JPC SYSTEMIC PATHOLOGY
Signalment (AFIP 2086741): 11-year-old male Boston terrier
HISTORY: The dog has a history of tricuspid and mitral valve insufficiency.
Lung: Affecting up to 60% of the distal margins of examined lung sections, alveoli are filled and expanded by accumulations of an amorphous, homogeneous, amphophilic, anisotropic, hyaline material up to 200um in diameter that are often surrounded by granulomatous inflammation characterized by macrophages that occasionally contain phagocitized material, rare multinucleate giant cell macrophages, 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 containing brown to black granular pigment (anthracosilicosis).
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, granulomatous, multifocal, moderate, with abundant intra- and extracellular, homogenous, amphophilic, hyaline material, Boston terrier, canine.
CONDITION: Pulmonary hyalinosis
Signalment (AFIP 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.
Lung: Multifocally affecting 60% of this section, alveoli are filled and expanded by abundant acicular to rhomboid-shaped, intensely eosinophilic crystals which are often packed within macrophages and rare multinucleate giant cell macrophages. Multifocally, bronchiolar epithelium 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, macrophages also contain a 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)
- Important note: This systemic presents two unrelated entities, both with amorphous material that accumulates in pulmonary macrophages
- 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, though B6 and 129 strains have higher prevalence
- Crystals composed primarily of Ym1 and/or Ym2 chitinase
- May arise spontaneously, as a response to pulmonary inflammation, or secondary to pulmonary neoplasia
- Spontaneous form may be related to deficiency in p47 Phox
PATHOGENESIS: Unknown, suspected response to chronic lung injury (e.g. pneumoconiosis or experimental radiation pneumonitis)
TYPICAL CLINICAL FINDINGS: None; often incidental finding
TYPICAL GROSS FINDINGS:
- Grayish white to tan, nodular or confluent, firm to gritty, mainly subpleural foci, especially at the narrow ventral margins of the lungs
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Multifocal pulmonary accumulations of macrophages and giant cells containing hyaline amorphous or laminated amphophilic material; birefringent
- Macrophages and giant cells are often surrounded by plasma cells, lymphocytes and small amounts of fibrous connective tissue
Acidophilic Macrophage Pneumonia
- Free and intrahistiocytic (including multinucleate giant cells) acicular to rhomboid eosinophilic crystals within alveoli and bronchioles; also may see crystals in bronchiolar epithelium; may be accompanied by a mild granulomatous interstitial pneumonia
ADDITIONAL DIAGNOSTIC TESTS:
- Special stains: Material is strongly PAS positive and Alcian blue and oil red O positive
- GMS, Giemsa, Prussian blue, Congo Red, and toluidine blue staining is negative
- Alveolar proteinosis (phospholipidosis): Acellular granular acidophilic or amphophillic material; consists of surfactant proteins and phospholipids; strongly PAS positive; inflammatory changes usually minimal; occurs in rats, mice and goats
- Corpora amylacea: Are NOT birefringent; concentrically laminated; often have pigmented core; incite only slight inflammation; PAS weakly positive
- Pulmonary microlithiasis: Concentrically laminated PAS-positive concretions; diffuse lesion; extracellular deposits; composed of calcium and phosphorus
- Vegetable aspiration: Honeycomb mesh when stained with silver impregnation; a few of the granulomas may have coagulation necrosis
- Endogenous lipid pneumonia (cholesterol pneumonia): Numerous lipid-laden macrophages
- Mice and rats:
- Often associated with AMP, hyaline eosinophilic material is present in the cytoplasm of olfactory, nasal respiratory, middle ear, trachea, lung, stomach, gall bladder, bile duct or pancreatic duct epithelium
- Square to rhomboid extracellular crystals may accumulate in associated glands
- Crystals composed of Ym1 and Ym2 chitinase
- Recent report of pulmonary hyalinosis in captive sugar gliders
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:94-95.
- Billups LH, Liu SK, Kelly DF, Garner FM. Pulmonary granulomas associated with PAS-positive bodies in brachycephalic dogs. Vet Pathol.1972;9:294-300.
- 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.
- Dagle GE, Filipy RE, Adee RR, Stuart BO. Pulmonary hyalinosis in dogs. Vet Pathol. 1976;13:138-42.
- Hoenerhoff MJ, Starost MF, Ward JM. Eosinophilic crystalline pneumonia as a major cause of death in 129S4/SvJae mice. Vet Pathol. 2006:682-688.
- Radaelli E, Castiglioni V, Recordati C, et al. The Pathology of Aging 129S6/SvEvTac Mice. Vet Pathol. 2016 Mar;53(2):477-92.
- Sokol SA, Agnew DW, Lewis AD, et al. Pulmonary hyalinosis in captive sugar gliders (Petaurus breviceps). J Vet Diagn Invest. 2017 Apr 1:1040638717703683. [Epub ahead of print]
- Ward JM, Yoon M, Anver MR, et al. Hyalinosis and Ym1/Ym2 gene expression in the stomach and respiratory tract of 129S4/SvJae and wild-type and CYP1A2-null B6, 129 mice. Am J Pathol. 2001 Jan;158(1):323-32.