JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-M04 (NP)

 

Slide A: Signalment (JPC #2086741): 11-year-old male Boston terrier

 

HISTORY: The dog has a history of tricuspid and mitral valve insufficiency.

 

HISTOPATHOLOGIC DESCRIPTION:  

Lung: Approximately 60% of the distal margins of lung are consolidated, characterized by alveoli that are filled and expanded by accumulations of amorphous, homogeneous, amphophilic, anisotropic, hyaline material up to 200µm in diameter that is often surrounded by granulomatous inflammation characterized by macrophages that occasionally contain phagocytized material, rare multinucleate giant cells, and lamellar bands of reactive fibroblasts and collagen (fibrosis), admixed with low numbers of plasma cells and lymphocytes. Multifocally there is moderate type II pneumocyte hyperplasia. The perivascular and peribronchiolar adventitia is expanded by clear space with ectatic lymphatics (edema) and low numbers of lymphocytes and plasma cells. Multifocally there are small clusters of macrophages that contain brown to black, granular, intracytoplasmic pigment (anthracosilicosis).

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, granulomatous, multifocal, moderate, with abundant intra- and extracellular, homogenous, amphophilic, hyaline material, Boston terrier, canine.

 

CONDITION: Pulmonary hyalinosis

 

Slide B: Signalment (JPC #2695446): 18-week-old C57BL/6L viable moth-eaten male mouse (Mus musculus)

 

HISTORY: This mouse was from a mutant colony maintained at the Jackson laboratory.

 

HISTOPATHOLOGIC DESCRIPTION:  

Lung: Multifocally affecting 60% of this section, alveoli are variably filled and expanded by abundant acicular to rhomboid-shaped, intensely eosinophilic crystals that are often intracellular within macrophages and rare multinucleate giant cells. Multifocally, bronchiolar epithelial cytoplasm is expanded by similar eosinophilic crystalline material.  In more severely affected areas, alveolar septa are thickened by moderate type II pneumocyte hyperplasia and a mild increase in fibrous connective tissue (fibrosis). Multifocally, alveolar macrophages contain intracytoplasmic, light brown, granular to globular pigment (hemosiderin). The perivascular and peribronchiolar adventitia is expanded by clear space with ectatic lymphatics (edema) and low numbers of lymphocytes and plasma cells.

 

MORPHOLOGIC DIAGNOSIS: Lung: Alveolitis, granulomatous, multifocal, moderate, with abundant intrahistiocytic eosinophilic crystalline material and hemosiderosis, C57BL/6L viable moth-eaten mouse (Mus musculus), rodent.

 

CONDITION: Acidophilic macrophage pneumonia (eosinophilic crystalline pneumonia)

 

CAUSE: Unknown

 

GENERAL DISCUSSION: 

 

Pulmonary hyalinosis

• Occasional incidental finding in older dogs, mostly brachycephalic breeds, especially boxers 
• Pulmonary granulomas with PAS-positive bodies

 

Acidophilic Macrophage Pneumonia (AMP, eosinophilic crystalline pneumonia)

• Seen in all mouse strains; B6 (especially moth-eaten mutation), 129, and Swiss strains have higher prevalence
• Intrahisitocytic and free crystals composed primarily of Ym1 and/or Ym2 chitinase

 

PATHOGENESIS:  

Pulmonary hyalinosis:

 

Acidophilic Macrophage Pneumonia:

• May arise spontaneously, as a response to pulmonary inflammation, or secondary to pulmonary neoplasia
• Spontaneous form may be related to deficiency in p47 Phox

 

TYPICAL CLINICAL FINDINGS:  

Pulmonary hyalinosis: None; often incidental finding

 

Acidophilic Macrophage Pneumonia: Dyspnea, can cause mortality especially in B6 mice

 

TYPICAL GROSS FINDINGS: 

Pulmonary hyalinosis: Grayish white to tan, nodular or confluent, firm to gritty, mainly subpleural foci, especially at the narrow ventral margins of the lungs

 

Acidophilic Macrophage Pneumonia: Lobar to diffuse tan to red discoloration of the non-collapsing lungs

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Pulmonary hyalinosis

• Multifocal pulmonary accumulations of macrophages and giant cells containing hyaline amorphous or laminated amphophilic material; birefringent

 

Acidophilic Macrophage Pneumonia 

• Free and intrahistiocytic (including multinucleate giant cells) acicular to rhomboid eosinophilic crystals within: lumina of alveoli, alveolar ducts, terminal airways, and bronchiolar glands 
• May be accompanied by a mild granulomatous interstitial pneumonia

 

ADDITIONAL DIAGNOSTIC TESTS:

Pulmonary hyalinosis

• Histochemical stains: 

• Positive: Material is strongly PAS positive, Alcian blue positive

 

DIFFERENTIAL DIAGNOSIS:

Pulmonary hyalinosis

• Alveolar microlithiasis: numerous phosphorus-rich lamellated “microliths” or “calcospherites”; extracellular material. 
• Pulmonary lipidosis: alveoli filled with foamy macrophages containing endogenous or exogenous lipid 
• Corpora amylacea: Are NOT birefringent; concentrically laminated; often have pigmented core; incite only slight inflammation; PAS weakly positive

 

Acidophilic Macrophage Pneumonia 

• Alveolar lipoproteinosis (phospholipidosis): Intra-alveolar acellular granular acidophilic or amphophilic material; consists of surfactant proteins and phospholipids; strongly PAS positive; TII pneumocyte hypertrophy; associated with toxic aerosol inhalation; occurs in rats, mice and goats 
• Gross: Pneumocystis carinii causes non-collapsing pneumonia in immune compromised mice

 

COMPARATIVE PATHOLOGY:  

• Mice and rats

• Epithelial Hyalinosis

• Often associated with AMP, similar hyaline eosinophilic material is present in the cytoplasm of olfactory, nasal respiratory, middle ear, trachea, lung, stomach, gall bladder, bile duct, and/or pancreatic duct epithelium
• Square to rhomboid extracellular crystals may accumulate in associated glands, and cause bile duct and gallbladder dilatation and thickening
• Crystals composed of Ym1 and Ym2 chitinase

 

References:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:3, 94-95, 100.
2. Caswell JL, Williams KJ. Respiratory system. In: Maxie ME, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 2. Philadelphia, PA: Elsevier; 2016:517.
3. Lopez A, Martinson SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:571. 
4. Radaelli E, Castiglioni V, Recordati C, et al. The Pathology of Aging 129S6/SvEvTac Mice. Vet Pathol. 2016 Mar;53(2):477-92.

 

 

Click the slide to view.

---