Signalment:  

3-month-old mixed breed male puppy (Canis familiars). This puppy presented for a complete necropsy following euthanasia. It had a 1.5 week history of myoclonus and tested positive for canine distemper virus on PCR. This puppy was previously vaccinated twice with standard puppy vaccines (DH2PP) and housed with six other puppies who were also positive for canine distemper virus.


Gross Description:  

The puppy was thin, had a body condition score of 2/5 and was in fair post-mortem condition. The lungs failed to fully collapse after opening the thoracic cavity. Diffusely, lung lobes were pale pink and rubbery to firm when palpated. Multifocally, there were variably sized, yellow to greenish firm slightly raised areas of consolidation. Sectioned pulmonary parenchyma bulged and oozed small amounts of serous fluid. The trachea contained moderate amounts of serosanguineous fluid mixed with mucus. Teeth were grossly normal.


Histopathologic Description:

Teeth, alveolar bone and gingiva: Each section has deciduous and developing permanent teeth. In the permanent tooth, ameloblasts lining enamel are multifocally swollen, hypereosinophilic, and have fragmented to vacuolated cytoplasm (degeneration). Frequently, ameloblasts contain intracytoplasmic and intranuclear 3-5 μm diameter, round to irregular, bright eosinophilic inclusions. Syncytia with 5-20 nuclei and abundant eosinophilic cytoplasm are multifocally present and contain similar intracytoplasmic inclusions. Ameloblasts are occasionally disorganized with loss of cell polarity and are piled 5-6 cell layers deep. Rarely, there is individual cell necrosis of ameloblasts characterized by shrunken cells, loss of cellular details and pyknotic nuclei. (The dentin and/or enamel are artifactually dislocated in some sections.)

Findings in other tissues (not submitted) include necrosuppurative bronchopneumonia, demyelination of cerebellum and brain stem, neuronal degeneration and necrosis of cervical, thoracic, and lumbar spinal cord segments, myocardial degeneration and necrosis, and lymphoid depletion of the spleen, lymph nodes and tonsils. Similar inclusions were present in the respiratory epithelium of the lung and trachea, mucosal epithelium of the renal pelvis and urinary bladder, astrocytes of the cerebrum and cerebellum and neurons of the spinal cord. 


Morphologic Diagnosis:  

Teeth, ameloblasts: degeneration and necrosis, multifocal, moderate to severe, with syncytia and eosinophilic intranuclear and intracytoplasmic inclusions.


Condition:  

Distemper


Contributor Comment:  

Canine distemper virus (CDV) is known to cause systemic disease in dogs, fox, coyotes, ferrets and other animals worldwide due to its ability to infect a variety of cell types, including neuroendocrine, epithelial, mesenchymal, and hematopoietic.(1,6) CDV is in the Morbillivirus genus and is closely related to measles virus and rinderpest virus.(3,6) The virus is described as a 150-250 nm diameter enveloped virion containing a single negative-sense RNA strand that encodes for various glycoproteins.(3,6) The H glycoprotein is likely used for attachment to the host cell during initial infection, therefore adequate immune response against H protein may lessen or prevent disease.(6)

Transmission of CDV occurs via nasal or oral routes where the virus replicates immediately in the lymphoid tissue causing marked immunosuppression.(1,3,6) Depending on the host response, age and virus strain, the animal will either clear the infection or develop systemic disease. The virus has a propensity to infect epithelial cells in various organs, especially the central nervous system.(3,6) Dogs with partial immunity can be viremic and shed virus for an extended period of time in secretions; clinical signs in these animals are minor to absent and can later manifest as hyperkeratosis of the foot pad and nose.(3,6) Disease following vaccination with modified live CDV vaccine has been occasionally reported;(3,6) however, widespread use of prophylactic vaccination has successfully controlled the disease and is currently uncommon in vaccinated dog populations.(3) A rare condition caused by CDV infection in mature vaccinated dogs is a progressive chronic encephalomyelitis known as old dog encephalitis.(1,3,6)

Clinical signs manifest as respiratory, neurologic, and/or enteric disease. Less commonly, young dogs can develop dental lesions, ocular lesions, and neonatal myocardial degeneration and necrosis.(3) Dental lesions following infection may include necrosis and cystic degeneration of ameloblasts, formation of syncytia, disorganization of ameloblasts, and prominent eosinophilic cytoplasmic viral inclusions.(3,5) Delayed changes in the enamel occur in animals that survive infection and are described as focal defects in the enamel, which appear as depressions (pits) or well-delineated areas of hypoplasia.(3,4) This occurs because the virus directly infects ameloblasts and causes disruption of enamel formation.(4) Other dental abnormalities attributed to CDV include dental impaction, partial eruption, and oligodontia.(2) In the present case, the puppy was euthanized before gross or microscopic evidence of enamel hypoplasia could be detected. 

CDV can be diagnosed by a variety of methods; however, molecular assays such as reverse transcriptase polymerase chain reaction (RT-PCR) and real-time RT-PCR are considered sensitive and specific.(6) Distinction between field and vaccine strains is possible via nested RT-PCR assays. Postmortem diagnosis is achieved when there is evidence of systemic or CNS disease and the presence of characteristic inclusion bodies supported by positive immunohistochemistry (IHC) or other ancillary tests. Ameloblasts in the present case had intense multifocal cytoplasmic staining for CDV, which correlated with histologic findings. Additionally, cerebrum and brainstem were IHC positive for CDV. In this case, an unequivocal diagnosis of CDV was made due to the spectrum of gross and microscopic lesions seen along with CDV positive ameloblasts and the reported clinical history. 


JPC Diagnosis:  

Developing tooth, ameloblasts; stratum intermedium: Degeneration and necrosis, multifocal, moderate, with eosinophilic intracytoplasmic viral inclusions and multinucleated viral syncytial cells.


Conference Comment:  

Conference participants agreed that this is an excellent case, providing a unique microscopic view of a lesion that most pathologists have only seen as a gross photograph.

The contributor provides a thorough review of the pathology of canine distemper virus. In addition to canine distemper, measles and rinderpest virus, the genus Morbillivirus comprises peste-des-petits-ruminants virus of goats and sheep, dolphin/porpoise morbillivirus, and phocine distemper virus.(1) Canine distemper virus has a broad host range; besides canids, infection has also been demonstrated in mustelids (ferrets, mink), raccoons, collared peccaries, non-human primates, seals, and felids, including lions, tigers, lynx, bobcat and even domestic cats.(1,6,7)

The signaling lymphocyte activation molecule (SLAM) is a receptor used by morbilliviruses to invade immune cells.(7) Variations in species specificity and infection of aberrant species with canine distemper virus was historically thought to result from amino acid alterations in SLAM and/or the hemagglutinin (HA) protein that binds SLAM; however, recent studies suggest that variability of the hemagglutinin protein is less important in determining infectivity and pathogenicity in various host species than was previously believed. Regardless, CDV has emerged as a potentially devastating pathogen in certain wild felid populations.(7)

Although morbilliviruses are notable for producing both intracytoplasmic and intranuclear viral inclusions, conference participants observed that, in this case, intranuclear inclusions were poorly discernible, possibly as a result of the decalcification process.


References:

1. Beineke A. Pathogenesis and immunopathology of systemic and nervous canine distemper. Vet Immunol Immunopathol. 2009;127:1-18. 

2. Bittegeko SB, Arnbjerg J, Nkya R, Tevik A. Multiple dental developmental abnormalities following canine distemper infection. J Am Animal Hospital Assoc. 1995;31:42-45.

3. Caswell JL Williams KJ. Respiratory System. In: Maxie MG, ed. Jubb, Kennedy, and Palmers Pathology of Domestic Animals, 5th ed. Vol. 2. Philadelphia, PA: Elsevier Saunders; 2007:635-638.

4. Dubielzig RR. The effect of canine distemper virus on the ameloblastic layer of the developing tooth. Vet Pathol. 1979;16:268-270. 

5. Dubielzig RR, Higgins RJ, Krakowka S. Lesions of the enamel organ of developing dog teeth following experimental inoculation of gnotobiotic puppies with canine distemper virus. Vet Pathol. 1981;18:684-689. 

6. Martella V. Canine distemper virus. Vet Clin North Am Small Anim Pract. 2008;38:787-797. 

7. Terio KA, Craft ME. Canine distemper virus (CDV) in another big cat: should CDV be renamed carnivore distemper virus? MBio. 2013;4(5):e00702-13.



Click the slide to view.



4-1. Lungs


4-2. Developing permanent tooth (tooth bud)


4-3. Developing permanent tooth (tooth bud)


4-4. Developing permanent tooth (tooth bud)



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