JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2016

I-M19

 

Signalment (JPC# 2507404):  Adult male Sprague-Dawley rat

HISTORY:  This rat was in the control group of a subchronic toxicity study. Gross morphological changes were limited to bilaterally enlarged pinnae.

HISTOPATHOLOGIC DESCRIPTION:  Pinna:  The pinna is thickened up to 5mm by nodules of disrupted and disorganized auricular cartilage.  In some areas, cartilage is characterized by thick, irregular islands of amphophilic cartilaginous matrix surrounding aggregates of closely approximated chondrocyte lacunae (chondromatous regeneration).  Occasionally, islands of cartilage exhibit loss of basophilic staining within the matrix (degeneration) or are fragmented with shrunken, hypereosinophilic, pyknotic chondrocytes or empty lacunae (necrosis).  Diffusely infiltrating the dermis and separating and surrounding myocytes, as well as multifocally infiltrating the perichondrium and disrupting auricular cartilage, is an inflammatory infiltrate composed of many viable neutrophils, macrophages, lymphocytes, plasma cells and few Langhans-type multinucleated giant cells, admixed with reactive fibroblasts, immature fibrous connective tissue and small caliber blood vessels (granulation tissue) progressing to more mature fibrous connective tissue.  Multifocally, the cartilage matrix is replaced by eosinophilic, homogenous material that surrounds osteocytes within lacunae, and contains extensive areas of basophilic, angular to granular mineralized matrix (osseous metaplasia).  Osteoblasts and multinucleated osteoclasts surround these metaplastic islands and trabeculae of woven bone which also contain bone marrow.  Multifocally, dermal collagen fibers are loosely arranged and separated by an eosinophilic amorphous material and lymphatics are moderately ectatic and filled with eosinophilic proteinaceous fluid (edema).  The overlying epidermis is mildly hyperplastic with mild acanthosis and intracellular edema.

MORPHOLOGIC DIAGNOSIS:  Pinna, cartilage:  Degeneration, multifocal, moderate, with cartilaginous regeneration, fibroplasia, osseous metaplasia and granulomatous dermatitis, Sprague-Dawley rat, rodent.

ETIOLOGIC DIAGNOSIS:  Idiopathic auricular chondritis

CONDITION:  Auricular chondritis

GENERAL DISCUSSION: 

• Etiology unknown, hereditary basis has been suggested
• Aged Sprague-Dawley, Wistar, and fawn-hooded rats predisposed
• Disease is always bilateral; increased incidence with age
• Resembles condition inducible in rats by immunization with Type II collagen, a predominant component of cartilaginous matrix
• Has been proposed as a model for relapsing polychondritis, a human disease
• Involving several cartilage-containing tissues including the ear

PATHOGENESIS:

• Trauma (cagemates, metal ear tags) suspected as inciting cause, but frequently occurs without history or evidence of trauma
• Speculated that metal ions (Zn and Cu and Fe) from metal ear tags incite autoimmune process via matrix metalloproteinases
• Tagged ears have increased amounts of Metallothionein (MT-I and MT-II) with increased expression of Th 1 cytokines (IFN-γ, TNF-α, and IL-2)
• Two proposed mechanisms of osseochondrous proliferation:
  • Cartilage degeneration (characterized by chondrolysis and splitting of pinnal cartilage plate) > perichondrial fibrous proliferation > differentiates into fibroadipose tissue > progresses to fibrochondrous and/or osseochondrous tissue
  • Focal granulomatous inflammation without chondrolysis > fibroblasts proliferate within the granulomatous inflammation > differentiate into fibrochondrous tissue with subsequent chondrous and osseous differentiation

TYPICAL CLINICAL FINDINGS: 

• In fully developed lesions, ears are misshapen and contain firm nodules
• Usually, there is no evidence of inflammation, pain, or pruritus
• Lesions reach a static point, but do not regress completely

TYPICAL GROSS FINDINGS: 

• Firm, multinodular to diffuse thickening of pinnae
• Bilateral lesions extend peripherally from the base of the pinnae
• Occasionally, pinnae are uniformly thickened rather than having nodular lesions

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• There is degeneration and lysis of the auricular cartilage plate with granulomatous inflammation and proliferative immature cartilaginous nodules and fibrosis
• Osseous metaplasia is characteristic in advanced lesions

ADDITIONAL DIAGNOSTIC TESTS: 

• Diagnosis is made on the basis of history, clinical signs, and histopathology

COMPARATIVE PATHOLOGY: 

• Human: Relapsing polychondritis is associated with auricular chondritis, inflamed cartilage in other sites, and antibodies to type II collagen, IgG and C3
• Mice: Rare, associated with trauma to pinna (metal ear tags)
• Antibodies to type II collagen have not been demonstrated in the spontaneous auricular chondropathy of rats, and unlike relapsing polychondritis, only auricular cartilage is involved
• Cats, dogs, horses: Rare condition also known as relapsing polychondritis thought to be an immune mediated response to type II collagen in cartilage (rarely have concurrent polyarthritis, tracheal and laryngeal chondritis, nasal chondritis, etc)

REFERENCES: 

1. Chiu T, and Lee KP. Auricular chondropathy in aging rats. Vet Pathol. 1984;21(5):500-504.
2. Khan AJ, Lynfield Y, Baldwin H. Relapsing polychondritis: Case report and review of the literature. 1994;54(2):98‑100.
3. Kitagaki, M, Suwa T, Yanagi M, Shiratori K. Auricular chondritis in young ear-tagged Crj:CD (SD)IGS rats. Lab Anim Sci. 2003; 37(3): 249-253.
4. Kitagaki M. and Hirota M. Auricular chondritis caused by metal ear tagging in C57BL/6 mice. Vet Pathol. 2007; 44:458-466.
5. Linton CG, Gordon BE, Richardson JA. Diagnostic exercise: Thickened auricular pinnae in a Sprague Dawley rat. Lab Anim Sci. 1994; 44(1):69-70.
6. McEwen BJ, Barsoum NJ. Auricular chondritis in Wistar rats. Lab Anim Sci. 1990; 24(3):280-283.
7. Meingassner JG. Sympathetic auricular chondritis in rats: A model of autoimmune disease. Lab Anim Sci. 1991; 25:68-78.
8. Percy DH, Barthold SW. Rat. In: Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:159-160.
9. Yoshitomi K, Brown HR. The ear and pinna. In: Boorman G, Eustis S, Elwell MR, Montgomery CA, MacKenzie WF, eds. Pathology of the Fischer Rat. New York, NY:Academic Press; 1990: 227-238.

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