JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

August 2023

P-B16

 

Signalment (JPC #4081936-02): Domestic brown (fancy) rat

 

HISTORY: This 13-month-old female domestic brown (fancy) pet rat presented for acute weight loss, lethargy, behavioral change, and hair loss. At clinical presentation, the rat was dull but responsive and tachycardic.

 

HISTOPATHOLOGIC DESCRIPTION:  

SLIDE A: Lung (2 sections): Affecting 40-50% of the two lung sections, bronchioles are diffusely markedly ectatic (bronchiectasis), compressing adjacent parenchyma. Bronchiolar lumens are variably filled to occluded by an exudate composed of basophilic to eosinophilic cellular and karryorhectic necrotic debris, mineral, viable and degenerate neutrophils, fewer large foamy macrophages, multinucleate giant cells (foreign body and Langhans type), lymphocytes, plasma cells, and mucus. This exudate often extends thorough the bronchiolar wall, infiltrating the peribronchiolar connective tissue and filling adjacent alveoli. Multifocally, bronchioles exhibit one or more of the following changes: Discontinuous walls with loss or sloughing of the bronchiolar epithelium (necrosis); attenuation with loss of cilia (degeneration); or hyperplasia, piling up to 5 cell layers deep with goblet cell hyperplasia and rare mitoses (regeneration). Multifocally, bronchiolar cilia are colonized by numerous lightly basophilic filamentous (0.5 x 8 µm) bacilli. There are peribronchiolar and perivascular infiltrates of lymphocytes, plasma cells (mild BALT hyperplasia), and fewer foamy macrophages that often contain brown globular to granular pigment (hemosiderin). Multifocally within adjacent, less affected alveoli, there is a pale eosinophilic homogenous fluid (edema) admixed with increased numbers of foamy alveolar macrophages. Multifocally, alveolar septa are mildly expanded by edema and few macrophages.  

 

SLIDE B: Warthin-Starry stain: There is heavy colonization of the ciliary borders of bronchiolar epithelial cells by slender, filamentous, argyrophilic bacteria that are 0.5 X 8 microns and are usually arranged parallel to the cilia.

 

MORPHOLOGIC DIAGNOSIS: Lung: Bronchiolitis, necrosuppurative and lymphohistiocytic, chronic-active, multifocal to coalescing, moderate, with bronchiectasis, mild bronchiolar associated lymphoid hyperplasia, and many cilia-associated filamentous argyrophilic bacilli, domestic brown (fancy) rat, rodent.

 

ETIOLOGIC DIAGNOSIS: Filobacterial bronchopneumonia

 

CAUSE: Filobacterium rodentium (formerly CAR bacillus)

 

GENERAL DISCUSSION: 

• Gram-negative, argyrophilic, filamentous, gliding bacteria that colonizes the ciliated epithelium of airways.
• Previously unclassified and known as CAR bacillus; recently rodent isolates have been named and classified as Filobacterium rodentium under the family Filobacteriaceae within phylum Bacteroidetes; non-rodent isolates are not included in the recent classification
• Different bacterial species, possibly of different genera, may represent CAR bacilli in different mammalian hosts
• Colonize the ciliated epithelium of the respiratory tract of rats, mice, gerbils, rabbits, goats, pigs, cattle, cats, and wild deer 
• F. rodentium can produce significant chronic respiratory disease, particularly in rats, but most rats with clinical disease are co-infected with one or more agents: Mycoplasma pulmonis, Sendai virus, coronavirus, Streptococcus pneumoniae, Corynebacterium kutscheri, Bordetella bronchiseptica, Klebsiella pneumoniae, or Pasteurella pneumotropica
• Retrospective staining suggests that CAR bacillus may have been associated with outbreaks of respiratory disease for decades

 

PATHOGENESIS:

• Direct contact
  • Dam to offspring
  • Intracage
• Colonization of the upper respiratory tract and airways
• F. rodentium interdigitate between ciliaàinduce lymphocytic bronchitis and bronchiolitis, bronchiectasis, and abscesses

 

TYPICAL CLINICAL FINDINGS:

 

TYPICAL GROSS FINDINGS: 

• Noncollapsing lungs; cranioventral lung lobe consolidation
• Slightly elevated opaque yellow to gray foci tracking airways may be visible on the pleural surface

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Chronic suppurative bronchitis and bronchiolitis
• Bronchial and bronchiolar epithelial hyperplasia and hypertrophy, mucosal and peribronchial lymphoplasmacytic infiltrates, and neutrophilic exudation 
• Bronchiectasis
• Mucopurulent alveolitis
• Can be subclinical with minimal or no lesions
• Slender filamentous bacteria present within the ciliated borders of bronchiolar epithelial cells, lying parallel to and among the cilia
• Gram-negative, argyrophilic (Warthin-Starry) filamentous bacilli

 

ULTRASTRUCTURAL FINDINGS:

• Increased epithelial cell height, decreased club (formerly Clara) cells, increased goblet cells
• Decreased numbers of cilia on ciliated cells
• Bacilli among and parallel to cilia with one end of the organism on or near the cell membrane
• Bacilli are 0.15 - 0.35 µm in diameter, 3.5 - 9.0 µm long, fusiform, with a taper and rounded slightly knobbed ends

 

ADDITIONAL DIAGNOSTIC TESTS:

• IFA, ELISA, PCR
• Can be grown in cell culture, cell culture medium, and embryonated hen’s eggs

 

DIFFERENTIAL DIAGNOSIS: 

• Mycoplasma pulmonis (P-B01) is the most important differential diagnosis for F. rodentium; lesions may be identical, except for the lack of organisms visible among the cilia
• Corynebacterium kutscheri (P-B05) – Large colonies of Gram-positive bacilli; multifocal suppurative pneumonia (abscesses) without bronchiectasis
• Streptococcus pneumoniae (P-B07) – Large colonies of Gram-positive cocci; fibrinopurulent bronchopneumonia, pleuritis, pericarditis, meningitis
• Sendai virus (P-V05, parainfluenza 1) – Usually subclinical; bronchitis, bronchiolitis, and alveolitis
• Rat coronavirus (D-V05, S-V02; sialodacryoadenitis virus and Parker's rat coronavirus): Produce lacrimal, salivary, and pulmonary lesions in young rats.
• Pneumonia virus of mice/pneumovirus (paramyxovirus) – Acute multifocal, non-suppurative vasculitis and interstitial alveolitis with necrosis
• Pneumocystis carinii (P-F07) – Diffuse interstitial pneumonia with alveolar flooding by an eosinophilic foamy or “honeycomb” exudate (edema + organisms) with fungal cysts containing fungal bodies

 

COMPARATIVE PATHOLOGY:

• There are distinct antigenic differences between CAR bacillus in different species; supported by the recent classification of rodent isolates into the species Filobacterium rodentium
• In calves, there is an association between CAR bacilli and the presence of lymphoid follicles in the airway wall; unknown if the relationship is causal.
• Porcine CAR bacilli are nonpathogenic and found in pigs with and without respiratory disease.
• In rabbits, 16sRNA analysis indicates that the rabbit isolate belongs to a different genus than the rat CAR bacillus; rabbits develop rhinitis following inoculation with rabbit isolate, but not rat isolate.

 

 

References: 

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents & Rabbits, 4th ed. Ames, IA: Blackwell Publishing Ltd; 2016:61, 133-134, 201, 272-273. 
2. Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier; 2015:547. 
3. Delaney MA, Treuting PM, Rothenburger JL. Rodentia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals, Cambridge, MA Academic Press; 2018: 510.

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