- Email: [email protected]
Intestinal schwannoma in a rhesus monkey
J. Comp. Path, 1990 Vol. 103
Intestinal Schwannoma
in a R h e s u s M o n k e y
T. A. Barbolt and Mary Alice M. Egy Toxicology Department, Sterling Research Group, Rensselaer, NY 12144, U.S.A. Summary An intestinal schwannoma (neurilemmoma) was found in an aged female rhesus monkey culled from a research colony. The neoplasm was characterized principally by palisades of spindle-shaped cells (Antoni type A) surrounded by thick argyrophilic fibres, while plump cells with areas of vacuolation (Antoni type B) were observed to a lesser extent. Thick hyalinized perivascular cuffs were prominent and multifocal thromboses were present in cavernous vascular channels. Electron microscopic examination of the intercellular matrix between Antoni type A cells revealed long-spacing (100 to 120nm) collagen fibrils. Although the mass had expanded beyond the confines of the muscularis externa, the cytological features of the neoplasm appeared benign. Introduction Schwannomas of the small intestine have rarely been reported for man (Cedermark, 1949; Iliev, 1977;Juvara, Priscu, Velican and Halalau, 1967) or the dog (Patnaik, Hurvitz and Johnson, 1977); and no reference has been located regarding its occurrence in monkeys. The macroscopic, histomorphological and ultrastructural characteristics of a peripheral nerve neoplasm in the intestinal wall of a rhesus monkey is the subject of this case report.
Case Report A wild-caught female rhesus monkey (Macaca mulatta), maintained in captivity for more than 20 years, was culled from the research colony because of age and poor general condition, and was killed humanely by intravenous injection of sodium pentobarbital. At necropsy, a mottled white and dark mass (5"0 x 3"5 x 2"5 cm) protruded from the jejunum. There were no other abnormal macroscopic observations.
Materials and Methods Representative samples of the mass were fixed in 10 per cent neutral buffered formalin, embedded in paraffin wax, sectioned 4 gm thick, and stained with haematoxy.lin and eosin (HE), Masson's trichrome and Gomori's reticulum stains for histomorphological evaluation. Samples were taken from formalin fixative for retrospective ultrastructural evaluation. Blocks (1 mm 3) were selected from different areas of the mass, rinsed with phosphate buffer, post-fixed in 1 per cent phosphate-buffered osmium tetroxide, dehydrated in ascending concentrations of ethanol, infiltrated with propylene oxide 0021-9975/90/080471 + 05 $03.00/0
© 1990 Academic Press Limited
472
T. A. Barbolt and Mary Alice M. Egy
and embedded in Araldite 502-LX 112. Ultrathin sections (70 nm) were stained with uranyl acetate and lead citrate and examined with a Hitachi H7000 transmission electron microscope operated at 75 kV. Results
Histomorphological evaluation indicated that the neoplasm originated in the submucosa, presumably from the submucosal nerve plexus (Meissner's plexus), although the mass had expanded beyond the confines of the muscularis externa (Fig. 1). The mucosa overlying the mass was elevated, but histomorphologically normal, and the muscularis mucosa was intact. The mass was surrounded by an attenuated muscularis externa at the site of origin and a thin, incomplete collagenous capsule. Spindle-shaped cells (Antoni type A) arranged in palisades (Fig. 2) with an organoid pattern in some areas constituted most of the neoplasm, whereas plump cells with areas ofvacuolation (Antoni T y p e B) were observed to a lesser extent (Fig. 3). Mitotic figures were rare and areas of necrosis were not a feature of this neoplasm. A thick hyalinized perivascular cuff was observed around some blood vessels (Fig. 4), and multifocal thromboses were present in cavernous vascular channels observed throughout the mass. Variable amounts of collagen were demonstrated by the trichrome stain, and thick argyrophilic fibres surrounding individual cells and groups of cells were revealed by the reticulum stain (Fig. 5). Uhrastructurally, Antoni type A tissue was characterized by spindle-shaped cells aligned in parallel with scant cytoplasm, elongated nuclei with smooth borders, prominent nucleoli and marginated chromatin. These cells were joined by desmosomes and were frequently separated along part of their length by a b u n d a n t intercellular amorphous basement membrane-like material admixed with collagen fibrils (Fig. 6). Some of these collagen fibrils had a period length of 100 to 120 n m (Fig. 7). The period length of typical collagen fibrils observed in most areas was approximately 60 nm. Hyalinized perivascular cuffs were characterized by reduplicated layers o f basal lamina and loosely aggregated collagen fibres. In addition, bundles of myofilaments similar to those seen in smooth muscle cells were present in the basal aspect of endothelial cells. Antoni type B cells were loosely packed with a normal array of organelles including polymorphic nuclei with prominent nucleoli and margination of c h r o m a t i n (Fig. 8). M e m b r a n e - b o u n d vacuoles (0"1 to 22 gm diameter) were observed in m a n y of these cells and eosinophils were frequently observed. Discussion
T h e intestinal neoplasm from this aged rhesus monkey was interpreted as a s c h w a n n o m a (neurilemmoma), based principally on the presence of palisades of Antoni type A cells, areas of Antoni type B cells, and hyalinized perivascular cuffs (Morson, 1976; Ashley, 1978; Cordy, 1978; Erlandson and Woodruff, 1982; Laber-Laird, Jokinen and Jerome, 1988). Further evidence was the presence of thick argyrophilic fibres between Antoni type A cells and multifocal thromboses in cavernous vascular channels, which is not uncommon in these neoplasms.
Intestinal Schwannoma
Fig, 1. Submucosal mass expanding beyond the confines of the muscularis externa. HE x 6. Fig, 2.
Palisades of Antoni Type A cells. H E x 120.
Fig, 3.
Vacuolar Antoni Type B cells. Trichrome × 120.
Fig. 4.
Hyalinized perlvascutar cuffs. HE × 60.
473
474
T.A. Barbolt and Mary Alice M. Egy
Fig. 5.
Numerous interlacing argyrophilic fibres. Gomori's reticulum × 120.
Fig. 6.
Antoni Type A cells with abundant intercellular amorphous material. Uranyl acetate a n d lead citrate × 3000.
Fig, 7,
Long-spacing collagen with a period lengtil of 100 to 120 rim, Uranyl acetate and lead citrate x 60 000.
Fig, 8,
Antoni Type B cells. Uranyl acetate and lead citrate x 3000.
Intestinal S c h w a n n o m a
475
Ultrastructural examination revealed thickened basement m e m b r a n e material surrounding individual cells and areas of long-spacing collagen (Luse bodies) characteristic of these neoplasms (Luse, 1960; Waggener, 1966; Ghadially, 1988). The significance of the presence of long-spacing collagen is n o t known, although it has also been reported to be found normally in the eye, as well as in d a m a g e d nerves (Harkin and Reed, 1969). Although the mass expanded beyond the confines of the muscularis externa, the cytological features of the neoplasm appeared benign, and distant metastases were not observed macroscopically. While most reported intestinal neoplasms for non-human primates have been adenocarcinomas (Squire, Goodman, Valeris, Fredrickson Strandberg, Levitte, Lingeman, Harshbarger a n d Daive, 1978; De Paoli and McClure, 1982), this is the first known reported case of an intestinal schwannoma. References
Ashley, D. J. B. (1978). Evans' Histological Appearance.~ of Tumours. Vol. 2, 3rd edit. Churchill Livingstone, New York, pp. 482-485. Cedermark, J. (1949). Neurinomas of the gastrointestinal tract. International College of Surgeons Journal, 12, 5-11. Cordy, D. (1978). Tumors of the nervous system and eye. In: Tumors in Domestic Animals. 2nd edit. J. E. Moulton, Ed. University of California Press, Berkeley, CA, pp. 442-443. De Paoli, A. and McClure, H. M. (1982). Gastrointestinal neoplasms in nonhuman primates: A review and report of eleven new cases. Veterinary Pathology, 19, 104125. Erlandson, R. A. and Woodruff, J. M. (1982). Peripheral nerve sheath tumors: an electron microscopic study of 43 cases. Cancer, 49, 273-287. Ghadially, F. N. (1988). Ultrastructural Pathology of the Cell and Matrix. 3rd edit. Butterworths, Boston, p. 1234. Harkin, J. C. and Reed, R.J. (1969). Tumors of the Peripheral Nervous System. Second Series, Fascicle 3 of Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Washington, D.C.p. 43. Iliev, H. (1977). Neurinoma of the small intestine. Acta Chirugia Iugoslavia, 24, 297-302. Juvara, I., Priscu, A., Velican, D. and Halalau, F. (1967). Clinical and anatomicopathological aspects in neurinoma of the small intestine. Romanian Medical Review, 21, 64-68. Laber-Laird, K. E., Jokinen, M. P. and Jerome, C. P. (1988). Naturally occurring schwannoma in a Fischer 344 rat. Veterinary Pathology, 25, 320-322. Luse, S. (1960). Electron microscope studies of brain tumors. Neurology, 10, 881-905. Morson, B. C. (1976). Histological Typing of Intestinal Tumours. World Health Organization, Geneva. Patnaik, A. K., Hurvitz, A. I. and Johnson, G. F. (1977). Canine gastrointestinal neoplasms. Veterinary Pathology, 14, 547-555. Squire, R. A., Goodman, D. G., Valeris, M. G., Fredrickson, T., Strandberg, J. D., Levitte, M. H., Lingeman, C. H., Harshbarger, J. C. and Daive, C. J. (1978). Tumors. In: Pathology of Laboratory Animals, Vol. II, K. Benirschke, F. M. Garner and T. C. Jones, Eds. Springer Verlag, New York, p. 1145. Waggener, J. D. (1966). Ultrastructure of benign peripheral nerve sheath tumors. Cancer, 19, 699-709.
Received, January 22nd, 1990 1 Accepted, May 19th, 1990
Intestinal Schwannoma
in a R h e s u s M o n k e y
T. A. Barbolt and Mary Alice M. Egy Toxicology Department, Sterling Research Group, Rensselaer, NY 12144, U.S.A. Summary An intestinal schwannoma (neurilemmoma) was found in an aged female rhesus monkey culled from a research colony. The neoplasm was characterized principally by palisades of spindle-shaped cells (Antoni type A) surrounded by thick argyrophilic fibres, while plump cells with areas of vacuolation (Antoni type B) were observed to a lesser extent. Thick hyalinized perivascular cuffs were prominent and multifocal thromboses were present in cavernous vascular channels. Electron microscopic examination of the intercellular matrix between Antoni type A cells revealed long-spacing (100 to 120nm) collagen fibrils. Although the mass had expanded beyond the confines of the muscularis externa, the cytological features of the neoplasm appeared benign. Introduction Schwannomas of the small intestine have rarely been reported for man (Cedermark, 1949; Iliev, 1977;Juvara, Priscu, Velican and Halalau, 1967) or the dog (Patnaik, Hurvitz and Johnson, 1977); and no reference has been located regarding its occurrence in monkeys. The macroscopic, histomorphological and ultrastructural characteristics of a peripheral nerve neoplasm in the intestinal wall of a rhesus monkey is the subject of this case report.
Case Report A wild-caught female rhesus monkey (Macaca mulatta), maintained in captivity for more than 20 years, was culled from the research colony because of age and poor general condition, and was killed humanely by intravenous injection of sodium pentobarbital. At necropsy, a mottled white and dark mass (5"0 x 3"5 x 2"5 cm) protruded from the jejunum. There were no other abnormal macroscopic observations.
Materials and Methods Representative samples of the mass were fixed in 10 per cent neutral buffered formalin, embedded in paraffin wax, sectioned 4 gm thick, and stained with haematoxy.lin and eosin (HE), Masson's trichrome and Gomori's reticulum stains for histomorphological evaluation. Samples were taken from formalin fixative for retrospective ultrastructural evaluation. Blocks (1 mm 3) were selected from different areas of the mass, rinsed with phosphate buffer, post-fixed in 1 per cent phosphate-buffered osmium tetroxide, dehydrated in ascending concentrations of ethanol, infiltrated with propylene oxide 0021-9975/90/080471 + 05 $03.00/0
© 1990 Academic Press Limited
472
T. A. Barbolt and Mary Alice M. Egy
and embedded in Araldite 502-LX 112. Ultrathin sections (70 nm) were stained with uranyl acetate and lead citrate and examined with a Hitachi H7000 transmission electron microscope operated at 75 kV. Results
Histomorphological evaluation indicated that the neoplasm originated in the submucosa, presumably from the submucosal nerve plexus (Meissner's plexus), although the mass had expanded beyond the confines of the muscularis externa (Fig. 1). The mucosa overlying the mass was elevated, but histomorphologically normal, and the muscularis mucosa was intact. The mass was surrounded by an attenuated muscularis externa at the site of origin and a thin, incomplete collagenous capsule. Spindle-shaped cells (Antoni type A) arranged in palisades (Fig. 2) with an organoid pattern in some areas constituted most of the neoplasm, whereas plump cells with areas ofvacuolation (Antoni T y p e B) were observed to a lesser extent (Fig. 3). Mitotic figures were rare and areas of necrosis were not a feature of this neoplasm. A thick hyalinized perivascular cuff was observed around some blood vessels (Fig. 4), and multifocal thromboses were present in cavernous vascular channels observed throughout the mass. Variable amounts of collagen were demonstrated by the trichrome stain, and thick argyrophilic fibres surrounding individual cells and groups of cells were revealed by the reticulum stain (Fig. 5). Uhrastructurally, Antoni type A tissue was characterized by spindle-shaped cells aligned in parallel with scant cytoplasm, elongated nuclei with smooth borders, prominent nucleoli and marginated chromatin. These cells were joined by desmosomes and were frequently separated along part of their length by a b u n d a n t intercellular amorphous basement membrane-like material admixed with collagen fibrils (Fig. 6). Some of these collagen fibrils had a period length of 100 to 120 n m (Fig. 7). The period length of typical collagen fibrils observed in most areas was approximately 60 nm. Hyalinized perivascular cuffs were characterized by reduplicated layers o f basal lamina and loosely aggregated collagen fibres. In addition, bundles of myofilaments similar to those seen in smooth muscle cells were present in the basal aspect of endothelial cells. Antoni type B cells were loosely packed with a normal array of organelles including polymorphic nuclei with prominent nucleoli and margination of c h r o m a t i n (Fig. 8). M e m b r a n e - b o u n d vacuoles (0"1 to 22 gm diameter) were observed in m a n y of these cells and eosinophils were frequently observed. Discussion
T h e intestinal neoplasm from this aged rhesus monkey was interpreted as a s c h w a n n o m a (neurilemmoma), based principally on the presence of palisades of Antoni type A cells, areas of Antoni type B cells, and hyalinized perivascular cuffs (Morson, 1976; Ashley, 1978; Cordy, 1978; Erlandson and Woodruff, 1982; Laber-Laird, Jokinen and Jerome, 1988). Further evidence was the presence of thick argyrophilic fibres between Antoni type A cells and multifocal thromboses in cavernous vascular channels, which is not uncommon in these neoplasms.
Intestinal Schwannoma
Fig, 1. Submucosal mass expanding beyond the confines of the muscularis externa. HE x 6. Fig, 2.
Palisades of Antoni Type A cells. H E x 120.
Fig, 3.
Vacuolar Antoni Type B cells. Trichrome × 120.
Fig. 4.
Hyalinized perlvascutar cuffs. HE × 60.
473
474
T.A. Barbolt and Mary Alice M. Egy
Fig. 5.
Numerous interlacing argyrophilic fibres. Gomori's reticulum × 120.
Fig. 6.
Antoni Type A cells with abundant intercellular amorphous material. Uranyl acetate a n d lead citrate × 3000.
Fig, 7,
Long-spacing collagen with a period lengtil of 100 to 120 rim, Uranyl acetate and lead citrate x 60 000.
Fig, 8,
Antoni Type B cells. Uranyl acetate and lead citrate x 3000.
Intestinal S c h w a n n o m a
475
Ultrastructural examination revealed thickened basement m e m b r a n e material surrounding individual cells and areas of long-spacing collagen (Luse bodies) characteristic of these neoplasms (Luse, 1960; Waggener, 1966; Ghadially, 1988). The significance of the presence of long-spacing collagen is n o t known, although it has also been reported to be found normally in the eye, as well as in d a m a g e d nerves (Harkin and Reed, 1969). Although the mass expanded beyond the confines of the muscularis externa, the cytological features of the neoplasm appeared benign, and distant metastases were not observed macroscopically. While most reported intestinal neoplasms for non-human primates have been adenocarcinomas (Squire, Goodman, Valeris, Fredrickson Strandberg, Levitte, Lingeman, Harshbarger a n d Daive, 1978; De Paoli and McClure, 1982), this is the first known reported case of an intestinal schwannoma. References
Ashley, D. J. B. (1978). Evans' Histological Appearance.~ of Tumours. Vol. 2, 3rd edit. Churchill Livingstone, New York, pp. 482-485. Cedermark, J. (1949). Neurinomas of the gastrointestinal tract. International College of Surgeons Journal, 12, 5-11. Cordy, D. (1978). Tumors of the nervous system and eye. In: Tumors in Domestic Animals. 2nd edit. J. E. Moulton, Ed. University of California Press, Berkeley, CA, pp. 442-443. De Paoli, A. and McClure, H. M. (1982). Gastrointestinal neoplasms in nonhuman primates: A review and report of eleven new cases. Veterinary Pathology, 19, 104125. Erlandson, R. A. and Woodruff, J. M. (1982). Peripheral nerve sheath tumors: an electron microscopic study of 43 cases. Cancer, 49, 273-287. Ghadially, F. N. (1988). Ultrastructural Pathology of the Cell and Matrix. 3rd edit. Butterworths, Boston, p. 1234. Harkin, J. C. and Reed, R.J. (1969). Tumors of the Peripheral Nervous System. Second Series, Fascicle 3 of Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Washington, D.C.p. 43. Iliev, H. (1977). Neurinoma of the small intestine. Acta Chirugia Iugoslavia, 24, 297-302. Juvara, I., Priscu, A., Velican, D. and Halalau, F. (1967). Clinical and anatomicopathological aspects in neurinoma of the small intestine. Romanian Medical Review, 21, 64-68. Laber-Laird, K. E., Jokinen, M. P. and Jerome, C. P. (1988). Naturally occurring schwannoma in a Fischer 344 rat. Veterinary Pathology, 25, 320-322. Luse, S. (1960). Electron microscope studies of brain tumors. Neurology, 10, 881-905. Morson, B. C. (1976). Histological Typing of Intestinal Tumours. World Health Organization, Geneva. Patnaik, A. K., Hurvitz, A. I. and Johnson, G. F. (1977). Canine gastrointestinal neoplasms. Veterinary Pathology, 14, 547-555. Squire, R. A., Goodman, D. G., Valeris, M. G., Fredrickson, T., Strandberg, J. D., Levitte, M. H., Lingeman, C. H., Harshbarger, J. C. and Daive, C. J. (1978). Tumors. In: Pathology of Laboratory Animals, Vol. II, K. Benirschke, F. M. Garner and T. C. Jones, Eds. Springer Verlag, New York, p. 1145. Waggener, J. D. (1966). Ultrastructure of benign peripheral nerve sheath tumors. Cancer, 19, 699-709.
Received, January 22nd, 1990 1 Accepted, May 19th, 1990