AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2019

I-M22 (NP)

 

Signalment (JPC 21474-26): Middle-aged, breed unspecified dog

 

HISTORY: Skin biopsy from a dog that had become increasingly lethargic and had haircoat thinning and loss over the trunk.

 

HISTOPATHOLOGIC DESCRIPTION: Haired skin: Diffusely, there is mild epidermal and moderate infundibular orthokeratotic hyperkeratosis. Multifocally there is melanin pigment in all layers of the epidermis (hyperpigmentation). Follicular infundibula are distended up to 0.2mm by concentric layers of keratin admixed with cellular debris and melanin, and lined by attenuated external root sheath epithelium. Nearly 100% of follicles are in telogen phase, approximately 50% of which lack hair shafts (hairless telogen, AKA kenogen). Follicles within the deeper dermis are shrunken (follicular atrophy) and have thickened external root sheaths, lack internal root sheaths, and contain irregular lamellations of brightly eosinophilic tricholemmal keratin (flame follicles). Dermal collagen fibers are shrunken and separated by abundant clear space (edema). Occasionally, arrector pili muscles have pale vacuolated sarcoplasm. Multifocally, apocrine glands are mildly ectatic and lined by attenuated epithelium.

 

MORPHOLOGIC DIAGNOSIS: Haired skin: Follicular atrophy, diffuse, moderate, with follicular and epidermal orthokeratotic hyperkeratosis, multifocal epidermal hyperpigmentation, flame follicles, and follicular ectasia, breed unspecified, canine

 

CONDITION: Hypothyroidism

 

GENERAL DISCUSSION:

·      Most common endocrine skin disease of the dog

·      Most common in middle-aged or older dogs, with no sex predilection

·      Causes are either primary (>90%) or secondary (due to decreased TSH secretion):

·      Primary: Lymphocytic thyroiditis (E-M01) or thyroid atrophy, thyroid neoplasia, developmental defects of the thyroid gland

·      Secondary: Pituitary neoplasia (hypopituitarism), iodine deficiency or excess, hypothalamic defects, iatrogenic via surgery or drugs

·      Predisposition in many breeds: Doberman Pinscher, Golden Retriever, Chow Chow, Great Dane, Irish Wolfhound, Boxer, English Bulldog, Dachshund, Afghan Hound, Newfoundland, Alaskan Malamute, Brittany Spaniel, Poodle, Irish Setter, and Miniature Schnauzer

·      Familial hypothyroidism in giant schnauzers

·      Congenital hypothyroidism with goiter reported in Tenterfield Terriers, as well as Toy Fox and Rat Terriers – due to dyshormonogenesis, caused by thyroid gland failure to produce sufficient hormone to inhibit pituitary release of TSH

 

PATHOGENESIS:

·      Primary hypothyroidism is divided into two main categories: (1) Lymphocytic thyroiditis, and (2) Idiopathic thyroid atrophy

·      The disease can progress from lymphocytic thyroiditisà antibody-positive hypothyroidism à non-inflammatory thyroid atrophy

·      The autoimmune mechanism responsible for primary hypothyroidism is unknown

·      Receptors for thyroid hormones are on sebocytes and cells of the outer root sheath and dermal papilla

·      Thyroid hormones stimulate anagen stage of hair cycle; in hypothyroidism there is an increase in telogen follicles and empty follicles (kenogen)

·      Telogen follicles lose hair shafts easily, resulting in alopecia

·      Thyroid hormones influence serum and cutaneous fatty acid concentrations and sebaceous gland function resulting in seborrhea; seborrhea predisposes the dog to secondary staphylococcal or Malassezia infections

·      Secondary dermatitis is also due to alterations in the cutaneous barrier and immune dysfunction; pruritus may be present when secondary infection is present

·      Myxedema occurs in some hypothyroid dogs; thyroid hormones help regulate production of dermal glycosaminoglycans; hyaluronic acid accumulates in the dermis with lack of these hormones

 

TYPICAL CLINICAL FINDINGS:

·      Cutaneous signs in dogs:

·      Alopecia develops in areas of friction (elbows, hips, neck, bridge of nose) and on the entire length of the tail

·      Bilaterally symmetric truncal alopecia less common than previously thought

·      Seborrhea; dry, coarse, brittle, easily epilated haircoat that fails to regrow after clipping

·      Hyperpigmentation and hypotrichosis with fine retained hairs that give appearance of a “puppy coat”

·      Myxedema (mucin accumulation) occurs in severe cases and may result in “tragic facial expression”

·      Non-cutaneous signs in dogs:

·      Weakness, stiffness, decreased exercise tolerance, muscle wasting, and obesity are classic clinical signs that may or may not be present

  • Normocytic-normochromic nonregenerative anemia in 50% of dogs
  • Hypercholesterolemia (80% of dogs) can lead to atherosclerotic changes in vessels of the heart, kidney, and GI tract (C-M05)

 

TYPICAL GROSS FINDINGS:

·      Alopecia of tail (“rat tail”) and in areas of friction

·      Secondary seborrheic skin disease, pyoderma, pododermatitis, and/or otitis externa

·      Myxedema, if present, is most pronounced on the face (forehead, eyelids, around the lips)

·      Hyperpigmentation, lichenification, and comedones (not specific)

  • Atherosclerotic changes in vessels of the heart, kidney, and GI tract

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·      Non-specific and simply suggest an endocrinopathy: Orthokeratotic hyperkeratosis with follicular keratosis, epidermal hyperplasia, and hair follicles in hairless telogen (kenogen)

·      Acanthosis of epidermis and follicular infundibulm in the face of follicular growth cycle arrest (telogen phase) helps differentiate hypothyroidism

·      Other possible histologic changes: increased dermal mucin (myxedema), thickened dermis, flame follicles, follicular infundibular hyperkeratosis with plugging of the follicular opening, epidermal melanosis, vacuolation of hypertrophied arrector pili muscles, and secondary staphylococcal and/or malassezial dermatitis

 

ADDITIONAL DIAGNOSTIC TESTS:

·      Total T4 (TT4) is sensitive, but not specific; if TT4 is decreased then thyroid stimulating hormone (TSH) and/or free T4 by dialysis (fT4D) should be measured

·      Decreased fT4D is highly specific for hypothyroidism in non-sighthound dogs

  • Greyhounds and other sight hounds normally have lower total T4 and free T4 concentrations than other dogs

·      Serum T3 correlates poorly with clinical disease; TT4 may be decreased in non-thyroidal illnesses (euthyroid sick syndrome)

 

DIFFERENTIAL DIAGNOSIS:

·      Other endocrine dermatoses may have similar gross and microscopic findings thus clinical differentiation is required

·      Hyperadrenocorticism/hyperglucocorticoidism (I-M23): Dystrophic mineralization involving dermal collagen, dermal thinning, epidermal and sebaceous atrophy

·      Telogen effluvium: Very uncommon, increased numbers of hair follicles in telogen phase

·      Alopecia X: Specific affected breeds (plush coated dogs such as Pomeranians); diffuse, prominent formation of flame follicles

·      Hyperestrogenism (I-M23): Consider other clinical signs; in males, may be due to canine Sertoli cell tumor (often associated with cryptorchidism)

·      Estrogen-responsive and testosterone-responsive dermatoses

·      Follicular dysplasia

 

COMPARATIVE PATHOLOGY:

·      Hypothyroidism in other animals occurs less frequently and is usually in association with iodine deficiency and goiter

·      Sheep and cattle: Hereditary in Merino sheep and Afrikaner cattle - defect in biosynthesis of thyroid hormone produces symmetrical hypotrichosis and thick, myxedematous, wrinkled skin

·      Goats: Saanen and dwarf goat strains - hereditary congenital thyroglobulin deficiency produces symmetrical hypotrichosis and thick, myxedematous, scaly skin

·      Cats: Naturally occurring disease has only rarely been reported; hypothyroidism in cats is almost always iatrogenic following treatment for hyperthyroidism

  • Other possible causes: Familial hypothyroidism in Abyssinian cats

·      Birds: TSH stimulation test needed in birds due to short circulating half-life of thyroid hormones and seasonal fluctuations

 

REFERENCES:

1.    Ferguson DC, Hoenig M. Endocrine system. In: Latimer KS, ed. Veterinary Laboratory Medicine Clinical Pathology. 5th ed. Oxford, UK: Wiley-Blackwell; 2011:312-313

2.    Hargis AM, Myers S. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017: 1134-1135.

3.    Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 5th ed. Philadelphia, Pennsylvania: Elsevier; 2016:587-588


Click the slide to view.



Click on image for diagnostic series.



Back | Home | Contact Us | Links | Help |