JPC SYSTEMIC PATHOLOGY
ENDOCRINE SYSTEM
January 2022
E-M02 (NP)

SIGNALMENT (JPC #1669664):  3-year-old male German shepherd military working dog

HISTORY:  Incidental finding in a dog that died during anesthesia for treatment of an infected tooth.

HISTOPATHOLOGIC DESCRIPTION (Slide A):  Pituitary gland: Focally separating the pars distalis and pars intermedia and compressing and displacing the pars nervosa is an irregularly round, 4 mm diameter cyst lined by pseudostratified cuboidal to columnar epithelium that is multifocally ciliated. The cyst is filled with amorphous amphophilic homogenous material (mucinous protein). 

MORPHOLOGIC DIAGNOSIS:  Pituitary gland:  Cyst, focal, German shepherd dog, canine.

CONDITION:  Cystic remnant of the craniopharyngeal duct (Rathke's pouch)

SIGNALMENT (JPC #4104652): Maned wolf from National Zoo

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION (Slide B):  Pituitary gland: Multifocally expanding the pars distalis are variably sized pseudocysts ranging from 30um to 1.5mm with no distinct epithelial lining, often surrounded by acidophils and chromophobes, and containing variable amounts of eosinophilic homogenous material (secretory product).

MORPHOLOGIC DIAGNOSIS: Pituitary gland, pars distalis: Pseudocysts, multiple, maned wolf, Chrysocyon brachyurus.   

GENERAL DISCUSSION:

• Three types of pituitary cysts:
  • Cysts caused by remnants of the distal craniopharyngeal duct (inside Rathke’s pouch – the primitive evagination of the oral cavity which forms the space occupied by the pituitary gland in embryogenesis): Normally disappear at birth; most common in brachycephalic breeds of dog; often found at periphery of pars tuberalis and pars distalis
  • Cysts derived from the proximal end of the craniopharyngeal duct (pharyngeal hypophysis): Located in the dorsal aspect of the oral cavity, may project into nasopharynx; most common in brachycephalic breeds of dog
  • Cysts resulting from failure of differentiation of oropharyngeal ectoderm of Rathke’s pouch: Pituitary dwarfism in dogs is usually associated with failure of the oropharyngeal ectoderm of Rathke's pouch to differentiate into trophic hormone-secreting cells of the pars distalis which results in absence of adenohyphosis; it is an autosomal recessive trait in German shepherd dogs caused by deletion of exon 5 in LHX3 gene
• According to a recent study), pituitary cysts and cyst-like lesions are the most common lesion in cats and dogs; they stated that cyst-like lesions with no epithelial lining arise from pituitary tissue degeneration or blockage of secretion (Polledo, Vet Pathol. 2018)

TYPICAL CLINICAL FINDINGS:

• These are usually incidental; large cysts may cause pressure atrophy of the optic chiasm resulting in visual deficits, or they may cause hormonal dysregulation resulting in diabetes insipidus, obesity, gonadal atrophy, decreased basal metabolic rate, or hypoglycemia
• Cysts from proximal craniopharyngeal duct may cause respiratory distress
• Pituitary dwarfism: Decreased GH, TSH, prolaction, gonadotropins, and decreased activity of IGF-1, ACTH may be normal or decreased; atrophy of the thyroid gland and adrenal cortex due to lack of trophic hormones

TYPICAL GROSS FINDINGS:

• Usually none with incidental cysts
• Pituitary dwarfism: Affected puppies are normal until about 2 months of age
  • Slow growth rate, “coyote” or “fox-like” appearance
  • Retention of puppy hair, progressive bilateral symmetrical alopecia
  • Skin hyperpigmentation
  • Permanent dentition is delayed or absent and epiphyseal closure is delayed up to 4 years of age
  • External genitalia remains infantile and estrus is irregular or absent

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Uni- or multiloculated cyst lined by pseudostratified, ciliated, columnar epithelium +/- goblet cells
• Squamous epithelium-lined cysts may be derived from the oropharyngeal end of the craniopharyngeal duct in dogs
• Cyst wall may contain partially mineralized woven bone
• Cyst often filled with mucin; may contain keratin and desquamated cells
• Cyst rupture may result in local inflammatory response and subsequent fibrosis
• Cysts associated with pituitary dwarfism (absence of adenohypophysis) are morphologically distinct from remnants of the distal craniopharyngeal duct (abnormal accumulation of colloid in the residual lumen of Rathke’s pouch)

ADDITIONAL DIAGNOSTIC TESTS:

• Pituitary dwarfism:
  • Positive response of the thyroid and adrenal gland to exogenous stimulation (may be no response in chronic cases because of secondary atrophy of glands); e.g.
  • Somatomedin (IGF-1) levels are low with no response to stimulation (clonidine); somatomedin is a cartilage growth-promoting peptide whose production in the liver and plasma activity is controlled by somatotropin
  • Exogenous insulin causes prolonged hypoglycemia in somatomedin-deficient animals
  • With administration of TSH releasing hormone, if the pituitary is functional it will release TSH, which will result in an increase in T4

DIFFERENTIAL DIAGNOSIS:

• Other space-occupying masses in the pituitary region:
  • Pituitary adenoma
  • Meningioma
  • Supracellar germ cell tumor
  • Craniopharyngiomas form from primitive rests of epithelial cells derived from the formation of the craniopharyngeal duct / Rathke’s pouch
• Immunodeficient dwarfism has been reported in an inbred colony of Weimaraner dogs characterized by somatostatin deficiency, congenital absence of thymic cortex, and deficient lymphocyte blastogenic response to mitogens

COMPARATIVE PATHOLOGY:

• Persistence of the craniopharyngeal duct is rare in domestic animals other than the dog
• Pars distalis cysts occur in young dogs (German shepherd dog, beagle)
• Pituitary cysts reported in horses, a macaque, gorilla, chimpanzee, and baboons
• In rats, remnants of the intrasellar portion of the pharyngeal hypophysis may develop into cysts, most commonly at the periphery of the pars distalis and the pars tuberalis
• The spontaneous dwarf rat is an animal model for pituitary dwarfism; these rats do not have somatostatin secreting cells in the anterior pituitary gland at any age

REFERENCES:

1. Bakthavatchalu V, Muthupalani S, Marini RP, Fox JG. Endocrinopathy in aging ferrets. Vet Pathol. 2016; 53(2):349-365.
2. Banks WJ. Applied Veterinary Histology. 3rd ed. St. Louis, MO: Mosby, Inc.; 1993:408-12.
3. Leitenbacher J, Herbach N. Age-related qualitative histological and quantitative stereological changes in equine pituitary. J Comp Pathol. 2016; 154(2-3):215-224.
4. Miller MA. Endocrine system. In: Zachary JF, McGavin MD, ed. Pathologic Basis of Veterinary Disease. 6^th St. Louis, MO: Elsevier; 2017:717.
5. Miller MA, Bruyette DS, Scott-Moncrieff JC, Owen TJ, et al. Histopathological findings in canine pituitary glands. Vet Pathol. 2018;55(6):871-879.
6. Polledo L, Grinwis GCM, Graham P, Dunning M, Baiker K. Pathological findings in the pituitary glands of dogs and cats. Vet Pathol. 2018; 55(6):880-888.
7. Rosol TJ, Gröne A. Endocrine glands.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:279-281.

Click the slide to view.

---