JPC SYSTEMIC PATHOLOGY

REPRODUCTIVE SYSTEM

January 2025

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). Mesodermal elements consist of 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 undergo 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 in strain 129/Sv-ter mice have an autosomal recessive mode of inheritance; males homozygous for the mutant ter gene are often affected
• 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 may arise from embryonic stem cells (“germ 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 disorganized, 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 (replaced by vertebrae in late-stage embryo)	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, melanocytes)	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
• On cytology, teratomas typically have mature epithelial cells and keratin on a necrotic background with neutrophilic and histiocytic inflammation. There may be cells with apical cilia suggestive of respiratory epithelium

 

ADDITIONAL DIAGNOSTIC TESTS:

• Immunohistochemistry:

• Cytokeratin: Epithelial tissues
• Vimentin: Mesenchymal tissues
• Glial fibrillary acidic protein (GFAP), synaptophysin: Neural tissues (ectodermal)
• Muscle specific 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 (“benign cystic teratomas”)

 

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
• Rhesus Macaque: One of the two most common ovarian tumors (along with granulosa cell tumors), also reported in cynomolgus and pigtailed macaques, baboons, chimpanzees (teratomas more common in old-world rather than new-world monkeys) 
• Ovarian teratomas in other species: 

• Reported in the bitch, sow, mare, cow, deer, camelids, wild ungulates, and several avian species (chicken, raptors, a heron, a pigeon, turkeys); extremely rare in queens
• Case report: metastatic ovarian teratocarcinoma in a mare (Charles, J Comp Pathol. 2020)
• Fish: Reported in bass, salmon

 

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: Reported; testicular tumors in general are more common in the budgerigar 

 

Extragonadal Teratomas

• “Germ cell tumors” arise from ectopic embryonic germ cells which would ordinarily become gonadal tissue; extragonadal teratomas generally occur along midline in young animals because of this pathogenesis
  1. Other germ cell tumors include seminoma, dysgerminoma, choriocarcinoma, & entodermal sinus tumor
• Ferret: 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

 

REFERENCES:

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4. Brannick EM, Newkirk KM, Schaefer MW. Neoplasia and Tumor Biology. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:344, 369.
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