Read-Only Case Details Reviewed: Mar 2010

JPC SYSTEMIC PATHOLOGY
ENDOCRINE SYSTEM
January 2022
R-N08

SIGNALMENT (JPC #2019038): Female B6C3F1 mouse

HISTORY: This mouse had a large cystic abdominal mass.

HISTOPATHOLOGIC DESCRIPTION: Ovary: Effacing 90% of normal ovarian architecture and compressing remaining few ovarian follicles and scant stroma is an unencapsulated, poorly demarcated, densely cellular, multiloculated neoplasm composed of tissue differentiated toward all three primordial germ layers. Ectodermal elements consist of neural tissue and cysts lined by frequently keratinizing squamous epithelium. Neural tissue consists of neurons, glial cells, and clusters of small, hyperchromatic primitive neuroblastic cells embedded in neuropil. Cysts are lined by stratified squamous epithelium that multifocally exhibits gradual keratinization through a granular cell layer and are filled by variable amounts of lamellated keratin and keratin debris with few neutrophils or eosinophilic to amphophilic, homogeneous to fibrillar material. Endodermal elements include numerous variably sized cysts up to 3 mm in diameter which are either lined by a single layer of cuboidal epithelium with multifocal subjacent tubules or pseudostratified columnar epithelium with multifocal cilia and goblet cells (respiratory epithelium) admixed with several small foci of gastric mucosa with mucous neck cells and fewer parietal cells. Mesodermal elements consist of dermal collagen with melanophages and bundles of smooth muscle. Mitoses in all cell populations average less than 1 per 2.37 mm² (10 HPF).

MORPHOLOGIC DIAGNOSIS: Ovary: Teratoma, B6C3F1 mouse, rodent.

GENERAL DISCUSSION:

Teratomas are uncommon germ cell neoplasms in which totipotential germ cells have undergone somatic differentiation to at least two (may be one if multiple representatives of the same germ line) of the three germinal layers (endoderm, mesoderm, and ectoderm including neuroectoderm)
Teratomas in domestic animals are usually well-differentiated and benign
Most teratomas arise in the gonads; extragenital teratomas are exceedingly rare

PATHOGENESIS:

Teratomas arise from totipotential primordial germ cells
Teratomas are parthenogenic tumors that develop from a single germ cell that has completed its first meiotic division but not its second
Teratoma cells are XX diploid cells that are homozygous at chromosomal loci for which the host is heterozygous; lack of heterozygosity is the result of parthenogenic meiotic division
Extragonadal teratomas are believed to arise from embryonic stem cells

TYPICAL CLINICAL FINDINGS:

Ovarian or testicular mass that may be palpable
Teratomas do not elaborate hormones

TYPICAL GROSS FINDINGS:

Varied color and texture, red-tan, often have cystic and solid areas
May contain hair, skin, sebaceous material, bone, cartilage, teeth
Extragonadal teratomas are found on midline, including sacrococcygeal region, retroperitoneum, anterior mediastinum, and the central nervous system (and adrenal glands in ferrets)

TYPICAL MICROSCOPIC FINDINGS:

A variety of often chaotically arranged, mature embryonic tissues from 2-3 germ layers in any combination;
Nervous tissue is almost always present, adipose tissue and respiratory epithelium is common

Ectoderm	Mesoderm	Endoderm
Epidermis of skin and its derivatives (sweat glands, hair follicles)	Notochord	Epithelial lining of digestive tract, salivary gland
Epithelial lining of mouth, nose, and anus	Skeletal system (bone and cartilage)	Epithelial lining of respiratory system
Cornea, retina, and lens of eye	Muscular system (skeletal and smooth muscle)	Epithelial lining of urethra, urinary bladder, and reproductive system
Nervous tissue (central and peripheral, melanoblasts)	Connective tissue, adipose	Liver
Sensory receptors in epidermis and epithelia of eye, ear, and nose	Urinary system	Pancreas
Adrenal medulla	Circulatory (cardiovascular and lymphatic) systems	Epithelial component of the thymus and tonsils
Tooth enamel	Reproductive system (gonads, ducts, accessory glands)	Thyroid and parathyroid glands
Epithelium of pineal and pituitary glands	Dermis of skin	Trachea, bronchi, lungs
Mammary glands	Adrenal cortex	Epithelial lining of the tympanic cavity and auditory tube
Inner ear	Hematopoietic system (spleen, blood cells)	Prostate
	Tooth dentin	Pharynx

Atrophy of compressed adjacent parenchyma

ADDITIONAL DIAGNOSTIC TESTS:

Immunohistochemistry:
Cytokeratin: Epithelial tissues
Vimentin: Mesenchymal tissues
Glial fibrillary acidic protein (GFAP), synaptophysin: Neural tissues (ectodermal)
Muscle actin, smooth muscle actin, desmin: Muscle (mesodermal)

DIFFERENTIAL DIAGNOSIS:

Fetus in Fetu: One monozygotic twin is completely within the body of the other twin. Tissues are arranged around vertebral axis
Dermoid cyst

Other ovarian germ cell tumors:

Dysgerminoma (R-N06): Benign; germ cells that have not undergone somatic differentiation; solid sheets of round to polygonal cells with high mitotic rate
Choriocarcinoma (R-N16): Trophoblastic differentiation; large, pleomorphic trophoblastic giant cells, syncytiotrophoblasts, smaller cytotrophoblasts, and prominent blood-filled spaces
Embryonal carcinoma: Exceedingly rare; may contain multinucleated giant cells resembling syncytiotrophoblastic cells, lacks cytotrophoblastic cells; immunoreactivity to α-fetoprotein supports this diagnosis
Yolk sac carcinoma: Rare; AKA endodermal sinus tumor; germ cells differentiate into mesoblast and yolk sac endoderm; endodermal sinus pattern with pathognomonic Schiller-Duval bodies (glomeruloid papillary structures with a fibrovascular core covered by columnar cells); nests and ribbons of neoplastic epithelium in periodic acid-Schiff (PAS) positive material
Epidermoid cyst: Rare; arises from single germ layer
Teratocarcinoma: Features of teratoma and embryonal carcinoma, reported in the horse

COMPARATIVE PATHOLOGY:

Ovarian Teratomas

Guinea Pig: Reproductive tract neoplasms are common; teratoma is the most common ovarian tumor
Ovarian teratomas in other species:
Reported in the bitch, sow, mare, cow, and several avian species (chicken, raptors, a heron, a pigeon, turkeys); extremely rare in queens
Case report: Emu with ovarian teratocarcinoma with coelomic teratocarcinomatosis (Leal de Araujo, J Comp Pathol. 2018)
Case report: Cat with malignant estrogen-producing ovarian teratoma with atrophy of the contralateral ovary (Machida, J Comp Pathol. 2017); there is only one other case report (human) of an estrogen-secreting teratoma
Case report: metastatic ovarian teratocarcinoma in a mare (Charles, J Comp Pathol. 2020)

Testicular Teratomas

Testicular teratomas are rare in most domestic animals other than colts
Horse: Testicular teratomas are periodically found in foals, especially in cryptorchid testicles, with unknown cause or effect of/from retained testicle
Mice:
129/Sv mice (AKA 129S4/SvJae) frequently develop testicular teratomas (up to 10% of males by 3 weeks of age)
ter+/ter+ homozygous mice frequently develop testicular teratomas (94% of older mice, with up to 75% bilateral involvement)
129 strain chimeras: develop extragonadal teratomas in the perigenital region or midline
Birds: Teratomas of avian species are most commonly testicular

Extragonadal Teratomas

Ferret: the adrenal gland is the most common site of origin of teratomas; unilateral and bilateral adrenal gland teratomas have been recorded; unlike other ferret adrenal proliferations, teratomas do not elaborate hormones
Birds: reported sites include the cranium, retrobulbar area, eye, brain, mediastinum, and coelom
Case report: Male cat with a congenital coccygeal teratoma, previously not reported in domestic animals (Kegler, J Comp Pathol. 2014)

REFERENCES:

Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016: 3, 115-116, 251.
Charles LN. Metastatic Ovarian Teratocarcinoma in a Horse. J Comp Pathol. 2020;181:68-72.
Foster RA. Male genital system. In: Maxie MG, ed. Jubb Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:496.
Foster RA. Male reproductive system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1210-1211.
Foster RA. Female reproductive system and mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2016: 1161.
Fox JG, Muthupalani S, Kiupel M, Williams B. Neoplastic diseases. In: Fox JG, Marini RP. Biology and Diseases of the Ferret. 3rd ed. Ames, IA: Wiley; 2014: 595.
Kegler K, Kröner B, Baumgärtner W, Wohlsein P. Feline coccygeal teratoma: immunohistochemical characterization of immature tissue components. J Comp Pathol. 2014;151(2-3):195-201.
Kirejczyk S, Pinelli C, Gonzalez O, Kumar S, Dick E Jr, Gumber S. Urogenital Lesions in Nonhuman Primates at 2 National Primate Research Centers. Vet Pathol. 2021;58(1):147-160
Leal de Araujo J, Perry A, Wild J, Kleinschmdit L, Hoppes S, Rech RR. Ovarian teratocarcinoma in an emu (Dromaius novaehollandiae): histopathological and immunohistochemical characterization. J Comp Pathol. 2018;159:31-35.
Machida Y, Michishita M, Wada M, et. al. Malignant oestrogen-producing teratoma in a cat. J Comp Pathol. 2017;156:178-182.
Schlafer DH, Foster RA. Female genital system. In: Maxie MG, ed. Jubb Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:377-378.
Tavella VJ, Walters JN, Crofton LM, LeRoith T. Mixed germ cell tumor composed of a tridermic testicular teratoma and seminoma in a rooster. J Vet Diagn Invest. 2019;31(3):395-398.