JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2018004): Unknown age, female Sprague‑Dawley rat
HISTORY: This Sprague‑Dawley rat was sacrificed at the termination of a steroid dose‑range‑finding study. This animal was in the high‑dose group fed a diet providing approximately 20 mg steroid/kg BW/day for 13 weeks.
HISTOPATHOLOGIC DESCRIPTION: Lung: Affecting 80% of the section, alveolar lumina are expanded by eosinophilic foamy to granular material admixed with low numbers of degenerative neutrophils, macrophages, sloughed epithelial cells and fewer lymphocytes and plasma cells. These inflammatory cells also mildly expand the alveolar septa. Within the eosinophilic exudate and rarely within macrophages are numerous vague, ill-defined, 4-8 um, pale staining round to oval fungal cysts. Multifocally alveoli are lined by plump cuboidal epithelium (type II pneumocyte hyperplasia). Multifocally there are perivascular and peribronchiolar aggregates of moderate numbers of plasma cells, fewer lymphocytes and macrophages with mildly ectatic lymphatics. Multifocally, the pleura is lined by enlarged mesothelium (hypertrophy).
Slide B: Lung (GMS): There are numerous 3-4 um round to oval fungal cysts within alveoli and macrophages that stain black with central pallor.
MORPHOLOGIC DIAGNOSIS: Lung: Interstitial pneumonia, neutrophilic and histiocytic, diffuse, mild, with type II pneumocyte hyperplasia and foamy alveolar exudate with numerous intraalveolar and intrahistiocytic fungal cysts, etiology consistent with Pneumocystis carinii, Sprague‑Dawley rat, rodent
ETIOLOGIC DIAGNOSIS: Pulmonary pneumocystosis
CAUSE: Pneumocystis carinii
- Atypical fungus of worldwide distribution causing pneumonia in immunocompromised animals of a variety of species
- Related to ascomycetous yeasts (e.g. Candida albicans) based on genetic sequencing; biologically, behaves like a protozoan
- Individual strains are morphologically indistinguishable but retain high species specificity (not zoonotic and not transmitted to different species)
- Organism occurs in two forms (both occur in the lung):
- Trophic form: 1-4 um, irregularly shaped, uninucleate
- Cysts: 4-8 um, thick walled, multinucleate with 8 intracystic bodies
- Infective stage unknown and life cycle not completely understood; most commonly appears as an opportunistic infection in an immunocompromised patient (SCID mice, HIV/SIV)
- In immunosuppressed animals, intracystic bodies released from cyst and adhere to type I pneumocytes, mediated by fibronectin-binding integrins and major surface glycoprotein (glycoprotein A), then develop into trophic forms
- Alveolar-capillary membrane is disrupted causing epithelial cell necrosis and sloughing
- Host response leads to type II pneumocyte hypertrophy and hyperplasia
- In severe cases, significant alveolar-capillary disruption can lead to dissemination and extrapulmonary pneumocystosis
- Macrophages and cell-mediated immune responses essential to control Pneumocystis, hence clinical disease implies impairment of these responses
TYPICAL CLINICAL FINDINGS:
- Exercise intolerance, respiratory difficulties, weight loss
TYPICAL GROSS FINDINGS:
- Diffuse or patchy, red to pale-pink to yellow-brown, firm rubbery consolidation
- Failure to collapse
- May be altered by coexisting viral or bacterial infection
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Diffuse interstitial pneumonia with alveolar flooding by an eosinophilic foamy or “honeycomb” exudate (edema + organisms) with fungal cysts containing fungal bodies
- carinii stains poorly with H&E; however, large amounts of eosinophilic foam without significant inflammation should put this at the top of the rule out list
- Use GMS stain for better visualization of yeast
- Variable type II pneumocyte hyperplasia and fibrosis
- Trophozoites extend filopodia deep into the plasma membrane of epithelium and anchor to the cell by bulging of the apical portion of the filopodia
ADDITIONAL DIAGNOSTIC TESTS:
- Trophozoites stain with Giemsa (red nucleus, blue cytoplasm)
- Cysts stain with Gomori Methenamine Silver (GMS) (black with central pallor)
- Bronchoalveolar lavage to recover cysts or trophozoites
- Fairly unique when H&E combined with GMS
- Recently shown that lesions of rat respiratory virus are due to carinii
- In mice, prior to staining with GMS or Giemsa, consider: Sendai virus, pneumonia virus of mice, and pulmonary edema secondary to congestive heart failure
- Immunosuppressed laboratory animals: Athymic rats and mice, SCID mice, SIV monkeys
- Species specific
- carinii & wakefieldiae (rat)
- murina (mouse)
- carinii (nonhuman primates)
- carinii sp. nov. orytolagi (rabbit)
- carinii special form (sp. f.) equi (horse, CID Arabian foals, especially; often associated with Rhodococcus)
- carinii sp. f. suis (pig- secondary to PRRS)
- Dogs: Often associated with canine distemper virus
- Hereditary immunodeficiency in miniature dachshunds
- Humans: found in 60% of AIDS patients ( jiroveci).
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