Respiratory System

Lung - Vacuolization, Cytoplasmic

Narrative
Comment:
Cytoplasmic vacuolization in the lungs is most commonly seen in the airway epithelium of mice (Figure 1, Figure 2, Figure 3, and Figure 4) but may also be seen in other species and in other types of epithelial cells. Cytoplasmic vacuolization is generally thought to represent a reversible degenerative change. The vacuolization may represent distended and pinched off endoplasmic reticulum. Mitochondrial damage may lead to insufficient beta-oxidation and accumulation of triglycerides within the mitochondria or cytoplasm. Damage to cellular components involved in protein synthesis may lead to decreased levels of apolipoproteins, which lead to decreased lipid transport and the accumulation of lipid in the cytoplasm. The vacuoles may be large and distend the cytoplasm, but frequently the vacuoles are very small (i.e., visible only with electron microscopy) and numerous and give the cytoplasm a pale or bluish gray appearance. Since cytoplasmic vacuolization is thought to be a degenerative change, it is often accompanied by other changes associated with tissue damage, such as inflammation and necrosis.
Recommendations:
Lung - Vacuolization, Cytoplasmic should be diagnosed and graded. The site (e.g., bronchus, bronchiole, alveolus) should be specified as part of the diagnosis. If the cytoplasmic vacuolization is a feature of a more severe degenerative or necrotic change, then degeneration or necrosis should be the recorded lesion (see  Lung - Epithelium - Necrosis and  Lung - Regeneration ) and the vacuolization should be described in the narrative. Associated lesions, such as inflammation, should be diagnosed and graded separately.
Related Links:
Lung - Epithelium - Necrosis
Lung - Regeneration
References:

Kumar V, Abbas AK, Fausto N. 2005. Robbins and Cotran Pathologic Basis of Disease, 7th ed. Elsevier Saunders, Philadelphia, 20.

National Toxicology Program. 1991. NTP TOX 5. Toxicity Studies of Cobalt Sulfate Heptahydrate in F344/N Rats and B6C3F1 Mice (Inhalation Studies).  NIH Publication No. 91-3124. NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/11946

National Toxicology Program. 2011. NTP TR 564. Toxicology and Carcinogenesis Studies of 1-Bromopropane (CAS No. 106-94-5) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/34854

Plopper CG, Van Winkle LS, Fanucchi MV, Malburg SR, Nishio SJ, Chang A, Buckpitt AR. 2001. Early events in naphthalene-induced acute Clara cell toxicity. II. Comparison of glutathione depletion and histopathology by airway location. Am J Respir Cell Mol Biol 24:272-281.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/11245626

Wallig MA. 2002. Morphological manifestation of toxic cell injury. In: Handbook of Toxicologic Pathology (Haschek WM, Rousseaux CG, Wallig MA, eds). Academic Press, San Diego, CA, 39-65.

  • Image of bronchiolar vacuolization, cytoplasmic in the lung from a female B6C3F1/N mouse in a chronic study

    Lung, Bronchiole - Vacuolization, Cytoplasmic in a female B6C3F1/N mouse from a chronic study (higher magnification of Figure 1). Most of the cells have also lost their cilia.

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Lung, Bronchiole - Vacuolization, Cytoplasmic in a female B6C3F1/N mouse from a chronic study. The bronchiolar epithelial cells have vacuolated cytoplasm.
Lung, Bronchiole - Vacuolization, Cytoplasmic in a female B6C3F1/N mouse from a chronic study. The bronchiolar epithelial cells have vacuolated cytoplasm.
Lung, Bronchiole - Vacuolization, Cytoplasmic in a female B6C3F1/N mouse from a chronic study (higher magnification of Figure 1). Most of the cells have also lost their cilia.
Lung, Bronchiole - Vacuolization, Cytoplasmic in a female B6C3F1/N mouse from a chronic study (higher magnification of Figure 1). Most of the cells have also lost their cilia.
Lung, Bronchiole - Vacuolization, Cytoplasmic in a female B6C3F1/N mouse from a chronic study. The bronchiolar epithelial cells contain clear, intracytoplasmic vacuoles.
Lung, Bronchiole - Vacuolization, Cytoplasmic in a female B6C3F1/N mouse from a chronic study. The bronchiolar epithelial cells contain clear, intracytoplasmic vacuoles.
Lung, Bronchiole - Vacuolization, Cytoplasmic in a female B6C3F1/N mouse from a chronic study. The bronchiolar epithelial cells contain clear, intracytoplasmic vacuoles and have lost their cilia.
Lung, Bronchiole - Vacuolization, Cytoplasmic in a female B6C3F1/N mouse from a chronic study. The bronchiolar epithelial cells contain clear, intracytoplasmic vacuoles and have lost their cilia.

Authors

Mark F. Cesta, DVM, PhD, DACVP
Staff Scientist/NTP Pathologist
NTP Pathology Group
National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC


Darlene Dixon, DVM, PhD, DACVP
Group Leader
Molecular Pathogenesis Group
National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC


Ronald A. Herbert, DVM, PhD
Group Leader/NTP Pathologist
Pathology Support Group
National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC


Lauren M. Staska, DVM, PhD, DACVP
Senior Pathologist
WIL Research
Hillsborough, NC

Reviewers

Gary A. Boorman, DVM, PhD, DACVP, DABT, DACLAM
Pathologist
Covance Laboratories, Inc.
Chantilly, VA

Robert C. Sills, DVM, PhD, FIATP
Chief, Cellular and Molecular Pathology Branch
National Toxicology Program
National Institute of Environmental Health Sciences, Research Triangle Park, NC