J Med Primatol doi:10.1111/jmp.12167
CASE REPORT
An extragonadal teratoma in a female cynomolgus monkey (Macaca fascicularis) S.H. Schelling & D. Morton Drug Safety Research & Development, Pfizer, Inc., Andover, MA, USA
Keywords germ cell – neoplasm – nonhuman primate – retroperitoneum Correspondence Scott H. Schelling, DVM, Dip. ACVP, Drug Safety Research and Development, Pfizer, Inc., Building G, Office 3002C, 1 Burtt Road, Andover, MA 01810-5901, USA. Tel.: 978-247-1503; fax: 845-474-4065; e-mail: [email protected]
Abstract Extragonadal teratomas have not been reported in nonhuman primates. A female cynomolgus monkey, a vehicle control in an exploratory toxicity study, was necropsied. Microscopic examination of an extragonadal mass in the animal’s craniodorsal retroperitoneum revealed a teratoma. This is the first report of an extragonadal teratoma in a nonhuman primate.
Accepted January 6, 2015
Introduction Teratomas are uncommon neoplasms that contain mature or immature tissues derived from two or three germ cell layers [6]. Although competing theories for their origin exist [3, 4], it is generally accepted that teratomas arise from totipotential primordial germ cells such as those in the ovaries and testes and sometimes in sequestered midline embryonic rests [6]. In nonhuman primates, ovarian teratomas have been reported in cynomolgus and rhesus macaques and other species [1, 5]; to the authors’ knowledge, there have been no reports of testicular teratomas in nonhuman primates or of extragonadal teratomas in either sex [2, 7].
ularis), a vehicle control animal in an exploratory toxicity study, was fasted overnight prior to scheduled euthanasia and necropsy. The animal’s external surface and thoracic and abdominal cavities were examined macroscopically. A limited set of tissues [i.e., a retroperitoneal mass and the reproductive tract (i.e., ovaries, uterus, cervix, and vagina)] was collected at necropsy. All tissues were fixed in 10% neutral buffered formalin. Tissues examined by light microscopy were processed routinely, except for the retroperitoneal mass which was demineralized prior to trimming and processing, embedded in paraffin, sectioned at approximately 5 lm, and stained with hematoxylin and eosin. Results
Materials and methods Humane care guidelines The animal subject of this report was part of a study that was conducted in accordance with the current guidelines for animal welfare. All procedures performed on these animals were in accordance with regulations and established guidelines and were reviewed and approved by Pfizer’s Institutional Animal Care and Use Committee. A clinically asymptomatic, 63-month-old, 3.7-kg, female, Mauritian cynomolgus monkey (Macaca fascicJ Med Primatol 44 (2015) 113–115 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
At necropsy, an irregularly shaped, multinodular, 6 9 4 9 2 cm mass was observed within the craniodorsal retroperitoneum to the left of midline (Fig. 1A). The mottled, pale tan and blue-gray mass compressed the subjacent left adrenal gland and was easily dissected from nearby viscera. It had solid, soft, and hard (i.e., bone-like) regions and cystic foci. A pale green-brown, opaque, non-odorous, viscous fluid exuded from the cut surfaces of the cysts. The ovaries, uterus, and cervix were macroscopically unremarkable and situated within the caudal abdominal cavity and pelvic canal. 113
Extragonadal teratoma in a nonhuman primate
Schelling and Morton
(A)
(B)
(C)
(D)
(E)
(F)
Fig. 1 (A) At necropsy, a multinodular, retroperitoneal mass (t) was located near the dorsal midline of the cranial abdomen adjacent to the left adrenal gland (a), stomach (st), and spleen (sp). The left kidney and liver were excised to facilitate visualization of the mass. (B) Well-differentiated neural tissue (n) containing neurons and glial cells and skeletal muscle (m) within the teratoma. HE, 209 objective. (C) Lamellar bone (b) and bone marrow (bm) within the teratoma. HE, 209 objective. (D) Tooth (t) surrounded by alveolar bone (b) within the teratoma. HE, 49 objective. (E) Well-differentiated stratified squamous keratinized epithelium (e) and sebaceous gland (s) line a keratin (k)-filled cyst within the teratoma. HE, 209 objective. (F) Multilayered epithelium with goblet cells (g) and cilia (c) lines a mucin-filled cyst within the teratoma. HE, 409 objective.
Solid portions of the mass were characterized microscopically by disorderly, variably shaped expanses of fibrous connective tissue, skeletal muscle, adipose tissue, hyaline cartilage, neural tissue (Fig. 1B), and bone, some particles of which contained bone marrow (Fig. 1C). In one fragment of osseous tissue that resembled a jaw, a cementum-covered tooth was anchored in its socket by a periodontal ligament (Fig. 1D). Some cysts within the mass were keratin-filled and lined by a pigmented, stratified squamous keratinized epithelium contiguous with randomly scattered sebaceous glands in the subjacent fibroadipose tissue (Fig. 1E). Other cysts contained a mucin-like substance, and were lined by a goblet cell-rich, multilayered, ciliated epithelium (Fig. 1F), or were empty and lined by a multilayered arrangement of transitional epithelium-like cells. The microscopic characteristics of the mass supported a diagnosis of teratoma. Microscopic evaluation of the ovaries revealed evidence of recent ovulation in one (i.e., corpus hemorrhagicum), and the morphologic
features of the endometrium and vaginal epithelium were consistent with the early luteal phase of the menstrual cycle. Discussion In humans, extragonadal teratomas tend to occur in midline structures (e.g., anterior mediastinum, retroperitoneum, sacrococcygeal region, and pineal gland) [3]. Primary retroperitoneal teratomas account for up to 11% of retroperitoneal neoplasms and are most commonly identified in neonates and young adults; their diagnosis is facilitated by imaging (e.g., ultrasonography, computed tomography, and magnetic resonance imaging) [3]. Acknowledgment The authors thank Mary Payette, Brett Sylvester, and Michael Wadanoli for technical assistance.
References 1 Cline JM, Wood CE, Vidal JD, Tarara RP, Buse E, Weinbauer GF, de Rijk EP, van Esch E: Selected background findings and interpreta-
114
tion of common lesions in the female reproductive system in macaques. Toxicol Pathol 2008; 36: 142s–63s.
2 Cline JM, Brignolo L, Ford EW: Urogenital system. In: Nonhuman Primates in Biomedical Research: Diseases, 2nd edn, Vol. 2. Abee,
J Med Primatol 44 (2015) 113–115 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Schelling and Morton
Mansfield, Tardiff & Morris (eds). San Diego, CA: Academic Press, 2012; 483–562. 3 Gatcombe HG, Assikis V, Kooby D, Johnstone PA: Primary retroperitoneal teratomas: a review of the literature. J Surg Oncol 2004; 86:107–13. 4 Lakhoo K: Neonatal tumours. Early Hum Dev 2010; 86:643–7.
Extragonadal teratoma in a nonhuman primate
5 Marr-Belvin AK, Bailey CC, Knight HL, Klumpp SA, Westmoreland SV, Miller AD: Ovarian pathology in rhesus macaques: a 12-year retrospective. J Med Primatol 2010; 39:170–6. 6 Stricker TP, Kumar V: Neoplasia. In: Robbins and Cotran Pathologic Basis of Disease, 8th edn. Kumar, Abbas, Fausto & Aster (eds). Phila-
J Med Primatol 44 (2015) 113–115 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
delphia, PA: Saunders, 2010; 259– 330. 7 Vidal JD, Mirsky ML, Colman K, Whitney KM, Creasy DM: Reproductive system and mammary gland. In: Toxicologic Pathology: Nonclinical Safety Assessment. Sahota, Popp, Hardisty & Gopinath (eds). Boca Raton, FL: CRC Press, 2013; 717–830.
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Copyright of Journal of Medical Primatology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
CASE REPORT
An extragonadal teratoma in a female cynomolgus monkey (Macaca fascicularis) S.H. Schelling & D. Morton Drug Safety Research & Development, Pfizer, Inc., Andover, MA, USA
Keywords germ cell – neoplasm – nonhuman primate – retroperitoneum Correspondence Scott H. Schelling, DVM, Dip. ACVP, Drug Safety Research and Development, Pfizer, Inc., Building G, Office 3002C, 1 Burtt Road, Andover, MA 01810-5901, USA. Tel.: 978-247-1503; fax: 845-474-4065; e-mail: [email protected]
Abstract Extragonadal teratomas have not been reported in nonhuman primates. A female cynomolgus monkey, a vehicle control in an exploratory toxicity study, was necropsied. Microscopic examination of an extragonadal mass in the animal’s craniodorsal retroperitoneum revealed a teratoma. This is the first report of an extragonadal teratoma in a nonhuman primate.
Accepted January 6, 2015
Introduction Teratomas are uncommon neoplasms that contain mature or immature tissues derived from two or three germ cell layers [6]. Although competing theories for their origin exist [3, 4], it is generally accepted that teratomas arise from totipotential primordial germ cells such as those in the ovaries and testes and sometimes in sequestered midline embryonic rests [6]. In nonhuman primates, ovarian teratomas have been reported in cynomolgus and rhesus macaques and other species [1, 5]; to the authors’ knowledge, there have been no reports of testicular teratomas in nonhuman primates or of extragonadal teratomas in either sex [2, 7].
ularis), a vehicle control animal in an exploratory toxicity study, was fasted overnight prior to scheduled euthanasia and necropsy. The animal’s external surface and thoracic and abdominal cavities were examined macroscopically. A limited set of tissues [i.e., a retroperitoneal mass and the reproductive tract (i.e., ovaries, uterus, cervix, and vagina)] was collected at necropsy. All tissues were fixed in 10% neutral buffered formalin. Tissues examined by light microscopy were processed routinely, except for the retroperitoneal mass which was demineralized prior to trimming and processing, embedded in paraffin, sectioned at approximately 5 lm, and stained with hematoxylin and eosin. Results
Materials and methods Humane care guidelines The animal subject of this report was part of a study that was conducted in accordance with the current guidelines for animal welfare. All procedures performed on these animals were in accordance with regulations and established guidelines and were reviewed and approved by Pfizer’s Institutional Animal Care and Use Committee. A clinically asymptomatic, 63-month-old, 3.7-kg, female, Mauritian cynomolgus monkey (Macaca fascicJ Med Primatol 44 (2015) 113–115 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
At necropsy, an irregularly shaped, multinodular, 6 9 4 9 2 cm mass was observed within the craniodorsal retroperitoneum to the left of midline (Fig. 1A). The mottled, pale tan and blue-gray mass compressed the subjacent left adrenal gland and was easily dissected from nearby viscera. It had solid, soft, and hard (i.e., bone-like) regions and cystic foci. A pale green-brown, opaque, non-odorous, viscous fluid exuded from the cut surfaces of the cysts. The ovaries, uterus, and cervix were macroscopically unremarkable and situated within the caudal abdominal cavity and pelvic canal. 113
Extragonadal teratoma in a nonhuman primate
Schelling and Morton
(A)
(B)
(C)
(D)
(E)
(F)
Fig. 1 (A) At necropsy, a multinodular, retroperitoneal mass (t) was located near the dorsal midline of the cranial abdomen adjacent to the left adrenal gland (a), stomach (st), and spleen (sp). The left kidney and liver were excised to facilitate visualization of the mass. (B) Well-differentiated neural tissue (n) containing neurons and glial cells and skeletal muscle (m) within the teratoma. HE, 209 objective. (C) Lamellar bone (b) and bone marrow (bm) within the teratoma. HE, 209 objective. (D) Tooth (t) surrounded by alveolar bone (b) within the teratoma. HE, 49 objective. (E) Well-differentiated stratified squamous keratinized epithelium (e) and sebaceous gland (s) line a keratin (k)-filled cyst within the teratoma. HE, 209 objective. (F) Multilayered epithelium with goblet cells (g) and cilia (c) lines a mucin-filled cyst within the teratoma. HE, 409 objective.
Solid portions of the mass were characterized microscopically by disorderly, variably shaped expanses of fibrous connective tissue, skeletal muscle, adipose tissue, hyaline cartilage, neural tissue (Fig. 1B), and bone, some particles of which contained bone marrow (Fig. 1C). In one fragment of osseous tissue that resembled a jaw, a cementum-covered tooth was anchored in its socket by a periodontal ligament (Fig. 1D). Some cysts within the mass were keratin-filled and lined by a pigmented, stratified squamous keratinized epithelium contiguous with randomly scattered sebaceous glands in the subjacent fibroadipose tissue (Fig. 1E). Other cysts contained a mucin-like substance, and were lined by a goblet cell-rich, multilayered, ciliated epithelium (Fig. 1F), or were empty and lined by a multilayered arrangement of transitional epithelium-like cells. The microscopic characteristics of the mass supported a diagnosis of teratoma. Microscopic evaluation of the ovaries revealed evidence of recent ovulation in one (i.e., corpus hemorrhagicum), and the morphologic
features of the endometrium and vaginal epithelium were consistent with the early luteal phase of the menstrual cycle. Discussion In humans, extragonadal teratomas tend to occur in midline structures (e.g., anterior mediastinum, retroperitoneum, sacrococcygeal region, and pineal gland) [3]. Primary retroperitoneal teratomas account for up to 11% of retroperitoneal neoplasms and are most commonly identified in neonates and young adults; their diagnosis is facilitated by imaging (e.g., ultrasonography, computed tomography, and magnetic resonance imaging) [3]. Acknowledgment The authors thank Mary Payette, Brett Sylvester, and Michael Wadanoli for technical assistance.
References 1 Cline JM, Wood CE, Vidal JD, Tarara RP, Buse E, Weinbauer GF, de Rijk EP, van Esch E: Selected background findings and interpreta-
114
tion of common lesions in the female reproductive system in macaques. Toxicol Pathol 2008; 36: 142s–63s.
2 Cline JM, Brignolo L, Ford EW: Urogenital system. In: Nonhuman Primates in Biomedical Research: Diseases, 2nd edn, Vol. 2. Abee,
J Med Primatol 44 (2015) 113–115 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Schelling and Morton
Mansfield, Tardiff & Morris (eds). San Diego, CA: Academic Press, 2012; 483–562. 3 Gatcombe HG, Assikis V, Kooby D, Johnstone PA: Primary retroperitoneal teratomas: a review of the literature. J Surg Oncol 2004; 86:107–13. 4 Lakhoo K: Neonatal tumours. Early Hum Dev 2010; 86:643–7.
Extragonadal teratoma in a nonhuman primate
5 Marr-Belvin AK, Bailey CC, Knight HL, Klumpp SA, Westmoreland SV, Miller AD: Ovarian pathology in rhesus macaques: a 12-year retrospective. J Med Primatol 2010; 39:170–6. 6 Stricker TP, Kumar V: Neoplasia. In: Robbins and Cotran Pathologic Basis of Disease, 8th edn. Kumar, Abbas, Fausto & Aster (eds). Phila-
J Med Primatol 44 (2015) 113–115 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
delphia, PA: Saunders, 2010; 259– 330. 7 Vidal JD, Mirsky ML, Colman K, Whitney KM, Creasy DM: Reproductive system and mammary gland. In: Toxicologic Pathology: Nonclinical Safety Assessment. Sahota, Popp, Hardisty & Gopinath (eds). Boca Raton, FL: CRC Press, 2013; 717–830.
115
Copyright of Journal of Medical Primatology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
