of epithelium, respiratory mucosa, gastric mucosa, mucous and mucoserous glands, collagenous connective tissue, cartilage and fat.
A teratoma is a tumor composed of multiple kinds of tissues foreign to the part in which it arises [14]. While usually found in the ovaries or testes, they occasionally arise in other paramidline or midline sites, including the central nervous system. Although I found no report of intrathecal teratomas in animals, intracranial teratomas have been described in several animal species; some of the earlier cases may not represent true teratomas. Three reports [3, 7, 121, unavailable for review, have been cited by others [l,5, 61 as descriptions of teratomas in the cerebellum of an ox, the cerebellopontine angle of a guinea pig, and the tuber cinereum of a rabbit. In addition there have been reports of teratomas in the optic chiasm [5] and the infundibuluni [8] in two rabbits; in the cerebellum of a chicken [4]; attached to the velum interpositum between the cerebral hemispheres in a horse [9]; and in the right side of the cerebellum in another horse [13]. The latter tumor was diagnosed as a choriocarcinomatous teratoma, possibly metastatic from an undiscovered testicular tumor. The rarity of these tumors precludes conclusions regarding incidence and species, sex, age and site predilection in animals. The literature is more extensive regarding central nervous system teratomas in man [2, 10, 11, 141. Both intracranial and intraspinal teratomas are usually seen in the first two decades of life with a peak incidence in the second decade; some, however, do not become manifest until adult life. While they constitute only 0.5% of all intracranial tumors, they account for 2 % of all central nervous system tumors in children under 15 years old. Most intracranial teratomas arise in the pineal region but other sites of predilection include the third ventricle, the pituitary fossa and the posterior fossa. Those arising in the pineal gland are found almost exclusively in males; in other sites no sex predilection is noted. Although usually 525
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526
Bishop
Fig. 1: Ependymal cells within neuropil of teratoma forming rosettes (single arrow), one with lumen and cilia (double arrow). HE.
solitary, multiple tumors have been reported and they are occasionally bilateral. Spinal teratomas are rare in both sexes and have been associated with spina bifida. They may be extradural, intradural or intramedullary and can occur at any level of the cord, although they are found most commonly in the sacrococcygeal region. Case History A juvenile male New Zealand White rabbit, one of 26 obtained from a local supplier, was killed because it had head and eye incoordination. The rabbit was necropsied 4 hours after it was killed. The rabbit weighed 2.6 kilograms and was in excellent condition. Blocks of tissue were fixed in neutral buffered formalin, sectioned at 6 micrometers and stained with modified Mayer’s hematoxylin and eosin ( H E ) . Selected sections of brain were stained with Mallory’s phosphotungstic acid hematoxylin (PTAH), Holzer’s PTAH, periodic acidSchiff (PAS), Masson’s trichrome and alcian blue.
Results There were chronic cholangitis and pericholangitis caused by parasitism by Eimeria stiedae, and mild chronic enteritis. The brain weighed 10.5 grams (0.4% of the body weight). A 1-centimeter-wide tumor that extended 6 millimeters below its base of attachment was found when the fixed brain was sectioned coronally. It was a dorsoventrally flat, ovoid, solid and cystic mass attached by a broad stalk along the midline of the preoptic area and the tuber cinereum of the hypothalamus. The
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
Intracranial Teratomas
527
Fig. 2: Coronal section of teratoma. Most of tumor composed of mature neuropil. Cyst-bounded area (arrow). HE.
anterior-posterior length was not determined. Anteriorly the tumor incorporated the optic nerves in its dorsolateral aspects; posteriorly it involved the infundibulum but not the mammillary bodies or the glandular lobe of the pituitary. Involvement of the pituitary stalk, severed when the brain was removed from the skull, was not seen grossly but was evident histologically. Most of the mass consisted of mature neuropil containing all neuroglial elements as well as myelinated fibers. There was no clear demarcation between the neuropil of the mass and that of the brain; however, slit-like and tubular ependymal-lined spaces, scattered throughout the tumor neuropil, were most frequent within the stalk of the tumor (fig. 1). In several areas ependymal cells formed clusters of single cells or fashioned circular palisades without lumina. There were cysts up to 3.5 millimeters in diameter. Some were empty and lined by a single layer of ciliated cuboidal epithelium while others contained mucus and PAS-positive globules and were lined by ciliated simple or pseudostratified columnar epithelium. Rarely, cysts were lined by stratified squamous epithelium, either non-keratinized or keratinized, and contained sloughed cells or keratinized debris. Several cysts were clustered on one side of the mass (fig. 2). They were lined
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
528
Bishop
Fig. 3: Higher magnification of part of figure 2. Respiratory mucosa with cilia, goblet cells and underlying seromucous glands. HE.
primarily with ciliated cuboidal epithelium; however, where the cysts were contiguous the lining graded into typical respiratory mucosa, complete with ciliated pseudostratified columnar epithelium and goblet cells (fig. 3 ) . Beneath this respiratory mucosa were mucous and seromucous glands embedded in collagenous connective tissue; some of these communicated with the lumen of the nearest cyst. A single minute cluster of cells resembling gastric mucosa was found adjacent to the largest cyst. Another focus contained serous glands, two small nodules of cartilage and fat cells, all resting in collagenous connective tissue (fig. 4). A few heterophils, plasma cells and lymphocytes were scattered throughout this entire area. Alcian blue stain demonstrated acid mucopolysaccharides as amorphous material within cyst lumina and goblet cells and as cytoplasmic granules in serous glands. There were PAS-positive globules in cyst lumina and within the cytoplasm of columnar lining cells and serous glands. In sections stained with Masson’s trichrome the matrix of the cartilage stained pale blue, and orange-blue granules were seen in the cytoplasm of parietal-like cells. Basilar bodies were visible in ependymal cells stained with Holzer’s PTAH .
Discussion Classification of a mass as a teratoma depends on the presence of tissues derived from at least two germ layers and evidence of progressive growth. In this case, the
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
Intracranial Teratomas
529
Fig. 4: Serous glands, cartilage (arrow) and fat cells embedded in collagenous connective tissue. HE.
presence of neural tissue and stratified squamous epithelium of ectodermal origin and cartilage, fat and collagenous connective tissue of mesodermal origin provide evidence of two germ layers. The small focus of cells resembling gastric mucosa suggests entoderm is represented, while the respiratory mucosa and associated glands may have originated from either ectoderm or entoderm. Although there is no histologic evidence of active cell proliferation, the size of the mass and the presence of clinical signs are consistent with slow growth. Based on these findings and the maturity of the tissues, this mass is considered a benign teratoma. In man, most intracranial teratomas arise in males in the pineal gland and are frequently associated with signs of hypothalamic dysfunction [2, 10, 11, 141. There have been no reports of pineal involvement in animals. Although the tumor in this case and the three previously reported intracranial teratomas in rabbits arose in the region of the hypothalamus, specific signs of hypothalamic dysfunction have not been noted.
Acknowledgements Supported in part by Laboratory Animal Training Grant number RR05007; Animal Resource Support for Biomedical Research Grant number RR00130; and the National Cancer Institute’s Animal Pathology Support Grant number N01-CP-65768, National Institutes of Health, United States Public Health Service, Bethesda, Md. I thank Ms. Diane Stewart, HT (ASCP), and Ms. Dolores Taylor, HT (ASCP), for histologic sections and Mr. Raymond E. Lund, RBP, FBPA, for photomicrographs.
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
530
Bishop
References 1 COHRS,P.; JAFFE,R.; MEESEN,H.: Pathologie der Laboratoriumstiere, pp. 488-489, 497; Springer-Verlag, Berlin, 1958 2 GAILLARD, J.A.: Differentiation and organization in teratomas in Neoplasia and Cell Differentiation, ed. G.V. Sherbet; pp. 319-349, Karger, Basel, 1974 3 JOEST,E.: Uber ein Kleinhirnteratom beim Rind. Berl Tierarztl Hochschule Dresden 6:150, 1911 4 JONES,D.: Avian cerebellar teratoma. Avian Dis 8580-584, 1964 5 KERSTING, G.; HAMMERSEN, F.: Ein Teratom der Chiasmagegend beim Kaninchen. Zentralbl Veterinaermed 5601-608, 1958 6 LUGINBUHL, H.; FANKHAUSER, R.; MCGRATH, J. T.: Spontaneous neoplasms of the nervous system in animals. Prog Neurol Surg 2:85-164, 1968 7 LUTZ,B .: Ein Teratom am Kleinhirnbruckenwinkel beim Meerschweinchen. Berl Wien Neur Inst 18:111, 1910 8 MARGULIES, A,: Ueber ein Teratom der Hypophyse bei einem Kaninchen. Neurol Centralbl 20:1026-1031, 1901 9 METTAM, A.E.: Embryoma of the brain of the horse. J Comp Pathol28:52-53, 1915 10 RUBINSTEIN, L.J.: Tumors of the Central Nervous System, Atlas of Tumor Pathology, 2nd Ser., Fasc. 6, pp. 275-276, 285-286; Armed Forces Institute of Pathology, Washington, D.C., 1972 11 RUSSEL,D.S.; RUBINSTEIN, L.J.: Pathology of Tumors of the Nervous System, pp. 1316, 3rd ed.; Williams and Wilkins, Baltimore, 1971 12 SHIMA, R.: Ein Teratom im Kaninchenhirn. Berl Wien Neur Inst 14:373, 1908 13 TSIROYIANNIS, E . ; SPAIS,A , ; LAZARIDIS, T.: A propos d’un teratome chorioepitheliomateux du cervelet chez le cheval. Ann Med Vet 102:121-126, 1958 14 WILLIS,R.A.: The Borderland of Embryology and Pathology, pp. 430-454; Butterworth, London, 1958
Request reprints from Dr. Lynn Bishop, Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21205 (USA).
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
Intracranial Teratoma in a Domestic Rabbit L. BISHOP
Division of Comparative Medicine and Department of Pathology, T h e Johns Hopkins Medical Institutions, Baltimore, Md.
Abstract. A solid and cystic suprasellar teratoma was found in a rabbit killed because of incoordination. The tumor consisted of neural cells, cysts lined by various types of epithelium, respiratory mucosa, gastric mucosa, mucous and mucoserous glands, collagenous connective tissue, cartilage and fat.
A teratoma is a tumor composed of multiple kinds of tissues foreign to the part in which it arises [14]. While usually found in the ovaries or testes, they occasionally arise in other paramidline or midline sites, including the central nervous system. Although I found no report of intrathecal teratomas in animals, intracranial teratomas have been described in several animal species; some of the earlier cases may not represent true teratomas. Three reports [3, 7, 121, unavailable for review, have been cited by others [l,5, 61 as descriptions of teratomas in the cerebellum of an ox, the cerebellopontine angle of a guinea pig, and the tuber cinereum of a rabbit. In addition there have been reports of teratomas in the optic chiasm [5] and the infundibuluni [8] in two rabbits; in the cerebellum of a chicken [4]; attached to the velum interpositum between the cerebral hemispheres in a horse [9]; and in the right side of the cerebellum in another horse [13]. The latter tumor was diagnosed as a choriocarcinomatous teratoma, possibly metastatic from an undiscovered testicular tumor. The rarity of these tumors precludes conclusions regarding incidence and species, sex, age and site predilection in animals. The literature is more extensive regarding central nervous system teratomas in man [2, 10, 11, 141. Both intracranial and intraspinal teratomas are usually seen in the first two decades of life with a peak incidence in the second decade; some, however, do not become manifest until adult life. While they constitute only 0.5% of all intracranial tumors, they account for 2 % of all central nervous system tumors in children under 15 years old. Most intracranial teratomas arise in the pineal region but other sites of predilection include the third ventricle, the pituitary fossa and the posterior fossa. Those arising in the pineal gland are found almost exclusively in males; in other sites no sex predilection is noted. Although usually 525
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
526
Bishop
Fig. 1: Ependymal cells within neuropil of teratoma forming rosettes (single arrow), one with lumen and cilia (double arrow). HE.
solitary, multiple tumors have been reported and they are occasionally bilateral. Spinal teratomas are rare in both sexes and have been associated with spina bifida. They may be extradural, intradural or intramedullary and can occur at any level of the cord, although they are found most commonly in the sacrococcygeal region. Case History A juvenile male New Zealand White rabbit, one of 26 obtained from a local supplier, was killed because it had head and eye incoordination. The rabbit was necropsied 4 hours after it was killed. The rabbit weighed 2.6 kilograms and was in excellent condition. Blocks of tissue were fixed in neutral buffered formalin, sectioned at 6 micrometers and stained with modified Mayer’s hematoxylin and eosin ( H E ) . Selected sections of brain were stained with Mallory’s phosphotungstic acid hematoxylin (PTAH), Holzer’s PTAH, periodic acidSchiff (PAS), Masson’s trichrome and alcian blue.
Results There were chronic cholangitis and pericholangitis caused by parasitism by Eimeria stiedae, and mild chronic enteritis. The brain weighed 10.5 grams (0.4% of the body weight). A 1-centimeter-wide tumor that extended 6 millimeters below its base of attachment was found when the fixed brain was sectioned coronally. It was a dorsoventrally flat, ovoid, solid and cystic mass attached by a broad stalk along the midline of the preoptic area and the tuber cinereum of the hypothalamus. The
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
Intracranial Teratomas
527
Fig. 2: Coronal section of teratoma. Most of tumor composed of mature neuropil. Cyst-bounded area (arrow). HE.
anterior-posterior length was not determined. Anteriorly the tumor incorporated the optic nerves in its dorsolateral aspects; posteriorly it involved the infundibulum but not the mammillary bodies or the glandular lobe of the pituitary. Involvement of the pituitary stalk, severed when the brain was removed from the skull, was not seen grossly but was evident histologically. Most of the mass consisted of mature neuropil containing all neuroglial elements as well as myelinated fibers. There was no clear demarcation between the neuropil of the mass and that of the brain; however, slit-like and tubular ependymal-lined spaces, scattered throughout the tumor neuropil, were most frequent within the stalk of the tumor (fig. 1). In several areas ependymal cells formed clusters of single cells or fashioned circular palisades without lumina. There were cysts up to 3.5 millimeters in diameter. Some were empty and lined by a single layer of ciliated cuboidal epithelium while others contained mucus and PAS-positive globules and were lined by ciliated simple or pseudostratified columnar epithelium. Rarely, cysts were lined by stratified squamous epithelium, either non-keratinized or keratinized, and contained sloughed cells or keratinized debris. Several cysts were clustered on one side of the mass (fig. 2). They were lined
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
528
Bishop
Fig. 3: Higher magnification of part of figure 2. Respiratory mucosa with cilia, goblet cells and underlying seromucous glands. HE.
primarily with ciliated cuboidal epithelium; however, where the cysts were contiguous the lining graded into typical respiratory mucosa, complete with ciliated pseudostratified columnar epithelium and goblet cells (fig. 3 ) . Beneath this respiratory mucosa were mucous and seromucous glands embedded in collagenous connective tissue; some of these communicated with the lumen of the nearest cyst. A single minute cluster of cells resembling gastric mucosa was found adjacent to the largest cyst. Another focus contained serous glands, two small nodules of cartilage and fat cells, all resting in collagenous connective tissue (fig. 4). A few heterophils, plasma cells and lymphocytes were scattered throughout this entire area. Alcian blue stain demonstrated acid mucopolysaccharides as amorphous material within cyst lumina and goblet cells and as cytoplasmic granules in serous glands. There were PAS-positive globules in cyst lumina and within the cytoplasm of columnar lining cells and serous glands. In sections stained with Masson’s trichrome the matrix of the cartilage stained pale blue, and orange-blue granules were seen in the cytoplasm of parietal-like cells. Basilar bodies were visible in ependymal cells stained with Holzer’s PTAH .
Discussion Classification of a mass as a teratoma depends on the presence of tissues derived from at least two germ layers and evidence of progressive growth. In this case, the
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
Intracranial Teratomas
529
Fig. 4: Serous glands, cartilage (arrow) and fat cells embedded in collagenous connective tissue. HE.
presence of neural tissue and stratified squamous epithelium of ectodermal origin and cartilage, fat and collagenous connective tissue of mesodermal origin provide evidence of two germ layers. The small focus of cells resembling gastric mucosa suggests entoderm is represented, while the respiratory mucosa and associated glands may have originated from either ectoderm or entoderm. Although there is no histologic evidence of active cell proliferation, the size of the mass and the presence of clinical signs are consistent with slow growth. Based on these findings and the maturity of the tissues, this mass is considered a benign teratoma. In man, most intracranial teratomas arise in males in the pineal gland and are frequently associated with signs of hypothalamic dysfunction [2, 10, 11, 141. There have been no reports of pineal involvement in animals. Although the tumor in this case and the three previously reported intracranial teratomas in rabbits arose in the region of the hypothalamus, specific signs of hypothalamic dysfunction have not been noted.
Acknowledgements Supported in part by Laboratory Animal Training Grant number RR05007; Animal Resource Support for Biomedical Research Grant number RR00130; and the National Cancer Institute’s Animal Pathology Support Grant number N01-CP-65768, National Institutes of Health, United States Public Health Service, Bethesda, Md. I thank Ms. Diane Stewart, HT (ASCP), and Ms. Dolores Taylor, HT (ASCP), for histologic sections and Mr. Raymond E. Lund, RBP, FBPA, for photomicrographs.
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
530
Bishop
References 1 COHRS,P.; JAFFE,R.; MEESEN,H.: Pathologie der Laboratoriumstiere, pp. 488-489, 497; Springer-Verlag, Berlin, 1958 2 GAILLARD, J.A.: Differentiation and organization in teratomas in Neoplasia and Cell Differentiation, ed. G.V. Sherbet; pp. 319-349, Karger, Basel, 1974 3 JOEST,E.: Uber ein Kleinhirnteratom beim Rind. Berl Tierarztl Hochschule Dresden 6:150, 1911 4 JONES,D.: Avian cerebellar teratoma. Avian Dis 8580-584, 1964 5 KERSTING, G.; HAMMERSEN, F.: Ein Teratom der Chiasmagegend beim Kaninchen. Zentralbl Veterinaermed 5601-608, 1958 6 LUGINBUHL, H.; FANKHAUSER, R.; MCGRATH, J. T.: Spontaneous neoplasms of the nervous system in animals. Prog Neurol Surg 2:85-164, 1968 7 LUTZ,B .: Ein Teratom am Kleinhirnbruckenwinkel beim Meerschweinchen. Berl Wien Neur Inst 18:111, 1910 8 MARGULIES, A,: Ueber ein Teratom der Hypophyse bei einem Kaninchen. Neurol Centralbl 20:1026-1031, 1901 9 METTAM, A.E.: Embryoma of the brain of the horse. J Comp Pathol28:52-53, 1915 10 RUBINSTEIN, L.J.: Tumors of the Central Nervous System, Atlas of Tumor Pathology, 2nd Ser., Fasc. 6, pp. 275-276, 285-286; Armed Forces Institute of Pathology, Washington, D.C., 1972 11 RUSSEL,D.S.; RUBINSTEIN, L.J.: Pathology of Tumors of the Nervous System, pp. 1316, 3rd ed.; Williams and Wilkins, Baltimore, 1971 12 SHIMA, R.: Ein Teratom im Kaninchenhirn. Berl Wien Neur Inst 14:373, 1908 13 TSIROYIANNIS, E . ; SPAIS,A , ; LAZARIDIS, T.: A propos d’un teratome chorioepitheliomateux du cervelet chez le cheval. Ann Med Vet 102:121-126, 1958 14 WILLIS,R.A.: The Borderland of Embryology and Pathology, pp. 430-454; Butterworth, London, 1958
Request reprints from Dr. Lynn Bishop, Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21205 (USA).
Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on April 17, 2015
